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Publisher: John Wiley and Sons   (Total: 1589 journals)

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Showing 1 - 200 of 1589 Journals sorted alphabetically
Abacus     Hybrid Journal   (Followers: 12, SJR: 0.48, h-index: 22)
About Campus     Hybrid Journal   (Followers: 5)
Academic Emergency Medicine     Hybrid Journal   (Followers: 65, SJR: 1.385, h-index: 91)
Accounting & Finance     Hybrid Journal   (Followers: 47, SJR: 0.547, h-index: 30)
ACEP NOW     Free   (Followers: 1)
Acta Anaesthesiologica Scandinavica     Hybrid Journal   (Followers: 52, SJR: 1.02, h-index: 88)
Acta Archaeologica     Hybrid Journal   (Followers: 164, 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: 15, SJR: 1.197, h-index: 81)
Acta Ophthalmologica     Hybrid Journal   (Followers: 6, 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: 35, SJR: 2.518, h-index: 113)
Acta Zoologica     Hybrid Journal   (Followers: 7, SJR: 0.459, h-index: 29)
Acute Medicine & Surgery     Hybrid Journal   (Followers: 4)
Addiction     Hybrid Journal   (Followers: 35, SJR: 2.086, h-index: 143)
Addiction Biology     Hybrid Journal   (Followers: 14, SJR: 2.091, h-index: 57)
Adultspan J.     Hybrid Journal   (SJR: 0.127, h-index: 4)
Advanced Energy Materials     Hybrid Journal   (Followers: 27, SJR: 6.411, h-index: 86)
Advanced Engineering Materials     Hybrid Journal   (Followers: 26, 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: 268, 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: 17, SJR: 2.729, h-index: 121)
Advances in Polymer Technology     Hybrid Journal   (Followers: 13, 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: 10)
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: 15, 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: 33, SJR: 2.833, h-index: 138)
Alimentary Pharmacology & Therapeutics Symposium Series     Hybrid Journal   (Followers: 3)
Allergy     Hybrid Journal   (Followers: 51, SJR: 3.048, h-index: 129)
Alternatives to the High Cost of Litigation     Hybrid Journal   (Followers: 3)
American Anthropologist     Hybrid Journal   (Followers: 148, 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: 92, SJR: 2.325, h-index: 51)
American J. of Economics and Sociology     Hybrid Journal   (Followers: 29, SJR: 0.211, h-index: 26)
American J. of Hematology     Hybrid Journal   (Followers: 34, SJR: 1.761, h-index: 77)
American J. of Human Biology     Hybrid Journal   (Followers: 12, 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: 16, 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: 37, SJR: 1.41, h-index: 88)
American J. of Political Science     Hybrid Journal   (Followers: 276, SJR: 5.101, h-index: 114)
American J. of Primatology     Hybrid Journal   (Followers: 15, SJR: 1.197, h-index: 63)
American J. of Reproductive Immunology     Hybrid Journal   (Followers: 3, SJR: 1.347, h-index: 75)
American J. of Transplantation     Hybrid Journal   (Followers: 17, SJR: 2.792, h-index: 140)
American J. on Addictions     Hybrid Journal   (Followers: 9, SJR: 0.843, h-index: 57)
Anaesthesia     Hybrid Journal   (Followers: 138, SJR: 1.404, h-index: 88)
Analyses of Social Issues and Public Policy     Hybrid Journal   (Followers: 9, SJR: 0.397, h-index: 18)
Analytic Philosophy     Hybrid Journal   (Followers: 18)
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: 220)
Angewandte Chemie Intl. Edition     Hybrid Journal   (Followers: 222, 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 Human Genetics     Hybrid Journal   (Followers: 9, SJR: 1.191, h-index: 67)
Annals of Neurology     Hybrid Journal   (Followers: 47, 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: 13)
Annual Review of Information Science and Technology     Hybrid Journal   (Followers: 14)
Anthropology & Education Quarterly     Hybrid Journal   (Followers: 25, SJR: 0.72, h-index: 31)
Anthropology & Humanism     Hybrid Journal   (Followers: 17, 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: 89, SJR: 0.545, h-index: 15)
Antipode     Hybrid Journal   (Followers: 49, 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: 70, SJR: 0.754, h-index: 69)
Applied Organometallic Chemistry     Hybrid Journal   (Followers: 7, SJR: 0.632, h-index: 58)
Applied Psychology     Hybrid Journal   (Followers: 206, SJR: 1.023, h-index: 64)
Applied Psychology: Health and Well-Being     Hybrid Journal   (Followers: 49, 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: 14, 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: 11, 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: 27, 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: 25, 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: 12, SJR: 0.938, h-index: 57)
Art History     Hybrid Journal   (Followers: 245, SJR: 0.153, h-index: 13)
Arthritis & Rheumatology     Hybrid Journal   (Followers: 52, SJR: 1.984, h-index: 20)
Arthritis Care & Research     Hybrid Journal   (Followers: 27, 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: 15)
Asia & the Pacific Policy Studies     Open Access   (Followers: 16)
Asia Pacific J. of Human Resources     Hybrid Journal   (Followers: 320, 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   (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: 5, 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: 2, SJR: 0.701, h-index: 40)
Atmospheric Science Letters     Open Access   (Followers: 29, 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: 47, SJR: 0.814, h-index: 49)
Australian and New Zealand J. of Public Health     Hybrid Journal   (Followers: 11, SJR: 0.82, h-index: 62)
Australian Dental J.     Hybrid Journal   (Followers: 7, SJR: 0.482, h-index: 46)
Australian Economic History Review     Hybrid Journal   (Followers: 5, 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: 14, 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: 406, SJR: 0.418, h-index: 29)
Australian J. of Rural Health     Hybrid Journal   (Followers: 5, SJR: 0.43, h-index: 34)
Australian Occupational Therapy J.     Hybrid Journal   (Followers: 72, SJR: 0.59, h-index: 29)
Australian Psychologist     Hybrid Journal   (Followers: 12, SJR: 0.331, h-index: 31)
Australian Veterinary J.     Hybrid Journal   (Followers: 21, SJR: 0.459, h-index: 45)
Autism Research     Hybrid Journal   (Followers: 36, 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: 9, SJR: 0.297, h-index: 23)
Behavioral Sciences & the Law     Hybrid Journal   (Followers: 24, 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: 16, SJR: 1.172, h-index: 90)
Biological Reviews     Hybrid Journal   (Followers: 4, 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: 6, 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: 141, SJR: 1.633, h-index: 146)
Biotechnology J.     Hybrid Journal   (Followers: 14, 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: 6, SJR: 0.468, h-index: 47)
Birth Defects Research Part C : Embryo Today : Reviews     Hybrid Journal   (SJR: 1.513, h-index: 55)
BJOG : An Intl. J. of Obstetrics and Gynaecology     Partially Free   (Followers: 243, SJR: 2.083, h-index: 125)

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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  [1589 journals]
  • Advances in Nanoporous Anodic Alumina-Based Biosensors to Detect
           Biomarkers of Clinical Significance: A Review
    • Authors: Gayathri Rajeev; Beatriz Prieto Simon, Lluis F. Marsal, Nicolas H. Voelcker
      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.
      PubDate: 2017-12-05T08:01:51.651533-05:
      DOI: 10.1002/adhm.201700904
  • Transduction Methods for Cytosolic Delivery of Proteins and Bioconjugates
           into Living Cells
    • Authors: Manuela Chiper; Karen Niederreither, Guy Zuber
      Abstract: The human organism and its constituting cells rely on interplay between multiple proteins exerting specific functions. Progress in molecular biotechnologies has facilitated the production of recombinant proteins. When administrated to patients, recombinant proteins can provide important healthcare benefits. To date, most therapeutic proteins must act from the extracellular environment, with their targets being secreted modulators or extracellular receptors. This is because proteins cannot passively diffuse across the plasma membrane into the cytosol. To expand the scope of action of proteins for cytosolic targets (representing more than 40% of the genome) effective methods assisting protein cytosolic entry are being developed. To date, direct protein delivery is extremely tedious and inefficient in cultured cells, even more so in animal models of pathology. Novel techniques are changing this limitation, as recently developed in vitro methods can robustly convey large amount of proteins into cell cultures. Moreover, advances in protein formulation or protein conjugates are slowly, but surely demonstrating efficiency for targeted cytosolic entry of functional protein in vivo in tumor xenograft models. In this review, various methods and recently developed techniques for protein transport into cells are summarized. They are put into perspective to address the challenges encountered during delivery.Direct delivery of recombinant proteins into the cytosol represents an alternative to genetic intervention. Cytosolic-active proteins heavily rely on assistance to pass across the plasma membrane. Here, various methods and approaches enabling cytosolic protein delivery are reviewed, along with their scope of action.
      PubDate: 2017-12-05T08:01:27.232887-05:
      DOI: 10.1002/adhm.201701040
  • Biodegradable Nanoparticles Enhanced Adhesiveness of Mussel-Like Hydrogels
           at Tissue Interface
    • Authors: Nikhil Pandey; Amirhossein Hakamivala, Cancan Xu, Prashant Hariharan, Boris Radionov, Zhong Huang, Jun Liao, Liping Tang, Philippe Zimmern, Kytai T. Nguyen, Yi Hong
      Abstract: Popular bioadhesives, such as fibrin, cyanoacrylate, and albumin–glutaraldehyde based materials, have been applied for clinical applications in wound healing, drug delivery, and bone and soft tissue engineering; however, their performances are limited by weak adhesion strength and rapid degradation. In this study a mussel-inspired, nanocomposite-based, biodegradable tissue adhesive is developed by blending poly(lactic-co-glycolic acid) (PLGA) or N-hydroxysuccinimide modified PLGA nanoparticles (PLGA-NHS) with mussel-inspired alginate–dopamine polymer (Alg-Dopa). Adhesive strength measurement of the nanocomposites on porcine skin–muscle constructs reveals that the incorporation of nanoparticles in Alg-Dopa significantly enhances the tissue adhesive strength compared to the mussel-inspired adhesive alone. The nanocomposite formed by PLGA-NHS nanoparticles shows higher lap shear strength of 33 ± 3 kPa, compared to that of Alg-Dopa hydrogel alone (14 ± 2 kPa). In addition, these nanocomposites are degradable and cytocompatible in vitro, and elicit in vivo minimal inflammatory responses in a rat model, suggesting clinical potential of these nanocomposites as bioadhesives.Blending biodegradable nanoparticles into mussel-inspired biodegradable adhesives significantly enhances the adhesive strength between two tissues. The biodegradable nanocomposite adhesive exhibits good cell compatibility in vitro and good tissue compatibility in vivo. It can serve as a safe and strong tissue glue for surgery and tissue repair.
      PubDate: 2017-12-04T08:26:20.379586-05:
      DOI: 10.1002/adhm.201701069
  • Peptide-Functionalized Polyurethane Coatings Prepared via Grafting-To
           Strategy to Selectively Promote Endothelialization
    • Authors: Xin Ding; Willy Chin, Chuen Neng Lee, James L. Hedrick, Yi Yan Yang
      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.
      PubDate: 2017-12-04T04:07:27.436099-05:
      DOI: 10.1002/adhm.201700944
  • Photoporation Using Carbon Nanotubes for Intracellular Delivery of
           Molecules and Its Relationship to Photoacoustic Pressure
    • Authors: Stefany Y. Holguin; Michael D. Gray, Princeton Joseph, Naresh N. Thadhani, Mark R. Prausnitz
      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.
      PubDate: 2017-12-04T04:04:33.410711-05:
      DOI: 10.1002/adhm.201701007
  • Recent Progress in Micro/Nanoreactors toward the Creation of Artificial
    • Authors: Maria Godoy-Gallardo; Maria J. York-Duran, Leticia Hosta-Rigau
      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.
      PubDate: 2017-12-04T04:04:07.04459-05:0
      DOI: 10.1002/adhm.201700917
  • Biomaterials-Based Approaches to Tumor Spheroid and Organoid Modeling
    • Authors: Pradip Shahi Thakuri; Chun Liu, Gary D. Luker, Hossein Tavana
      Abstract: Evolving understanding of structural and biological complexity of tumors has stimulated development of physiologically relevant tumor models for cancer research and drug discovery. A major motivation for developing new tumor models is to recreate the 3D environment of tumors and context-mediated functional regulation of cancer cells. Such models overcome many limitations of standard monolayer cancer cell cultures. Under defined culture conditions, cancer cells self-assemble into 3D constructs known as spheroids. Additionally, cancer cells may recapitulate steps in embryonic development to self-organize into 3D cultures known as organoids. Importantly, spheroids and organoids reproduce morphology and biologic properties of tumors, providing valuable new tools for research, drug discovery, and precision medicine in cancer. This Progress Report discusses uses of both natural and synthetic biomaterials to culture cancer cells as spheroids or organoids, specifically highlighting studies that demonstrate how these models recapitulate key properties of native tumors. The report concludes with the perspectives on the utility of these models and areas of need for future developments to more closely mimic pathologic events in tumors.State-of-the-art approaches using natural, synthetic, and composite biomaterials for 3D tumor modeling are presented in this Progress Report. Furthermore, it is discussed how these models uniquely reproduce key properties of native tumors to facilitate basic and applied cancer research and cancer drug discovery efforts.
      PubDate: 2017-12-04T04:01:50.184307-05:
      DOI: 10.1002/adhm.201700980
  • Iron Oxide Nanoparticles: Innovative Tool in Cancer Diagnosis and Therapy
    • Authors: Pavla Martinkova; Martin Brtnicky, Jindrich Kynicky, Miroslav Pohanka
      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.
