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Publisher: John Wiley and Sons   (Total: 1597 journals)

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Showing 1 - 200 of 1597 Journals sorted alphabetically
Abacus     Hybrid Journal   (Followers: 13, SJR: 0.48, h-index: 22)
About Campus     Hybrid Journal   (Followers: 5)
Academic Emergency Medicine     Hybrid Journal   (Followers: 67, SJR: 1.385, h-index: 91)
Accounting & Finance     Hybrid Journal   (Followers: 49, SJR: 0.547, h-index: 30)
ACEP NOW     Free   (Followers: 1)
Acta Anaesthesiologica Scandinavica     Hybrid Journal   (Followers: 55, SJR: 1.02, h-index: 88)
Acta Archaeologica     Hybrid Journal   (Followers: 175, SJR: 0.101, h-index: 9)
Acta Geologica Sinica (English Edition)     Hybrid Journal   (Followers: 3, SJR: 0.552, h-index: 41)
Acta Neurologica Scandinavica     Hybrid Journal   (Followers: 5, SJR: 1.203, h-index: 74)
Acta Obstetricia et Gynecologica Scandinavica     Hybrid Journal   (Followers: 14, SJR: 1.197, h-index: 81)
Acta Ophthalmologica     Hybrid Journal   (Followers: 7, SJR: 0.112, h-index: 1)
Acta Paediatrica     Hybrid Journal   (Followers: 56, SJR: 0.794, h-index: 88)
Acta Physiologica     Hybrid Journal   (Followers: 6, SJR: 1.69, h-index: 88)
Acta Polymerica     Hybrid Journal   (Followers: 9)
Acta Psychiatrica Scandinavica     Hybrid Journal   (Followers: 37, SJR: 2.518, h-index: 113)
Acta Zoologica     Hybrid Journal   (Followers: 7, SJR: 0.459, h-index: 29)
Acute Medicine & Surgery     Hybrid Journal   (Followers: 5)
Addiction     Hybrid Journal   (Followers: 36, SJR: 2.086, h-index: 143)
Addiction Biology     Hybrid Journal   (Followers: 15, SJR: 2.091, h-index: 57)
Adultspan J.     Hybrid Journal   (SJR: 0.127, h-index: 4)
Advanced Energy Materials     Hybrid Journal   (Followers: 26, SJR: 6.411, h-index: 86)
Advanced Engineering Materials     Hybrid Journal   (Followers: 28, SJR: 0.81, h-index: 81)
Advanced Functional Materials     Hybrid Journal   (Followers: 51, SJR: 5.21, h-index: 203)
Advanced Healthcare Materials     Hybrid Journal   (Followers: 14, SJR: 0.232, h-index: 7)
Advanced Materials     Hybrid Journal   (Followers: 283, SJR: 9.021, h-index: 345)
Advanced Materials Interfaces     Hybrid Journal   (Followers: 6, SJR: 1.177, h-index: 10)
Advanced Optical Materials     Hybrid Journal   (Followers: 7, SJR: 2.488, h-index: 21)
Advanced Science     Open Access   (Followers: 5)
Advanced Synthesis & Catalysis     Hybrid Journal   (Followers: 18, SJR: 2.729, h-index: 121)
Advances in Polymer Technology     Hybrid Journal   (Followers: 14, SJR: 0.344, h-index: 31)
Africa Confidential     Hybrid Journal   (Followers: 21)
Africa Research Bulletin: Economic, Financial and Technical Series     Hybrid Journal   (Followers: 13)
Africa Research Bulletin: Political, Social and Cultural Series     Hybrid Journal   (Followers: 11)
African Development Review     Hybrid Journal   (Followers: 33, SJR: 0.275, h-index: 17)
African J. of Ecology     Hybrid Journal   (Followers: 16, SJR: 0.477, h-index: 39)
Aggressive Behavior     Hybrid Journal   (Followers: 17, SJR: 1.391, h-index: 66)
Aging Cell     Open Access   (Followers: 11, SJR: 4.374, h-index: 95)
Agribusiness : an Intl. J.     Hybrid Journal   (Followers: 3, SJR: 0.627, h-index: 14)
Agricultural and Forest Entomology     Hybrid Journal   (Followers: 16, SJR: 0.925, h-index: 43)
Agricultural Economics     Hybrid Journal   (Followers: 45, SJR: 1.099, h-index: 51)
AIChE J.     Hybrid Journal   (Followers: 32, SJR: 1.122, h-index: 120)
Alcoholism and Drug Abuse Weekly     Hybrid Journal   (Followers: 7)
Alcoholism Clinical and Experimental Research     Hybrid Journal   (Followers: 7, SJR: 1.416, h-index: 125)
Alimentary Pharmacology & Therapeutics     Hybrid Journal   (Followers: 34, SJR: 2.833, h-index: 138)
Alimentary Pharmacology & Therapeutics Symposium Series     Hybrid Journal   (Followers: 3)
Allergy     Hybrid Journal   (Followers: 50, SJR: 3.048, h-index: 129)
Alternatives to the High Cost of Litigation     Hybrid Journal   (Followers: 3)
American Anthropologist     Hybrid Journal   (Followers: 153, SJR: 0.951, h-index: 61)
American Business Law J.     Hybrid Journal   (Followers: 24, SJR: 0.205, h-index: 17)
American Ethnologist     Hybrid Journal   (Followers: 93, SJR: 2.325, h-index: 51)
American J. of Economics and Sociology     Hybrid Journal   (Followers: 30, SJR: 0.211, h-index: 26)
American J. of Hematology     Hybrid Journal   (Followers: 35, SJR: 1.761, h-index: 77)
American J. of Human Biology     Hybrid Journal   (Followers: 13, SJR: 1.018, h-index: 58)
American J. of Industrial Medicine     Hybrid Journal   (Followers: 16, SJR: 0.993, h-index: 85)
American J. of Medical Genetics Part A     Hybrid Journal   (Followers: 17, SJR: 1.115, h-index: 61)
American J. of Medical Genetics Part B: Neuropsychiatric Genetics     Hybrid Journal   (Followers: 4, SJR: 1.771, h-index: 107)
American J. of Medical Genetics Part C: Seminars in Medical Genetics     Partially Free   (Followers: 6, SJR: 2.315, h-index: 79)
American J. of Physical Anthropology     Hybrid Journal   (Followers: 38, SJR: 1.41, h-index: 88)
American J. of Political Science     Hybrid Journal   (Followers: 302, SJR: 5.101, h-index: 114)
American J. of Primatology     Hybrid Journal   (Followers: 14, SJR: 1.197, h-index: 63)
American J. of Reproductive Immunology     Hybrid Journal   (Followers: 4, SJR: 1.347, h-index: 75)
American J. of Transplantation     Hybrid Journal   (Followers: 19, SJR: 2.792, h-index: 140)
American J. on Addictions     Hybrid Journal   (Followers: 10, SJR: 0.843, h-index: 57)
Anaesthesia     Hybrid Journal   (Followers: 146, SJR: 1.404, h-index: 88)
Analyses of Social Issues and Public Policy     Hybrid Journal   (Followers: 10, SJR: 0.397, h-index: 18)
Analytic Philosophy     Hybrid Journal   (Followers: 20)
Anatomia, Histologia, Embryologia: J. of Veterinary Medicine Series C     Hybrid Journal   (Followers: 3, SJR: 0.295, h-index: 27)
Anatomical Sciences Education     Hybrid Journal   (Followers: 1, SJR: 0.633, h-index: 24)
Andrologia     Hybrid Journal   (Followers: 2, SJR: 0.528, h-index: 45)
Andrology     Hybrid Journal   (Followers: 2, SJR: 0.979, h-index: 14)
Angewandte Chemie     Hybrid Journal   (Followers: 176)
Angewandte Chemie Intl. Edition     Hybrid Journal   (Followers: 239, SJR: 6.229, h-index: 397)
Animal Conservation     Hybrid Journal   (Followers: 41, SJR: 1.576, h-index: 62)
Animal Genetics     Hybrid Journal   (Followers: 8, SJR: 0.957, h-index: 67)
Animal Science J.     Hybrid Journal   (Followers: 6, SJR: 0.569, h-index: 24)
Annalen der Physik     Hybrid Journal   (Followers: 5, SJR: 1.46, h-index: 40)
Annals of Anthropological Practice     Partially Free   (Followers: 2, SJR: 0.187, h-index: 5)
Annals of Applied Biology     Hybrid Journal   (Followers: 7, SJR: 0.816, h-index: 56)
Annals of Clinical and Translational Neurology     Open Access   (Followers: 1)
Annals of Gastroenterological Surgery     Open Access  
Annals of Human Genetics     Hybrid Journal   (Followers: 9, SJR: 1.191, h-index: 67)
Annals of Neurology     Hybrid Journal   (Followers: 49, SJR: 5.584, h-index: 241)
Annals of Noninvasive Electrocardiology     Hybrid Journal   (Followers: 1, SJR: 0.531, h-index: 38)
Annals of Public and Cooperative Economics     Hybrid Journal   (Followers: 8, SJR: 0.336, h-index: 23)
Annals of the New York Academy of Sciences     Hybrid Journal   (Followers: 5, SJR: 2.389, h-index: 189)
Annual Bulletin of Historical Literature     Hybrid Journal   (Followers: 12)
Annual Review of Information Science and Technology     Hybrid Journal   (Followers: 14)
Anthropology & Education Quarterly     Hybrid Journal   (Followers: 26, SJR: 0.72, h-index: 31)
Anthropology & Humanism     Hybrid Journal   (Followers: 18, SJR: 0.137, h-index: 3)
Anthropology News     Hybrid Journal   (Followers: 15)
Anthropology of Consciousness     Hybrid Journal   (Followers: 11, SJR: 0.172, h-index: 5)
Anthropology of Work Review     Hybrid Journal   (Followers: 11, SJR: 0.256, h-index: 5)
Anthropology Today     Hybrid Journal   (Followers: 94, SJR: 0.545, h-index: 15)
Antipode     Hybrid Journal   (Followers: 54, SJR: 2.212, h-index: 69)
Anz J. of Surgery     Hybrid Journal   (Followers: 8, SJR: 0.432, h-index: 59)
Anzeiger für Schädlingskunde     Hybrid Journal   (Followers: 1)
Apmis     Hybrid Journal   (Followers: 1, SJR: 0.855, h-index: 73)
Applied Cognitive Psychology     Hybrid Journal   (Followers: 74, SJR: 0.754, h-index: 69)
Applied Organometallic Chemistry     Hybrid Journal   (Followers: 7, SJR: 0.632, h-index: 58)
Applied Psychology     Hybrid Journal   (Followers: 167, SJR: 1.023, h-index: 64)
Applied Psychology: Health and Well-Being     Hybrid Journal   (Followers: 53, SJR: 0.868, h-index: 13)
Applied Stochastic Models in Business and Industry     Hybrid Journal   (Followers: 5, SJR: 0.613, h-index: 24)
Aquaculture Nutrition     Hybrid Journal   (Followers: 12, SJR: 1.025, h-index: 55)
Aquaculture Research     Hybrid Journal   (Followers: 31, SJR: 0.807, h-index: 60)
Aquatic Conservation Marine and Freshwater Ecosystems     Hybrid Journal   (Followers: 36, SJR: 1.047, h-index: 57)
Arabian Archaeology and Epigraphy     Hybrid Journal   (Followers: 12, SJR: 0.453, h-index: 11)
Archaeological Prospection     Hybrid Journal   (Followers: 12, SJR: 0.922, h-index: 21)
Archaeology in Oceania     Hybrid Journal   (Followers: 13, SJR: 0.745, h-index: 18)
Archaeometry     Hybrid Journal   (Followers: 31, SJR: 0.809, h-index: 48)
Archeological Papers of The American Anthropological Association     Hybrid Journal   (Followers: 15, SJR: 0.156, h-index: 2)
Architectural Design     Hybrid Journal   (Followers: 29, SJR: 0.261, h-index: 9)
Archiv der Pharmazie     Hybrid Journal   (Followers: 3, SJR: 0.628, h-index: 43)
Archives of Drug Information     Hybrid Journal   (Followers: 5)
Archives of Insect Biochemistry and Physiology     Hybrid Journal   (SJR: 0.768, h-index: 54)
Area     Hybrid Journal   (Followers: 13, SJR: 0.938, h-index: 57)
Art History     Hybrid Journal   (Followers: 273, SJR: 0.153, h-index: 13)
Arthritis & Rheumatology     Hybrid Journal   (Followers: 56, SJR: 1.984, h-index: 20)
Arthritis Care & Research     Hybrid Journal   (Followers: 29, SJR: 2.256, h-index: 114)
Artificial Organs     Hybrid Journal   (Followers: 1, SJR: 0.872, h-index: 60)
ASHE Higher Education Reports     Hybrid Journal   (Followers: 16)
Asia & the Pacific Policy Studies     Open Access   (Followers: 17)
Asia Pacific J. of Human Resources     Hybrid Journal   (Followers: 329, SJR: 0.494, h-index: 19)
Asia Pacific Viewpoint     Hybrid Journal   (Followers: 1, SJR: 0.616, h-index: 26)
Asia-Pacific J. of Chemical Engineering     Hybrid Journal   (Followers: 8, SJR: 0.345, h-index: 20)
Asia-pacific J. of Clinical Oncology     Hybrid Journal   (Followers: 6, SJR: 0.554, h-index: 14)
Asia-Pacific J. of Financial Studies     Hybrid Journal   (SJR: 0.241, h-index: 7)
Asia-Pacific Psychiatry     Hybrid Journal   (Followers: 4, SJR: 0.377, h-index: 7)
Asian Economic J.     Hybrid Journal   (Followers: 8, SJR: 0.234, h-index: 21)
Asian Economic Policy Review     Hybrid Journal   (Followers: 4, SJR: 0.196, h-index: 12)
Asian J. of Control     Hybrid Journal   (SJR: 0.862, h-index: 34)
Asian J. of Endoscopic Surgery     Hybrid Journal   (Followers: 1, SJR: 0.394, h-index: 7)
Asian J. of Organic Chemistry     Hybrid Journal   (Followers: 6, SJR: 1.443, h-index: 19)
Asian J. of Social Psychology     Hybrid Journal   (Followers: 6, SJR: 0.665, h-index: 37)
Asian Politics and Policy     Hybrid Journal   (Followers: 12, SJR: 0.207, h-index: 7)
Asian Social Work and Policy Review     Hybrid Journal   (Followers: 5, SJR: 0.318, h-index: 5)
Asian-pacific Economic Literature     Hybrid Journal   (Followers: 5, SJR: 0.168, h-index: 15)
Assessment Update     Hybrid Journal   (Followers: 4)
Astronomische Nachrichten     Hybrid Journal   (Followers: 3, SJR: 0.701, h-index: 40)
Atmospheric Science Letters     Open Access   (Followers: 30, SJR: 1.332, h-index: 27)
Austral Ecology     Hybrid Journal   (Followers: 15, SJR: 1.095, h-index: 66)
Austral Entomology     Hybrid Journal   (Followers: 9, SJR: 0.524, h-index: 28)
Australasian J. of Dermatology     Hybrid Journal   (Followers: 8, SJR: 0.714, h-index: 40)
Australasian J. On Ageing     Hybrid Journal   (Followers: 6, SJR: 0.39, h-index: 22)
Australian & New Zealand J. of Statistics     Hybrid Journal   (Followers: 14, SJR: 0.275, h-index: 28)
Australian Accounting Review     Hybrid Journal   (Followers: 3, SJR: 0.709, h-index: 14)
Australian and New Zealand J. of Family Therapy (ANZJFT)     Hybrid Journal   (Followers: 3, SJR: 0.382, h-index: 12)
Australian and New Zealand J. of Obstetrics and Gynaecology     Hybrid Journal   (Followers: 46, SJR: 0.814, h-index: 49)
Australian and New Zealand J. of Public Health     Hybrid Journal   (Followers: 13, SJR: 0.82, h-index: 62)
Australian Dental J.     Hybrid Journal   (Followers: 6, SJR: 0.482, h-index: 46)
Australian Economic History Review     Hybrid Journal   (Followers: 6, SJR: 0.171, h-index: 12)
Australian Economic Papers     Hybrid Journal   (Followers: 31, SJR: 0.23, h-index: 9)
Australian Economic Review     Hybrid Journal   (Followers: 6, SJR: 0.357, h-index: 21)
Australian Endodontic J.     Hybrid Journal   (Followers: 3, SJR: 0.513, h-index: 24)
Australian J. of Agricultural and Resource Economics     Hybrid Journal   (Followers: 3, SJR: 0.765, h-index: 36)
Australian J. of Grape and Wine Research     Hybrid Journal   (Followers: 5, SJR: 0.879, h-index: 56)
Australian J. of Politics & History     Hybrid Journal   (Followers: 15, SJR: 0.203, h-index: 14)
Australian J. of Psychology     Hybrid Journal   (Followers: 18, SJR: 0.384, h-index: 30)
Australian J. of Public Administration     Hybrid Journal   (Followers: 443, SJR: 0.418, h-index: 29)
Australian J. of Rural Health     Hybrid Journal   (Followers: 6, SJR: 0.43, h-index: 34)
Australian Occupational Therapy J.     Hybrid Journal   (Followers: 75, SJR: 0.59, h-index: 29)
Australian Psychologist     Hybrid Journal   (Followers: 11, SJR: 0.331, h-index: 31)
Australian Veterinary J.     Hybrid Journal   (Followers: 23, SJR: 0.459, h-index: 45)
Autism Research     Hybrid Journal   (Followers: 38, SJR: 2.126, h-index: 39)
Autonomic & Autacoid Pharmacology     Hybrid Journal   (SJR: 0.371, h-index: 29)
Banks in Insurance Report     Hybrid Journal   (Followers: 1)
Basic & Clinical Pharmacology & Toxicology     Hybrid Journal   (Followers: 11, SJR: 0.539, h-index: 70)
Basic and Applied Pathology     Open Access   (Followers: 2, SJR: 0.113, h-index: 4)
Basin Research     Hybrid Journal   (Followers: 5, SJR: 1.54, h-index: 60)
Bauphysik     Hybrid Journal   (Followers: 2, SJR: 0.194, h-index: 5)
Bauregelliste A, Bauregelliste B Und Liste C     Hybrid Journal  
Bautechnik     Hybrid Journal   (Followers: 1, SJR: 0.321, h-index: 11)
Behavioral Interventions     Hybrid Journal   (Followers: 10, SJR: 0.297, h-index: 23)
Behavioral Sciences & the Law     Hybrid Journal   (Followers: 23, SJR: 0.736, h-index: 57)
Berichte Zur Wissenschaftsgeschichte     Hybrid Journal   (Followers: 10, SJR: 0.11, h-index: 5)
Beton- und Stahlbetonbau     Hybrid Journal   (Followers: 2, SJR: 0.493, h-index: 14)
Biochemistry and Molecular Biology Education     Hybrid Journal   (Followers: 6, SJR: 0.311, h-index: 26)
Bioelectromagnetics     Hybrid Journal   (Followers: 1, SJR: 0.568, h-index: 64)
Bioengineering & Translational Medicine     Open Access  
BioEssays     Hybrid Journal   (Followers: 10, SJR: 3.104, h-index: 155)
Bioethics     Hybrid Journal   (Followers: 14, SJR: 0.686, h-index: 39)
Biofuels, Bioproducts and Biorefining     Hybrid Journal   (Followers: 1, SJR: 1.725, h-index: 56)
Biological J. of the Linnean Society     Hybrid Journal   (Followers: 18, SJR: 1.172, h-index: 90)
Biological Reviews     Hybrid Journal   (Followers: 5, SJR: 6.469, h-index: 114)
Biologie in Unserer Zeit (Biuz)     Hybrid Journal   (Followers: 41, SJR: 0.12, h-index: 1)
Biology of the Cell     Full-text available via subscription   (Followers: 9, SJR: 1.812, h-index: 69)
Biomedical Chromatography     Hybrid Journal   (Followers: 7, SJR: 0.572, h-index: 49)
Biometrical J.     Hybrid Journal   (Followers: 5, SJR: 0.784, h-index: 44)
Biometrics     Hybrid Journal   (Followers: 37, SJR: 1.906, h-index: 96)
Biopharmaceutics and Drug Disposition     Hybrid Journal   (Followers: 10, SJR: 0.715, h-index: 44)
Biopolymers     Hybrid Journal   (Followers: 18, SJR: 1.199, h-index: 104)
Biotechnology and Applied Biochemistry     Hybrid Journal   (Followers: 44, SJR: 0.415, h-index: 55)
Biotechnology and Bioengineering     Hybrid Journal   (Followers: 161, SJR: 1.633, h-index: 146)
Biotechnology J.     Hybrid Journal   (Followers: 15, SJR: 1.185, h-index: 51)
Biotechnology Progress     Hybrid Journal   (Followers: 39, SJR: 0.736, h-index: 101)
Biotropica     Hybrid Journal   (Followers: 20, SJR: 1.374, h-index: 71)
Bipolar Disorders     Hybrid Journal   (Followers: 9, SJR: 2.592, h-index: 100)
Birth     Hybrid Journal   (Followers: 38, SJR: 0.763, h-index: 64)
Birth Defects Research Part A : Clinical and Molecular Teratology     Hybrid Journal   (Followers: 2, SJR: 0.727, h-index: 77)
Birth Defects Research Part B: Developmental and Reproductive Toxicology     Hybrid Journal   (Followers: 8, SJR: 0.468, h-index: 47)
Birth Defects Research Part C : Embryo Today : Reviews     Hybrid Journal   (SJR: 1.513, h-index: 55)

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Journal Cover Advanced Healthcare Materials
  [SJR: 2.396]   [H-I: 29]   [14 followers]  Follow
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
   ISSN (Print) 2192-2659
   Published by John Wiley and Sons Homepage  [1597 journals]
  • Skin Conformal Polymer Electrodes for Clinical ECG and EEG Recordings
    • Authors: Flurin Stauffer; Moritz Thielen, Christina Sauter, Séverine Chardonnens, Simon Bachmann, Klas Tybrandt, Christian Peters, Christofer Hierold, Janos Vörös
      Abstract: Preparation-free and skin compliant biopotential electrodes with high recording quality enable wearables for future healthcare and the Internet of Humans. Here, super-soft and self-adhesive electrodes are presented for use on dry and hairy skin without skin preparation or attachment pressure. The electrodes show a skin-contact impedance of 50 kΩ cm2 at 10 Hz that is comparable to clinical standard gel electrodes and lower than existing dry electrodes. Microstructured electrodes inspired by grasshopper feet adhere repeatedly to the skin with a force of up to 0.1 N cm−2 without further attachment even during strong movement or deformation of the skin. Skin compliance and adhesive properties of the electrodes result in reduction of noise and motion artifacts superior to other dry electrodes reaching the performance of commercial gel electrodes. The signal quality is demonstrated by recording a high-fidelity electrocardiograms of a swimmer in water. Furthermore, an electrode with soft macropillars is used to detect alpha activity in the electroencephalograms from the back of the head through dense hair. Compared to gel electrodes, the soft biopotential electrodes are nearly imperceptible to the wearer and cause no skin irritations even after hours of application. The electrodes presented here could combine unobtrusive and long-term biopotential recordings with clinical-grade signal performance.This work presents soft and self-adhesive biopotential electrodes for use on dry and hairy skin without skin preparation. With 50 kΩ cm2, the impedance is comparable to clinical-standard gel electrodes. Microstructured electrodes adhere to the skin during strong movement or deformation, macrostructured pillars establish contact through dense hair. High-fidelity recordings of electrocardiograms during swimming and of electroencephalograms from the backhead are demonstrated.
      PubDate: 2018-01-13T01:05:02.272827-05:
      DOI: 10.1002/adhm.201700994
  • Flexible Modulation of CO-Release Using Various Nuclearity of Metal
           Carbonyl Clusters on Graphene Oxide for Stroke Remediation
    • Authors: Mein Jin Tan; Han-Chi Pan, Hui Ru Tan, Jian Wei Chai, Qi Feng Lim, Ten It Wong, Xiaodong Zhou, Zi-Yao Hong, Lun-De Liao, Kien Voon Kong
      Abstract: Utilizing the size-dependent adsorption properties of ruthenium carbonyl clusters (Ru–carbon monoxide (CO)) onto graphene oxide (GO), a facile CO-release platform for in situ vasodilation as a treatment for stroke-related vascular diseases is developed. The rate and amount of formation of the CO-release-active RuII(CO)2 species can be modulated by a simple mixing procedure at room temperature. The subsequent thermally induced oxidation of RuII(CO)2 to RuO2 on the GO surface results in the release of CO. Further modulation of thermal and CO-release properties can be achieved via a hybridization of medium- and high-nuclearity of Ru–CO clusters that produces a RuO2/RuII(CO)2/6Ru–CO–GO composite, where 6Ru–CO–GO provides a photothermally activated reservoir of RuII(CO)2 species and the combined infrared absorption properties of GO and RuO2 provides photothermal response for in situ CO-release. The RuO2/RuII(CO)2/6Ru–CO–GO composite does not produce any cytotoxicity and the efficacy of the composite is further demonstrated in a cortical photothrombotic ischemia rat model.By utilizing the size-dependent adsorption properties of Ru–carbon monoxide (CO) compounds with graphene oxide (GO), a facile method for the modulation of RuII(CO)2 for treatment of vascular-related stroke disease is demonstrated. The hybridization of medium- and high-nuclearity ruthenium carbonyl compounds with GO produces a biocompatible CO-release material with excellent infrared triggerable photothermal properties.
      PubDate: 2018-01-12T03:31:20.114326-05:
      DOI: 10.1002/adhm.201701113
  • Interfacial Mineral Fusion and Tubule Entanglement as a Means to Harden a
           Bone Augmentation Material
    • Authors: Erik A. B. Hughes; Sophie C. Cox, Megan E. Cooke, Owen G. Davies, Richard L. Williams, Thomas J. Hall, Liam M. Grover
      Abstract: A new bone augmenting material is reported, which is formed from calcium-loaded hydrogel-based spheres. On immersion of these spheres in a physiological medium, they become surrounded with a sheath of precipitate, which ruptures due to a build-up in osmotic pressure. This results in the formation of mineral tubes that protrude from the sphere surface. When brought into close contact with one another, these spheres become fused through the entanglement and subsequent interstitial mineralization of the mineral tubules. The tubular calcium phosphate induces the expression of osteogenic genes (runt-related transcription factor 2 (RUNX2), transcription factor SP7 (SP7), collagen type 1 alpha 1 (COL1A1), and bone gamma-carboxyglutamic acid-containing protein (BGLAP)) and promotes the formation of mineral nodules in preosteoblast cultures comparable to an apatitic calcium phosphate phase. Furthermore, alkaline phosphatase (ALP) is significantly upregulated in the presence of tubular materials after 10 d in culture compared with control groups (p < 0.001) and sintered apatite (p < 0.05). This is the first report of a bioceramic material that is formed in its entirety in situ and is therefore likely to provide a better proxy for biological mineral than other existing synthetic alternatives to bone grafts.A new bone-filling material based on the delivery of hydrogel-based spheres unifies in the presence of biological fluids rich in phosphate. Interfacial mineral fusion and tubule entanglement hardens the bone augmentation device. The demonstrated augmentation system presents a major first of its kind by possessing the capacity to form in its entirety in vivo.
      PubDate: 2018-01-11T12:44:28.045492-05:
      DOI: 10.1002/adhm.201701166
  • Exploiting Advanced Hydrogel Technologies to Address Key Challenges in
           Regenerative Medicine
    • Authors: Daniel A. Foyt; Michael D. A. Norman, Tracy T. L. Yu, Eileen Gentleman
      Abstract: Regenerative medicine aims to tackle a panoply of challenges from repairing focal damage to articular cartilage to preventing pathological tissue remodeling after myocardial infarction. Hydrogels are water-swollen networks formed from synthetic or naturally derived polymers and are emerging as important tools to address these challenges. Recent advances in hydrogel chemistries are enabling researchers to create hydrogels that can act as 3D ex vivo tissue models, allowing them to explore fundamental questions in cell biology by replicating tissues' dynamic and nonlinear physical properties. Enabled by cutting edge techniques such as 3D bioprinting, cell-laden hydrogels are also being developed with highly controlled tissue-specific architectures, vasculature, and biological functions that together can direct tissue repair. Moreover, advanced in situ forming and acellular hydrogels are increasingly finding use as delivery vehicles for bioactive compounds and in mediating host cell response. Here, advances in the design and fabrication of hydrogels for regenerative medicine are reviewed. It is also addressed how controlled chemistries are allowing for precise engineering of spatial and time-dependent properties in hydrogels with a look to how these materials will eventually translate to clinical applications.Hydrogels have proven to be versatile, important tools in regenerative medicine. Recent advances in hydrogel chemistries and 3D bioprinting technologies have enabled researchers to create hydrogels that can act as sophisticated 3D ex vivo tissue models and form materials with highly controlled tissue-specific architectures, vasculature, and biological functions. Here, these advances and how these materials will eventually translate to clinical applications are discussed.
      PubDate: 2018-01-09T05:54:30.189052-05:
      DOI: 10.1002/adhm.201700939
  • 3D Bioprinting of Self‐Standing Silk‐Based Bioink
    • Authors: Zhaozhu Zheng; Jianbing Wu, Meng Liu, Heng Wang, Chunmei Li, María J. Rodriguez, Gang Li, Xiaoqin Wang, David L. Kaplan
      Abstract: Silk/polyethylene glycol (PEG) hydrogels are studied as self‐standing bioinks for 3D printing for tissue engineering. The two components of the bioink, silk fibroin protein (silk) and PEG, are both Food and Drug Administration approved materials in drug and medical device products. Mixing PEG with silk induces silk β‐sheet structure formation and thus gelation and water insolubility due to physical crosslinking. A variety of constructs with high resolution, high shape fidelity, and homogeneous gel matrices are printed. When human bone marrow mesenchymal stem cells are premixed with the silk solution prior to printing and the constructs are cultured in this medium, the cell‐loaded constructs maintain their shape over at least 12 weeks. Interestingly, the cells grow faster in the higher silk concentration (10%, w/v) gel than in lower ones (7.5 and 5%, w/v), likely due to the difference in material stiffness and the amount of residual PEG remaining in the gel related to material hydrophobicity. Subcutaneous implantation of 7.5% (w/v) bioink gels with and without printed fibroblast cells in mice reveals that the cells survive and proliferate in the gel matrix for at least 6 week postimplantation. The results suggest that these silk/PEG bioink gels may provide suitable scaffold environments for cell printing and function.A new type of bioink composed of silk fibroin and polyethylene glycol (PEG) can be readily printed into desired geometries with self‐standing property and high fidelity. The 3D printed constructs with various cells loaded are cultivated in vitro and implanted in vivo in mice for more than 6 weeks to demonstrate cell survival and proliferation.
      PubDate: 2018-01-02T03:31:46.015224-05:
      DOI: 10.1002/adhm.201701026
  • Encapsulated Optically Responsive Cell Systems: Toward Smart Implants in
    • Authors: Christophe Boss; Nicolas Bouche, Umberto De Marchi
      Abstract: Managing increasingly prevalent chronic diseases will require close continuous monitoring of patients. Cell-based biosensors may be used for implantable diagnostic systems to monitor health status. Cells are indeed natural sensors in the body. Functional cellular systems can be maintained in the body for long-term implantation using cell encapsulation technology. By taking advantage of recent progress in miniaturized optoelectronic systems, the genetic engineering of optically responsive cells may be combined with cell encapsulation to generate smart implantable cell-based sensing systems. In biomedical research, cell-based biosensors may be used to study cell signaling, therapeutic effects, and dosing of bioactive molecules in preclinical models. Today, a wide variety of genetically encoded fluorescent sensors have been developed for real-time imaging of living cells. Here, recent developments in genetically encoded sensors, cell encapsulation, and ultrasmall optical systems are highlighted. The integration of these components in a new generation of biosensors is creating innovative smart in vivo cell-based systems, bringing novel perspectives for biomedical research and ultimately allowing unique health monitoring applications.By taking advantage of the recent progress in miniaturized optoelectronic systems, the genetic engineering of optically responsive cells may be combined with cell encapsulation to generate implantable cell-based sensing systems. The integration of these components in a new generation of biosensors is creating innovative smart in vivo cell-based systems, bringing novel perspectives for biomedical research and ultimately allowing unique health monitoring applications.
      PubDate: 2017-12-28T05:26:26.026246-05:
      DOI: 10.1002/adhm.201701148
  • Role of the Nucleus as a Sensor of Cell Environment Topography
    • Authors: Karine Anselme; Nayana Tusamda Wakhloo, Pablo Rougerie, Laurent Pieuchot
      Abstract: The proper integration of biophysical cues from the cell vicinity is crucial for cells to maintain homeostasis, cooperate with other cells within the tissues, and properly fulfill their biological function. It is therefore crucial to fully understand how cells integrate these extracellular signals for tissue engineering and regenerative medicine. Topography has emerged as a prominent component of the cellular microenvironment that has pleiotropic effects on cell behavior. This progress report focuses on the recent advances in the understanding of the topography sensing mechanism with a special emphasis on the role of the nucleus. Here, recent techniques developed for monitoring the nuclear mechanics are reviewed and the impact of various topographies and their consequences on nuclear organization, gene regulation, and stem cell fate is summarized. The role of the cell nucleus as a sensor of cell-scale topography is further discussed.Topography is a prominent component of the cellular microenvironment. The discovery of the role of the nucleus in the cellular response to topography has been demonstrated very recently. This progress report outlines the recent knowledge in the topography sensing mechanism with a special emphasis on the role of the cell nucleus as a sensor of cell-scale topography.
      PubDate: 2017-12-28T05:24:59.722123-05:
      DOI: 10.1002/adhm.201701154
  • Synthetic Cells Synthesize Therapeutic Proteins inside Tumors
    • Authors: Nitzan Krinsky; Maya Kaduri, Assaf Zinger, Janna Shainsky-Roitman, Mor Goldfeder, Itai Benhar, Dov Hershkovitz, Avi Schroeder
      Abstract: Synthetic cells, artificial cell-like particles, capable of autonomously synthesizing RNA and proteins based on a DNA template, are emerging platforms for studying cellular functions and for revealing the origins-of-life. Here, it is shown for the first time that artificial lipid-based vesicles, containing the molecular machinery necessary for transcription and translation, can be used to synthesize anticancer proteins inside tumors. The synthetic cells are engineered as stand-alone systems, sourcing nutrients from their biological microenvironment to trigger protein synthesis. When pre-loaded with template DNA, amino acids and energy-supplying molecules, up to 2 × 107 copies of green fluorescent protein are synthesized in each synthetic cell. A variety of proteins, having molecular weights reaching 66 kDa and with diagnostic and therapeutic activities, are synthesized inside the particles. Incubating synthetic cells, encoded to secrete Pseudomonas exotoxin A (PE) with 4T1 breast cancer cells in culture, resulted in killing of most of the malignant cells. In mice bearing 4T1 tumors, histological evaluation of the tumor tissue after a local injection of PE-producing particles indicates robust apoptosis. Synthetic cells are new platforms for synthesizing therapeutic proteins on-demand in diseased tissues.Synthetic cells contain all the nanoscale molecular machines and building blocks necessary for carrying out transcription and translation, including ribosomes, RNA polymerase, amino acids, and energy. Based on synthetically-encoded DNA, the particles synthesize diagnostic and therapeutic proteins in tumors.
      PubDate: 2017-12-28T05:24:34.960945-05:
      DOI: 10.1002/adhm.201701163
  • Tumor Microenvironment-Enabled Nanotherapy
    • Authors: Liying Wang; Minfeng Huo, Yu Chen, Jianlin Shi
      Abstract: Cancer is now one of the world's leading threats to human health. With the development of oncology in both biology and biomedicine, it has been demonstrated that abnormal physiochemical conditions and dysregulated biosynthetic intermediates in tumor microenvironment (TME) play a pivotal role in enabling tumor cells to defend or evade the damage by traditional clinical tumor therapeutics including surgery, chemotherapy, radiotherapy, etc. The fast advances of TME-enabled theranostic nanomedicine have offered promising perspectives, strategies, and approaches for combating cancer based on the novel concept of TME-enabled nanotherapy. In this comprehensive review, the origins of TME (e.g., enhanced permeability and retention effect, overexpressed biosynthetic intermediates, mild acidic nature, redox potentials, hypoxia) are initially introduced and discussed, followed by detailed discussion and overview on the state-of-the-art progresses in TME-enabled antitumor nanotherapies (e.g., chemo/chemodynamic therapy, photodynamic therapy, radiotherapy). Finally, the obstacles and challenges of future development on TME-enabled nanotherapies for further clinical translation are outlooked.The present review summarizes and overviews the origins and stimuli-responsiveness in tumor microenvironment (e.g., enhanced permeability and retention effect, overexpressed biosynthetic nutrients, H2O2, glutathione, mild acidic nature, and hypoxia) assisted nanotherapies (e.g., chemo/chemodynamic therapy, photodynamic therapy, radiotherapy). The obstacles and challenges of future development on TME-assisted nanotherapies for further clinical translation are also extensively outlooked.
      PubDate: 2017-12-28T05:23:40.855308-05:
      DOI: 10.1002/adhm.201701156
  • Moldable Hyaluronan Hydrogel Enabled by Dynamic Metal–Bisphosphonate
           Coordination Chemistry for Wound Healing
    • Authors: Liyang Shi; Yannan Zhao, Qifan Xie, Caixia Fan, Jöns Hilborn, Jianwu Dai, Dmitri. A. Ossipov
      Abstract: Biomaterial-based regenerative approaches would allow for cost-effective off-the-shelf solution for the treatment of wounds. Hyaluronan (HA)-based hydrogel is one attractive biomaterial candidate because it is involved in natural healing processes, including inflammation, granulation, and reepithelialization. Herein, dynamic metal–ligand coordination bonds are used to fabricate moldable supramolecular HA hydrogels with self-healing properties. To achieve reversible crosslinking of HA chains, the biopolymer is modified with pendant bisphosphonate (BP) ligands using carbodiimide coupling and chemoselective “click” reactions. Hydrogel is formed immediately after simple addition of silver (Ag+) ions to the solution of HA containing BP groups (HA-BP). Compared with previous HA-based wound healing hydrogels, the HA-BP·Ag+ hydrogel is highly suitable for clinical use as it can fill irregularly shaped wound defects without the need for premolding. The HA-BP·Ag+ hydrogel shows antimicrobial properties to both Gram-positive and Gram-negative bacterial strains, enabling prevention of infections in wound care. In vivo evaluation using a rat full-thickness skin wound model shows significantly lower wound remaining rate and a thicker layer of regenerated epidermis as compared with the group left without treatment. The presented moldable and self-healing supramolecular HA hydrogel with “ready-to-use” properties possesses a great potential for regenerative wound treatment.Dynamic coordination chemistry is applied to design novel moldable and self-healing hyaluronan hydrogel, based on crosslinking between Ag+ ions and bisphosphonate group linked to hyaluronan macromolecules. This hydrogel possesses antibacterial properties and the ability to accelerate skin wound healing in vivo. The hydrogel is highly suitable for clinical use as it can fill irregularly shaped wound defects without the need for premolding.