      PubDate: 2017-12-04T04:00:34.818038-05:
      DOI: 10.1002/adhm.201700932
  • Multiorgan Microphysiological Systems for Drug Development: Strategies,
           Advances, and Challenges
    • Authors: Ying I. Wang; Carlos Carmona, James J. Hickman, Michael L. Shuler
      Abstract: Traditional cell culture and animal models utilized for preclinical drug screening have led to high attrition rates of drug candidates in clinical trials due to their low predictive power for human response. Alternative models using human cells to build in vitro biomimetics of the human body with physiologically relevant organ–organ interactions hold great potential to act as “human surrogates” and provide more accurate prediction of drug effects in humans. This review is a comprehensive investigation into the development of tissue-engineered human cell-based microscale multiorgan models, or multiorgan microphysiological systems for drug testing. The evolution from traditional models to macro- and microscale multiorgan systems is discussed in regards to the rationale for recent global efforts in multiorgan microphysiological systems. Current advances in integrating cell culture and on-chip analytical technologies, as well as proof-of-concept applications for these multiorgan microsystems are discussed. Major challenges for the field, such as reproducibility and physiological relevance, are discussed with comparisons of the strengths and weaknesses of various systems to solve these challenges. Conclusions focus on the current development stage of multiorgan microphysiological systems and new trends in the field.Multiorgan microphysiological systems are in vitro microscale cell culture analog of the human body (body-on-a-chip). Tissue engineered single organ models are interconnected to reproduce complex multiorgan interactions. Such biomimetics of the human body can potentially serve as “human surrogates” to simulate human responses to drugs, providing pharmacokinetic and pharmacodynamic information.
      PubDate: 2017-12-04T03:53:15.481153-05:
      DOI: 10.1002/adhm.201701000
  • A Highly Selective 3D Spiked Ultraflexible Neural (SUN) Interface for
           Decoding Peripheral Nerve Sensory Information
    • Authors: Jiahui Wang; Xin Yuan Thow, Hao Wang, Sanghoon Lee, Kai Voges, Nitish V. Thakor, Shih-Cheng Yen, Chengkuo Lee
      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.
      PubDate: 2017-12-04T03:51:59.496337-05:
      DOI: 10.1002/adhm.201700987
  • Structured Macroporous Hydrogels: Progress, Challenges, and Opportunities
    • Authors: Kevin J. France; Fei Xu, Todd Hoare
      Abstract: Structured macroporous hydrogels that have controllable porosities on both the nanoscale and the microscale offer both the swelling and interfacial properties of bulk hydrogels as well as the transport properties of “hard” macroporous materials. While a variety of techniques such as solvent casting, freeze drying, gas foaming, and phase separation have been developed to fabricate structured macroporous hydrogels, the typically weak mechanics and isotropic pore structures achieved as well as the required use of solvent/additives in the preparation process all limit the potential applications of these materials, particularly in biomedical contexts. This review highlights recent developments in the field of structured macroporous hydrogels aiming to increase network strength, create anisotropy and directionality within the networks, and utilize solvent-free or additive-free fabrication methods. Such functional materials are well suited for not only biomedical applications like tissue engineering and drug delivery but also selective filtration, environmental sorption, and the physical templating of secondary networks.Structured macroporous hydrogels display porosities or feature sizes in the>100 nm to microns size range, allowing for accelerated swelling and increased diffusion versus traditional bulk hydrogels. This review summarizes the methods used to create such hydrogels and highlights recent developments in creating structured hydrogels with (1) enhanced mechanical strength, (2) anisotropic pore morphologies, and (3) solvent/additive-free preparation.
      PubDate: 2017-12-01T07:21:24.783843-05:
      DOI: 10.1002/adhm.201700927
  • Dendron-Grafted Polylysine-Based Dual-Modal Nanoprobe for Ultra-Early
           Diagnosis of Pancreatic Precancerosis via Targeting a Urokinase-Type
           Plasminogen Activator Receptor
    • Authors: Hui Li; Ping Wang, Wenyu Gong, Qi Wang, Jia Zhou, Wei-Hong Zhu, Yingsheng Cheng
      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.
      PubDate: 2017-12-01T03:26:52.317651-05:
      DOI: 10.1002/adhm.201700912
  • Ultrasensitive NIR-SERRS Probes with Multiplexed Ratiometric
           Quantification for In Vivo Antibody Leads Validation
    • Authors: Homan Kang; Sinyoung Jeong, Ahla Jo, Hyejin Chang, Jin-Kyoung Yang, Cheolhwan Jeong, San Kyeong, Youn Woo Lee, Animesh Samanta, Kaustabh Kumar Maiti, Myeong Geun Cha, Taek-Keun Kim, Sukmook Lee, Bong-Hyun Jun, Young-Tae Chang, Junho Chung, Ho-Young Lee, Dae Hong Jeong, Yoon-Sik Lee
      Abstract: Immunotargeting ability of antibodies may show significant difference between in vitro and in vivo. To select antibody leads with high affinity and specificity, it is necessary to perform in vivo validation of antibody candidates following in vitro antibody screening. Herein, a robust in vivo validation of anti-tetraspanin-8 antibody candidates against human colon cancer using ratiometric quantification method is reported. The validation is performed on a single mouse and analyzed by multiplexed surface-enhanced Raman scattering using ultrasensitive and near infrared (NIR)-active surface-enhanced resonance Raman scattering nanoprobes (NIR-SERRS dots). The NIR-SERRS dots are composed of NIR-active labels and Au/Ag hollow-shell assembled silica nanospheres. A 93% of NIR-SERRS dots is detectable at a single-particle level and signal intensity is 100-fold stronger than that from nonresonant molecule-labeled spherical Au NPs (80 nm). The result of SERRS-based antibody validation is comparable to that of the conventional method using single-photon-emission computed tomography. The NIR-SERRS-based strategy is an alternate validation method which provides cost-effective and accurate multiplexing measurements for antibody-based drug development.In vivo validation of antibody leads against human colon cancer is demonstrated in a single animal by ratiometric quantitative and multiplexed analysis with ultrasensitive and near-infrared-active surface-enhanced resonance Raman scattering probes.
      PubDate: 2017-12-01T03:25:57.402076-05:
      DOI: 10.1002/adhm.201700870
  • In Vivo FRET Imaging to Predict the Risk Associated with Hepatic
           Accumulation of Squalene-Based Prodrug Nanoparticles
    • Authors: Fanny Cayre; Simona Mura, Bohdan Andreiuk, Dunja Sobot, Sandrine Gouazou, Didier Desmaële, Andrey S. Klymchenko, Patrick Couvreur
      Abstract: Förster resonance energy transfer (FRET) is used here for the first time to monitor the in vivo fate of nanoparticles made of the squalene-gemcitabine prodrug and two novel derivatives of squalene with the cyanine dyes 5.5 and 7.5, which behave as efficient FRET pair in the NIR region. Following intravenous administration, nanoparticles initially accumulate in the liver, then they show loss of their integrity within 2 h and clearance of the squalene bioconjugates is observed within 24 h. Such awareness is a key prerequisite before introduction into clinical settings.Förster resonance energy transfer is used, for the first time, to monitor the in vivo fate of prodrug-based nanoparticles. After the initial hepatic accumulation, nanoparticles show loss of their integrity within 2 h and clearance of the squalene bioconjugates is observed within 24 h. Such awareness is a key prerequisite before introduction into clinical settings.
      PubDate: 2017-11-30T09:50:40.29362-05:0
      DOI: 10.1002/adhm.201700830
  • Cell-Based Drug Delivery and Use of Nano-and Microcarriers for Cell
    • Authors: Alexander S. Timin; Maxim M. Litvak, Dmitry A. Gorin, Elena N. Atochina-Vasserman, Dmitriy N. Atochin, Gleb B. Sukhorukov
      Abstract: Cell functionalization with recently developed various nano- and microcarriers for therapeutics has significantly expanded the application of cell therapy and targeted drug delivery for the effective treatment of a number of diseases. The aim of this progress report is to review the most recent advances in cell-based drug vehicles designed as biological transporter platforms for the targeted delivery of different drugs. For the design of cell-based drug vehicles, different pathways of cell functionalization, such as covalent and noncovalent surface modifications, internalization of carriers are considered in greater detail together with approaches for cell visualization in vivo. In addition, several animal models for the study of cell-assisted drug delivery are discussed. Finally, possible future developments and applications of cell-assisted drug vehicles toward targeted transport of drugs to a designated location with no or minimal immune response and toxicity are addressed in light of new pathways in the field of nanomedicine.A fresh outlook in advances for design of cell-based drug vehicles as biological transporter platform for targeted delivery of different drugs is presented in this progress report. An overview of the current strategies of cell functionalization by nano- and microcarriers are provided for the first time. Then, animal models for studying cell assisted drug delivery are discussed.
      PubDate: 2017-11-30T02:52:10.623384-05:
      DOI: 10.1002/adhm.201700818
  • Dynamic and Responsive Growth Factor Delivery from Electrospun and
           Hydrogel Tissue Engineering Materials
    • Authors: Kiara F. Bruggeman; Richard J. Williams, David R. Nisbet
      Abstract: Tissue engineering scaffolds are designed to mimic physical, chemical, and biological features of the extracellular matrix, thereby providing a constant support that is crucial to improved regenerative medicine outcomes. Beyond mechanical and structural support, the next generation of these materials must also consider the more dynamic presentation and delivery of drugs or growth factors to guide new and regenerating tissue development. These two aspects are explored expansively separately, but they must interact synergistically to achieve optimal regeneration. This review explores common tissue engineering materials types, electrospun polymers and hydrogels, and strategies used for incorporating drug delivery systems into these scaffolds.Tissue engineering materials need to be able to provide ongoing structural support as well as dynamically controlled drug delivery for optimal therapeutic outcomes. Electrospun and hydrogel materials are popular tissue engineering scaffolds for providing structural support, and this Progress Report explores the pros and cons of different drug delivery systems being developed for use in these materials.
      PubDate: 2017-11-30T02:51:16.783887-05:
      DOI: 10.1002/adhm.201700836
  • Controlling Protein Adsorption through Nanostructured Polymeric Surfaces
    • Authors: Izabela Firkowska-Boden; Xiaoyuan Zhang, Klaus D. Jandt
      Abstract: The initial host response to healthcare materials' surfaces after implantation is the adsorption of proteins from blood and interstitial fluids. This adsorbed protein layer modulates the biological/cellular responses to healthcare materials. This stresses the significance of the surface protein assembly for the biocompatibility and functionality of biomaterials and necessitates a profound fundamental understanding of the capability to control protein–surface interactions. This review, therefore, addresses this by systematically analyzing and discussing strategies to control protein adsorption on polymeric healthcare materials through the introduction of specific surface nanostructures. Relevant proteins, healthcare materials' surface properties, clinical applications of polymer healthcare materials, fabrication methods for nanostructured polymer surfaces, amorphous, semicrystalline and block copolymers are considered with a special emphasis on the topographical control of protein adsorption. The review shows that nanostructured polymer surfaces are powerful tools to control the amount, orientation, and order of adsorbed protein layers. It also shows that the understanding of the biological responses to such ordered protein adsorption is still in its infancy, yet it has immense potential for future healthcare materials. The review, which is—as far as it is known—the first one discussing protein adsorption on nanostructured polymer surfaces, concludes with highlighting important current research questions.Protein adsorption on biomaterials' surfaces is a very complex process impacting biocompatibility of healthcare materials. Nanostructured surfaces are recognized as a powerful tool to control protein–surface interactions. This review highlights recent studies relating nanostructured polymer surfaces represented by synthetic amorphous homopolymers, semicrystalline polymers, and block copolymers, and their ability to control the amount, conformation, and selectivity of protein adsorption.
      PubDate: 2017-11-30T02:48:58.019106-05:
      DOI: 10.1002/adhm.201700995
  • Microprinted Stem Cell Niches Reveal Compounding Effect of Colony Size on
           Stromal Cells-Mediated Neural Differentiation
    • Authors: Ramila Joshi; Pradip Shahi Thakuri, James C. Buchanan, Jun Li, Hossein Tavana
      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.
      PubDate: 2017-11-30T02:48:17.885346-05:
      DOI: 10.1002/adhm.201700832
  • Nanomaterial-Enabled Wearable Sensors for Healthcare
    • Authors: Shanshan Yao; Puchakayala Swetha, Yong Zhu
      Abstract: Highly sensitive wearable sensors that can be conformably attached to human skin or integrated with textiles to monitor the physiological parameters of human body or the surrounding environment have garnered tremendous interest. Owing to the large surface area and outstanding material properties, nanomaterials are promising building blocks for wearable sensors. Recent advances in the nanomaterial-enabled wearable sensors including temperature, electrophysiological, strain, tactile, electrochemical, and environmental sensors are presented in this review. Integration of multiple sensors for multimodal sensing and integration with other components into wearable systems are summarized. Representative applications of nanomaterial-enabled wearable sensors for healthcare, including continuous health monitoring, daily and sports activity tracking, and multifunctional electronic skin are highlighted. Finally, challenges, opportunities, and future perspectives in the field of nanomaterial-enabled wearable sensors are discussed.The development of nanomaterial-enabled wearable sensors, including temperature, electrophysiological, strain, tactile, and electrochemical sensors is summarized in this review including challenges and opportunities. The integration of multiple sensors and components into wearable systems is also reviewed. The applications of wearable sensors in health monitoring, activity tracking, and electronic skin are presented.