      PubDate: 2017-12-27T09:40:56.976122-05:
      DOI: 10.1002/adhm.201700973
  • Convenient Monitoring System of Intracellular microRNA Expression during
           Adipogenesis via Mechanical Stimulus‐Induced Exocytosis of Lipovesicular
           miRNA Beacon
    • Authors: Seungmin Han; Byunghoon Kang, Eunji Jang, Jisun Ki, Eunjung Kim, Mun-Young Jeong, Yong-Min Huh, Hye-Young Son, Seungjoo Haam
      Abstract: Noninvasive investigation of microRNAs (miRNAs) expression, which is deeply related to biological phenomena such as stem cell differentiation, in culture soup is particularly useful for monitoring of stem cell differentiation without phototoxicity of living cells, especially when cell morphologies remain unchanged during differentiation. However, real‐time detection of miRNA in culture soup is not recommended because of insufficient miRNA amounts in culture soup. In this study, a convenient method is introduced for real‐time assessing intracellular miRNA in culture soup by using lipovesicular miRNA beacon (Lipo‐mB) and mechanical stimulus‐mediated exocytosis. Pipetting‐harvest of culture soup induces exocytosis‐secretion of fluorescence signal of Lipo‐mB from cytoplasm into culture soup. To demonstrate this method, Lipo‐mB is applied for monitoring of adipogenesis by analyzing the expression levels of various intracellular miRNAs, which are related to adipogenesis regulators. The fluorescence intensity profile of the culture soup is correlated with the quantitative reverse‐transcription‐polymerase chain reaction data and absorbance of Oil Red O staining. These results demonstrate that Lipo‐mB can successfully monitor stem cell differentiation by sensing changes in miRNA expression from culture soup of living cells. Lipo‐mB can be further developed as an accurate sensing system for analyzing subtle differences in genotype, even when changes in phenotype cannot be observed.Convenient method for monitoring of intracellular microRNA (miRNA) expression level from culture soup. Lipovesicular miRNA beacon‐nanoplatform senses target miRNA in cytoplasm, and then it is secreted into culture soup by mechanical stimulus‐mediated exocytosis, which is pipetting‐harvest. The system can monitor stem cell differentiation from culture soup without phototoxicity on living cells and cellular fixation step.
      PubDate: 2017-12-27T02:47:03.017557-05:
      DOI: 10.1002/adhm.201701019
  • A Fluorescent Biofunctional DNA Hydrogel Prepared by Enzymatic
    • Authors: Jinhui Geng; Chi Yao, Xiaohong Kou, Jianpu Tang, Dan Luo, Dayong Yang
      Abstract: DNA has arisen as a promising building material for the construction of hydrogels owing to its unique properties such as designability and biocompatibility. All‐DNA hydrogels with only DNA molecules may have limited applications; hence a composite DNA hydrogel with multifunctional moieties is highly desired to cater for specific applications. Herein, a multifunctional DNA hydrogel is created by incorporating DNA with silver nanoclusters (AgNCs), in which AgNCs render the hydrogel simultaneously with fluorescent and antibacterial functions. A circular DNA is rationally designed, which allows for the elongation of DNA chain via an enzymatic polymerization as well as the formation of AgNCs onto DNA scaffolds. The resultant hybrid DNA hydrogel not only shows distinctive morphology and mechanical properties, but also exhibits fluorescent and antibacterial functions. These characteristics, along with its biocompatibility, will allow the hydrogel to be suitable for a variety of potential biomedical applications such as tissue engineering, wound dressing, biosensing, and bioimaging.A hybrid multifunctional DNA hydrogel constructed by enzymatic polymerization is reported. A circular DNA is rationally designed, which simultaneously allows for the elongation of DNA chain and the formation of silver nanoclusters onto DNA. The resultant hybrid DNA hydrogel not only shows distinctive morphology and mechanical properties, but also exhibits fluorescent and antibacterial functions.
      PubDate: 2017-12-27T02:46:47.516171-05:
      DOI: 10.1002/adhm.201700998
  • Advances and Opportunities in Nanoparticle‐ and Nanomaterial‐Based
           Vaccines against Bacterial Infections
    • Abstract: As the dawn of the postantibiotic era we approach, antibacterial vaccines are becoming increasingly important for managing bacterial infection and reducing the need for antibiotics. Despite the success of vaccination, vaccines remain unavailable for many pressing microbial diseases, including tuberculosis, chlamydia, and staphylococcus infections. Amid continuing research efforts in antibacterial vaccine development, the advancement of nanomaterial engineering has brought forth new opportunities in vaccine designs. With increasing knowledge in antibacterial immunity and immunologic adjuvants, innovative nanoparticles are designed to elicit the appropriate immune responses for effective antimicrobial defense. Rationally designed nanoparticles are demonstrated to overcome delivery barriers to shape the adaptive immunity. This article reviews the advances in nanoparticle‐ and nanomaterial‐based antibacterial vaccines and summarizes the development of nanoparticulate adjuvants for immune potentiation against microbial pathogens. In addition, challenges and progress in ongoing antibacterial vaccine development are discussed to highlight the opportunities for future vaccine designs.Nanoparticle vaccines for antibacterial vaccination present a compelling intervention toward disease management in the postantibiotic era. This review article summarizes advances in the field of nanoparticle antibacterial vaccines and highlights the strengths of different carrier platforms. Challenges and opportunities in vaccine development against several pressing microbial pathogens are also examined.
  • Phenylboronic Acid Functionalized Polycarbonate Hydrogels for Controlled
           Release of Polymyxin B in Pseudomonas Aeruginosa Infected Burn Wounds
    • Abstract: While physically crosslinked polycarbonate hydrogels are effective drug delivery platforms, their hydrophobic nature and lack of side chain functionality or affinity ligands for controlled release of hydrophilic drugs underscore the importance of their chemical compositions. This study evaluates an array of anionic hydrogel systems of phenylboronic acid functionalized triblock copolymers prepared via reversible physical interactions. Variation of key chemical functionalities while maintaining similar core structural features demonstrates the influence of the substitution position and protection of the boronic acid functionality on gel viscoelasticity and mechanical strength at physiological pH. The optimum gel systems obtained from the meta‐substituted copolymers (m‐PAP) are stable at physiological pH and nontoxic to mammalian dermal cells. The polymyxin B loaded m‐PAP hydrogels demonstrate controlled in vitro drug release kinetics and in vitro antimicrobial activity against Pseudomonas aeruginosa over 48 h. In vivo antimicrobial efficacy of the drug loaded hydrogels further corroborates the in vitro results, demonstrating sustained antimicrobial activity against P. aeruginosa burn wound infections. The current strategy described in this study demonstrates a straightforward approach in designing physiologically relevant boronic acid hydrogel systems for controlled release of cationic antimicrobials for future clinical applications.A physiologically stable hydrogel formulation from a meta‐substituted phenylboronic acid functionalized “ABA” triblock copolymer controls the release of polymyxin B via noncovalent matrix–drug interactions between the anionic polymer ligands and the cationic peptide. The biocompatible hydrogel demonstrates sustained in vitro and in vivo antimicrobial efficacy, against topical burn wound infections caused by Pseudomonas aeruginosa.
  • Nanoscaled Metal‐Organic Frameworks for Biosensing, Imaging, and
           Cancer Therapy
    • Abstract: Owing to the progressive development of metal‐organic frameworks (MOFs) synthetic processes and their unique characters associated with the excellent performance‐selectable composition, tunable pore scale, large surface area, and good thermal stability, MOFs have captured the interest and the imagination of an increasing number of scientists working in different fields. In the area of biomedical applications, MOFs are especially involved in sensing, molecular imaging, and drug delivery, with strong contributions to the whole nanomedicine area. Recently, these materials have been scaled down to nanometer sizes with the advancement of chemical synthesis gradually reaching an adjustable level. This review mainly discusses and summarizes the general synthesis, properties, and biomedical applications of nanoscaled MOFs and their composites in biosensing, imaging, and cancer therapy within the latest three years. The remaining challenges and future opportunities in this field, in terms of processing techniques, maximizing composite properties, and prospects for clinical applications, are also indicated.The recent progress in the development of nanoscaled metal‐organic frameworks for biomedical application is reviewed via a broad perspective. Typical examples in biosensing, molecular imaging, cancer treatment, and cancer theranostics are discussed. The remaining problems and promising breakthroughs in this field are also outlined.
  • Conceptually Novel Black Phosphorus/Cellulose Hydrogels as Promising
           Photothermal Agents for Effective Cancer Therapy
    • Abstract: Black phosphorus (BP) has recently emerged as an intriguing photothermal agent in photothermal therapy (PTT) against cancer by virtue of its high photothermal efficiency, biocompatibility, and biodegradability. However, naked BP is intrinsically characterized by easy oxidation (or natural degradation) and sedimentation inside the tumor microenvironment, leading to a short‐term therapeutic and inhomogeneous photothermal effect. Development of BP‐based nanocomposites for PTT against cancer therefore remains challenging. The present work demonstrates that green and injectable composite hydrogels based on cellulose and BP nanosheets (BPNSs) are of great efficiency for PTT against cancer. The resultant cellulose/BPNS‐based hydrogel possesses 3D networks with irregular micrometer‐sized pores and thin, strong cellulose‐formed walls and exhibits an excellent photothermal response, enhanced stability, and good flexibility. Importantly, this hydrogel nanoplatform is totally harmless and biocompatible both in vivo and in vitro. This work may facilitate the development of BP–polymer‐based photothermal agents in the form of hydrogels for biomedical‐related clinic applications.3D composite hydrogels based on 2D black phosphorus (BP) nanosheets and cellulose are developed in this work. Their morphology, physical properties, and biocompatibility/toxicity are investigated. Based on these characterizations, the 3D cellulose/BP composite hydrogel‐based nanoplatforms are realized for photothermal therapy against cancer, and their performance is evaluated.
  • Photothermally Controlled MHC Class I Restricted CD8+ T‐Cell Responses
           Elicited by Hyaluronic Acid Decorated Gold Nanoparticles as a Vaccine for
           Cancer Immunotherapy
    • Abstract: Cancer vaccines aim to induce a strong major histocompatibility complex class I (MHC‐I)‐restricted CD8+ cytotoxic T‐cell response, which is an important prerequisite for successful cancer immunotherapy. Herein, a hyaluronic acid (HA) and antigen (ovalbumin, OVA)‐decorated gold nanoparticle (AuNPs)‐based (HA‐OVA‐AuNPs) vaccine is developed for photothermally controlled cytosolic antigen delivery using near‐infrared (NIR) irradiation and is found to induce antigen‐specific CD8+ T‐cell responses. Chemical binding of thiolated HA and OVA to AuNPs facilitates antigen uptake of dendritic cells via receptor‐mediated endocytosis. HA‐OVA‐AuNPs exhibit enhanced NIR absorption and thermal energy translation. Cytosolic antigen delivery is then permitted through the photothermally controlled process of local heat‐mediated endo/lysosome disruption by laser irradiation along with reactive oxygen species generation, which helps to augment proteasome activity and downstream MHC I antigen presentation. Consequently, the HA‐OVA‐AuNPs nanovaccine can effectively evoke a potent anticancer immune response in mice under laser irradiation. This NIR‐responsive nanovaccine is promising as a potent vaccination method for improving cancer vaccine efficacy.Near infrared light (NIR)‐responsive gold nanoparticle‐based nanovaccine enhances the cross‐presentation of vaccines through photothermally controlled endo/lysosome disruption. Subcutaneous administration of this nanovaccine also induces major cytotoxic T lymphocytes (CTL) response accompanied by inhibition of tumor growth. Looking forward, this NIR‐responsive nanovaccine is promising as a potent method of vaccination for improving cancer vaccine efficacy.
  • Surface‐Enhanced Raman Scattering for Rapid Detection and
           Characterization of Antibiotic‐Resistant Bacteria
    • Abstract: As the prevalence of antibiotic‐resistant bacteria continues to rise, biosensing technologies are needed to enable rapid diagnosis of bacterial infections. Furthermore, understanding the unique biochemistry of resistance mechanisms can facilitate the development of next generation therapeutics. Surface‐enhanced Raman scattering (SERS) offers a potential solution to real‐time diagnostic technologies, as well as a route to fundamental, mechanistic studies. In the current review, SERS‐based approaches to the detection and characterization of antibiotic‐resistant bacteria are covered. The commonly used nanomaterials (nanoparticles and nanostructured surfaces) and surface modifications (antibodies, aptamers, reporters, etc.) for SERS bacterial detection and differentiation are discussed first, and followed by a review of SERS‐based detection of antibiotic‐resistant bacteria from environmental/food processing and clinical sources. Antibiotic susceptibility testing and minimum inhibitory concentration testing with SERS are then summarized. Finally, recent developments of SERS‐based chemical imaging/mapping of bacteria are reviewed.Surface‐enhanced Raman scattering (SERS)‐based approaches to detect and characterize antibiotic‐resistant bacteria are reviewed in this contribution. SERS technologies hold promise to enable rapid detection and fundamental understanding of resistance mechanisms. This review focuses on SERS‐active nanomaterials (nanoparticles and nanostructured surfaces) for bacterial detection and SERS‐based detection of antibiotic‐resistant bacteria. Recent developments in SERS‐based antibiotic susceptibility testing and bacterial mapping are also covered.
  • Graphene Materials in Antimicrobial Nanomedicine: Current Status and
           Future Perspectives
    • Abstract: Graphene materials (GMs), such as graphene, graphene oxide (GO), reduced GO (rGO), and graphene quantum dots (GQDs), are rapidly emerging as a new class of broad‐spectrum antimicrobial agents. This report describes their state‐of‐the‐art and potential future covering both fundamental aspects and biomedical applications. First, the current understanding of the antimicrobial mechanisms of GMs is illustrated, and the complex picture of underlying structure–property–activity relationships is sketched. Next, the different modes of utilization of antimicrobial GMs are explained, which include their use as colloidal dispersions, surface coatings, and photothermal/photodynamic therapy agents. Due to their practical relevance, the examples where GMs function as synergistic agents or release platforms for metal ions and/or antibiotic drugs are also discussed. Later, the applicability of GMs in the design of wound dressings, infection‐protective coatings, and antibiotic‐like formulations (“nanoantibiotics”) is assessed. Notably, to support our assessments, the existing clinical applications of conventional carbon materials are also evaluated. Finally, the key hurdles of the field are highlighted, and several possible directions for future investigations are proposed. We hope that the roadmap provided here will encourage researchers to tackle remaining challenges toward clinical translation of promising research findings and help realize the potential of GMs in antimicrobial nanomedicine.This report explains the current state and potential research directions of antimicrobial graphenes focusing on three major aspects: (i) the mechanisms of antimicrobial activity referring to structure–property–activity relationships, (ii) proposed modes for utilization in biomedical antimicrobial applications, (iii) remaining questions concerning the fundamental understanding and critical considerations for future use in clinical settings.
  • Novel 3D Hybrid Nanofiber Aerogels Coupled with BMP‐2 Peptides for
           Cranial Bone Regeneration
    • Abstract: An ideal synthetic bone graft is a combination of the porous and nanofibrous structure presented by natural bone tissue as well as osteoinductive biochemical factors such as bone morphogenetic protein 2 (BMP‐2). In this work, ultralight 3D hybrid nanofiber aerogels composed of electrospun PLGA‐collagen‐gelatin and Sr–Cu codoped bioactive glass fibers with incorporation of heptaglutamate E7 domain specific BMP‐2 peptides have been developed and evaluated for their potential in cranial bone defect healing. The nanofiber aerogels are surgically implanted into 8 mm × 1 mm (diameter × thickness) critical‐sized defects created in rat calvariae. A sustained release of E7‐BMP‐2 peptide from the degradable hybrid aerogels significantly enhances bone healing and defect closure over 8 weeks in comparison to unfilled defects. Histomorphometry and X‐ray microcomputed tomography (µ‐CT) analysis reveal greater bone volume and bone formation area in case of the E7‐BMP‐2 peptide loaded hybrid nanofiber aerogels. Further, histopathology data divulged a near complete nanofiber aerogel degradation along with enhanced vascularization of the regenerated tissue. Together, this study for the first time demonstrates the fabrication of 3D hybrid nanofiber aerogels from 2D electrospun fibers and their loading with therapeutic osteoinductive BMP‐2 mimicking peptide for cranial bone tissue regeneration.This study reports novel 3D hybrid nanofiber aerogels that topically deliver trace metal ions and bone morphogenetic protein 2 peptides to promote neovascularization and cranial bone regeneration.
  • Point‐of‐Care Identification of Bacteria Using Protein‐Encapsulated
           Gold Nanoclusters
    • Abstract: The rapid, simple, and reliable identification of the most prevalent pathogens is essential for clinical diagnostics, biology, and food safety. Herein, four protein‐encapsulated gold nanoclusters (protein–AuNCs) are designed and prepared as a sensor array for rapid identification of bacteria. The discrimination of six kinds of bacteria, including two kinds of drug‐resistant bacteria, is successfully realized by the as‐fabricated sensor array. The strategy presented here shows the advantages of easy synthesis and convenient to use. Furthermore, 100% classification accuracy is achieved by the sensor array consisting of two protein–AuNCs probes, demonstrating the design with sufficient diagnostic capacity. Taken together, the developed sensor array holds great promise for facile diagnosis of bacterial infection in resource‐limited settings.Four protein‐encapsulated gold nanoclusters with various binding affinities to bacteria are employed as sensor array to rapid identification of bacteria. Two kinds of the most prevalent pathogens and their drug‐resistant strains are well discriminated. The protocol holds great promise for point‐of‐care bacterial infection diagnosis because of the simple probe synthesis and bacterial identification procedures.
  • Hybrid Materials: Flexible Modulation of CO‐Release Using Various
           Nuclearity of Metal Carbonyl Clusters on Graphene Oxide for Stroke
           Remediation (Adv. Healthcare Mater. 5/2018)
    • Abstract: A facile CO‐release material for in‐situ vasodilation as a treatment for stroke‐related vascular diseases is developed by K.V. Kong, L.D. Liao and co‐workers in article number 1701113. Utilizing the size dependent adsorption properties of ruthenium carbonyl clusters (Ru‐CO) onto graphene oxide (GO), the rate and amount of formation of the CO release‐active RuII(CO)2 species can be modulated by a simple mixing procedure. Further modulation of thermal and CO release properties can be achieved via a hybridization of medium‐ and high‐ nuclearity of Ru‐CO clusters that can provide photo‐thermal response for in‐situ CO release in a cortical photo‐thrombotic ischemia rat model.
  • Tissue Engineering: Silicon Carbide Nanoparticles as an Effective
           Bioadhesive to Bond Collagen Containing Composite Gel Layers for Tissue
           Engineering Applications (Adv. Healthcare Mater. 5/2018)
    • Abstract: In article number 1701385, Ponnambalam Ravi Selvaganapathy and co‐workers use a lamination‐based planar processing strategy enabled by nanoparticle adhesives to address one of the prominent technical challenges found in the tissue engineering field – the incorporation of perfusable hollow networks for nutrient and waste transport within artificial 3D tissue constructs. Without these vascular‐like networks, the cells embedded within the constructs would quickly become necrotic. Silicon Carbide, used as a nanoadhesive, has been shown to be very effective in adhering microstructured layers of biologically important extracellular matrices containing collagen to form perfusable 3D netoworks suitable for growing cells.
  • Wearable Biosensors: Disposable Morpho menelaus Based Flexible
           Microfluidic and Electronic Sensor for the Diagnosis of Neurodegenerative
           Disease (Adv. Healthcare Mater. 5/2018)
    • Abstract: A disposable Morpho menelaus based wearable biosensor with integration of a microfluidic system and electronic networks is presented in article number 1701306 by Zhongze Gu and co‐workers. The excellent structural and optical characteristics of the Morpho menelaus are exploited for flexible sensors, which enable biochemical‐physiological hybrid monitoring of neurodegenerative disease for the early diagnosis.
  • Masthead: (Adv. Healthcare Mater. 5/2018)
  • Advances in Magnetic Nanoparticles for Biomedical Applications
    • Abstract: Magnetic nanoparticles (NPs) are emerging as an important class of biomedical functional nanomaterials in areas such as hyperthermia, drug release, tissue engineering, theranostic, and lab‐on‐a‐chip, due to their exclusive chemical and physical properties. Although some works can be found reviewing the main application of magnetic NPs in the area of biomedical engineering, recent and intense progress on magnetic nanoparticle research, from synthesis to surface functionalization strategies, demands for a work that includes, summarizes, and debates current directions and ongoing advancements in this research field. Thus, the present work addresses the structure, synthesis, properties, and the incorporation of magnetic NPs in nanocomposites, highlighting the most relevant effects of the synthesis on the magnetic and structural properties of the magnetic NPs and how these effects limit their utilization in the biomedical area. Furthermore, this review next focuses on the application of magnetic NPs on the biomedical field. Finally, a discussion of the main challenges and an outlook of the future developments in the use of magnetic NPs for advanced biomedical applications are critically provided.Magnetic nanoparticles (NPs) are emerging as a new class of biomedical functional nanomaterials in the areas of hyperthermia, drug release, tissue engineering, theranostic, and lab‐on‐a‐chip. This review first addresses the structure, synthesis, properties, and the incorporation of magnetic NPs on the nanocomposite systems, and then emphasizes the biofunctionalization and their practical usefulness. In the end, the challenges and outlook are addressed.
  • Advances in Nanoporous Anodic Alumina‐Based Biosensors to Detect
           Biomarkers of Clinical Significance: A Review
    • Abstract: There is a strong and growing demand for compact, portable, rapid, and low‐cost devices to detect biomarkers of interest in clinical and point‐of‐care diagnostics. Such devices aid in early diagnosis of diseases without the need to rely on expensive and time‐consuming large instruments in dedicated laboratories. Over the last decade, numerous biosensors have been developed for detection of a wide range of clinical biomarkers including proteins, nucleic acids, growth factors, and bacterial enzymes. Various transduction techniques have been reported based on biosensor technology that deliver substantial advances in analytical performance, including sensitivity, reproducibility, selectivity, and speed for monitoring a wide range of human health conditions. Nanoporous anodic alumina (NAA) has been used extensively for biosensing applications due to its inherent optical and electrochemical properties, ease of fabrication, large surface area, tunable properties, and high stability in aqueous environment. This review focuses on NAA‐based biosensing systems for detection of clinically significant biomarkers using various detection techniques with the main focus being on electrochemical and optical transduction methods. The review covers an overview of the importance of biosensors for biomarkers detection, general (surface and structural) properties and fabrication of NAA, and NAA‐based biomarker sensing systems.The application of nanoporous anodic alumina as a material for developing biosensing platforms for detection of clinically relevant biomarkers is summarized in this review. Biosensors for the detection of proteins, nucleic acids, and pathogens using various detection techniques, with the main focus being on electrochemical and optical transduction methods, are discussed.
  • Recent Progress in Micro/Nanoreactors toward the Creation of Artificial
    • Abstract: Artificial organelles created from a bottom up approach are a new type of engineered materials, which are not designed to be living but, instead, to mimic some specific functions inside cells. By doing so, artificial organelles are expected to become a powerful tool in biomedicine. They can act as nanoreactors to convert a prodrug into a drug inside the cells or as carriers encapsulating therapeutic enzymes to replace malfunctioning organelles in pathological conditions. For the design of artificial organelles, several requirements need to be fulfilled: a compartmentalized structure that can encapsulate the synthetic machinery to perform an enzymatic function, as well as a means to allow for communication between the interior of the artificial organelle and the external environment, so that substrates and products can diffuse in and out the carrier allowing for continuous enzymatic reactions. The most recent and exciting advances in architectures that fulfill the aforementioned requirements are featured in this review. Artificial organelles are classified depending on their constituting materials, being lipid and polymer‐based systems the most prominent ones. Finally, special emphasis will be put on the intracellular response of these newly emerging systems.The creation of artificial organelles created from a bottom up approach is an emerging research field that aims at the creation of architectures that mimic specific functions intracellularly, thus becoming an essential tool in the biomedical field. Examples include enzymatic nanoreactors able to convert a prodrug into a drug or carriers encapsulating a therapeutic enzyme to replace for a malfunctioning organelle.
  • Biomaterials for Skin Substitutes
    • Abstract: Patients with extensive burns rely on the use of tissue engineered skin due to a lack of sufficient donor tissue, but it is a challenge to identify reliable and economical scaffold materials and donor cell sources for the generation of a functional skin substitute. The current review attempts to evaluate the performance of the wide range of biomaterials available for generating skin substitutes, including both natural biopolymers and synthetic polymers, in terms of tissue response and potential for use in the operating room. Natural biopolymers display an improved cell response, while synthetic polymers provide better control over chemical composition and mechanical properties. It is suggested that not one material meets all the requirements for a skin substitute. Rather, a composite scaffold fabricated from both natural and synthetic biomaterials may allow for the generation of skin substitutes that meet all clinical requirements including a tailored wound size and type, the degree of burn, the patient age, and the available preparation technique. This review aims to be a valuable directory for researchers in the field to find the optimal material or combination of materials based on their specific application.Natural and synthetic biomaterials that are used to make skin substitute are reviewed in the current paper. The most effective strategy to develop skin substitutes, in terms of material selection, would be using a combination of natural and synthetic biomaterials that can provide a natural and at the same time highly tunable environment for the cells.
  • Iron Oxide Nanoparticles: Innovative Tool in Cancer Diagnosis and Therapy
    • Abstract: Although cancer is one of the most dangerous and the second most lethal disease in the world, current therapy including surgery, chemotherapy, radiotherapy, etc., is highly insufficient not in the view of therapy success rate or the amount of side effects. Accordingly, procedures with better outcomes are highly desirable. Iron oxide nanoparticles (IONPs) present an innovative tool—ideal for innovation and implementation into practice. This review is focused on summarizing some well‐known facts about pharmacokinetics, toxicity, and the types of IONPs, and furthermore, provides a survey of their use in cancer diagnosis and therapy.Cancer represents one of the most dangerous diseases of present days and research for the most innovative and noninvasive diagnostic, and therapeutic methods is a contemporary issue since the current medical approaches are not complying with the development of the disease. Magnetic nanoparticles fulfill a demanding need in this clinical area and should be integrated into practice.
  • Progress Toward the Clinical Translation of Bioinspired Peptide and
           Protein Assemblies
    • Abstract: Supramolecular materials composed of proteins and peptides have been receiving considerable attention toward a range of diseases and conditions from vaccines to drug delivery. Owing to the relative newness of this class of materials, the bulk of work to date has been preclinical. However, examples of approved treatments particularly in vaccines, dentistry, and hemostasis demonstrate the translational potential of supramolecular polypeptides. Critical milestones in the clinical development of this class of materials and currently approved supramolecular polypeptide therapies are described in this study. Additional examples of not‐yet‐approved materials that are steadily advancing toward clinical use are also featured. Spherical assemblies such as virus‐like particles, designed protein nanoparticles, and spherical peptide amphiphiles are highlighted, followed by fiber‐forming systems such as fibrillizing peptides, fiber‐forming peptide‐amphiphiles, and filamentous bacteriophages.Supramolecular peptide biomaterials are being advanced toward clinical applications. This progress report describes self‐assembled polypeptide biomaterials that have been translated into clinical applications, along with those making steady progress toward patients. Although the majority of new supramolecular polypeptide materials have yet to be translated, the regulatory approval and commercialization of several examples is encouraging for the field.
  • A Highly Selective 3D Spiked Ultraflexible Neural (SUN) Interface for
           Decoding Peripheral Nerve Sensory Information
    • Abstract: Artificial sensors on the skin are proposed as a way to capture information that can be used in intracortical microstimulation or peripheral intraneural stimulation to restore sensory feedback to persons with tetraplegia. However, the ability of these artificial sensors to replicate the density and complexity of the natural mechanoreceptors is limited. One relatively unexplored approach is to make use of the signals from surviving tactile and proprioceptive receptors in existing limbs by recording from their transmitting axons within the primary sensory nerves. Here, a novel spiked ultraflexible neural (SUN) interface that is implanted into the peripheral nervous system to capture sensory information from these mechanoreceptors in acute rat experiments is described. The novel 3D design, which integrates spiked structures for intrafascicular nerve recording with an ultraflexible substrate, enables a unique conformal interface to the target nerve. With the high‐quality recording (average signal‐to‐noise‐ratio of 1.4) provided by the electrode, tactile from proprioceptive stimuli can be differentiated in terms of the firing rate. In toe pinching experiments, high spatial resolution classification can be achieved with support vector machine classifier. Further work remains to be done to assess the chronic recording capability of the SUN interface.A spiked ultraflexible neural interface is successfully used to record sensory signal from the peripheral nervous system. The 3D spiked electrodes enable intrafascicular access to nerve fascicles, while the flexible substrate enables conformal contact with the nerve. With the excellent recording capabilities of this neural interface, different types of sensory signals, as well as signals from different parts of the body, are differentiated successfully.
  • Synthesis of Metal Nanoparticles in Metal‐Phenolic Networks: Catalytic
           and Antimicrobial Applications of Coated Textiles
    • Abstract: The synthesis of metal nanoparticle (NP)‐coated textiles (nanotextiles) is achieved by a dipping process in water without toxic chemicals or complicated synthetic procedures. By taking advantage of the unique nature of tannic acid, metal‐phenolic network‐coated textiles serve as reducing and stabilizing sites for the generation of metal nanoparticles of controllable size. The textiles can be decorated with various metal nanoparticles, including palladium, silver, or gold, and exhibit properties derived from the presence of the metal nanoparticles, for example, catalytic activity in water (>96% over five cycles using palladium nanoparticles) and antibacterial activity against Gram‐negative bacteria (inhibition of Escherichia coli using silver nanoparticles) that outperforms a commercial bandage. The reported strategy offers opportunities for the development of hybrid nanomaterials that may have application in fields outside of catalysis and antimicrobials, such as sensing and smart clothing.Just dipping produces metal nanoparticle‐coated textiles (nanotextiles) without involving toxic chemicals or complicated synthetic steps. This versatile method enables the incorporation of various metal nanoparticles of controllable size, including palladium, silver, or gold, on the textiles. These nanotextiles show >96% catalytic activity in water over five cycles and superior antibacterial activity when compared against a commercial antibacterial bandage.
  • Microprinted Stem Cell Niches Reveal Compounding Effect of Colony Size on
           Stromal Cells‐Mediated Neural Differentiation
    • Abstract: Microenvironmental factors have a major impact on differentiation of embryonic stem cells (ESCs). Here, a novel phenomenon that size of ESC colonies has a significant regulatory role on stromal cells induced differentiation of ESCs to neural cells is reported. Using a robotic cell microprinting technology, defined densities of ESCs are confined within aqueous nanodrops over a layer of supporting stromal cells immersed in a second, immiscible aqueous phase to generate ESC colonies of defined sizes. Temporal protein and gene expression studies demonstrate that larger ESC colonies generate disproportionally more neural cells and longer neurite processes. Unlike previous studies that attribute neural differentiation of ESCs solely to interactions with stromal cells, it is found that increased intercellular signaling of ESCs significantly enhances neural differentiation. This study offers an approach to generate neural cells with improved efficiency for potential use in translational research.This study reports the colony size mediated regulation of neural differentiation of embryonic stem cells (ESCs) in stromal cell coculture niche. ESC colonies of defined sizes are generated over a layer of supporting stromal cells and temporal protein and gene expression studies are used to demonstrate that larger ESC colonies show disproportionately greater neural differentiation.
  • Development of Antifouling and Bactericidal Coatings for Platelet Storage
           Bags Using Dopamine Chemistry
    • Abstract: Platelets have a limited shelf life, due to the risk of bacterial contamination and platelet quality loss. Most platelet storage bags are made of a mixture of polyvinyl chloride with a plasticizer, denoted as pPVC. To improve biocompatibility of pPVC with platelets and to inhibit bacterial biofilm formation, an antifouling polymer coating is developed using mussel‐inspired chemistry. A copolymer of N,N‐dimethylacrylamide and N‐(3‐aminopropyl)methacrylamide hydrochloride is synthesized and coupled with catechol groups, named DA51‐cat. Under mild aqueous conditions, pPVC is first equilibrated with an anchoring polydopamine layer, followed by a DA51‐cat layer. Measurements show this coating decreases fibrinogen adsorption to 5% of the control surfaces. One‐step coating with DA51‐cat does not coat pPVC efficiently although it is sufficient for coating silicon wafers and gold substrates. The dual layer coating on platelet bags resists bacterial biofilm formation and considerably decreases platelet adhesion. A cationic antimicrobial peptide, E6, is conjugated to DA51‐cat then coated on silicon wafers and introduces bactericidal activity to these surfaces. Time‐of‐flight second ion‐mass spectroscopy is successfully applied to characterize these surfaces. pPVC is widely used in medical devices; this method provides an approach to controlling biofouling and bacterial growth on it without elaborate surface modification procedures.A facile two‐step coating of platelet storage bag material with polydopamine and DA51‐cat under mild aqueous conditions protects it against fibrinogen adsorption and platelet and bacterial adhesion. Addition of an antimicrobial peptide to DA51‐cat introduces bactericidal activity, demonstrating the potential of such an approach for improving platelet storage, one of the challenges in blood product transfusion.
  • Heparinization of Beta Tricalcium Phosphate: Osteo‐immunomodulatory
    • Abstract: Immune cells play a vital role in regulating bone dynamics. This has boosted the interest in developing biomaterials that can modulate both the immune and skeletal systems. In this study, calcium phosphates discs (i.e., beta‐tricalcium phosphate, β‐TCP) are functionalized with heparin to investigate the effects on immune and stem cell responses. The results show that the functionalized surfaces downregulate the release of hydrogen peroxide and proinflammatory cytokines (tumor necrosis factor alpha and interleukin 1 beta) from human monocytes and neutrophils, compared to nonfunctionalized discs. The macrophages show both elongated and round shapes on the two ceramic substrates, but the morphology of cells on heparinized β‐TCP tends toward a higher elongation after 72 h. The heparinized substrates support rat mesenchymal stem cell (MSC) adhesion and proliferation, and anticipate the differentiation toward the osteoblastic lineage as compared to β‐TCP and control. The coupling between the inflammatory response and osteogenesis is assessed by culturing MSCs with the macrophage supernatants. The downregulation of inflammation in contact with the heparinized substrates induces higher expression of bone‐related markers by MSCs.Heparinized calcium phosphates represent an excellent platform to modulate osteoimmune response. Heparinization offers a wide range of benefits observed by the downregulation of oxidative stress, inflammation and the improvement of mesenchymal stem cell differentiation. Moreover, a coupling of inflammation and osteogenesis, investigated through the cytokine containing supernatants from macrophage cell cultures, is evidenced by a pro‐osteogenic effect on rat mesenchymal stem cell.
  • 30 s Response Time of K+ Ion‐Selective Hydrogels Functionalized with
           18‐Crown‐6 Ether Based on QCM Sensor
    • Abstract: Potassium detection is critical in monitoring imbalances in electrolytes and physiological status. The development of rapid and robust potassium sensors is desirable in clinical chemistry and point‐of‐care applications. In this study, composite supramolecular hydrogels are investigated: polyethylene glycol methacrylate and acrylamide copolymer (P(PEGMA‐co‐AM)) are functionalized with 18‐crown‐6 ether by employing surface initiated polymerization. Real‐time potassium ion monitoring is realized by combining these compounds with quartz crystal microbalance. The device demonstrates a rapid response time of ≈30 s and a concentration detection range from 0.5 to 7.0 × 10−3m. These hydrogels also exhibit high reusability and K+ ion selectivity relative to other cations in biofluids such as Na+, NH4+, Mg2+, and Ca2+. These results provide a new approach for sensing alkali metal ions using P(PEGMA‐co‐AM) hydrogels.The polyethylene glycol methacrylate and acrylamide copolymer are functionalized with 18‐crown‐6 ether by employing surface‐initiated polymerization. Real‐time potassium ion monitoring is realized by quartz crystal microbalance. The sensor demonstrates a rapid response time of ≈30 s, a concentration detection range from 0.5 × 10−3 to 7.0 × 10−3m, high reusability and selectivity relative to Na+, NH4+, Mg2+, and Ca2+.
  • Dendron‐Grafted Polylysine‐Based Dual‐Modal Nanoprobe for
           Ultra‐Early Diagnosis of Pancreatic Precancerosis via Targeting a
           Urokinase‐Type Plasminogen Activator Receptor
    • Abstract: Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer death. Early detection of precancerous pancreatic intraepithelial neoplasia (PanIN) tissues is an urgent challenge to improve the PDAC prognosis. Here, a urokinase‐type plasminogen activator receptor (uPAR)‐targeted magnetic resonance (MR)/near‐infrared fluorescence (NIRF) dual‐modal nanoprobe dendron‐grafted polylysine (DGL)‐U11 for ultra‐early detection of pancreatic precancerosis is reported. Because of its good biocompatibility and biodegradability, globular architecture, and well‐defined reactive groups, the DGL is chosen as the platform to load with a pancreatic tumor‐targeting peptide U11, a magnetic resonance contrast agent Gd3+‐diethylene triamine pentaacetic acid, and a near‐infrared fluorescent cyanine dye Cy5.5. The nanoprobe DGL‐U11 has several preferable characteristics, such as active peptide targeting to activator receptor, good biocompatibility, dual‐modal imaging diagnosis, and well controlled diameter in a range of 15–25 nm. Upon incorporation of the active U11 peptide target to the overexpressed activator receptor uPAR, the targeted nanoprobe DGL‐U11 can increase to the earlier PanIN‐II stage through in vivo NIRF imaging. Labeled with both MR and NIRF bioimaging reporters, the uPAR‐targeted dual‐modal nanoprobe is very effective in the targeted imaging of precancerous PanINs and PDAC lesions with high sensitivity and spatial resolution, providing a promising platform to the ultra‐early detection of PDAC.Active targeting dual‐modal bioimaging: a urokinase‐type plasminogen activator receptor‐targeted magnetic resonance/near‐infrared fluorescence nanoprobe dendron‐grafted polylysine‐U11 based on a dendritic functionalization strategy provides a platform for an ultra‐early detection of pancreatic ductal adenocarcinoma.