      PubDate: 2017-11-30T02:47:40.888223-05:
      DOI: 10.1002/adhm.201700889
  • Mesoporous Silica and Organosilica Nanoparticles: Physical Chemistry,
           Biosafety, Delivery Strategies, and Biomedical Applications
    • Authors: Jonas G. Croissant; Yevhen Fatieiev, Abdulaziz Almalik, Niveen M. Khashab
      Abstract: Predetermining the physico-chemical properties, biosafety, and stimuli-responsiveness of nanomaterials in biological environments is essential for safe and effective biomedical applications. At the forefront of biomedical research, mesoporous silica nanoparticles and mesoporous organosilica nanoparticles are increasingly investigated to predict their biological outcome by materials design. In this review, it is first chronicled that how the nanomaterial design of pure silica, partially hybridized organosilica, and fully hybridized organosilica (periodic mesoporous organosilicas) governs not only the physico-chemical properties but also the biosafety of the nanoparticles. The impact of the hybridization on the biocompatibility, protein corona, biodistribution, biodegradability, and clearance of the silica-based particles is described. Then, the influence of the surface engineering, the framework hybridization, as well as the morphology of the particles, on the ability to load and controllably deliver drugs under internal biological stimuli (e.g., pH, redox, enzymes) and external noninvasive stimuli (e.g., light, magnetic, ultrasound) are presented. To conclude, trends in the biomedical applications of silica and organosilica nanovectors are delineated, such as unconventional bioimaging techniques, large cargo delivery, combination therapy, gaseous molecule delivery, antimicrobial protection, and Alzheimer's disease therapy.Predetermining the biological outcome of nanomaterials by design is essential for safe and effective biomedical applications. In this Review, it is chronicled that how the nanomaterial design of pure silica, partially hybridized organosilica, and fully hybridized organosilica governs not only their physico-chemical properties but also their biocompatibility, protein corona, biodistribution, biodegradability, and clearance. Cargo loading/delivery strategies and trending biomedical applications are also discussed.
      PubDate: 2017-11-30T02:46:26.805482-05:
      DOI: 10.1002/adhm.201700831
  • The Role of Nanomechanics in Healthcare
    • Authors: Pranjal Nautiyal; Fahad Alam, Kantesh Balani, Arvind Agarwal
      Abstract: Nanomechanics has played a vital role in pushing our capability to detect, probe, and manipulate the biological species, such as proteins, cells, and tissues, paving way to a deeper knowledge and superior strategies for healthcare. Nanomechanical characterization techniques, such as atomic force microscopy, nanoindentation, nanotribology, optical tweezers, and other hybrid techniques have been utilized to understand the mechanics and kinetics of biospecies. Investigation of the mechanics of cells and tissues has provided critical information about mechanical characteristics of host body environments. This information has been utilized for developing biomimetic materials and structures for tissue engineering and artificial implants. This review summarizes nanomechanical characterization techniques and their potential applications in healthcare research. The principles and examples of label‐free detection of cancers and myocardial infarction by nanomechanical cantilevers are discussed. The vital importance of nanomechanics in regenerative medicine is highlighted from the perspective of material selection and design for developing biocompatible scaffolds. This review interconnects the advancements made in fundamental materials science research and biomedical technology, and therefore provides scientific insight that is of common interest to the researchers working in different disciplines of healthcare science and technology.Nanomechanics is playing a vital role in pushing our capability to detect, probe, and manipulate the biological species, such as proteins, cells and tissues, paving way to knowledge and strategies for superior healthcare. Nanomechanics has enabled early diagnosis of life‐threatening diseases, as well as facilitated the development of biomimetic implants for tissue engineering and prosthesis.
      PubDate: 2017-11-29T02:12:04.61544-05:0
      DOI: 10.1002/adhm.201700793
  • Organ Bioprinting: Are We There Yet'
    • Authors: Guifang Gao; Ying Huang, Arndt F. Schilling, Karen Hubbell, Xiaofeng Cui
      Abstract: About 15 years ago, bioprinting was coined as one of the ultimate solutions to engineer vascularized tissues, which was impossible to accomplish using the conventional tissue fabrication approaches. With the advances of 3D‐printing technology during the past decades, one may expect 3D bioprinting being developed as much as 3D printing. Unfortunately, this is not the case. The printing principles of bioprinting are dramatically different from those applied in industrialized 3D printing, as they have to take the living components into account. While the conventional 3D‐printing technologies are actually applied for biological or biomedical applications, true 3D bioprinting involving direct printing of cells and other biological substances for tissue reconstruction is still in its infancy. In this progress report, the current status of bioprinting in academia and industry is subjectively evaluated. The progress made is acknowledged, and the existing bottlenecks in bioprinting are discussed. Recent breakthroughs from a variety of associated fields, including mechanical engineering, robotic engineering, computing engineering, chemistry, material science, cellular biology, molecular biology, system control, and medicine may overcome some of these current bottlenecks. For this to happen, a convergence of these areas into a systemic research area “3D bioprinting” is needed to develop bioprinting as a viable approach for creating fully functional organs for standard clinical diagnosis and treatment including transplantation.Bioprinting involving direct printing of cells and other biological substances for tissue or organ reconstruction is still in its infancy. A transdisciplinary effort combining the best international expertise in biology, engineering, chemistry, optics, robotics, material science, medicine, noninvasive diagnostic imaging as well as computer‐aided design, to name just the most obvious, is needed to hopefully generate the necessary innovations in this fascinating field.
      PubDate: 2017-11-29T02:10:30.641806-05:
      DOI: 10.1002/adhm.201701018
  • Multilineage Constructs for Scaffold‐Based Tissue Engineering: A Review
           of Tissue‐Specific Challenges
    • Authors: Timothée Baudequin; Maryam Tabrizian
      Abstract: There is a growing interest in the regeneration of tissue in interfacial regions, where biological, physical, and chemical attributes vary across tissue type. The simultaneous use of distinct cell lineages can help in developing in vitro structures, analogous to native composite tissues. This literature review gathers the recent reports that have investigated multiple cell types of various sources and lineages in a coculture system for tissue‐engineered constructs. Such studies aim at mimicking the native organization of tissues and their interfaces, and/or to improve the development of complex tissue substitutes. This paper thus distinguishes itself from those focusing on technical aspects of coculturing for a single specific tissue. The first part of this review is dedicated to variables of cocultured tissue engineering such as scaffold, cells, and in vitro culture environment. Next, tissue‐specific coculture methods and approaches are covered for the most studied tissues. Finally, cross‐analysis is performed to highlight emerging trends in coculture principles and to discuss how tissue‐specific challenges can inspire new approaches for regeneration of different interfaces to improve the outcomes of various tissue engineering strategies.There is a growing interest in the regeneration of tissue in interfacial regions. The simultaneous use of distinct cell lineages can help in developing in vitro structures, analogous to native composite tissues. This literature review gathers the recent reports that have investigated multiple cell types of various sources and lineages in a coculture system for tissue‐engineered constructs.
      PubDate: 2017-11-28T03:41:53.345426-05:
      DOI: 10.1002/adhm.201700734
  • Hydrogel Encapsulation Facilitates Rapid‐Cooling Cryopreservation of
           Stem Cell‐Laden Core–Shell Microcapsules as Cell–Biomaterial
    • Authors: Gang Zhao; Xiaoli Liu, Kaixuan Zhu, Xiaoming He
      Abstract: Core–shell structured stem cell microencapsulation in hydrogel has wide applications in tissue engineering, regenerative medicine, and cell‐based therapies because it offers an ideal immunoisolative microenvironment for cell delivery and 3D culture. Long‐term storage of such microcapsules as cell–biomaterial constructs by cryopreservation is an enabling technology for their wide distribution and ready availability for clinical transplantation. However, most of the existing studies focus on cryopreservation of single cells or cells in microcapsules without a core–shell structure (i.e., hydrogel beads). The goal of this study is to achieve cryopreservation of stem cells encapsulated in core–shell microcapsules as cell–biomaterial constructs or biocomposites. To this end, a capillary microfluidics‐based core–shell alginate hydrogel encapsulation technology is developed to produce porcine adipose‐derived stem cell‐laden microcapsules for vitreous cryopreservation with very low concentration (2 mol L−1) of cell membrane penetrating cryoprotective agents (CPAs) by suppressing ice formation. This may provide a low‐CPA and cost‐effective approach for vitreous cryopreservation of “ready‐to‐use” stem cell–biomaterial constructs, facilitating their off‐the‐shelf availability and widespread applications.Alginate hydrogel encapsulation by capillary microfluidics facilitates rapid‐cooling cryopreservation of stem cell‐laden core–shell microcapsules as cell–biomaterial constructs. It enables vitreous cryopreservation of encapsulated stem cells with very low concentrations of penetrating cryoprotective agents, providing a cost‐effective and high‐throughput approach for long‐term storage of stem cells and stem cell–biomaterial constructs.
      PubDate: 2017-11-27T08:05:00.930115-05:
      DOI: 10.1002/adhm.201700988
  • Functionalizing PLGA and PLGA Derivatives for Drug Delivery and Tissue
           Regeneration Applications
    • Authors: Cláudia Martins; Flávia Sousa, Francisca Araújo, Bruno Sarmento
      Abstract: Poly(lactic‐co‐glycolic) acid (PLGA) is one of the most versatile biomedical polymers, already approved by regulatory authorities to be used in human research and clinics. Due to its valuable characteristics, PLGA can be tailored to acquire desirable features for control bioactive payload or scaffold matrix. Moreover, its chemical modification with other polymers or bioconjugation with molecules may render PLGA with functional properties that make it the Holy Grail among the synthetic polymers to be applied in the biomedical field. In this review, the physical–chemical properties of PLGA, its synthesis, degradation, and conjugation with other polymers or molecules are revised in detail, as well as its applications in drug delivery and regeneration fields. A particular focus is given to successful examples of products already on the market or at the late stages of trials, reinforcing the potential of this polymer in the biomedical field.The awareness of the physical–chemical characteristics of poly(lactic‐co‐glycolic) acid, all of its potential and pitfalls, either alone or upon conjugation/functionalization with other polymers and molecules, opens new avenues in its application in the biomedical field, especially in drug delivery and tissue regeneration.
      PubDate: 2017-11-24T09:37:25.416715-05:
      DOI: 10.1002/adhm.201701035
  • Developing a Clinically Relevant Tissue Engineered Heart Valve—A
           Review of Current Approaches
    • Authors: Aline L. Y. Nachlas; Siyi Li, Michael E. Davis
      Abstract: Tissue engineered heart valves (TEHVs) have the potential to address the shortcomings of current implants through the combination of cells and bioactive biomaterials that promote growth and proper mechanical function in physiological conditions. The ideal TEHV should be anti‐thrombogenic, biocompatible, durable, and resistant to calcification, and should exhibit a physiological hemodynamic profile. In addition, TEHVs may possess the capability to integrate and grow with somatic growth, eliminating the need for multiple surgeries children must undergo. Thus, this review assesses clinically available heart valve prostheses, outlines the design criteria for developing a heart valve, and evaluates three types of biomaterials (decellularized, natural, and synthetic) for tissue engineering heart valves. While significant progress has been made in biomaterials and fabrication techniques, a viable tissue engineered heart valve has yet to be translated into a clinical product. Thus, current strategies and future perspectives are also discussed to facilitate the development of new approaches and considerations for heart valve tissue engineering.Heart valve tissue engineering can address limitations of current implants through the combination of cells and biomaterials that promote growth and mechanical function in physiological conditions. This Review assesses current valve prosthesis, outlines the design criteria for developing a valve, evaluates three types of biomaterials (decellularized, natural, and synthetic), and discusses current strategies and future perspectives for valve tissue engineering.
      PubDate: 2017-11-24T09:36:44.980044-05:
      DOI: 10.1002/adhm.201700918
  • Biomimetic Materials and Fabrication Approaches for Bone Tissue
    • Authors: Hwan D. Kim; Sivashanmugam Amirthalingam, Seunghyun L. Kim, Seunghun S. Lee, Jayakumar Rangasamy, Nathaniel S. Hwang
      Abstract: Various strategies have been explored to overcome critically sized bone defects via bone tissue engineering approaches that incorporate biomimetic scaffolds. Biomimetic scaffolds may provide a novel platform for phenotypically stable tissue formation and stem cell differentiation. In recent years, osteoinductive and inorganic biomimetic scaffold materials have been optimized to offer an osteo‐friendly microenvironment for the osteogenic commitment of stem cells. Furthermore, scaffold structures with a microarchitecture design similar to native bone tissue are necessary for successful bone tissue regeneration. For this reason, various methods for fabricating 3D porous structures have been developed. Innovative techniques, such as 3D printing methods, are currently being utilized for optimal host stem cell infiltration, vascularization, nutrient transfer, and stem cell differentiation. In this progress report, biomimetic materials and fabrication approaches that are currently being utilized for biomimetic scaffold design are reviewed.Biomimetic scaffolds may provide a platform for phenotypically stable tissue formation and stem cell differentiation for bone tissue engineering. For this reason, various methods for engineering 2 or 3D structures have been developed. In this Progress Report, the biomimetic materials and fabrication approaches that are currently being utilized for biomimetic bone scaffold design are discussed.
      PubDate: 2017-11-24T07:42:19.195826-05:
      DOI: 10.1002/adhm.201700612
  • Tumor Cell Dynamics: Microenvironmental Stiffness of 3D Polymeric
           Structures to Study Invasive Rates of Cancer Cells (Adv. Healthcare Mater.