  • Peptide‐Functionalized Polyurethane Coatings Prepared via Grafting‐To
           Strategy to Selectively Promote Endothelialization
    • Abstract: Endothelialization, formation of endothelial cells (ECs) layer on cardiovascular implant surface, is considered an ideal approach to prevent restenosis (renarrowing of blood vessel mainly due to the accumulation of proliferated vascular smooth muscle cells, SMCs) and thrombosis. In this study, the possibility of using polyurethane (PU) as a coating platform for functionalization with peptide to enhance endothelialization on implants is explored. PUs are synthesized through metal‐free organocatalytic polymerization followed by chemical conjugation with an EC‐specific REDV peptide through thiol–ene reaction. Meanwhile, the free isocyanate groups of PU allow for covalent grafting of REDV‐functionalized PU (PU/REDV) to silanize implant materials (nitinol and PET). PU/REDV coating with peptide grafting density of ≈2 nmol cm−2 selectively accommodates primary human umbilical vein ECs (HUVECs) and retards spreading of primary human umbilical artery SMCs (HUASMCs). In addition, a layer of HUVECs is formed within 3 d on PU/REDV‐coated surfaces, while proliferation of HUASMCs is inhibited. The selectivity is further confirmed by coculture of HUVECs and HUASMCs. Moreover, the PU/REDV‐coated surfaces are less thrombogenic as evidenced by reduced number and activity of adhered platelets. Therefore, PU/REDV can be potentially used as a coating of cardiovascular implants to prevent restenosis and thrombosis by promoting endothelialization.The versatile polyurethanes are explored as a platform material for medical device coating. Polyurethanes are conjugated with endothelial‐cell‐specific peptide REDV, and the conjugates are covalently coated on vascular implant materials through “grafting‐to” approach. The coating selectively enhances adhesion of endothelial cell while reduces adhesion of both smooth muscle cell and platelets, thus promoting endothelialization of implants.
  • pH/Ultrasound Dual‐Responsive Gas Generator for Ultrasound
           Imaging‐Guided Therapeutic Inertial Cavitation and Sonodynamic Therapy
    • Abstract: Herein, a pH/ultrasound dual‐responsive gas generator is reported, which is based on mesoporous calcium carbonate (MCC) nanoparticles by loading sonosensitizer (hematoporphyrin monomethyl ether (HMME)) and modifying surface hyaluronic acid (HA). After pinpointing tumor regions with prominent targeting efficiency, HMME/MCC‐HA decomposes instantaneously under the cotriggering of tumoral inherent acidic condition and ultrasound (US) irradiation, concurrently accompanying with CO2 generation and HMME release with spatial/temporal resolution. Afterward, the CO2 bubbling and bursting effect under US stimulus results in cavitation‐mediated irreversible cell necrosis, as well as the blood vessel destruction to further occlude the blood supply, providing a “bystander effect.” Meanwhile, reactive oxygen species generated from HMME can target the apoptotic pathways for effective sonodynamic therapy. Thus, the combination of apoptosis/necrosis with multimechanisms consequently results in a remarkable antitumor therapeutic efficacy, simultaneously minimizing the side effects on major organs. Moreover, the echogenic property of CO2 make the nanoplatform as a powerful ultrasound contrast agent to identify cancerous lesions. Based on the above findings, such all‐in‐one drug delivery platform of HMME/MCC‐HA is utilized to provide the US imaging guidance for therapeutic inertial cavitation and sonodynamic therapy simultaneously, which highlights possibilities of advancing cancer theranostics in biomedical fields.The sonosensitizer loaded mesoporous calcium carbonate nanoparticles decompose instantaneously under the cotriggering of tumoral inherent acidic condition and ultrasound irradiation. The released CO2 and sonosensitizer exploited the merits of synergistic combination of therapeutic inertial cavitation and sonodynamic therapy simultaneously, resulting in antitumor effects with multimechanisms.
  • Fluorination Enhances Serum Stability of Bioreducible Poly(amido amine)
           Polyplexes and Enables Efficient Intravenous siRNA Delivery
    • Abstract: The use of small interfering RNA (siRNA) in cancer treatment has been limited by the lack of effective systemic delivery methods. Although synthetic polycations have been widely explored in siRNA delivery, polycation/siRNA polyplexes often suffer from insufficient stability in vivo. Here, rationally designed siRNA delivery systems that meet the requirements for systemic siRNA delivery to distant tumors are reported. The hypothesis that modular design of delivery systems based on poly(amido amine)s that combine fluorination for systemic stability with bioreducibility for easy intracellular siRNA release, and PEGylation for improved safety and colloidal stability will overcome problems with contradicting siRNA delivery demands is tested. PEGylated, fluorinated, and bioreducible copolymers (PEG‐PCD‐F) with different degree of fluorination are thus synthesized. The fluorinated copolymers readily formed polyplexes with siRNA and achieved greatly improved gene silencing efficacy in multiple cell lines in vitro when compared with nonfluorinated controls. The results show fluorination‐induced enhancement of stability, cellular uptake, and endosomal escape of the polyplexes, while exhibiting efficient siRNA release in reducing intracellular environment. PEG‐PCD‐F polyplexes with siRNA against Bcl2 inhibit breast tumor growth following systemic intravenous administration. The results provide strong evidence of successful combination of bioreducibility with fluorination and PEGylation to achieve systemic siRNA polyplex delivery.A modular strategy to the design of small interfering RNA (siRNA) polyplexes is reported. The approach combines fluorination, bioreducibility, and PEGylation. It improves serum stability due to fluorous interactions and leads to facile intracellular siRNA release due to disulfide reduction. Improved colloidal stability is contributed by the poly(ethylene glycol). Using siBcl2, the polyplexes inhibit tumor growth following intravenous administration.
  • Photoporation Using Carbon Nanotubes for Intracellular Delivery of
           Molecules and Its Relationship to Photoacoustic Pressure
    • Abstract: Exposure of carbon‐black (CB) nanoparticles to near‐infrared nanosecond‐pulsed laser energy can cause efficient intracellular delivery of molecules by photoporation. Here, cellular bioeffects of multi‐walled carbon nanotubes (MWCNTs) and single‐walled carbon nanotubes (SWCNTs) are compared to those of CB nanoparticles. In DU145 prostate‐cancer cells, photoporation using CB nanoparticles transitions from (i) cells with molecular uptake to (ii) nonviable cells to (iii) fragmented cells with increasing laser fluence, as seen previously. In contrast, photoporation with MWCNTs causes uptake and, at higher fluence, fragmentation, but does not generate nonviable cells, and SWCNTs show little evidence of bioeffects, except at extreme laser conditions, which generate nonviable cells and fragmentation, but no significant uptake. These different behaviors cannot be explained by photoacoustic pressure output from the particles. All particle types emit a single, ≈100 ns, mostly positive‐pressure pulse that increases in amplitude with laser fluence. Different particle types emit different peak pressures, which are highest for SWCNTs, followed by CB nanoparticles and then MWCNTs, which does not correlate with cellular bioeffects between different particle types. This study concludes that cellular bioeffects depend strongly on the type of carbon nanoparticle used during photoporation and that photoacoustic pressure is unlikely to play a direct mechanistic role in the observed bioeffects.Cellular bioeffects of photoporation depend on laser energy and carbon nanoparticle type. Nanosecond‐pulsed laser irradiation yields different cellular bioeffects for carbon‐black nanoparticles, multi‐walled carbon nanotubes, or single‐walled carbon nanotubes. Energy mechanisms associated with multi‐walled nanotubes produce the highest intracellular uptake with high cell viability. Lack of bioeffects correlation with photoacoustic pressure suggests it may not play a mechanistic role.
  • A Capsule‐Type Microrobot with Pick‐and‐Drop Motion for Targeted
           Drug and Cell Delivery
    • Abstract: A capsule‐type microrobot exhibits “pick‐and‐drop” (P&D) motion to hold a particle within a confined volume and transports it via a corkscrewing motion. The P&D motion is possible because the capsule‐type microrobot has two parts: a plunger and a cap. The fabricated microrobots are wirelessly controlled by a magnetic manipulator. Drugs or cells can be encapsulated in the container of the capsule‐type microrobot by the P&D motion or attached to the surface of the cap, which can be used as a supporting structure. Therefore, the capsule‐type microrobot can deliver suspended or adherent cells. The drug or cells are minimally exposed or not completely exposed to the surrounding fluid and do not experience shear force when encapsulated in the container. As a proof‐of‐concept, secure transportation of microparticles in the confined volume of the capsule via P&D motion is demonstrated. In addition, the cap is used as a scaffold for neuronal cell culture on a rat brain slice to demonstrate its biocompatibility and feasibility for targeted cell delivery. The proposed capsule‐type microrobot is suitable for diverse applications, as it protects the encapsulated materials.A capsule‐type microrobot exhibits “pick‐and‐drop” (P&D) motion to hold a particle within a confined volume and transport it via a corkscrewing motion. Drugs or cells can be encapsulated in the container of the microrobot by the P&D motion or attached to the surface of the cap, which can be used as a supporting structure.
  • Tropoelastin Implants That Accelerate Wound Repair
    • Abstract: A novel, pure, synthetic material is presented that promotes the repair of full‐thickness skin wounds. The active component is tropoelastin and leverages its ability to promote new blood vessel formation and its cell recruiting properties to accelerate wound repair. Key to the technology is the use of a novel heat‐based, stabilized form of human tropoelastin which allows for tunable resorption. This implantable material contributes a tailored insert that can be shaped to the wound bed, where it hydrates to form a conformable protein hydrogel. Significant benefits in the extent of wound healing, dermal repair, and regeneration of mature epithelium in healthy pigs are demonstrated. The implant is compatible with initial co‐treatment with full‐ and split‐thickness skin grafts. The implant's superiority to sterile bandaging, commercial hydrogel and dermal regeneration template products is shown. On this basis, a new concept for a prefabricated tissue repair material for point‐of‐care treatment of open wounds is provided.Heat‐stabilized tropoelastin provides a novel scalable approach to production of elastic materials. This is attractive because no chemicals are used to generate these elastic structures. The resulting heat‐treated tropoelastin promotes the repair of full‐thickness wounds.
  • Multifunctional Cell Instructive Silk‐Bioactive Glass Composite
           Reinforced Scaffolds Toward Osteoinductive, Proangiogenic, and Resorbable
           Bone Grafts
    • Abstract: The successful regeneration of large volume bone defects necessitates the use of proangiogenic and resorbable scaffolding matrix. Impaired and slow ingrowth of host vasculature within implanted grafts greatly compromises its effective osseointegration. By addressing this, it is demonstrated that the use of copper doped bioactive glass functionalizes silk microfiber reinforcements to improve the physicochemical and osteoinductive properties of two silk scaffolding matrices (mulberry Bombyx mori and non‐mulberry Antheraea assama) employed in the study. The reinforced composite matrices increase the surface area and present an open porous biomimetic micromillieu favoring stem cell and endothelial cell migration within the matrix. Biochemical results indicate the stabilization of hypoxia‐inducible factor‐1α and expression of C‐X‐C chemokine receptor type‐4 in adipose derived human mesenchymal stem cells, which regulate the downstream proangiogenic signaling and endothelial cell homing, respectively. Osteoinduction, matrix turnover, and resorption effectiveness are favored better in the non‐mulberry silk matrices. The composite matrices significantly promote neo‐osseous tissue formation in volumetric femur defect in rabbits with periosteal restoration seen in the non‐mulberry silk composite matrices. Evidences of total resorption, enhanced vascular‐fibrous tissue ingrowth within the scaffold, vouch for the potential clinical translation of these developed composite silk matrices.Silk fibroin (mulberry and endemic Indian non‐mulberry silk), a widely renowned biopolymer herein is used to derive cell instructive bone scaffolding platforms. These bioactive glass functionalized silk microfibers reinforce composite matrices dictated stem cell differentiation, matrix maturation, endothelial cell migration, homing and network formation in vitro and consequently help in complete restoration of volumetric bone defects in rabbit femurs.
  • Tough Composite Hydrogels with High Loading and Local Release of
           Biological Drugs
    • Abstract: Hydrogels are under active development for controlled drug delivery, but their clinical translation is limited by low drug loading capacity, deficiencies in mechanical toughness and storage stability, and poor control over the drug release that often results in burst release and short release duration. This work reports a design of composite clay hydrogels, which simultaneously achieve a spectrum of mechanical, storage, and drug loading/releasing properties to address the critical needs from translational perspectives. The clay nanoparticles provide large surface areas to adsorb biological drugs, and assemble into microparticles that are physically trapped within and toughen hydrogel networks. The composite hydrogels demonstrate feasibility of storage, and extended release of large quantities of an insulin‐like growth factor‐1 mimetic protein (8 mg mL−1) over four weeks. The release rate is primarily governed by ionic exchange and can be upregulated by low pH, which is typical for injured tissues. A rodent model of Achilles tendon injury is used to demonstrate that the composite hydrogels allow for highly extended and localized release of biological drugs in vivo, while demonstrating biodegradation and biocompatibility. These attributes make the composite hydrogel a promising system for drug delivery and regenerative medicine.This work reports biocompatible composite hydrogels with high loading and extremely extended, localized release of biological drugs. The hydrogels demonstrate high mechanical toughness (sustain >80% compressive strains), large drug loading capacity (8 mg mL−1), extended release duration (28 d), and highly localized drug release (the ratio of tissue‐ and serum‐level of the drug >10 000).
  • Injectable, Tough Alginate Cryogels as Cancer Vaccines
    • Abstract: A covalently crosslinked methacrylated (MA)‐alginate cryogel vaccine has been previously shown to generate a potent response against murine melanoma, but is not mechanically robust and requires a large 16G needle for delivery. Here, covalent and ionic crosslinking of cryogels are combined with the hypothesis that this will result in a tough MA‐alginate cryogel with improved injectability. All tough cryogels can be injected through a smaller, 18G needle without sustaining any damage, while covalently crosslinked‐only cryogels break after injection. Cytosine‐phosphodiester‐guanine (CpG)‐delivering tough cryogels effectively activate dendritic cells (DCs). Granulocyte macrophage colony‐stimulating factor releasing tough cryogels recruit four times more DCs than blank gels by day 7 in vivo. The tough cryogel vaccine induces strong antigen‐specific cytotoxic T‐lymphocyte and humoral responses. These vaccines prevent tumor formation in 80% of mice inoculated with HER2/neu‐overexpressing DD breast cancer cells. The MA‐alginate tough cryogels provide a promising minimally invasive delivery platform for cancer vaccinations.Combining covalent and ionic crosslinking of cryogels results in a tough methacrylated‐alginate cryogel with improved injectability in vitro and in vivo. The tough‐cryogel‐based cancer vaccine generates strong antigen‐specific cellular and humoral responses in vivo, and induces potent antibreast cancer prophylactic efficacy in mice. The tough cryogels are a promising minimally invasive delivery platform for cancer vaccinations.
  • Broad‐Spectrum Neutralization of Pore‐Forming Toxins with Human
           Erythrocyte Membrane‐Coated Nanosponges
    • Abstract: Neutralization of bacterial toxins has become a compelling approach to treating bacterial infections as it may pose less selective pressure for the development of bacterial resistance. Currently, the majority of toxin neutralization platforms act by targeting the molecular structure of the toxin, which requires toxin identification and customized design for different diseases. Therefore, their development has been challenged by the enormous number and complexity of bacterial toxins. Herein, biomimetic toxin nanosponges are formulated by coating membranes of human red blood cells (hRBCs) onto polymeric nanoparticles, which act as a toxin decoy to absorb and neutralize a broad‐spectrum of hemolytic toxins regardless of their molecular structure. When tested with model pore‐forming toxins, including melittin, α‐hemolysin of methicillin‐resistant Staphylococcus aureus, listeriolysin O of Listeria monocytogenes, and streptolysin O of Group A Streptococcus, the hRBC nanosponges are able to completely inhibit toxin‐induced hemolysis in a concentration‐dependent manner. In addition, the nanosponge‐detained toxins show no cytotoxicity when tested on human umbilical vein endothelial cells and no lethality when injected into mice, which together indicate effective toxin neutralization. Overall, these results demonstrate the broad applicability and high effectiveness of the hRBC nanosponges as a novel antivirulence platform against hemolytic toxins from various strains of bacteria.Biomimetic toxin nanosponges made of human RBC membranes are prepared and tested against four distinct pore‐forming toxins. The results demonstrate that the nanosponges can completely inhibit the virulence of the toxins in a concentration‐dependent manner both in vitro and in vivo. Similar design and test can be readily applied to other cell membrane‐coated nanosponges for broad antivirulence applications.
  • Excitation‐Dependent Theranostic Nanosheet for Cancer Treatment
    • Abstract: In this work, a novel ruthenium complex loaded monolayer layered double hydroxide (LDH) (denoted as Ru(C‐bpy)2/mLDH) as supramolecular nanosensor is synthesized, which is greatly exclusive to the hypoxic tumor microenvironment. The Ru(C‐bpy)2/mLDH ultrathin sheet displays not only enhanced luminescence lifetime compared to the parent Ru(C‐bpy)2 alone, but also improved oxygen responsibility under an excitation of 488 or 800 nm. Moreover, the Ru(C‐bpy)2/mLDH is possessed of two‐photon fluorescence imaging ability under the 800 nm irradiation. In addition, the Ru(C‐bpy)2/mLDH can generate singlet oxygen with a high yield (φ∆) of 0.28 under the 520 nm irradiation, while the φ∆ of Ru(C‐bpy)2 is 0.19. Therefore, the Ru(C‐bpy)2/mLDH can be applied as a supramolecular theranostic agent with light‐switchable cancer imaging and photodynamic therapy properties.Ruthenium complex is loaded to the monolayer of layered double hydroxides to gain supramolecular nanosheet (Ru(C‐bpy)2/mLDH) as a theranostic agent, which exhibits oxygen sensitivity for photoluminescent imaging of hypoxia condition in solid tumor and the capacity to generate singlet oxygen for photodynamic therapy. The therapeutic and diagnostic functions can be switched by alternating the excitation wavelength.
  • 2D Ultrathin MXene‐Based Drug‐Delivery Nanoplatform for Synergistic
           Photothermal Ablation and Chemotherapy of Cancer
    • Abstract: Two‐dimensional (2D) MXenes, as a new 2D functional material nanosystem, have been extensively explored for broad applications. However, their specific performance and applications in theranostic nanomedicine have still rarely been explored. This work reports on the drug‐delivery performance and synergistic therapeutic efficiency of Ti3C2 MXenes for highly efficient tumor eradication. These Ti3C2 MXenes not only possess high drug‐loading capability of as high as 211.8%, but also exhibit both pH‐responsive and near infrared laser‐triggered on‐demand drug release. Especially, based on the high photothermal‐conversion capability of Ti3C2 MXenes, they have been further explored for efficient tumor eradication by synergistic photothermal ablation and chemotherapy, which has been systematically demonstrated both in vitro and in vivo. These Ti3C2 MXenes have also been demonstrated as the desirable contrast agents for photoacoustic imaging, showing the potential for diagnostic‐imaging guidance and monitoring during therapy. The high in vivo histocompatibility of Ti3C2 and their easy excretion out of the body have been evaluated and demonstrated, showing the potential high biosafety for further clinical translation. This work paves a new way for broadening biomedical applications of MXenes in nanomedicine where they can exert the high performance and functionality for synergistic therapy, especially on combating cancer.Two‐dimensional (2D) Ti3C2 MXene‐based nanosheets have been successfully constructed for controllable drug releasing and synergistic photothermal hyperthermia/chemotherapy against cancer. Especially, based on the high photothermal‐conversion capability of 2D Ti3C2 MXenes, they have been further explored for highly efficient tumor eradication by synergistic Ti3C2‐assisted photothermal ablation and chemotherapy, which has been systematically demonstrated both in vitro and in vivo.