    • Authors: Enrico Domenico Lemma; Barbara Spagnolo, Francesco Rizzi, Stefania Corvaglia, Marco Pisanello, Massimo De Vittorio, Ferruccio Pisanello
      Abstract: Three‐dimensional cage‐like microscaffolds with tailored Young's modulus are used to induce different invasive behaviours of cancer cells according to structural stiffness by Enrico Domenico Lemma, Ferruccio Pisanello, and co‐workers in article number 1700888. Tumor cells invasion is boosted by softer architectures and by the presence of stiffness “weak spots” within overall rigid scaffolds, enabling more detailed analysis on mechanical interactions between tumor cells and the extracellular matrix.
      PubDate: 2017-11-22T05:42:13.370145-05:
      DOI: 10.1002/adhm.201770115
  • Contents: (Adv. Healthcare Mater. 22/2017)
    • PubDate: 2017-11-22T05:42:11.075777-05:
      DOI: 10.1002/adhm.201770113
  • Masthead: (Adv. Healthcare Mater. 22/2017)
    • PubDate: 2017-11-22T05:42:09.79265-05:0
      DOI: 10.1002/adhm.201770114
  • Memory‐Shape Implants: Fast Setting Silk Fibroin Bioink for Bioprinting
           of Patient‐Specific Memory‐Shape Implants (Adv. Healthcare Mater.
    • Authors: João B. Costa; Joana Silva-Correia, Joaquim M. Oliveira, Rui L. Reis
      Abstract: A silk fibroin bioink for the production of patient‐specific memory‐shape implants is proposed by Joaquim M. Oliveira and co‐workers in article number 1701021 using a fast setting enzymatic‐based cross‐linking reaction. The reproducibility and the reliability of this bioink allow the production of different scaffolds with superior mechanical performance. Its versatility gives new opportunity concerning tissue engineering approaches, in particular for the biofabrication of patient‐specific memory‐shape implants.
      PubDate: 2017-11-22T05:42:06.942196-05:
      DOI: 10.1002/adhm.201770111
  • Personalized Medicine: Engineered Paper‐Based Cell Culture Platforms
           (Adv. Healthcare Mater. 22/2017)
    • Authors: Darlin Lantigua; Yan Ni Kelly, Baris Unal, Gulden Camci-Unal
      Abstract: Engineered paper‐based cell culture platforms demonstrate great promise for personalized medicine, diagnostics, disease models, organ‐on‐paper systems, and tissue origami and engineering. Gulden Camci‐Unal and co‐workers provide an overview of engineered paper‐based platforms for culture and analysis of various types of cells in article number 1700619.
      PubDate: 2017-11-22T05:42:06.848913-05:
      DOI: 10.1002/adhm.201770112
  • pH/Ultrasound Dual‐Responsive Gas Generator for Ultrasound
           Imaging‐Guided Therapeutic Inertial Cavitation and Sonodynamic Therapy
    • Authors: Qianhua Feng; Wanxia Zhang, Xuemei Yang, Yuzhen Li, Yongwei Hao, Hongling Zhang, Lin Hou, Zhenzhong Zhang
      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.
      PubDate: 2017-11-15T13:41:25.818936-05:
      DOI: 10.1002/adhm.201700957
  • Placental Drug Transport‐on‐a‐Chip: A Microengineered In Vitro Model
           of Transporter‐Mediated Drug Efflux in the Human Placental Barrier
    • Authors: Cassidy Blundell; Yoon-Suk Yi, Lin Ma, Emily R. Tess, Megan J. Farrell, Andrei Georgescu, Lauren M. Aleksunes, Dongeun Huh
      Abstract: The current lack of knowledge about the effect of maternally administered drugs on the developing fetus is a major public health concern worldwide. The first critical step toward predicting the safety of medications in pregnancy is to screen drug compounds for their ability to cross the placenta. However, this type of preclinical study has been hampered by the limited capacity of existing in vitro and ex vivo models to mimic physiological drug transport across the maternal–fetal interface in the human placenta. Here the proof‐of‐principle for utilizing a microengineered model of the human placental barrier to simulate and investigate drug transfer from the maternal to the fetal circulation is demonstrated. Using the gestational diabetes drug glyburide as a model compound, it is shown that the microphysiological system is capable of reconstituting efflux transporter‐mediated active transport function of the human placental barrier to limit fetal exposure to maternally administered drugs. The data provide evidence that the placenta‐on‐a‐chip may serve as a new screening platform to enable more accurate prediction of drug transport in the human placenta.This paper presents a microengineered model of the human placental barrier for investigation of maternal–fetal drug transfer in pregnancy. The placenta‐on‐a‐chip system reconstitutes efflux transporter‐mediated transport of a test compound, demonstrating proof‐of‐principle for use as a screening platform for prediction of drug transport in pregnancy.
      PubDate: 2017-11-09T12:02:27.666258-05:
      DOI: 10.1002/adhm.201700786
  • 3D Maskless Micropatterning for Regeneration of Highly Organized Tubular
    • Authors: Chi Ma; Tiejun Qu, Bei Chang, Yan Jing, Jerry Q. Feng, Xiaohua Liu
      Abstract: Micropatterning is a widely used powerful tool to create highly ordered microstructures on material surfaces. However, due to technical limitations, the integration of micropatterned microstructures into bioinspired 3D scaffolds to successfully regenerate well‐organized functional tissues is not achieved. In this work, a unique maskless micropatterning technology is reported to create 3D nanofibrous matrices with highly organized tubular architecture for tissue regeneration. This micropatterning method is a laser‐guided, noncontact, high‐precision, flexible computer programming of machining process that can create highly ordered tubules with the density ranged from 1000 to 60 000 mm−2 and the size varied from 300 nm to 30 µm in the bioinspired 3D matrix. The tubular architecture presents pivotal biophysical cues to control dental pulp stem cell alignment, migration, polarization, and differentiation. More importantly, when using this 3D tubular hierarchical matrix as a scaffold, this study successfully regenerates functional tubular dentin that has the same well‐organized microstructure as its natural counterpart. This 3D maskless micropattern approach represents a powerful avenue not only for the exploration of cell–material interactions in 3D, but also for the regeneration of functional tissues with well‐organized microstructures.A unique maskless micropatterning technology is developed to create 3D nanofibrous matrices with highly organized tubular architecture for tissue regeneration. The tubular architecture presents crucial biophysical cues to dental pulp stem cell migration, polarization, and differentiation. When using this 3D tubular hierarchical matrix as a scaffold, functional tubular dentin is successfully regenerated with the same well‐organized microstructure as its natural counterpart.
      PubDate: 2017-11-09T12:01:57.128701-05:
      DOI: 10.1002/adhm.201700738
  • Preventing Obstructions of Nanosized Drug Delivery Systems by the
           Extracellular Matrix
    • Authors: Luise Tomasetti; Miriam Breunig
      Abstract: Although nanosized drug delivery systems are promising tools for the treatment of severe diseases, the extracellular matrix (ECM) constitutes a major obstacle that endangers therapeutic success. Mobility of diffusing species is restricted not only by small pore size (down to as low as 3 nm) but also by electrostatic interactions with the network. This article evaluates commonly used in vitro models of ECM, analytical methods, and particle types with respect to their similarity to native conditions in the target tissue. In this cross‐study evaluation, results from a wide variety of mobility studies are analyzed to discern general principles of particle–ECM interactions. For instance, cross‐linked networks and a negative network charge are essential to reliably recapitulate key features of the native ECM. Commonly used ECM mimics comprised of one or two components can lead to mobility calculations which have low fidelity to in vivo results. In addition, analytical methods must be tailored to the properties of both the matrix and the diffusing species to deliver accurate results. Finally, nanoparticles must be sufficiently small to penetrate the matrix pores (ideally Rd/p < 0.5; d = particle diameter, p = pore size) and carry a neutral surface charge to avoid obstructions. Larger (Rd/p >> 1) or positively charged particles are trapped.Nanoparticle obstruction by the extracellular matrix endangers therapeutic success. Mobility is restricted by the small pores of the matrix and by electrostatic interactions with the network. Only particle diameters that do not exceed the pore sizes of the matrix (Rd/p < 1) and that have neutral or negative surface charge can pass the barrier. Larger or positively charged particles are trapped.
      PubDate: 2017-11-09T12:00:59.364776-05:
      DOI: 10.1002/adhm.201700739
  • Progress Toward the Clinical Translation of Bioinspired Peptide and
           Protein Assemblies
    • Authors: Kelly M. Hainline; Chelsea N. Fries, Joel H. Collier
      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.
      PubDate: 2017-11-08T05:30:42.098846-05:
      DOI: 10.1002/adhm.201700930
  • Microenvironmental Stiffness of 3D Polymeric Structures to Study Invasive
           Rates of Cancer Cells
    • Authors: Enrico Domenico Lemma; Barbara Spagnolo, Francesco Rizzi, Stefania Corvaglia, Marco Pisanello, Massimo De Vittorio, Ferruccio Pisanello
      Abstract: Cells are highly dynamic elements, continuously interacting with the extracellular environment. Mechanical forces sensed and applied by cells are responsible for cellular adhesion, motility, and deformation, and are heavily involved in determining cancer spreading and metastasis formation. Cell/extracellular matrix interactions are commonly analyzed with the use of hydrogels and 3D microfabricated scaffolds. However, currently available techniques have a limited control over the stiffness of microscaffolds and do not allow for separating environmental properties from biological processes in driving cell mechanical behavior, including nuclear deformability and cell invasiveness. Herein, a new approach is presented to study tumor cell invasiveness by exploiting an innovative class of polymeric scaffolds based on two‐photon lithography to control the stiffness of deterministic microenvironments in 3D. This is obtained by fine‐tuning of the laser power during the lithography, thus locally modifying both structural and mechanical properties in the same fabrication process. Cage‐like structures and cylindric stent‐like microscaffolds are fabricated with different Young's modulus and stiffness gradients, allowing obtaining new insights on the mechanical interplay between tumor cells and the surrounding environments. In particular, cell invasion is mostly driven by softer architectures, and the introduction of 3D stiffness “weak spots” is shown to boost the rate at which cancer cells invade the scaffolds. The possibility to modulate structural compliance also allowed estimating the force distribution exerted by a single cell on the scaffold, revealing that both pushing and pulling forces are involved in the cell–structure interaction. Overall, exploiting this method to obtain a wide range of 3D architectures with locally engineered stiffness can pave the way for unique applications to study tumor cell dynamics.Two‐photon lithography is a powerful technique to design and microfabricate 3D structures, with applications in a variety of fields including cell mechanosensing. Stiffness modulation of 3D microenvironments is used to monitor cancer cell invasive behavior in the presence of stiffness gradients and to model cell/structure mechanical interactions.
      PubDate: 2017-11-06T04:36:31.302202-05:
      DOI: 10.1002/adhm.201700888
  • Fast Setting Silk Fibroin Bioink for Bioprinting of Patient‐Specific
           Memory‐Shape Implants
    • Authors: João B. Costa; Joana Silva-Correia, Joaquim M. Oliveira, Rui L. Reis
      Abstract: The pursuit for the “perfect” biomimetic and personalized implant for musculoskeletal tissue regeneration remains a big challenge. 3D printing technology that makes use of a novel and promising biomaterials can be part of the solution. In this study, a fast setting enzymatic‐crosslinked silk fibroin (SF) bioink for 3D bioprinting is developed. Their properties are fine‐tuned and different structures with good resolution, reproducibility, and reliability can be fabricated. Many potential applications exist for the SF bioinks including 3D bioprinted scaffolds and patient‐specific implants exhibiting unique characteristics such as good mechanical properties, memory‐shape feature, suitable degradation, and tunable pore architecture and morphology.A silk fibroin (SF) bioink for the production of patient‐specific memory‐shape implants is proposed using a fast setting enzymatic‐based cross‐linking reaction. The reproducibility and the reliability of the SF bioinks allow the production of different scaffolds with superior mechanical performance. The versatility of the SF bioink gives new opportunity concerning tissue engineering approaches, in particular for the biofabrication of patient‐specific memory‐shape implants.
      PubDate: 2017-11-06T04:34:57.958771-05:
      DOI: 10.1002/adhm.201701021
  • Incorporation of a Ligand Peptide for Immune Inhibitory Receptor LAIR‐1
           on Biomaterial Surfaces Inhibits Macrophage Inflammatory Responses
    • Authors: Yoon Kyung Kim; Shu-Hui Chu, Jessica Y. Hsieh, Cody M. Kamoku, Andrea J. Tenner, Wendy F. Liu, Szu-Wen Wang
      Abstract: Leukocyte‐associated immunoglobulin‐like receptor‐1 (LAIR‐1) is an inhibitory receptor broadly expressed on immune cells, with its ligands residing within the extracellular matrix protein collagen. In this study, surfaces are modified with a LAIR‐1 ligand peptide (LP), and it is observed that macrophages cultured on LAIR‐1 LP‐conjugated surfaces exhibit significantly reduced secretion of inflammatory cytokines in response to proinflammatory stimuli that reflect an injured environment. These downregulated mediators include TNF‐α, MIP‐1α, MIP‐1β, MIP‐2, RANTES, and MIG. Knockdown of LAIR‐1 using siRNA abrogates this inhibition of cytokine secretion, supporting the specificity of the inhibitory effect to this receptor. These results are the first to demonstrate that integration of LAIR‐1 ligands with biomaterials could suppress inflammatory responses.Modification of material surfaces with a ligand peptide for immune inhibitory receptor, leukocyte‐associated immunoglobulin‐like receptor‐1 (LAIR‐1), significantly reduces the secretion of inflammatory cytokines of macrophages in response to proinflammatory stimuli. The LAIR‐1 ligand peptide is derived from the extracellular matrix protein collagen, and the incorporation of this ligand peptide to biomaterial surfaces may be a strategy to suppress local inflammatory responses toward implanted materials.
      PubDate: 2017-10-30T10:35:47.684568-05:
      DOI: 10.1002/adhm.201700707
  • Calcium Phosphate–Collagen Scaffold with Aligned Pore Channels for
           Enhanced Osteochondral Regeneration
    • Authors: Yun-Jeong Seong; In-Gu Kang, Eun-Ho Song, Hyoun-Ee Kim, Seol-Ha Jeong
      Abstract: This study reports the development of a bilayered scaffold with aligned channels produced via a sequential coextrusion and unidirectional freezing process to facilitate upward bone‐marrow stem‐cell migration. The biomimetic scaffold with collagen and biphasic calcium phosphate (BCP) layers is successfully fabricated with matching of the cartilage and bone layers. The aligned structure results in an enhancement of the compressive strength, and the channels enable tight anchoring of the collagen layers on the BCP scaffolds compared with a randomly structured porous scaffold. An in vitro evaluation demonstrates that the aligned channels guide the cells to attach on the surface in highly stretched shapes and migrate upward faster than the random structure. In addition, in vivo assessment reveals that the aligned channels yield superior osteochondral tissue regeneration compared with the random structure. Moreover, the channel diameter greatly affects the tissue regeneration, and the scaffold with a channel diameter of ≈270 µm exhibits the optimal regeneration because of sufficient nutrient supply and adequate tissue ingrowth. These findings indicate that the introduction of aligned channels to a bilayered scaffold provides an effective approach for osteochondral tissue regeneration.An innovative bilayered scaffold design consisting of aligned channels is proposed to enhance cell and tissue migration for effective regeneration of osteochondral tissue.
      PubDate: 2017-10-27T02:52:44.05402-05:0
      DOI: 10.1002/adhm.201700966
  • Rational Design of a New Self‐Codelivery System from Redox‐Sensitive
           Camptothecin–Cytarabine Conjugate Assembly for Effectively Synergistic
           Anticancer Therapy
    • Authors: Wenxiu He; Xu Hu, Wei Jiang, Ruiling Liu, Di Zhang, Jing Zhang, Zhonghao Li, Yuxia Luan
      Abstract: Herein, two careful selected anticancer drugs camptothecin (CPT) and cytarabine (Ara‐C) with different biological action mechanisms and different water solubility are conjugated together through a glutathione (GSH) cleavable disulfide bond to construct a redox‐sensitive drug–drug conjugate, which can self‐assemble into nanoparticles, thus notably improving the water solubility of CPT and the cell membrane permeability of Ara‐C. Compared with free drugs, the self‐assembled CPT‐ss‐Ara nanoparticles can concentrate in tumor tissues through the enhanced permeability and retention (EPR) effect, then they can be rapidly internalized by tumor cells and degrade into free drugs for killing the tumor cells when exposed to the reductive environment (GSH) of tumor cells, thereby reducing the injury to normal cells. Meanwhile, the CPT‐ss‐Ara nanoparticles can effectively protect CPT and Ara‐C molecules from biological inactivation before their arrival in tumor microenvironment since free CPT and Ara‐C are easy to partly lose their therapy efficacy due to their structure degradation in blood circulation. The in vitro and in vivo anticancer experimental results indicate that simultaneous release of free CPT and Ara‐C can realize synergistic chemotherapy effects, thus markedly improve their anticancer activity. Therefore, our designed carrier‐free, redox‐sensitive CPT‐ss‐Ara nanoparticles might have promising clinical application to combat cancers.Based on the therapy drawbacks of individual camptothecin (CPT) or Ara‐C anticancer drug, CPT and Ara‐C are cleverly conjugated together through a disulfide bond to construct a redox‐sensitive drug–drug conjugate for realizing an “all‐in‐one” carrier‐free drug codelivery system to overcome the drawbacks of individual CPT or Ara‐C for cancer therapy.
      PubDate: 2017-10-27T02:51:53.303299-05:
      DOI: 10.1002/adhm.201700829
  • Human Periodontal Ligament‐ and Gingiva‐derived Mesenchymal Stem Cells
           Promote Nerve Regeneration When Encapsulated in Alginate/Hyaluronic Acid
           3D Scaffold
    • Authors: Sahar Ansari; Ivana M. Diniz, Chider Chen, Patricia Sarrion, Ali Tamayol, Benjamin M. Wu, Alireza Moshaverinia
      Abstract: Repair or regeneration of damaged nerves is still a challenging clinical task in reconstructive surgeries and regenerative medicine. Here, it is demonstrated that periodontal ligament stem cells (PDLSCs) and gingival mesenchymal stem cells (GMSCs) isolated from adult human periodontal and gingival tissues assume neuronal phenotype in vitro and in vivo via a subcutaneous transplantation model in nude mice. PDLSCs and GMSCs are encapsulated in a 3D scaffold based on alginate and hyaluronic acid hydrogels capable of sustained release of human nerve growth factor (NGF). The elasticity of the hydrogels affects the proliferation and differentiation of encapsulated MSCs within scaffolds. Moreover, it is observed that PDLSCs and GMSCs are stained positive for βIII‐tubulin, while exhibiting high levels of gene expression related to neurogenic differentiation (βIII‐tubulin and glial fibrillary acidic protein) via quantitative polymerase chain reaction (qPCR). Western blot analysis shows the importance of elasticity of the matrix and the presence of NGF in the neurogenic differentiation of encapsulated MSCs. In vivo, immunofluorescence staining for neurogenic specific protein markers confirms islands of dense positively stained structures inside transplanted hydrogels. As far as it is known, this study is the first demonstration of the application of PDLSCs and GMSCs as promising cell therapy candidates for nerve regeneration.A 3D delivery system is fabricated based on alginate/hyaluronic acid hydrogels as a promising candidate for cell‐based neural tissue engineering. Periodontal ligament stem cells and gingival mesenchymal stem cells (MSCs) are encapsulated in the engineered scaffold and it is demonstrated that proliferation and neurogenic differentiation of encapsulated MSCs is regulated by matrix elasticity and the presence of suitable signaling molecules.
      PubDate: 2017-10-27T02:51:00.79641-05:0
      DOI: 10.1002/adhm.201700670
  • Engineered Paper‐Based Cell Culture Platforms
    • Authors: Darlin Lantigua; Yan Ni Kelly, Baris Unal, Gulden Camci-Unal
      Abstract: Paper is used in various applications in biomedical research including diagnostics, separations, and cell cultures. Paper can be conveniently engineered due to its tunable and flexible nature, and is amenable to high‐throughput sample preparation and analysis. Paper‐based platforms are used to culture primary cells, tumor cells, patient biopsies, stem cells, fibroblasts, osteoblasts, immune cells, bacteria, fungi, and plant cells. These platforms are compatible with standard analytical assays that are typically used to monitor cell behavior. Due to its thickness and porous nature, there are no mass transport limitations to/from the cells in paper scaffolds. It is possible to pattern paper in different scales (micrometer to centimeter), generate modular configurations in 3D, fabricate multicellular and compartmentalized tissue mimetics for clinical applications, and recover cells from the scaffolds for further analysis. 3D paper constructs can provide physiologically relevant tissue models for personalized medicine. Layer‐by layer strategies to assemble tissue‐like structures from low‐cost and biocompatible paper‐based materials offer unique opportunities that include understanding fundamental biology, developing disease models, and assembling different tissues for organ‐on‐paper applications. Paper‐based platforms can also be used for origami‐inspired tissue engineering. This work provides an overview of recent progress in engineered paper‐based biomaterials and platforms to culture and analyze cells.Engineered paper‐based cell culture platforms have been shown to be particularly promising for health diagnostics, tissue engineering, and personalized medicine. Here, a comprehensive overview of engineered paper‐based biomaterials and platforms to culture and analyze cells is provided.
      PubDate: 2017-10-27T01:02:03.216604-05:
      DOI: 10.1002/adhm.201700619
  • Scaffold‐Based microRNA Therapies in Regenerative Medicine and
    • Authors: Caroline M. Curtin; Irene Mencía Castaño, Fergal J. O'Brien
      Abstract: microRNA‐based therapies are an advantageous strategy with applications in both regenerative medicine (RM) and cancer treatments. microRNAs (miRNAs) are an evolutionary conserved class of small RNA molecules that modulate up to one third of the human nonprotein coding genome. Thus, synthetic miRNA activators and inhibitors hold immense potential to finely balance gene expression and reestablish tissue health. Ongoing industry‐sponsored clinical trials inspire a new miRNA therapeutics era, but progress largely relies on the development of safe and efficient delivery systems. The emerging application of biomaterial scaffolds for this purpose offers spatiotemporal control and circumvents biological and mechanical barriers that impede successful miRNA delivery. The nascent research in scaffold‐mediated miRNA therapies translates know‐how learnt from studies in antitumoral and genetic disorders as well as work on plasmid (p)DNA/siRNA delivery to expand the miRNA therapies arena. In this progress report, the state of the art methods of regulating miRNAs are reviewed. Relevant miRNA delivery vectors and scaffold systems applied to‐date for RM and cancer treatment applications are discussed, as well as the challenges involved in their design. Overall, this progress report demonstrates the opportunity that exists for the application of miRNA‐activated scaffolds in the future of RM and cancer treatments.MicroRNA‐based therapies hold immense potential to finely balance gene expression and reestablish tissue health, but their progress largely relies on the development of safe and effective delivery systems. In this Progress Report future opportunities and current challenges that exist in the emerging application of biomaterial scaffolds as microRNA delivery platforms for regenerative medicine and cancer treatments are illustrated.
      PubDate: 2017-10-25T10:06:24.546064-05:
      DOI: 10.1002/adhm.201700695
  • Fundamentals of Laser‐Based Hydrogel Degradation and Applications in
           Cell and Tissue Engineering
    • Authors: Shantanu Pradhan; Keely A. Keller, John L. Sperduto, John H. Slater
      Abstract: The cell and tissue engineering fields have profited immensely through the implementation of highly structured biomaterials. The development and implementation of advanced biofabrication techniques have established new avenues for generating biomimetic scaffolds for a multitude of cell and tissue engineering applications. Among these, laser‐based degradation of biomaterials is implemented to achieve user‐directed features and functionalities within biomimetic scaffolds. This review offers an overview of the physical mechanisms that govern laser–material interactions and specifically, laser–hydrogel interactions. The influences of both laser and material properties on efficient, high‐resolution hydrogel degradation are discussed and the current application space in cell and tissue engineering is reviewed. This review aims to acquaint readers with the capability and uses of laser‐based degradation of biomaterials, so that it may be easily and widely adopted.The fundamental mechanisms, based on laser and hydrogel properties that mediate laser‐based hydrogel degradation are discussed here, and the current application space in cell and tissue engineering is presented. The aim is to acquaint readers with the capabilities and limitations of laser‐based hydrogel degradation so that it may be easily and widely adopted for biofabrication and other applications.
      PubDate: 2017-10-24T11:52:53.13141-05:0
      DOI: 10.1002/adhm.201700681
  • Biomolecule‐Responsive Hydrogels in Medicine
    • Authors: Ghorbanali Sharifzadeh; Hossein Hosseinkhani
      Abstract: Recent advances and applications of biomolecule‐responsive hydrogels, namely, glucose‐responsive hydrogels, protein‐responsive hydrogels, and nucleic‐acid‐responsive hydrogels are highlighted. However, achieving the ultimate purpose of using biomolecule‐responsive hydrogels in preclinical and clinical areas is still at the very early stage and calls for more novel designing concepts and advance ideas. On the way toward the real/clinical application of biomolecule‐responsive hydrogels, plenty of factors should be extensively studied and examined under both in vitro and in vivo conditions. For example, biocompatibility, biointegration, and toxicity of biomolecule‐responsive hydrogels should be carefully evaluated. From the living body's point of view, biocompatibility is seriously depended on the interactions at the tissue/polymer interface. These interactions are influenced by physical nature, chemical structure, surface properties, and degradation of the materials. In addition, the developments of advanced hydrogels with tunable biological and mechanical properties which cause no/low side effects are of great importance.Biomolecules such as glucose, proteins, nucleic acids and polypeptides, involved in all living organisms, serve as the most fundamental and vital parts of living systems. Biomolecule‐responsive hydrogels are divided into three categories: glucose‐responsive hydrogels, protein‐responsive hydrogels, and nucleic acid‐responsive hydrogels. These modified hydrogels can be applied in various medical areas including: cancer, drug/gene delivery, regenerative medicine and tissue engineering.
      PubDate: 2017-10-23T00:42:51.317913-05:
      DOI: 10.1002/adhm.201700801
  • Connecting Biology to Electronics: Molecular Communication via Redox
    • Authors: Yi Liu; Jinyang Li, Tanya Tschirhart, Jessica L. Terrell, Eunkyoung Kim, Chen-Yu Tsao, Deanna L. Kelly, William E. Bentley, Gregory F. Payne
      Abstract: Biology and electronics are both expert at for accessing, analyzing, and responding to information. Biology uses ions, small molecules, and macromolecules to receive, analyze, store, and transmit information, whereas electronic devices receive input in the form of electromagnetic radiation, process the information using electrons, and then transmit output as electromagnetic waves. Generating the capabilities to connect biology–electronic modalities offers exciting opportunities to shape the future of biosensors, point‐of‐care medicine, and wearable/implantable devices. Redox reactions offer unique opportunities for bio‐device communication that spans the molecular modalities of biology and electrical modality of devices. Here, an approach to search for redox information through an interactive electrochemical probing that is analogous to sonar is adopted. The capabilities of this approach to access global chemical information as well as information of specific redox‐active chemical entities are illustrated using recent examples. An example of the use of synthetic biology to recognize external molecular information, process this information through intracellular signal transduction pathways, and generate output responses that can be detected by electrical modalities is also provided. Finally, exciting results in the use of redox reactions to actuate biology are provided to illustrate that synthetic biology offers the potential to guide biological response through electrical cues.Redox reactions span the molecular modality of biology and the electrical modality of devices. Here, an approach to search for redox information through an interactive electrochemical probing that is analogous to sonar is adopted. The capabilities of this approach to access chemical information are illustrated using recent examples. Exciting results in the use of redox to actuate biology are also provided.