  • A Novel, Well‐Resolved Direct Laser Bioprinting System for Rapid Cell
           Encapsulation and Microwell Fabrication
    • Abstract: A direct laser bioprinting (DLBP) system is introduced in this work. The DLBP system applies visible‐laser‐induced photo‐crosslinking at a wavelength of 405 nm using the photoinitiator VA‐086. It is shown that such a system can fabricate vertical structures with fine features (less than 50 µm) and high cell viability (greater than 95%). Experimental characterizations and theoretical simulations are presented, and good agreement is seen between the experiments and theory. The DLBP system is applied to the fabrication of (1) cell‐laden hydrogel microgrids, (2) hydrogel microwells, as well as a test of (3) cell encapsulation, and (4) cell seeding. The DLBP system is found to be a promising tool for bioprinting.Existing bioprinting methods have difficulties in achieving high cell viability and fine resolution simultaneously. This work introduces a new type of bioprinting method named “direct laser bioprinting” (DLBP). The DLBP utilizes the focused laser beamspot to selectively photo‐crosslink a hydrogel prepolymer solution. It is proven to perform the rapid fabrication of cell‐laden hydrogels with fine resolution and high cell viability.
  • Progress of Multicompartmental Particles for Medical Applications
    • Abstract: Particulate materials are becoming increasingly used in the literature for medical applications, but translation to the clinical setting has remained challenging as many particle systems face challenges from in vivo barriers. Multicompartmental particles that can incorporate several materials in an individual particle may allow for more intricate control and addressing of issues that otherwise standard particles are unable to. Here, some of the advances made in the use of multicompartmental particles for medical applications are briefly described.Multicompartmental particles comprise a broad class of anisotropic particles that have become of interest in a variety of applications. As more sophisticated and reliable materials processing techniques are developed, increasingly robust data are published demonstrating their potential, particularly in medical applications. Here, the recent progress in the development of multicompartmental particles in medicine is reviewed.
  • Advances in Carbon Nanotubes–Hydrogel Hybrids in Nanomedicine for
    • Abstract: In spite of significant advancement in hydrogel technology, low mechanical strength and lack of electrical conductivity have limited their next‐level biomedical applications for skeletal muscles, cardiac and neural cells. Host–guest chemistry based hybrid nanocomposites systems have gained attention as they completely overcome these pitfalls and generate bioscaffolds with tunable electrical and mechanical characteristics. In recent years, carbon nanotube (CNT)‐based hybrid hydrogels have emerged as innovative candidates with diverse applications in regenerative medicines, tissue engineering, drug delivery devices, implantable devices, biosensing, and biorobotics. This article is an attempt to recapitulate the advancement in synthesis and characterization of hybrid hydrogels and provide deep insights toward their functioning and success as biomedical devices. The improved comparative performance and biocompatibility of CNT–hydrogels hybrids systems developed for targeted biomedical applications are addressed here. Recent updates toward diverse applications and limitations of CNT hybrid hydrogels is the strength of the review. This will provide a holistic approach toward understanding of CNT‐based hydrogels and their applications in nanotheranostics.Host‐guest chemistry based organic‐inorganic nanocomposites composed of 3D hydrogel and carbon nanotubes (CNTs) have revolutionized the hydrogel/CNTs technologies with improved performance in the area of regenerative medicine, tissue engineering, targeted drug delivery, implantable devices, bio‐sensing and bio‐robotics. This review highlights the synthesis of CNT hybrid hydrogels and provides the recent updates on CNTs‐hydrogel hybrid systems and their biomedical applications.
  • Nanogenerator for Biomedical Applications
    • Abstract: In the past 10 years, the development of nanogenerators (NG) has enabled different systems to operate without external power supply. NG have the ability to harvest the mechanical energies in different forms. Human body motions and activities can also serve as the energy source to drive NG and enable self‐powered healthcare system. In this review, a summary of several major actual applications of NG in the biomedical fields is made including the circulatory system, the neural system, cell modulation, microbe disinfection, and biodegradable electronics. Nevertheless, there are still many challenges for NG to be actually adopted in clinical applications, including the miniaturization, duration, encapsulation, and output performance. It is also very important to further combine the NG development more precisely with the medical principles. In future, NG can serve as highly promising complementary or even alternative power suppliers to traditional batteries for the healthcare electronics.To date, the major applications of nanogenerators (NG) in the biomedical fields include the circulatory system, the neural system, cell modulation, microbe disinfection, and biodegradable electronics. In the future, NG can serve as highly promising complementary or even alternative power suppliers to the traditional batteries for healthcare electronics.
  • Gellan Gum Hydrogels with Enzyme‐Sensitive Biodegradation and
           Endothelial Cell Biorecognition Sites
    • Abstract: The survival of a biomaterial or tissue engineered construct is mainly hampered by the deficient microcirculation in its core, and limited nutrients and oxygen availability to the implanted or colonizing host cells. Aiming to address these issues, we herein propose bioresponsive gellan gum (GG) hydrogels that are biodegradable by metalloproteinase 1 (MMP‐1) and enable endothelial cells adhesion and proliferation. GG is chemically functionalized with divinyl sulfone (DVS) and then biofunctionalized with thiol cell‐adhesive peptides (T1 or C16) to confer GG endothelial cell biorecognition cues. Biodegradable hydrogels are then formed by Michael type addition of GGDVS or/and peptide‐functionalized GGDVS with a dithiol peptide crosslinker sensitive to MMP‐1. The mechanical properties (6 to 5580 Pa), swelling (17 to 11), MMP‐1‐driven degradation (up to 70%), and molecules diffusion coefficients of hydrogels are tuned by increasing the polymer amount and crosslinking density. Human umbilical cord vein endothelial cells depict a polarized elongated morphology when encapsulated within T1‐containing hydrogels, in contrast to the round morphology observed in C16‐containing hydrogels. Cell organization is favored as early as 1 d of cell culture within the T1‐modified hydrogels with higher concentration of peptide, while cell proliferation is higher in T1‐modified hydrogels with higher modulus. In conclusion, biodegradable and bioresponsive GGDVS hydrogels are promising endothelial cell responsive materials that can be used for vascularization strategies.Gellan gum (GG) hydrogels are extensively studied in the tissue engineering and regenerative medicine field but their lack of cell adhesion sites and cell‐mediated degradation hinders their application in a cell‐responsive environment. Herein, for the first time, a one‐step chemical modification of GG is proposed, which allows the attachment of any thiol peptide and crosslinking with a biscisteine peptide.
  • Biomaterials for Regenerative Medicine Approaches for the Anterior Segment
           of the Eye
    • Abstract: The role of biomaterials in tissue engineering and regenerative medicine strategies to treat vision loss associated with damage to tissues in the anterior segment of the eye has been studied for several years. This has mostly involved replacement and support for the cornea and conjunctiva. These are complex tissues with specific functional requirements for different parts of the tissue. Amniotic membrane (AM) is used in clinical practice to transplant autologous or allogenic cells to the corneal surface. Fibrin gels have also progressed to clinical use under specific conditions. Alternatives to AM such as collagen gels, other natural materials, for example keratin and silks, and synthetic polymers have received considerable attention in laboratory and animal studies. This experience is building a body of evidence to demonstrate the potential of tissue engineering and regenerative medicine in corneal and conjunctival reconstruction and can also lead to other applications in the anterior segment of the eye, for example, the trabecular meshwork. There is a real clinical need for new procedures to overcome vision loss but there are also opportunities for developments in ocular applications to lead to biomaterials innovations for use in other clinical areas.Biomaterials have an important role in the development of tissue engineering and regenerative medicine strategies to replace or support reconstruction of the ocular surface to overcome vision loss. Current clinical practice uses amniotic membrane to transplant cells to the cornea but natural and synthetic polymers are under development with the potential to provide increased availability and control of the properties.
  • Acute Oral Administration of Single‐Walled Carbon Nanotubes Increases
           Intestinal Permeability and Inflammatory Responses: Association with the
           Changes in Gut Microbiota in Mice
    • Abstract: With the increasing production and widespread potential applications of single‐walled carbon nanotubes (SWCNTs), the possible impacts of oral administration of SWCNTs on gastrointestinal tract at currently occupational exposure limits and potential biomedical applications should be concerned. To address the concerns, mice are orally administrated of SWCNTs at doses of 0.05, 0.5, and 2.5 mg kg−1 body weight per day for 7 d. The investigation shows that SWCNT treatment had promoted intestinal injuries at the acute dose of 2.5 mg kg−1 per day, including increase of histological lesion scores, intestinal permeability, and proinflammatory cytokine (IL‐1β, IL‐6, and TNF‐α) secretion. Analysis of gut microbiota composition using 16S rRNA gene sequencing approach reveals that acute oral administration of SWCNTs induces significant shifts of the predominant microbe phyla from Firmicutes to Bacteroidetes and increases abundance of proinflammatory bacteria Alitipes_uncultured_bacterium and Lachnospiraceae bacterium A4. These notable findings suggest that SWCNT‐induced intestinal injury is linked to SWCNT interaction with intestinal tract and gut bacteria and the consequent triggering of “metabolic inflammation” responses. Furthermore, the study has shown that oral administration of carbon nanomaterials, including SWCNTs, multiwalled CNTs, and graphene oxide, can lead to different inflammatory responses and specific alteration in gut microbiota in mice.The acute oral administration of single‐walled carbon nanotubes (SWCNTs) to mice induces increase in gut permeability, intestinal inflammatory responses, and structure of gut microbiota changes in the intestinal tract. Such impact is linked to SWCNTs that disturb intestinal integrity, perform its antibacterial activity, and drive the compositional alteration in gut microbiota, and consequently, trigger the “metabolic inflammation” responses.
  • A Silk Cranial Fixation System for Neurosurgery
    • Abstract: Cranial fixation should be safe, reliable, ideally degradable, and produce no hazardous residues and no artifacts on neuroimaging. Protein‐based fixation devices offer an exciting opportunity for this application. Here, the preclinical development and in vivo efficacy verification of a silk cranial fixation system in functional models are reported by addressing key challenges toward clinical use. A comprehensive study on this fixation system in rodent and canine animal models for up to 12 months is carried out. The silk fixation system shows a superb performance on the long‐term stability of the internal structural support for cranial flap fixation and bone reconnection and has good magnetic resonance imaging compatibility, and tolerability to high dose radiotherapy, underscoring the favorable clinical application of this system for neurosurgery compared to the current gold standard.A silk cranial fixation system for neurosurgery in long‐term animal models is reported by addressing key challenges toward clinical use, including manufacturing large‐size defect‐free silk parts, insight on structure–strength relations in bulk silk, tunable mechanical strengths and degradation rates, incorporating therapeutic agents, and compatibility with magnetic resonance imaging, X‐ray radiation, and Gamma sterilization.
  • Antigen‐Free Radionuclide‐Embedded Gold Nanoparticles for Dendritic
           Cell Maturation, Tracking, and Strong Antitumor Immunity
    • Abstract: Dendritic cell (DC)‐based cancer immunotherapy requires efficient maturation of DCs and sensitive monitoring of DCs localized in the lymph nodes that activate T cells. This paper reports a robust and simple surface chemistry for highly sensitive and stable radionuclide‐embedded gold nanoparticles (Poly‐Y‐RIe‐AuNPs) prepared with oligotyrosine‐modified AuNPs with additional Au shell formation as a promising positron emission tomography/computed tomography imaging agent. The multiple oligotyrosine binding sites modified on AuNPs provide excellent stability for conjugated radioisotopes by forming an Au shell. They can be heavily conjugated with radioisotope iodine, which enables sensitive tracking of DCs in the lymphatic system. More importantly, it is found that the maturation of DCs is possible solely with Poly‐Y‐RIe‐AuNPs without any additional stimulus for DC maturation. DCs matured by Poly‐Y‐RIe‐AuNPs induce antitumor immunity to cervical cancer comparable to that produced from DCs pulsated with tumor lysates. These results demonstrate that the peptide‐based surface chemistry of Poly‐Y‐RIe‐AuNPs is a simple and straightforward method to produce a highly sensitive and stable nuclear medicine imaging agent that also improves the efficiency of current antitumor immunotherapies.Polytyrosine peptide‐based surface chemistry on gold nanoparticles and additional Au shell formation is a simple and straightforward method to produce a highly sensitive and stable nuclear imaging agent (positron emission tomography/single photon emission computed tomography). The nanoparticle strongly induces the maturation of dendritic cells and it allows to sensitively track the migration of dendritic cells into the lymph node.
  • Well‐Controlled Cell‐Trapping Systems for Investigating Heterogeneous
           Cell–Cell Interactions
    • Abstract: Microfluidic systems have been developed for patterning single cells to study cell–cell interactions. However, patterning multiple types of cells to understand heterogeneous cell–cell interactions remains difficult. Here, it is aimed to develop a cell‐trapping device to assemble multiple types of cells in the well‐controlled order and morphology. This device mainly comprises a parylene sheet for assembling cells and a microcomb for controlling the cell‐trapping area. The cell‐trapping area is controlled by moving the parylene sheet on an SU‐8 microcomb using tweezers. Gentle downward flow is used as a driving force for the cell‐trapping. The assembly of cells on a parylene sheet with round and line‐shaped apertures is demonstrated. The cell–cell contacts of the trapped cells are then investigated by direct cell–cell transfer of calcein via connexin nanopores. Finally, using the device with a system for controlling the cell‐trapping area, three different types of cells in the well‐controlled order are assembled. The correct cell order rate obtained using the device is 27.9%, which is higher than that obtained without the sliding parylene system (0.74%). Furthermore, the occurrence of cell–cell contact between the three cell types assembled is verified. This cell‐patterning device will be a useful tool for investigating heterogeneous cell–cell interactions.This paper describes a device that enables assembling multiple types of cells in the well‐controlled order and morphology on the hydrodynamic flow. The cell‐trapping area of this device can be controlled by moving the polymer sheet with line‐shaped on SU‐8 microcomb. Three or more different cell types can be patterned in the well‐controlled order and with cross‐patterned assembly of cells.
  • Hierarchical Design of Tissue Regenerative Constructs
    • Abstract: The worldwide shortage of organs fosters significant advancements in regenerative therapies. Tissue engineering and regeneration aim to supply or repair organs or tissues by combining material scaffolds, biochemical signals, and cells. The greatest challenge entails the creation of a suitable implantable or injectable 3D macroenvironment and microenvironment to allow for ex vivo or in vivo cell‐induced tissue formation. This review gives an overview of the essential components of tissue regenerating scaffolds, ranging from the molecular to the macroscopic scale in a hierarchical manner. Further, this review elaborates about recent pivotal technologies, such as photopatterning, electrospinning, 3D bioprinting, or the assembly of micrometer‐scale building blocks, which enable the incorporation of local heterogeneities, similar to most native extracellular matrices. These methods are applied to mimic a vast number of different tissues, including cartilage, bone, nerves, muscle, heart, and blood vessels. Despite the tremendous progress that has been made in the last decade, it remains a hurdle to build biomaterial constructs in vitro or in vivo with a native‐like structure and architecture, including spatiotemporal control of biofunctional domains and mechanical properties. New chemistries and assembly methods in water will be crucial to develop therapies that are clinically translatable and can evolve into organized and functional tissues.The generation of tissue regenerative constructs via hierarchical design criteria follows the fundamentals of life's natural order. Advances in synthesis and fabrication technologies allow implementation of mechanical, biochemical, and structural cues on length scales ranging from molecular to nano to micro to macro. Thereby, hierarchical orders are achieved for the next generation material‐based therapies.
  • Silicon Carbide Nanoparticles as an Effective Bioadhesive to Bond Collagen
           Containing Composite Gel Layers for Tissue Engineering Applications
    • Abstract: Additive manufacturing via layer‐by‐layer adhesive bonding holds much promise for scalable manufacturing of tissue‐like constructs, specifically scaffolds with integrated vascular networks for tissue engineering applications. However, there remains a lack of effective adhesives capable of composite layer fusion without affecting the integrity of patterned features. Here, the use of silicon carbide is introduced as an effective adhesive to achieve strong bonding (0.39 ± 0.03 kPa) between hybrid hydrogel films composed of alginate and collagen. The techniques have allowed us to fabricate multilayered, heterogeneous constructs with embedded high‐resolution microchannels (150 µm–1 mm) that are precisely interspaced (500–600 µm). Hydrogel layers are effectively bonded with silicon carbide nanoparticles without blocking the hollow microchannels and high cell viability (90.61 ± 3.28%) is maintained within the scaffold. Nanosilica is also tested and found to cause clogging of smaller microchannels when used for interlayer bonding, but is successfully used to attach synthetic polymers (e.g., Tygon) to the hydrogels (32.5 ± 2.12 mN bond strength). This allows us to form inlet and outlet interconnections to the gel constructs. This ability to integrate hollow channel networks into bulk soft material structures for perfusion can be useful in 3D tissue engineering applications.Composite hydrogel lamination for biofabrication of 3D hollow channel constructs. The novel use of adhesive nanoparticles for the creation of thick, multilayered hydrogel structures with embedded, perfusable hollow channel networks is demonstrated. These mechanically robust and cytocompatible scaffolding materials can serve as vascular substitutes in tissue engineering applications.
  • Silk‐Based Bioinks for 3D Bioprinting
    • Abstract: 3D bioprinting field is making remarkable progress; however, the development of critical sized engineered tissue construct is still a farfetched goal. Silk fibroin offers a promising choice for bioink material. Nature has imparted several unique structural features in silk protein to ensure spinnability by silkworms or spider. Researchers have modified the structure–property relationship by reverse engineering to further improve shear thinning behavior, high printability, cytocompatible gelation, and high structural fidelity. In this review, it is attempted to summarize the recent advancements made in the field of 3D bioprinting in context of two major sources of silk fibroin: silkworm silk and spider silk (native and recombinant). The challenges faced by current approaches in processing silk bioinks, cellular signaling pathways modulated by silk chemistry and secondary conformations, gaps in knowledge, and future directions acquired for pushing the field further toward clinic are further elaborated.3D bioprinting offers fascinating potential to develop clinically relevant tissue equivalents for diseased/damaged tissues of patients. Silk fibroin bioink offers printability, cytocompatible gelation, high structural fidelity that renders long‐term cell survivability, differentiation, and morphogenesis. This review highlights the advancements made in the field of 3D bioprinting of silk (silkworm silk, and spider silk) and future directions for clinical applications.
  • Dose and Timing of N‐Cadherin Mimetic Peptides Regulate MSC
           Chondrogenesis within Hydrogels
    • Abstract: The transmembrane glycoprotein N‐cadherin (NCad) mediates cell–cell interactions found during mesenchymal condensation and chondrogenesis. Here, NCad‐derived peptides (i.e., HAV) are incorporated into hyaluronic acid (HA) hydrogels with encapsulated mesenchymal stem cells (MSCs). Since the dose and timing of NCad signaling are dynamic, HAV peptide presentation is tuned via alterations in peptide concentration and incorporation of an ADAM10‐cleavable domain between the hydrogel and the HAV motif, respectively. HA hydrogels functionalized with HAV result in dose‐dependent increases in early chondrogenesis of encapsulated MSCs and resultant cartilage matrix production. For example, type II collagen and glycosaminoglycan production increase ≈9‐ and 2‐fold with the highest dose of HAV (i.e., 2 × 10−3m), respectively, when compared to unmodified hydrogels, while incorporation of an efficient ADAM10‐cleavable domain between the HAV peptide and hydrogel abolishes increases in chondrogenesis and matrix production. Treatment with a small‐molecule ADAM10 inhibitor restores the functional effect of the HAV peptide, indicating that timing and duration of HAV peptide presentation is crucial for robust chondrogenesis. This study demonstrates a nuanced approach to the biofunctionalization of hydrogels to better emulate the complex cell microenvironment during embryogenesis toward stem‐cell‐based cartilage production.The dose and timing of the presentation of an N‐cadherin mimetic peptide that represents a critical and dynamic cue in cartilage development can be tuned in 3D hydrogels to modulate and enhance chondrogenesis of human mesenchymal stem cells. This work presents a nuanced approach to incorporate biochemical signals that are tailored to the complex cell microenvironment found during tissue development.
  • Soy Protein/Cellulose Nanofiber Scaffolds Mimicking Skin Extracellular
           Matrix for Enhanced Wound Healing
    • Abstract: Historically, soy protein and extracts have been used extensively in foods due to their high protein and mineral content. More recently, soy protein has received attention for a variety of its potential health benefits, including enhanced skin regeneration. It has been reported that soy protein possesses bioactive molecules similar to extracellular matrix (ECM) proteins and estrogen. In wound healing, oral and topical soy has been heralded as a safe and cost‐effective alternative to animal protein and endogenous estrogen. However, engineering soy protein‐based fibrous dressings, while recapitulating ECM microenvironment and maintaining a moist environment, remains a challenge. Here, the development of an entirely plant‐based nanofibrous dressing comprised of cellulose acetate (CA) and soy protein hydrolysate (SPH) using rotary jet spinning is described. The spun nanofibers successfully mimic physicochemical properties of the native skin ECM and exhibit a high water retaining capability. In vitro, CA/SPH nanofibers promote fibroblast proliferation, migration, infiltration, and integrin β1 expression. In vivo, CA/SPH scaffolds accelerate re‐epithelialization and epidermal thinning as well as reduce scar formation and collagen anisotropy in a similar fashion to other fibrous scaffolds, but without the use of animal proteins or synthetic polymers. These results affirm the potential of CA/SPH nanofibers as a novel wound dressing.A plant‐based biomimetic cellulose/soy protein nanofibrous wound dressing is fabricated using rotary jet spinning. Its physicochemical properties mimic native extracellular matrix in skin and exhibit a high water‐retaining capability for enhanced wound healing. The plant hybrid wound dressing accelerates in vitro dermal fibroblast proliferation, spreading, and migration. Furthermore, it promotes re‐epithelialization and reduces epidermal thickness and scar area in mouse model.
  • DNA Nanotubes with Hydrophobic Environments: Toward New Platforms for
           Guest Encapsulation and Cellular Delivery
    • Abstract: Natural systems combine different supramolecular interactions in a hierarchical manner to build structures. In contrast, DNA nanotechnology relies almost exclusively on DNA base pairing for structure generation. Introducing other supramolecular interactions can expand the structural and functional range of DNA assemblies, but this requires an understanding of the interplay between these interactions. Here, an economic strategy to build DNA nanotubes functionalized with lipid‐like polymers is reported. When these polymers are linked to the nanotube using a spacer, they fold inside to create a hydrophobic environment within the nanotube; the nanotube can encapsulate small molecules and conditionally release them when specific DNA strands are added, as monitored by single‐molecule fluorescence microscopy. When the polymers are directly linked to the nanostructure without spacers, they interact intermolecularly to form a network of DNA bundles. This morphological switch can be directly observed using a strand displacement strategy. The two association modes result in different cellular uptake behavior. Nanotubes with internal hydrophobic association show dye‐mediated mitochondrial colocalization inside cells; while the bundles disassemble into smaller polymer‐coated structures that reduce the extent of nonspecific cellular uptake. This approach uncovers parameters to direct the hierarchical assembly of DNA nanostructures, and produces promising materials for targeted drug delivery.The construction of DNA nanotubes with a switchable hydrophobic environment is reported. Amphiphilic nanotubes with an internal hydrophobic environment encapsulate and release small molecules and show a fibrillar pattern inside cells. Changing the spacer length between the nanotube and the hydrophobic chains results in intermolecularly connected bundles that disassemble into smaller alkyl‐coated nanostructures and give a punctate intracellular pattern.
  • Photoacoustic‐Enabled Self‐Guidance in Magnetic‐Hyperthermia
           Fe@Fe3O4 Nanoparticles for Theranostics In Vivo
    • Abstract: Magnetic nanoparticles have gained much interest for theranostics benefited from their intrinsic integration of imaging and therapeutic abilities. Herein, c(RGDyK) peptide PEGylated Fe@Fe3O4 nanoparticles (RGD‐PEG‐MNPs) are developed for photoacoustic (PA)‐enabled self‐guidance in tumor‐targeting magnetic hyperthermia therapy in vivo. In the αvβ3‐positive U87MG glioblastoma xenograft model, the PA signal of RGD‐PEG‐MNPs reaches its maximum in the tumor at 6 h after intravenous administration. This signal is enhanced by 2.2‐folds compared to that of the preinjection and is also 2.2 times higher than that in the blocking group. It demonstrates the excellent targeting property of RGD‐PEG‐MNPs. With the guidance of the PA, an effective magnetic hyperthermia to tumor is achieved using RGD‐PEG‐MNPs.A single material‐based nanotheranostic agent of c(RGDyK) peptide PEGylated Fe@Fe3O4 nanoparticles is developed for targeting photoacoustic imaging guided magnetic hyperthermia therapy in the αvβ3‐positive U87MG glioblastoma xenograft model.
  • DNA Nanostructure‐Based Systems for Intelligent Delivery of
           Therapeutic Oligonucleotides
    • Abstract: In the beginning of the 21st century, therapeutic oligonucleotides have shown great potential for the treatment of many life‐threatening diseases. However, effective delivery of therapeutic oligonucleotides to the targeted location in vivo remains a major issue. As an emerging field, DNA nanotechnology is applied in many aspects including bioimaging, biosensing, and drug delivery. With sequence programming and optimization, a series of DNA nanostructures can be precisely engineered with defined size, shape, surface chemistry, and function. Simply with hybridization, therapeutic oligonucleotides including unmethylated cytosine–phosphate–guanine dinucleotide oligos, small interfering RNA (siRNA) or antisense RNA, single guide RNA of the regularly interspaced short palindromic repeat–Cas9 system, and aptamers, are successfully loaded on DNA nanostructures for delivery. In this progress report, the development history of DNA nanotechnology is first introduced, and then the mechanisms and means for cellular uptake of DNA nanostructures are discussed. Next, current approaches to deliver therapeutic oligonucleotides with DNA nanovehicles are summarized. In the end, the challenges and opportunities for DNA nanostructure‐based systems for the delivery of therapeutic oligonucleotides are discussed.As an emerging field, DNA nanotechnology allows the creation of various kinds of DNA nanostructures. Due to the intrinsic homogeneity, therapeutic oligonucleotides including unmethylated cytosine–phosphate–guanine dinucleotide oligos, siRNA or antisense RNA, single guide RNA of the clustered regularly interspaced short palindromic repeat–Cas9 system, and aptamers, are successfully loaded on DNA nanostructures for efficient and intelligent delivery.
  • The Current Landscape of 3D In Vitro Tumor Models: What Cancer Hallmarks
           Are Accessible for Drug Discovery'
    • Abstract: Cancer prognosis remains a lottery dependent on cancer type, disease stage at diagnosis, and personal genetics. While investment in research is at an all‐time high, new drugs are more likely to fail in clinical trials today than in the 1970s. In this review, a summary of current survival statistics in North America is provided, followed by an overview of the modern drug discovery process, classes of models used throughout different stages, and challenges associated with drug development efficiency are highlighted. Then, an overview of the cancer hallmarks that drive clinical progression is provided, and the range of available clinical therapies within the context of these hallmarks is categorized. Specifically, it is found that historically, the development of therapies is limited to a subset of possible targets. This provides evidence for the opportunities offered by novel disease‐relevant in vitro models that enable identification of novel targets that facilitate interactions between the tumor cells and their surrounding microenvironment. Next, an overview of the models currently reported in literature is provided, and the cancer biology they have been used to explore is highlighted. Finally, four priority areas are suggested for the field to accelerate adoption of in vitro tumour models for cancer drug discovery.Cancer prognosis remains a lottery. Investment in oncology drug development has never been higher. In this review, an overview of a number of topics is provided that are important to understand when embarking on developing in vitro tumor models that can both improve the efficiency of therapy discovery and enable the identification of drugs that have the potential to be clinically impactful.
  • Glioma‐Targeted Delivery of a Theranostic Liposome Integrated with
           Quantum Dots, Superparamagnetic Iron Oxide, and Cilengitide for
           Dual‐Imaging Guiding Cancer Surgery
    • Abstract: Herein, a theranostic liposome (QSC‐Lip) integrated with superparamagnetic iron oxide nanoparticles (SPIONs) and quantum dots (QDs) and cilengitide (CGT) into one platform is constructed to target glioma under magnetic targeting (MT) for guiding surgical resection of glioma. Transmission electron microscopy and X‐ray photoelectron spectroscopy confirm the complete coencapsulation of SPIONs and QDs in liposome. Besides, CGT is also effectively encapsulated into the liposome with an encapsulation efficiency of ∼88.9%. QSC‐Lip exhibits a diameter of 100 ± 1.24 nm, zeta potential of −17.10 ± 0.11 mV, and good stability in several mediums. Moreover, each cargo shows a biphasic release pattern from QSC‐Lip, a rapid initial release within initial 10 h followed by a sustained release. Cellular uptake of QSC‐Lip is significantly enhanced by C6 cells under MT. In vivo dual‐imaging studies show that QSC‐Lip not only produces an obvious negative‐contrast enhancement effect on glioma by magnetic resonance imaging but also makes tumor emitting fluorescence under MT. The dual‐imaging of QSC‐Lip guides the accurate resection of glioma by surgery. Besides, CGT is also specifically distributed to glioma after administration of QSC‐Lip under MT, resulting in an effective inhibition of tumors. The integrated liposome may be a potential carrier for theranostics of tumor.The accurate imaging of tumor margins is pivotal for the complete surgical resection of glioma. In this study, a theranostic liposome (QSC‐Lip) is constructed to target glioma under an exogenous magnetic field (magnetic targeting) for magnetic resonance imaging and fluorescence imaging. The dual‐imaging ability of QSC‐Lip has successfully guided the accurate resection of glioma by surgery.
  • Bioderived DNA Nanomachines for Potential Uses in Biosensing, Diagnostics,
           and Therapeutic Applications
    • Abstract: Beside its genomic properties, DNA is also recognized as a novel material in the field of nanoengineering. The specific bonding of base pairs can be used to direct the assembly of highly structured materials with specific nanoscale features such as periodic 2D arrays, 3D nanostructures, assembly of nanomaterials, and DNA nanomachines. In recent years, a variety of DNA nanomachines are developed because of their many potential applications in biosensing, diagnostics, and therapeutic applications. In this review, the fuel‐powered motors and secondary structure motors, whose working mechanisms are inspired or derived from natural phenomena and nanomachines, are discussed. The combination of DNA motors with other platforms is then discussed. In each section of these motors, their mechanisms and their usage in the biomedical field are described. Finally, it is believed that these DNA‐based nanomachines and hybrid motifs will become an integral point‐of‐care diagnostics and smart, site‐specific therapeutic delivery.Beside its genomic properties, DNA is also recognized as a novel material in the field of nanoengineering. In recent years, a variety of DNA nanomachines are developed because of their many potential applications in biosensing, diagnostics, and therapeutic applications. Each working mechanism is elucidated as to how it is used to create structures for DNA nanomachines in the biomedical field.
  • Biomimetic Architectures for Peripheral Nerve Repair: A Review of
           Biofabrication Strategies
    • Abstract: Biofabrication techniques have endeavored to improve the regeneration of the peripheral nervous system (PNS), but nothing has surpassed the performance of current clinical practices. However, these current approaches have intrinsic limitations that compromise patient care. The “gold standard” autograft provides the best outcomes but requires suitable donor material, while implantable hollow nerve guide conduits (NGCs) can only repair small nerve defects. This review places emphasis on approaches that create structural cues within a hollow NGC lumen in order to match or exceed the regenerative performance of the autograft. An overview of the PNS and nerve regeneration is provided. This is followed by an assessment of reported devices, divided into three major categories: isotropic hydrogel fillers, acting as unstructured interluminal support for regenerating nerves; fibrous interluminal fillers, presenting neurites with topographical guidance within the lumen; and patterned interluminal scaffolds, providing 3D support for nerve growth via structures that mimic native PNS tissue. Also presented is a critical framework to evaluate the impact of reported outcomes. While a universal and versatile nerve repair strategy remains elusive, outlined here is a roadmap of past, present, and emerging fabrication techniques to inform and motivate new developments in the field of peripheral nerve regeneration.Biofabrication strategies have made significant steps toward overcoming the clinical challenges of peripheral nerve repair. Many activities have focused on emulating the structural features of native nerve tissue which promote nerve regeneration, resulting in the development of a variety of fabrication techniques. This review discusses the most relevant approaches, highlights their biomimetic character, and assesses performance in achieving nerve repair.
  • Magnetic Macroporous Hydrogels as a Novel Approach for Perfused Stem Cell
           Culture in 3D Scaffolds via Contactless Motion Control
    • Abstract: There is an urgent need for 3D cell culture systems that avoid the oversimplifications and artifacts of conventional culture in 2D. However, 3D culture within the cavities of porous biomaterials or large 3D structures harboring high cell numbers is limited by the needs to nurture cells and to remove growth‐limiting metabolites. To overcome the diffusion‐limited transport of such soluble factors in 3D culture, mixing can be improved by pumping, stirring or shaking, but this in turn can lead to other problems. Using pumps typically requires custom‐made accessories that are not compatible with conventional cell culture disposables, thus interfering with cell production processes. Stirring or shaking allows little control over movement of scaffolds in media. To overcome these limitations, magnetic, macroporous hydrogels that can be moved or positioned within media in conventional cell culture tubes in a contactless manner are presented. The cytocompatibility of the developed biomaterial and the applied magnetic fields are verified for human hematopoietic stem and progenitor cells (HSPCs). The potential of this technique for perfusing 3D cultures is demonstrated in a proof‐of‐principle study that shows that controlled contactless movement of cell‐laden magnetic hydrogels in culture media can mimic the natural influence of differently perfused environments on HSPCs.Perfused 3D scaffolds promise to overcome the limitations of 2D culture systems. An innovative 3D magnetic hydrogel system that greatly improves the diffusion‐limited nutrient transport in state‐of‐the‐art approaches by moving the hydrogel contactless in conventional cell culture tubes is presented. The engineered system is verified with hematopoietic progenitor cell culture and shows the impact of perfused environments on cell behavior.
  • Wearable Wireless Tyrosinase Bandage and Microneedle Sensors: Toward
           Melanoma Screening
    • Abstract: Wearable bendable bandage‐based sensor and a minimally invasive microneedle biosensor are described toward rapid screening of skin melanoma. These wearable electrochemical sensors are capable of detecting the presence of the tyrosinase (TYR) enzyme cancer biomarker in the presence of its catechol substrate, immobilized on the transducer surface. In the presence of the surface TYR biomarker, the immobilized catechol is rapidly converted to benzoquinone that is detected amperometrically, with a current signal proportional to the TYR level. The flexible epidermal bandage sensor relies on printing stress‐enduring inks which display good resiliency against mechanical deformations, whereas the hollow microneedle device is filled with catechol‐coated carbon paste for assessing tissue TYR levels. The bandage sensor can thus be used directly on the skin whereas microneedle device can reach melanoma tissues under the skin. Both wearable sensors are interfaced to an ultralight flexible electronic board, which transmits data wirelessly to a mobile device. The analytical performance of the resulting bandage and microneedle sensing systems are evaluated using TYR‐containing agarose phantom gel and porcine skin. The new integrated conformal portable sensing platforms hold considerable promise for decentralized melanoma screening, and can be extended to the screening of other key biomarkers in skin moles.Illustration of the tyrosinase wearable bandage sensor toward skin cancer screening.
  • Two‐Photon‐Excited Silica and Organosilica Nanoparticles for
           Spatiotemporal Cancer Treatment
    • Abstract: Coherent two‐photon‐excited (TPE) therapy in the near‐infrared (NIR) provides safer cancer treatments than current therapies lacking spatial and temporal selectivities because it is characterized by a 3D spatial resolution of 1 µm3 and very low scattering. In this review, the principle of TPE and its significance in combination with organosilica nanoparticles (NPs) are introduced and then studies involving the design of pioneering TPE‐NIR organosilica nanomaterials are discussed for bioimaging, drug delivery, and photodynamic therapy. Organosilica nanoparticles and their rich and well‐established chemistry, tunable composition, porosity, size, and morphology provide ideal platforms for minimal side‐effect therapies via TPE‐NIR. Mesoporous silica and organosilica nanoparticles endowed with high surface areas can be functionalized to carry hydrophobic and biologically unstable two‐photon absorbers for drug delivery and diagnosis. Currently, most light‐actuated clinical therapeutic applications with NPs involve photodynamic therapy by singlet oxygen generation, but low photosensitizing efficiencies, tumor resistance, and lack of spatial resolution limit their applicability. On the contrary, higher photosensitizing yields, versatile therapies, and a unique spatial resolution are available with engineered two‐photon‐sensitive organosilica particles that selectively impact tumors while healthy tissues remain untouched. Patients suffering pathologies such as retinoblastoma, breast, and skin cancers will greatly benefit from TPE‐NIR ultrasensitive diagnosis and therapy.Two‐photon‐absorbing (2hνA) nanoparticles provide safer cancer treatment opportunities than current therapies lacking spatial and temporal selectivities thanks to their 3D spatial resolution of 1 µm3 and very low scattering. Herein, porous and nonporous 2hνA silica, organosilica, and gold‐silica nanoparticles are described for bioimaging, drug delivery, and photodynamic therapy via photolysis, energy transfer, and electron transfer mechanisms.