      PubDate: 2017-10-18T01:51:17.877181-05:
      DOI: 10.1002/adhm.201700789
  • Modern Therapeutic Approaches for Noninfectious Ocular Diseases Involving
    • Authors: Michelle L. Ratay; Elena Bellotti, Riccardo Gottardi, Steven R. Little
      Abstract: Dry eye disease, age‐related macular degeneration, and uveitis are ocular diseases that significantly affect the quality of life of millions of people each year. In these diseases, the action of chemokines, proinflammatory cytokines, and immune cells drives a local inflammatory response that results in ocular tissue damage. Multiple therapeutic strategies are developed to either address the symptoms or abate the underlying cause of these diseases. Herein, the challenges to deliver drugs to the relevant location in the eye for each of these diseases are reviewed along with current and innovative therapeutic approaches that attempt to restore homeostasis within the ocular microenvironment.Dry eye disease, age‐related macular degeneration, and uveitis are ocular diseases that significantly affect the quality of life of millions of people. In these diseases, an inflammatory response results in ocular tissue damage. This review outlines multiple types of therapeutic strategies aim to either address the symptoms or abate the underlying cause of these diseases.
      PubDate: 2017-10-16T03:29:29.705289-05:
      DOI: 10.1002/adhm.201700733
  • Organ‐On‐A‐Chip Platforms: A Convergence of Advanced Materials,
           Cells, and Microscale Technologies
    • Authors: Samad Ahadian; Robert Civitarese, Dawn Bannerman, Mohammad Hossein Mohammadi, Rick Lu, Erika Wang, Locke Davenport-Huyer, Ben Lai, Boyang Zhang, Yimu Zhao, Serena Mandla, Anastasia Korolj, Milica Radisic
      Abstract: Significant advances in biomaterials, stem cell biology, and microscale technologies have enabled the fabrication of biologically relevant tissues and organs. Such tissues and organs, referred to as organ‐on‐a‐chip (OOC) platforms, have emerged as a powerful tool in tissue analysis and disease modeling for biological and pharmacological applications. A variety of biomaterials are used in tissue fabrication providing multiple biological, structural, and mechanical cues in the regulation of cell behavior and tissue morphogenesis. Cells derived from humans enable the fabrication of personalized OOC platforms. Microscale technologies are specifically helpful in providing physiological microenvironments for tissues and organs. In this review, biomaterials, cells, and microscale technologies are described as essential components to construct OOC platforms. The latest developments in OOC platforms (e.g., liver, skeletal muscle, cardiac, cancer, lung, skin, bone, and brain) are then discussed as functional tools in simulating human physiology and metabolism. Future perspectives and major challenges in the development of OOC platforms toward accelerating clinical studies of drug discovery are finally highlighted.Due to the significant advances in biomaterial synthesis, cell biology, and microscale technologies, personalized organ‐on‐a‐chip (OOC) platforms have emerged as a powerful tool in disease modeling for drug discovery and prediction. Here, several OOC platforms fabricated using biomaterials, cells, and microscale technologies are described. Major challenges and perspectives in the development of physiologically relevant OOC platforms are then highlighted.
      PubDate: 2017-10-16T03:23:03.330231-05:
      DOI: 10.1002/adhm.201700506
  • Nanoparticle‐Based Therapeutics for Brain Injury
    • Authors: Vimala N. Bharadwaj; Duong T. Nguyen, Vikram D. Kodibagkar, Sarah E. Stabenfeldt
      Abstract: Brain injuries affect a large patient population with major physical and emotional suffering for patients and their relatives; at a significant cost to the society. Effective diagnostic and therapeutic options available for brain injuries are limited by the complex brain injury pathology involving blood–brain barrier (BBB). Brain injuries, including ischemic stroke and brain trauma, initiate BBB opening for a short period of time, which is followed by a second reopening for an extended time. The leaky BBB and/or the alterations in the receptor expression on BBB may provide opportunities for therapeutic delivery via nanoparticles (NPs). The approaches for therapeutic interventions via NP delivery are aimed at salvaging the pericontusional/penumbra area for possible neuroprotection and neurovascular unit preservation. The focus of this progress report is to provide a survey of NP strategies employed in cerebral ischemia and brain trauma and finally provide insights for improved NP‐based diagnostic/treatment approaches.Engineered nanoparticles have the potential to revolutionize the diagnosis and treatment of many diseases, and currently more than two‐dozen nanoparticle systems are approved by the US Food and Drug Administration. This progress report summarizes brain injury pathology (ischemic stroke and traumatic brain injury) and recent research on nanoparticle applications following brain injury and conclusively provides insights for future nanoparticle‐based diagnostic/treatment strategies.
      PubDate: 2017-10-16T03:11:26.459948-05:
      DOI: 10.1002/adhm.201700668
  • Open Fluidics: A Cell Culture Flow System Developed Over Wettability
           Contrast‐Based Chips
    • Authors: Nuno M. Oliveira; Rui L. Reis, João F. Mano
      Abstract: Biological tissues are recurrently exposed to several dynamic mechanical forces that influence cell behavior. On this work, the focus is on the shear stress forces induced by fluid flow. The study of flow‐induced effects on cells leads to important advances in cardiovascular, cancer, stem cell, and bone biology understanding. These studies are performed using cell culture flow (CCF) systems, mainly parallel plate flow chambers (PPFC), and microfluidic systems. Here, it is proposed an original CCF system based on the open fluidics concept. The system is developed using a planar superhydrophobic platform with hydrophilic paths. The paths work as channels to drive cell culture medium flows without using walls for liquid confinement. The liquid streams are controlled just based on the wettability contrast. To validate the concept, the effect of the shear stress stimulus in the osteogenic differentiation of C2C12 myoblast cells is studied. Combining bone morphogenic protein (specifically BMP‐2) stimulation with this mechanical stimulus, a synergistic effect is found on osteoblast differentiation. This effect is confirmed by the enhancement of alkaline phosphatase activity, a well‐known early marker of osteogenic differentiation. The suggested CCF system combines characteristics and advantages of both the PPFC and microfluidic systems.A new Cell Culture Flow System based on a planar superhydrophobic (SH) platform is developed. The engineered system is used for studying the shear stress influence on adherent cells. On the hydrophilic paths patterned on the superhydrophobic surface, cells are pre‐adhered and cultured under shear stress stimuli that is inflicted by the cell culture medium flowing over the cell monolayer.
      PubDate: 2017-10-16T03:07:31.842584-05:
      DOI: 10.1002/adhm.201700638
  • Controlling the Release of Small, Bioactive Proteins via Dual Mechanisms
           with Therapeutic Potential
    • Authors: Prathamesh M. Kharkar; Rebecca A. Scott, Laura P. Olney, Paige J. LeValley, Emanual Maverakis, Kristi L. Kiick, April M. Kloxin
      Abstract: Injectable delivery systems that respond to biologically relevant stimuli present an attractive strategy for tailorable drug release. Here, the design and synthesis of unique polymers are reported for the creation of hydrogels that are formed in situ and degrade in response to clinically relevant endogenous and exogenous stimuli, specifically reducing microenvironments and externally applied light. Hydrogels are formed with polyethylene glycol and heparin‐based polymers using a Michael‐type addition reaction. The resulting hydrogels are investigated for the local controlled release of low molecular weight proteins (e.g., growth factors and cytokines), which are of interest for regulating various cellular functions and fates in vivo yet remain difficult to deliver. Incorporation of reduction‐sensitive linkages and light‐degradable linkages affords significant changes in the release profiles of fibroblast growth factor‐2 (FGF‐2) in the presence of the reducing agent glutathione or light, respectively. The bioactivity of the released FGF‐2 is comparable to pristine FGF‐2, indicating the ability of these hydrogels to retain the bioactivity of cargo molecules during encapsulation and release. Further, in vivo studies demonstrate degradation‐mediated release of FGF‐2. Overall, our studies demonstrate the potential of these unique stimuli‐responsive chemistries for controlling the local release of low molecular weight proteins in response to clinically relevant stimuli.Injectable depots that sequester small bioactive proteins and respond to clinically relevant internal and external stimuli enable local controlled release of therapeutics in the body. Degradation of these depots in response to reducing microenvironments, such as found in tumors, and externally applied light allows tailored release of therapeutic proteins, including basic fibroblast growth factor, with relevance for a variety of biomedical applications.
      PubDate: 2017-10-12T14:29:24.890519-05:
      DOI: 10.1002/adhm.201700713
  • Synthesis of Metal Nanoparticles in Metal‐Phenolic Networks: Catalytic
           and Antimicrobial Applications of Coated Textiles
    • Authors: Gyeongwon Yun; Shuaijun Pan, Ting-Yi Wang, Junling Guo, Joseph J. Richardson, Frank Caruso
      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.
      PubDate: 2017-10-12T01:20:44.53068-05:0
      DOI: 10.1002/adhm.201700934
  • Scaffold Composition Determines the Angiogenic Outcome of Cell‐Based
           Vascular Endothelial Growth Factor Expression by Modulating Its
           Microenvironmental Distribution
    • Authors: Emanuele Gaudiello; Ludovic Melly, Giulia Cerino, Stefano Boccardo, Sasan Jalili-Firoozinezhad, Lifen Xu, Friedrich Eckstein, Ivan Martin, Beat A. Kaufmann, Andrea Banfi, Anna Marsano
      Abstract: Delivery of genetically modified cells overexpressing Vascular Endothelial Growth Factor (VEGF) is a promising approach to induce therapeutic angiogenesis in ischemic tissues. The effect of the protein is strictly modulated by its interaction with the components of the extracellular matrix. Its therapeutic potential depends on a sustained but controlled release at the microenvironmental level in order to avoid the formation of abnormal blood vessels. In this study, it is hypothesized that the composition of the scaffold plays a key role in modulating the binding, hence the therapeutic effect, of the VEGF released by 3D‐cell constructs. It is found that collagen sponges, which poorly bind VEGF, prevent the formation of localized hot spots of excessive concentration, therefore, precluding the development of aberrant angiogenesis despite uncontrolled expression by a genetically engineered population of adipose tissue‐derived stromal cells. On the contrary, after seeding on VEGF‐binding egg‐white scaffolds, the same cell population caused aberrantly enlarged vascular structures after 14 d. Collagen‐based engineered tissues also induced a safe and efficient angiogenesis in both the patch itself and the underlying myocardium in rat models. These findings open new perspectives on the control and the delivery of proangiogenic stimuli, and are fundamental for the vascularization of engineered tissues/organs.Promising angiogenic approaches rely on cell‐based delivery of exogenous VEGF. However, the 3D microenvironmental distribution of VEGF levels needs to be precisely controlled in vivo around each producing cell to avoid the formation of aberrant vascular structures. Our findings show that the matrix composition, used to deliver the genetically modified cells, is the unique discriminating factor between normal and aberrant angiogenesis.
      PubDate: 2017-10-10T00:11:23.659468-05:
      DOI: 10.1002/adhm.201700600
  • Synthesis, Functionalization, and Design of Magnetic Nanoparticles for
           Theranostic Applications
    • Authors: Jalal Mosayebi; Mehdi Kiyasatfar, Sophie Laurent
      Abstract: In order to translate nanotechnology into medical practice, magnetic nanoparticles (MNPs) have been presented as a class of non‐invasive nanomaterials for numerous biomedical applications. In particular, MNPs have opened a door for simultaneous diagnosis and brisk treatment of diseases in the form of theranostic agents. This review highlights the recent advances in preparation and utilization of MNPs from the synthesis and functionalization steps to the final design consideration in evading the body immune system for therapeutic and diagnostic applications with addressing the most recent examples of the literature in each section. This study provides a conceptual framework of a wide range of synthetic routes classified mainly as wet chemistry, state‐of‐the‐art microfluidic reactors, and biogenic routes, along with the most popular coating materials to stabilize resultant MNPs. Additionally, key aspects of prolonging the half‐life of MNPs via overcoming the sequential biological barriers are covered through unraveling the biophysical interactions at the bio–nano interface and giving a set of criteria to efficiently modulate MNPs' physicochemical properties. Furthermore, concepts of passive and active targeting for successful cell internalization, by respectively exploiting the unique properties of cancers and novel targeting ligands are described in detail. Finally, this study extensively covers the recent developments in magnetic drug targeting and hyperthermia as therapeutic applications of MNPs. In addition, multi‐modal imaging via fusion of magnetic resonance imaging, and also innovative magnetic particle imaging with other imaging techniques for early diagnosis of diseases are extensively provided.In this review, a wide range of synthetic routes for the preparation of magnetic nanoparticles (MNPs), classified as wet chemistry, microfluidic reactors, and biogenic routes is provided. Design considerations of MNPs for prolonging their half‐life via overcoming biological barriers as well as their therapeutic and diagnostic applications are also detailed.
      PubDate: 2017-10-09T03:20:37.497468-05:
      DOI: 10.1002/adhm.201700306
  • Organ‐on‐a‐Chip Systems for Women's Health Applications
    • Authors: Janna Nawroth; Julia Rogal, Martin Weiss, Sara Y. Brucker, Peter Loskill
      Abstract: Biomedical research, for a long time, has paid little attention to the influence of sex in many areas of study, ranging from molecular and cellular biology to animal models and clinical studies on human subjects. Many studies solely rely on male cells/tissues/animals/humans, although there are profound differences in male and female physiology, which can significantly impact disease mechanisms, toxicity of compounds, and efficacy of pharmaceuticals. In vitro systems have been traditionally very limited in their capacity to recapitulate female‐specific physiology and anatomy such as dynamic sex‐hormone levels and the complex interdependencies of female reproductive tract organs. However, the advent of microphysiological organ‐on‐a‐chip systems, which attempt to recreate the 3D structure and function of human organs, now gives researchers the opportunity to integrate cells and tissues from a variety of individuals. Moreover, adding a dynamic flow environment allows mimicking endocrine signaling during the menstrual cycle and pregnancy, as well as providing a controlled microfluidic environment for pharmacokinetic modeling. This review gives an introduction into preclinical and clinical research on women's health and discusses where organ‐on‐a‐chip systems are already utilized or have the potential to deliver new insights and enable entirely new types of studies.Microphysiological organ‐on‐a‐chip systems constitute a powerful new opportunity for translational as well as fundamental research in the field of women's health. The systems have the potential to help implement sex‐balanced preclinical studies as well as to provide novel mechanistic insides into both female‐specific diseases and sex‐differences of diseases affecting both sexes.
      PubDate: 2017-10-06T09:06:02.370832-05:
      DOI: 10.1002/adhm.201700550
  • A Physicochemically Optimized and Neuroconductive Biphasic Nerve Guidance
           Conduit for Peripheral Nerve Repair
    • Authors: Alan J. Ryan; William A. Lackington, Alan J. Hibbitts, Austyn Matheson, Tijna Alekseeva, Anna Stejskalova, Phoebe Roche, Fergal J. O'Brien
      Abstract: Clinically available hollow nerve guidance conduits (NGCs) have had limited success in treating large peripheral nerve injuries. This study aims to develop a biphasic NGC combining a physicochemically optimized collagen outer conduit to bridge the transected nerve, and a neuroconductive hyaluronic acid‐based luminal filler to support regeneration. The outer conduit is mechanically optimized by manipulating crosslinking and collagen density, allowing the engineering of a high wall permeability to mitigate the risk of neuroma formation, while also maintaining physiologically relevant stiffness and enzymatic degradation tuned to coincide with regeneration rates. Freeze‐drying is used to seamlessly integrate the luminal filler into the conduit, creating a longitudinally aligned pore microarchitecture. The luminal stiffness is modulated to support Schwann cells, with laminin incorporation further enhancing bioactivity by improving cell attachment and metabolic activity. Additionally, this biphasic NGC is shown to support neurogenesis and gliogenesis of neural progenitor cells and axonal outgrowth from dorsal root ganglia. These findings highlight the paradigm that a successful NGC requires the concerted optimization of both a mechanical support phase capable of bridging a nerve defect and a neuroconductive phase with an architecture capable of supporting both Schwann cells and neurons in order to achieve functional regenerative outcome.A biphasic nerve guidance conduit is fabricated by combining a physicochemically optimized collagen‐based outer conduit with a neuroconductive hyaluronic acid‐laminin luminal filler that has a longitudinally aligned porous microarchitecture capable of supporting dorsal root ganglia axonal outgrowth, neurogenesis & gliogenesis, and Schwann cell growth.
      PubDate: 2017-10-04T02:57:11.098385-05:
      DOI: 10.1002/adhm.201700954
  • Programmable Hydrogels for Cell Encapsulation and Neo‐Tissue Growth to
           Enable Personalized Tissue Engineering
    • Authors: Stephanie J. Bryant; Franck J. Vernerey
      Abstract: Biomimetic and biodegradable synthetic hydrogels are emerging as a promising platform for cell encapsulation and tissue engineering. Notably, synthetic‐based hydrogels offer highly programmable macroscopic properties (e.g., mechanical, swelling and transport properties) and degradation profiles through control over several tunable parameters (e.g., the initial network structure, degradation kinetics and behavior, and polymer properties). One component to success is the ability to maintain structural integrity as the hydrogel transitions to neo‐tissue. This seamless transition is complicated by the fact that cellular activity is highly variable among donors. Thus, computational models provide an important tool in tissue engineering due to their unique ability to explore the coupled processes of hydrogel degradation and neo‐tissue growth across multiple length scales. In addition, such models provide new opportunities to develop predictive computational tools to overcome the challenges with designing hydrogels for different donors. In this report, programmable properties of synthetic‐based hydrogels and their relation to the hydrogel's structural properties and their evolution with degradation are reviewed. This is followed by recent progress on the development of computational models that describe hydrogel degradation with neo‐tissue growth when cells are encapsulated in a hydrogel. Finally, the potential for predictive models to enable patient‐specific hydrogel designs for personalized tissue engineering is discussed.Synthetic‐based degradable hydrogels are promising for cell encapsulation. However, success requires the closely coupled processes of hydrogel degradation and neo‐tissue growth. Computational models can greatly assist hydrogel designs. A review of programmable hydrogel properties and their tunable parameters and recent progress in computational model development are presented. With the advent of computational models, creating personalized hydrogel designs is possible.
      PubDate: 2017-10-04T02:56:15.782032-05:
      DOI: 10.1002/adhm.201700605
  • Recent Advances in the Generation of Antibody–Nanomaterial
    • Authors: Amal J. Sivaram; Andri Wardiana, Christopher B. Howard, Stephen M. Mahler, Kristofer J. Thurecht
      Abstract: Targeted nanomedicines have significantly changed the way new therapeutics are designed to treat disease. Central to successful therapeutics is the ability to control the dynamics of protein–nanomaterial interactions to enhance the therapeutic effect of the nanomedicine. The aim of this review is to illustrate the diversity and versatility of the conjugation approaches involved in the synthesis of antibody–nanoparticle conjugates, and highlight significant new advances in the field of bioconjugation. Such nanomedicines have found utility as both advanced therapeutic agents, as well as more complex imaging contrast agents that can provide both anatomical and functional information of diseased tissue. While such conjugates show significant promise as next generation targeted nanomedicines, it is recognized that there are in fact no clinically approved targeted therapeutics on the market. This fact is reflected upon within this review, and attempts are made to draw some reasoning from the complexities associated with the bioconjugation chemistry approaches that are typically utilized. Present trends, as well as future directions of next generation targeted nanomedicines are also discussed.Antibody–nanoparticle conjugates are employed as advanced therapeutic agents. In this review, the different strategies used in the production of antibody‐conjugated nanoparticles are highlighted with the intention of providing the reader with a synopsis of current and emerging trends in the field. In particular, attempts are made to draw some reasoning from the complexities associated with the existing bioconjugation approaches.
      PubDate: 2017-09-29T12:07:18.921716-05:
      DOI: 10.1002/adhm.201700607
  • Droplet‐Templated Antisolvent Spherical Crystallization of Hydrophilic
           and Hydrophobic Drugs with an in situ Formed Binder
    • Authors: Tonghan Gu; Eunice W. Q. Yeap, Zheng Cao, Denise Z. L. Ng, Yinying Ren, Ran Chen, Saif A. Khan, T. Alan Hatton
      Abstract: This study presents a novel droplet‐templated antisolvent spherical crystallization method applicable to both hydrophilic and hydrophobic drugs. In both cases, an alginate hydrogel binder forms in situ, concurrently with the crystallization process, effectively binding the drug crystals into monodisperse spheres. This study presents a detailed process description with mass transfer modeling, and with characterization of the obtained alginate/drug spheres in terms of morphology, composition, and drug loading. Although glycine and carbamazepine are used as model hydrophilic and hydrophobic drugs, this method is easily generalized to other drugs, and offers several benefits such as minimal thermal impact, fast crystallization rates, high drug–binder loading ratios, and high selectivity toward metastable polymorphs.This paper presents a novel antisolvent crystallization method for both hydrophilic and hydrophobic drugs using droplets as templates and alginate hydrogel as an in situ binder. The simultaneous crystallization and gelation processes effectively encapsulate the precipitated crystals of different sizes into highly monodisperse spherical particles to facilitate the downstream formulation processes in pharmaceutical manufacturing.
      PubDate: 2017-09-29T12:04:43.733696-05:
      DOI: 10.1002/adhm.201700797
  • Droplet Microarray Based on Patterned Superhydrophobic Surfaces Prevents
           Stem Cell Differentiation and Enables High‐Throughput Stem Cell
    • Authors: Tina Tronser; Anna A. Popova, Mona Jaggy, Martin Bastmeyer, Pavel A. Levkin
      Abstract: Over the past decades, stem cells have attracted growing interest in fundamental biological and biomedical research as well as in regenerative medicine, due to their unique ability to self‐renew and differentiate into various cell types. Long‐term maintenance of the self‐renewal ability and inhibition of spontaneous differentiation, however, still remain challenging and are not fully understood. Uncontrolled spontaneous differentiation of stem cells makes high‐throughput screening of stem cells also difficult. This further hinders investigation of the underlying mechanisms of stem cell differentiation and the factors that might affect it. In this work, a dual functionality of nanoporous superhydrophobic–hydrophilic micropatterns is demonstrated in their ability to inhibit differentiation of mouse embryonic stem cells (mESCs) and at the same time enable formation of arrays of microdroplets (droplet microarray) via the effect of discontinuous dewetting. Such combination makes high‐throughput screening of undifferentiated mouse embryonic stem cells possible. The droplet microarray is used to investigate the development, differentiation, and maintenance of stemness of mESC, revealing the dependence of stem cell behavior on droplet volume in nano‐ and microliter scale. The inhibition of spontaneous differentiation of mESCs cultured on the droplet microarray for up to 72 h is observed. In addition, up to fourfold increased cell growth rate of mESCs cultured on our platform has been observed. The difference in the behavior of mESCs is attributed to the porosity and roughness of the polymer surface. This work demonstrates that the droplet microarray possesses the potential for the screening of mESCs under conditions of prolonged inhibition of stem cells' spontaneous differentiation. Such a platform can be useful for applications in the field of stem cell research, pharmacological testing of drug efficacy and toxicity, biomedical research as well as in the field of regenerative medicine and tissue engineering.The demonstrated nanoporous poly(2‐hydroxyethyl methacrylate‐co‐ethylene dimethacrylate) polymer with defined surface roughness possesses dual functionality enabling the generation of a miniaturized array of multiple droplets on a superhydrophobic–hydrophilic micropattern (droplet microarray) and simultaneously promoting a prolonged inhibition of spontaneous differentiation of mouse embryonic stem cells (mESCs). This renders a miniaturized platform allowing screening of mESC while maintaining their undifferentiated state.
      PubDate: 2017-09-29T12:03:24.920388-05:
      DOI: 10.1002/adhm.201700622
  • Development of Antifouling and Bactericidal Coatings for Platelet Storage
           Bags Using Dopamine Chemistry
    • Authors: Narges Hadjesfandiari; Marie Weinhart, Jayachandran N. Kizhakkedathu, Rainer Haag, Donald E. Brooks
      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.
      PubDate: 2017-09-29T12:03:08.594405-05:
      DOI: 10.1002/adhm.201700839
  • Preservation of Cell Structure, Metabolism, and Biotransformation Activity
           of Liver‐On‐Chip Organ Models by Hypothermic Storage
    • Authors: Marko Gröger; Julia Dinger, Michael Kiehntopf, Frank T. Peters, Ursula Rauen, Alexander S. Mosig
      Abstract: The liver is a central organ in the metabolization of nutrition, endogenous and exogenous substances, and xenobiotic drugs. The emerging organ‐on‐chip technology has paved the way to model essential liver functions as well as certain aspects of liver disease in vitro in liver‐on‐chip models. However, a broader use of this technology in biomedical research is limited by a lack of protocols that enable the short‐term preservation of preassembled liver‐on‐chip models for stocking or delivery to researchers outside the bioengineering community. For the first time, this study tested the ability of hypothermic storage of liver‐on‐chip models to preserve cell viability, tissue morphology, metabolism and biotransformation activity. In a systematic study with different preservation solutions, liver‐on‐chip function can be preserved for up to 2 d using a derivative of the tissue preservation solution TiProtec, containing high chloride ion concentrations and the iron chelators LK614 and deferoxamine, supplemented with polyethylene glycol (PEG). Hypothermic storage in this solution represents a promising method to preserve liver‐on‐chip function for at least 2 d and allows an easier access to liver‐on‐chip technology and its versatile and flexible use in biomedical research.Liver‐on‐chip has paved the way to model individual organ functions and disease aspects in vitro. However, due to the lack of reliable protocols for short‐term preservation (i.e., for stocking or shipment) its broader use is still limited. This study describes the use of specifically designed storage solutions that fully preserve liver‐on‐chip function for at least 2 d during hypothermic storage.