  • Disposable Morpho menelaus Based Flexible Microfluidic and Electronic
           Sensor for the Diagnosis of Neurodegenerative Disease
    • Abstract: Rapid early disease prevention or precise diagnosis is almost impossible in low‐resource settings. Natural ordered structures in nature have great potential for the development of ultrasensitive biosensors. Here, motivated by the unique structures and extraordinary functionalities of ordered structures in nature, a biosensor based on butterfly wings is presented. In this study, a flexible Morpho menelaus (M. menelaus) based wearable sensor is integrated with a microfluidic system and electronic networks to facilitate the diagnosis of neurodegenerative disease (ND). In the microfluidic section, the structural characteristics of the M. menelaus wings up layer are combined with SiO2 nanoparticles to form a heterostructure. The fluorescent enhancement property of the heterostructure is used to increase the fluorescent intensity for multiplex detection of two proteins: IgG and AD7c‐NTP. For the electronic section, conductive ink is blade‐coated on the under layer of wings for measuring resistance change rate to obtain the frequency of static tremors of ND patients. The disposable M. menelaus based flexible microfluidic and electronic sensor enables biochemical–physiological hybrid monitoring of ND. The sensor is also amenable to a variety of applications, such as comprehensive personal healthcare and human‐machine interaction.A butterfly‐wings‐based wearable biosensor is presented with the integration of a microfluidic system and electronic networks. The disposable Morpho menelaus based flexible microfluidic and electronic sensor enables biochemical–physiological hybrid monitoring of neurodegenerative diseases.
  • Superhydrophobic/Superhydrophilic Janus Fabrics Reducing Blood Loss
    • Abstract: Hemostatic fabrics are most commonly used in baseline emergency treatment; however, the unnecessary blood loss due to the excessive blood absorption by traditional superhydrophilic fabrics is overlooked. Herein, for the first time, superhydrophobic/superhydrophilic Janus fabrics (superhydrophobic on one side and superhydrophilic on the other) are proposed: the superhydrophilic part absorbs water in the blood to expedite the clotting while the superhydrophobic part prevents blood from further permeating. Compared with the common counterparts, effective bleeding control with reducing blood loss more than 50% can be achieved while the breathability largely remain by using Janus fabrics. The proposed prototypes can even prolong the survival time in the rat model with serious bleeding. This strategy for reducing blood loss via simply tuning wettability is promising for the practical applications.A simple strategy of integrating the opposite wettability in hemostatic fabrics is proposed. Reduced blood loss, effective bleeding control, and even prolonged survival time are achieved. Many other benefits like relieving the psychological stress, obscuring the wound from infection, and reducing the transmission of infectious blood diseases may be expected.
  • Physical Properties of Implanted Porous Bioscaffolds Regulate Skin Repair:
           Focusing on Mechanical and Structural Features
    • Abstract: Porous bioscaffolds are applied to facilitate skin repair since the early 1990s, but a perfect regeneration outcome has yet to be achieved. Until now, most efforts have focused on modulating the chemical properties of bioscaffolds, while physical properties are traditionally overlooked. Recent advances in mechanobiology and mechanotherapy have highlighted the importance of biomaterials' physical properties in the regulation of cellular behaviors and regenerative processes. In skin repair, the mechanical and structural features of porous bioscaffolds are two major physical properties that determine therapeutic efficacy. Here, first an overview of natural skin repair with an emphasis on the major biophysically sensitive cell types involved in this multistage process is provided, followed by an introduction of the four roles of bioscaffolds as skin implants. Then, how the mechanical and structural features of bioscaffolds influence these four roles is discussed. The mechanical and structural features of porous bioscaffolds should be tailored to balance the acceleration of wound closure and functional improvements of the repaired skin. This study emphasizes that decoupling and precise control of the mechanical and structural features of bioscaffolds are significant aspects that should be considered in future biomaterial optimization, which can build a foundation to ultimately achieve perfect skin regeneration outcomes.Adjustment of bioscaffolds' physical properties is able to improve the therapeutic efficacy of assisted skin repair. This report provides an overview on the current understanding of the four main roles that bioscaffolds play in assisted wound healing and highlights the influence of bioscaffolds' physical properties, especially mechanical and structural features to regulate these four roles and the resulting skin repair.
  • Nitric Oxide Dependent Degradation of Polyethylene Glycol‐Modified
           Single‐Walled Carbon Nanotubes: Implications for Intra‐Articular
    • Abstract: Polyethylene glycol (PEG)‐modified carbon nanotubes have been successfully employed for intra‐articular delivery in mice without systemic or local toxicity. However, the fate of the delivery system itself remains to be understood. In this study 2 kDa PEG‐modified single‐walled carbon nanotubes (PNTs) are synthesized, and trafficking and degradation following intra‐articular injection into the knee‐joint of healthy mice are studied. Using confocal Raman microspectroscopy, PNTs can be imaged in the knee‐joint and are found to either egress from the synovial cavity or undergo biodegradation over a period of 3 weeks. Raman analysis discloses that PNTs are oxidatively degraded mainly in the chondrocyte‐rich cartilage and meniscus regions while PNTs can also be detected in the synovial membrane regions, where macrophages can be found. Furthermore, using murine chondrocyte (ATDC‐5) and macrophage (RAW264.7) cell lines, biodegradation of PNTs in activated, nitric oxide (NO)‐producing chondrocytes, which is blocked upon pharmacological inhibition of inducible nitric oxide synthase (iNOS), can be shown. Biodegradation of PNTs in macrophages is also noted, but after a longer period of incubation. Finally, cell‐free degradation of PNTs upon incubation with the peroxynitrite‐generating compound, SIN‐1 is demonstrated. The present study paves the way for the use of PNTs as delivery systems in the treatment of diseases of the joint.Polyethylene glycol modified carbon nanotubes (PNTs) are injected intra‐articularly into the knee‐joint of C57BL/6 mice and their fate is monitored by using Raman spectroscopy–microscopy. Degradation of PNTs is documented mainly in the chondrocyte‐rich cartilage region. Subsequent in vitro experiments confirm nitric oxide‐dependent degradation of PNTs in activated murine chondrocytes as well as cell‐free, peroxynitrite‐mediated degradation of PNTs.
  • A Multifunctional Micellar Nanoplatform with pH‐Triggered Cell
           Penetration and Nuclear Targeting for Effective Cancer Therapy and
           Inhibition to Lung Metastasis
    • Abstract: The enhancement of cellular internalization and subsequent achievement of a nuclear targeting of nanocarriers play an important role in maximizing the therapeutic potency and minimizing the side effects of encapsulated drugs. Herein, a multifunctional micellar nanoplatform simultaneously with high cell penetration and nuclear targeting through pH‐triggered surface charge reversal is presented. The miscellar system is constructed from poly(ethylene glycol)‐poly(ε‐caprolactone) with 2,3‐dimethylmaleic anhydride‐Tat decoration (PECL/DA‐Tat). DA groups are used to mask the positive charge of Tat to prolong blood circulation of the nanocarriers. In the mildly acidic environment of tumor tissue, the system exhibits ultrasensitive negative to positive charge reversal, facilitating the cell internalization and subsequent nuclear targeting. The chemotherapeutic 10‐hydroxycamptothecin conjugated to methoxy polyethylene glycol, which is loaded in this micelle, obviously enhances cytotoxicity against tumor cells. The in vivo therapy in mice bearing 4T1 breast tumor reveals that the system has a significant enhancement of both the endocytosis and nuclear enrichment, showing a highly effective antitumor efficacy and inhibition to lung metastasis.The high cell penetration and nuclear targeting with a multifunctional micellar nanoplatform are successfully realized both in vitro and in vivo through pH‐triggered surface charge reversal. The delivered anticancer drug with this nanoplatform displays a highly effective antitumor efficacy and an inhibition to the spontaneous lung metastasis.
  • Functionalized Nanoparticles Efficiently Enhancing the Targeted Delivery,
           Tumor Penetration, and Anticancer Activity of
    • Abstract: The enhanced permeability and retention (EPR) effect of tumors is much more complex than initially defined, and it alone is not sufficient for targeted delivery of nanosized agents. Meanwhile, poor tumor penetration is another major challenge for the treatment of solid tumors using nanoparticles. Development of delivery systems for SN38, the active metabolite of CPT‐11 in human and a very potent anticancer molecule, has become an attractive research area. PEGx‐p(HEMASN38)y (x and y are viable), a prodrug synthesized by using polyethylene glycol (PEG) as initiator and SN38 as monomer through atom transfer radical polymeration (ATRP) method, is previously reported. Using PEG2.4K‐p(HEMASN38)3K as a model prodrug, herein an active‐targeted strategy decorated with cys‐arg‐gly‐asp‐lys (CRGDK), a peptide specifically binds to neuropilin‐1 overexpressed by tumor vessels and tumor cells, is successfully established to further improve the delivery and efficacy of SN38. CRGDK‐functionalized PEG2.4K‐p(HEMASN38)3K (C‐SN38) nanoparticles and nonfunctionalized control (B‐SN38) are prepared with two distinct sizes, 30 and 100 nm. Their physiochemical and biological characteristics are investigated in vitro and in vivo with multiple tumor models. It is demonstrated for the first time that CRGDK functionalization can be a promising strategy for efficient delivery of SN38, and C‐SN38 is a potent drug candidate for the treatment of neuropilin‐1 overexpressing tumors.Cys‐Arg‐Gly‐Asp‐Lys (CRGDK)‐functionalized PEG2.4K‐p(HEMASN38)3K (C‐SN38) and nonfunctionalized control (B‐SN38) are successfully synthesized and self‐assemble into nanoparticles with two distinct particle sizes, 30 and 100 nm. Further investigations indicate that C‐SN38 possesses significantly enhanced tumor accumulation, intratumor penetration, and anticancer activity compared with B‐SN38 in human tumors overexpressing neuropilin‐1. It is demonstrated for the first time that CRGDK functionalization is a promising strategy for improved delivery and efficacy of SN38.
  • Soft Artificial Bladder Detrusor
    • Abstract: Developing soft devices for invasive procedures bears great importance for human health. The softness and large strain actuation of responsive hydrogels promise the potential to fabricate soft devices, which can attach on and assist to the function of organs. The key challenges lie in the fabrication of soft devices with robust actuating ability and biocompatibility to the attached organ. This paper presents a solution that integrates the thermoresponsive hydrogel membrane with flexible electronics and silk scaffold into a balloon‐like soft device. As an example, the actuation assisting function of this soft device for shrinking an animal bladder is presented. The mechanical behaviors of the balloon‐like soft device are experimentally and theoretically investigated. The concepts are applicable to other applications such as soft implants, soft robotics, and microfluidics.A soft artificial bladder detrusor consisting of smart hydrogels, flexible electronic and silk scaffold is proposed. The artificial detrusor is fabricated to assist the shrinking of animal bladder. Experimental and theoretical investigations are conducted about the assisting behavior. The concept of muscle‐like actuation by smart materials provides new solutions for assisting the functions of organs.
  • Designing 3D Biological Surfaces via the Breath‐Figure Method
    • Abstract: The fabrication of biointerfaces that mimic cellular physiological environments is critical to understanding cell behaviors in vitro and for the design of tissue engineering. Breath figure is a self‐assemble method that uses water droplets condensed from moisture as template and ends up with a highly ordered hexagonal pore array; this approach is used to fabricate various biological substrates. This progress report provides an overview of strategies to achieve topographical modifications and chemical‐patterned arrays, such as modulation of the pore size, shape and selective decoration of the honeycomb holes. Using recent results in the biological fields, potential future applications and developments of honeycomb structures are commented upon.Breath figure provides a convenient approach to fabricating the honeycomb‐like substrates with highly ordered hexagonal pore arrays. There are many strategies to functionalize the honeycomb films for biological applications, including modulating chemistry, wettability, and morphological parameters. The honeycomb films exhibit high potential in biological fields including for cell scaffold, antibacteria, bio‐macromolecule arrays, bioseparation, and biosensors.
  • Enzyme‐Based Glucose Sensor: From Invasive to Wearable Device
    • Abstract: Blood glucose concentration is a key indicator of patients' health, particularly for symptoms associated with diabetes mellitus. Because of the large number of diabetic patients, many approaches for glucose measurement have been studied to enable continuous and accurate glucose level monitoring. Among them, electrochemical analysis is prominent because it is simple and quantitative. This technology has been incorporated into commercialized and research‐level devices from simple test strips to wearable devices and implantable systems. Although directly monitoring blood glucose assures accurate information, the invasive needle‐pinching step to collect blood often results in patients (particularly young patients) being reluctant to adopt the process. An implantable glucose sensor may avoid the burden of repeated blood collections, but it is quite invasive and requires periodic replacement of the sensor owing to biofouling and its short lifetime. Therefore, noninvasive methods to estimate blood glucose levels from tears, saliva, interstitial fluid (ISF), and sweat are currently being studied. This review discusses the evolution of enzyme‐based electrochemical glucose sensors, including materials, device structures, fabrication processes, and system engineering. Furthermore, invasive and noninvasive blood glucose monitoring methods using various biofluids or blood are described, highlighting the recent progress in the development of enzyme‐based glucose sensors and their integrated systems.Over the past decades, the electrochemical glucose sensors for diabetes care have improved tremendously, which enable a convenient tracking of blood glucose levels continuously. Here, the basic principles and recent progress in enzyme‐based electrochemical glucose sensors are reviewed, as well as their application to noninvasive blood glucose monitoring methods and to the conventional invasive methods.
  • Microfluidic Tumor–Vascular Model to Study Breast Cancer Cell
           Invasion and Intravasation
    • Abstract: Cancer is a major leading cause of disease‐related death in the world. The severe impact of cancer can be attributed to poor understanding of the mechanisms involved in earliest steps of the metastatic cascade, specifically invasion into the surrounding stroma and intravasation into the blood capillaries. However, conducting integrated biological studies of invasion and intravasation have been challenging, within in vivo models and traditional in vitro assay, due to difficulties in establishing a precise tumor microenvironment. To that end, in this work, a novel 3D microfluidic platform comprised of concentric three‐layer cell‐laden hydrogels for simultaneous investigation of breast cancer cell invasion and intravasation as well as vasculature maturation influenced by tumor–vascular crosstalk is developed. It was demonstrated that the presence of spontaneously formed vasculature enhance MDA‐MB‐231 invasion into the 3D stroma. Following invasion, cancer cells are visualized intravasating into the outer vasculature. Additionally, invading cancer cells significantly reduce vessel diameter while increasing permeability, consistent with previous in vivo studies. Major signaling cytokines involved in tumor–vascular crosstalk that govern cancer cell invasion and intravasation are further identified. Taken together, this platform will enable unique insights of critical biological events within the metastatic cascade, with significant potential for developing efficient cancer therapeutics.Cancer is a major leading cause of disease‐related death worldwide. The severe impact of cancer is due to poor understanding of the mechanisms within invasion and intravasation. Therefore, a novel 3D microfluidic platform comprised of concentric three‐layer cell‐laden hydrogels for simultaneous investigation of breast cancer cell invasion and intravasation along with vasculature maturation, influenced by tumor–vascular crosstalk, is developed.
  • Natural Humic‐Acid‐Based Phototheranostic Agent
    • Abstract: Humic acids, a major constituent of natural organic carbon resources, are naturally formed through the microbial biodegradation of animal and plant residues. Due to numerous physiologically active groups (phenol, carboxyl, and quinone), the biomedical applications of humic acid have been already investigated across different cultures for several centuries or even longer. In this work, sodium humate, the sodium salt of humic acid, is explored as phototheranostic agent for light‐induced photoacoustic imaging and photothermal therapy based on intrinsic absorption in the near‐infrared region. The purified colloidal sodium humate exhibits a high photothermal conversion efficiency up to 76.3%, much higher than that of the majority of state‐of‐the‐art photothermal agents including gold nanorods, Cu9S5 nanoparticles, antimonene quantum dots, and black phosphorus quantum dots, leading to obvious photoacoustic enhancement in vitro and in vivo. Besides, highly effective photothermal ablation of HeLa tumor is achieved through intratumoral injection. Impressively, sodium humate reveals ultralow toxicity at the cellular and animal levels. This work promises the great potential of humic acids as light‐mediated theranostic agents, thus expanding the application scope of traditional humic acids in biomedical field.Humic acids, a major constituent of natural organic carbon resources, are naturally formed through the microbial biodegradation of animal and plant residues. Herein, sodium humate, the sodium salt of humic acid, was explored as phototheranostic agent for light‐induced photoacoustic imaging and photothermal therapy based on intrinsic absorption in the near‐infrared region.
  • pH‐Responsive PEG–Doxorubicin‐Encapsulated Aza‐BODIPY
           Nanotheranostic Agent for Imaging‐Guided Synergistic Cancer Therapy
    • Abstract: Synergistic cancer therapy is of great interest for multiple advantages, such as excellent targeting accuracy, low side effects, and enhanced therapeutic efficiency. Herein, a near‐infrared photosensitizer aza‐BODIPY (AB) with high singlet oxygen quantum yield (ΦΔ = 82%) is designed and synthesized. With Schiff's base obtained from condensation reaction between doxorubicin (DOX) and polyethylene glycol‐benzaldehyde (PEG–CHO) as the polymer matrix, aza‐BODIPY is encapsulated to afford hydrophilic nanoparticles (DAB NPs). The DAB NPs exhibit high reactive oxygen species (ROS) generation rate and outstanding photothermal conversion efficiency (η = 38.3%) under irradiation. In vivo fluorescence‐ and photothermal‐imaging (PTI) results demonstrate that DAB NPs can specifically accumulate at tumor sites and serve as dual‐modal imaging probe for cancer diagnosis. Particularly, triggered by acidic tumor microenvironment, the HCN bond of Schiff's base would be broken simultaneously, resulting in the efficient release of DOX from DAB NPs at tumor sites as well as enhancing the targeting performance of chemotherapeutics. Compared with free DOX and aza‐BODIPY nanoparticles, DAB NPs can inhibit tumor growth more effectively through pH‐responsive photodynamic/photothermal/chemo synergistic therapy. This report may also present a practicable strategy to develop a pH‐responsive nanotheranostic agent for tumor targeting, imaging, and therapy.Herein, pH‐responsive PEG–doxorubicin‐encapsulated aza‐BODIPY nanoparticle (DAB NP) is prepared for fluorescence‐imaging‐ and photothermal‐imaging‐guided chemo/photodynamic/photothermal cancer therapy. Both in vitro and in vivo experiments demonstrate an excellent antitumor efficacy of DAB NPs, showing their great potential to be a pH‐responsive nanotheranostic agent for photothermal‐ and fluorescence‐imaging‐guided photodynamic/photothermal/chemo synergistic therapy in clinical.
  • Engineering Polymersomes for Diagnostics and Therapy
    • Abstract: Engineered polymer vesicles, termed as polymersomes, confer a flexibility to control their structure, properties, and functionality. Self‐assembly of amphiphilic copolymers leads to vesicles consisting of a hydrophobic bilayer membrane and hydrophilic core, each of which is loaded with a wide array of small and large molecules of interests. As such, polymersomes are increasingly being studied as carriers of imaging probes and therapeutic drugs. Effective delivery of polymersomes necessitates careful design of polymersomes. Therefore, this review article discusses the design strategies of polymersomes developed for enhanced transport and efficacy of imaging probes and therapeutic drugs. In particular, the article focuses on overviewing technologies to regulate the size, structure, shape, surface activity, and stimuli‐ responsiveness of polymersomes and discussing the extent to which these properties and structure of polymersomes influence the efficacy of cargo molecules. Taken together with future considerations, this article will serve to improve the controllability of polymersome functions and accelerate the use of polymersomes in biomedical applications.Polymersomes, as engineered polymer vesicles, are well received as efficient carriers for the delivery of diagnostic and therapeutic molecules. Chemical modifications to self‐assembling polymers allow customization of nanosized carriers for a wide variety of clinical applications. This review highlights the critical design features and discusses the current efforts to engineer polymersomes for the next generation of nanomedicine.
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