      PubDate: 2017-09-27T09:58:04.522963-05:
      DOI: 10.1002/adhm.201700616
  • Macromolecular Antiviral Agents against Zika, Ebola, SARS, and Other
           Pathogenic Viruses
    • Authors: Franziska Schandock; Camilla Frich Riber, Annika Röcker, Janis A. Müller, Mirja Harms, Paulina Gajda, Kaja Zuwala, Anna H. F. Andersen, Kaja Borup Løvschall, Martin Tolstrup, Florian Kreppel, Jan Münch, Alexander N. Zelikin
      Abstract: Viral pathogens continue to constitute a heavy burden on healthcare and socioeconomic systems. Efforts to create antiviral drugs repeatedly lag behind the advent of pathogens and growing understanding is that broad‐spectrum antiviral agents will make strongest impact in future antiviral efforts. This work performs selection of synthetic polymers as novel broadly active agents and demonstrates activity of these polymers against Zika, Ebola, Lassa, Lyssa, Rabies, Marburg, Ebola, influenza, herpes simplex, and human immunodeficiency viruses. Results presented herein offer structure–activity relationships for these pathogens in terms of their susceptibility to inhibition by polymers, and for polymers in terms of their anionic charge and hydrophobicity that make up broad‐spectrum antiviral agents. The identified leads cannot be predicted based on prior data on polymer‐based antivirals and represent promising candidates for further development as preventive microbicides.Broad spectrum antiviral agents are designed through systematic variation of the polymer composition, specifically the nature of the anionic charge of the polymer and hydrophobicity of the backbone. Structure–function relationship reveals unexpected lead candidates with inhibitory antiviral activity against all tested enveloped viruses.
      PubDate: 2017-09-25T11:12:57.258474-05:
      DOI: 10.1002/adhm.201700748
  • Organ‐on‐a‐Chip Technology for Reproducing Multiorgan
    • Authors: Seung Hwan Lee; Jong Hwan Sung
      Abstract: In the drug development process, the accurate prediction of drug efficacy and toxicity is important in order to reduce the cost, labor, and effort involved. For this purpose, conventional 2D cell culture models are used in the early phase of drug development. However, the differences between the in vitro and the in vivo systems have caused the failure of drugs in the later phase of the drug‐development process. Therefore, there is a need for a novel in vitro model system that can provide accurate information for evaluating the drug efficacy and toxicity through a closer recapitulation of the in vivo system. Recently, the idea of using microtechnology for mimicking the microscale tissue environment has become widespread, leading to the development of “organ‐on‐a‐chip.” Furthermore, the system is further developed for realizing a multiorgan model for mimicking interactions between multiple organs. These advancements are still ongoing and are aimed at ultimately developing “body‐on‐a‐chip” or “human‐on‐a‐chip” devices for predicting the response of the whole body. This review summarizes recently developed organ‐on‐a‐chip technologies, and their applications for reproducing multiorgan functions.Recent progresses in organ‐on‐a‐chip and multiorgan‐on‐a‐chip models are summarized in this review. The achievements in creating gut, liver, vascularized models, and multiorgan models are presented. The concepts of pharmacokinetics and pharmacodynamic modeling are introduced for designing and analyzing multiorgan systems. The future direction of the organ‐on‐a‐chip field and the existing challenges in improving the current models are discussed.
      PubDate: 2017-09-25T05:21:50.541653-05:
      DOI: 10.1002/adhm.201700419
  • Enhanced EGFR Targeting Activity of Plasmonic Nanostructures with
           Engineered GE11 Peptide
    • Authors: Francesca Biscaglia; Senthilkumar Rajendran, Paolo Conflitti, Clara Benna, Roberta Sommaggio, Lucio Litti, Simone Mocellin, Gianfranco Bocchinfuso, Antonio Rosato, Antonio Palleschi, Donato Nitti, Marina Gobbo, Moreno Meneghetti
      Abstract: Plasmonic nanostructures show important properties for biotechnological applications, but they have to be guided on the target for exploiting their potentialities. Antibodies are the natural molecules for targeting. However, their possible adverse immunogenic activity and their cost have suggested finding other valid substitutes. Small molecules like peptides can be an alternative source of targeting agents, even if, as single molecules, their binding affinity is usually not very good. GE11 is a small dodecapeptide with specific binding to the epidermal growth factor receptor (EGFR) and low immunogenicity. The present work shows that thousands of polyethylene glycol (PEG) chains modified with lysines and functionalized with GE11 on clusters of naked gold nanoparticles, obtained by laser ablation in water, achieves a better targeting activity than that recorded with nanoparticles decorated with the specific anti‐EGFR antibody Cetuximab (C225). The insertion of the cationic spacer between the polymeric part of the ligand and the targeting peptide allows for a proper presentation of GE11 on the surface of the nanosystems. Surface enhanced resonance Raman scattering signals of the plasmonic gold nanoparticles are used for quantifying the targeting activity. Molecular dynamic calculations suggest that subtle differences in the exposition of the peptide on the PEG sea are important for the targeting activity.Cell targeting activity of nanostructures is of great importance for biotechnology applications. Functionalization with antibodies is a natural choice but they can show adverse immunogenic activities and their cost is usually very high. Here it is shown that, for epidermal growth factor receptor targeting, thousands of small peptides with engineered functionalization and organized on naked gold nanoparticles offer an alternative with higher sensitivity and specificity.
      PubDate: 2017-09-25T05:21:22.705141-05:
      DOI: 10.1002/adhm.201700596
  • Pro‐Regenerative Hydrogel Restores Scarless Skin during Cutaneous
           Wound Healing
    • Authors: Guoming Sun
      Abstract: The transformation of fibrotic healing process to regenerative one has great potential to fully restore wounded skin. The M2 macrophage phenotype promotes constructive tissue remodeling and instructs tissue repair in a regenerative manner. It is hypothesized that hydrogels that can establish robustness of endogenous cells to regulate M2 phenotype will promote constructive dermal remodeling. Toward this end, a series of dextran‐based bioabsorbable hydrogels are developed and self‐crosslinkable dextran‐isocyanatoethyl methacrylate‐ethylamine (DexIEME) is identified as the potential scaffold. The initial screening study revealed that DexIEME has superior biocompatibility in varying concentrations. Although DexIEME brings about low proinflammatory responses, it promotes M2 macrophage phenotype. Then the optimized hydrogel formulation is tested for acute skin injuries using both murine and porcine models. Preliminary data demonstrated that the innovative DexIEME hydrogel promotes complete skin regeneration with hair regrowth on pre‐existing scars, while untreated scars remain intact. Preclinical studies further demonstrated that the DexIEME hydrogel regenerated perfect skin during deep porcine wound healing. Overall, the approach to investigate immune‐modulated hydrogels yields pro‐regenerative DexIEME hydrogel, which may lead to greater clinical success in treating deep dermal injury and attenuating scar formation.Pro‐regenerative hydrogel scaffolds that can unlock the body's innate powers of regeneration restore complete skin structures on both pre‐existing scarred skin and deep full skin injuries by producing mature epithelial structures with hair follicles and glands.
      PubDate: 2017-09-25T05:20:59.919873-05:
      DOI: 10.1002/adhm.201700659
  • Biomechanical Regulation of Mesenchymal Stem Cells for Cardiovascular
           Tissue Engineering
    • Authors: Kayla Henderson; Andrew D. Sligar, Victoria P. Le, Jason Lee, Aaron B. Baker
      Abstract: Mesenchymal stem cells (MSCs) are an appealing potential therapy for vascular diseases; however, many challenges remain in their clinical translation. While the use of biochemical, pharmacological, and substrate‐mediated treatments to condition MSCs has been subjected to intense investigation, there has been far less exploration of using these treatments in combination with applied mechanical force for conditioning MSCs toward vascular phenotypes. This review summarizes the current understanding of the use of applied mechanical forces to differentiate MSCs into vascular cells and enhance their therapeutic potential for cardiovascular disease. First recent work on the use of material‐based mechanical cues for differentiation of MSCs into vascular and cardiovascular phenotypes is examined. Then a summary of the studies using mechanical stretch or shear stress in combination with biochemical treatments to enhance vascular phenotypes in MSCs is presented.Published work relating to the use of mechanical forces to condition mesenchymal stem cells into vascular phenotypes for therapeutic applications is examined in this review. The synergistic interactions of substrate compliance, nanopatterning, and biochemical treatments with applied mechanical stretch or fluidic shear stress on the vascular and cardiac differentiation of mesenchymal stem cells are examined.
      PubDate: 2017-09-25T05:20:29.274891-05:
      DOI: 10.1002/adhm.201700556
  • The Influence of Hyaluronic Acid and Glioblastoma Cell Coculture on the
           Formation of Endothelial Cell Networks in Gelatin Hydrogels
    • Authors: Mai T. Ngo; Brendan A. Harley
      Abstract: Glioblastoma (GBM) is the most common and deadly form of brain cancer. Interactions between GBM cells and vasculature in vivo contribute to poor clinical outcomes, with GBM‐induced vessel co‐option, regression, and subsequent angiogenesis strongly influencing GBM invasion. Here, elements of the GBM perivascular niche are incorporated into a methacrylamide‐functionalized gelatin hydrogel as a means to examine GBM–vessel interactions. The complexity of 3D endothelial cell networks formed from human umbilical vein endothelial cells and normal human lung fibroblasts as a function of hydrogel properties and vascular endothelial growth factor (VEGF) presentation is presented. While overall length and branching of the endothelial cell networks decrease with increasing hydrogel stiffness and incorporation of brain‐mimetic hyaluronic acid, it can be separately altered by changing the vascular cell seeding density. It is shown that covalent incorporation of VEGF supports network formation as robustly as continuously available soluble VEGF. The impact of U87‐MG GBM cells on the endothelial cell networks is subsequently investigated. GBM cells localize in proximity to the endothelial cell networks and hasten network regression in vitro. Together, this in vitro platform recapitulates the close association between GBM cells and vessel structures as well as elements of vessel co‐option and regression preceding angiogenesis in vivo.The glioblastoma perivascular niche is incorporated into a gelatin hydrogel via coculture of endothelial, stromal, and glioblastoma cells. Endothelial network complexity can be manipulated through hydrogel stiffness and covalent immobilization of brain‐mimetic hyaluronic acid and vascular endothelial growth factor into the hydrogel network. Glioblastoma cells associate closely with endothelial cell networks and promote processes similar to vessel co‐option and regression seen in vivo.
      PubDate: 2017-09-22T01:01:48.843595-05:
      DOI: 10.1002/adhm.201700687
  • Coordination‐Accelerated “Iron Extraction” Enables Fast
           Biodegradation of Mesoporous Silica‐Based Hollow Nanoparticles
    • Authors: Liying Wang; Minfeng Huo, Yu Chen, Jianlin Shi
      Abstract: Biodegradation behavior of inorganic silica‐based nanoplatforms is of critical importance in their clinical translations, but still remains a great challenge in achieving this goal by composition regulation of biocompatible silica framework. In the present work, a chemical coordination‐accelerated biodegradation strategy to endow hollow mesoporous silica nanoparticles (HMSNs) with unique coordination‐responsive biodegradability, on‐demand coordination‐responsive drug releasing behavior, and significantly enhanced chemotherapeutic efficacy by directly doping iron (Fe) ions into the framework of mesoporous silica is reported. A simple but versatile dissolution‐regrowth strategy has been developed to enable the framework Fe doping via chemical bonding. The deferiprone‐mediated biodegradation of Fe‐doped HMSNs (Fe‐HMSNs) has been comprehensively evaluated both in simulated body fluid and intracellular level, which have exhibited a specific coordination‐accelerated biodegradation behavior. In addition to high biocompatibility of Fe‐HMSNs, the anticancer drug doxorubicin (DOX)‐loaded Fe‐HMSNs show enhanced tumor‐suppressing effect on 4T1 mammary cancer xenograft. This work paves a new way for tuning the biodegradation performance of mesoporous silica‐based nanoplatforms simply by biocompatible Fe‐ion doping into silica framework based on the specific coordination property between introduced metal Fe ions with Fe‐coordination proteins.Coordination‐accelerated biodegradation strategy: A chemical coordination‐accelerated biodegradation strategy is illustrated to endow hollow mesoporous silica nanoparticles with proteinous coordination‐responsive biodegradability (via “iron extraction”), on‐demand coordination‐responsive drug releasing behavior, and significantly enhanced chemotherapeutic efficacy by directly doping iron (Fe) ions into the framework of mesoporous silica.
      PubDate: 2017-09-21T01:11:43.004159-05:
      DOI: 10.1002/adhm.201700720
  • Accelerated Wound Healing on Skin by Electrical Stimulation with a
           Bioelectric Plaster
    • Authors: Hiroyuki Kai; Takeshi Yamauchi, Yudai Ogawa, Ayaka Tsubota, Takahiro Magome, Takeo Miyake, Kenshi Yamasaki, Matsuhiko Nishizawa
      Abstract: Wound healing on skin involves cell migration and proliferation in response to endogenous electric current. External electrical stimulation by electrical equipment is used to promote these biological processes for the treatment of chronic wounds and ulcers. Miniaturization of the electrical stimulation device for wound healing on skin will make this technology more widely available. Using flexible enzymatic electrodes and stretchable hydrogel, a stretchable bioelectric plaster is fabricated with a built‐in enzymatic biofuel cell (EBFC) that fits to skin and generates ionic current along the surface of the skin by enzymatic electrochemical reactions for more than 12 h. To investigate the efficacy of the fabricated bioelectric plaster, an artificial wound is made on the back skin of a live mouse and the wound healing is observed for 7 d in the presence and absence of the ionic current of the bioelectric plaster. The time course of the wound size as well as the hematoxylin and eosin staining of the skin section reveals that the ionic current of the plaster leads to faster and smoother wound healing. The present work demonstrates a proof of concept for the electrical manipulation of biological functions by EBFCs.Wound healing on skin is accelerated by a plaster device with a built‐in enzymatic biofuel cell that drives ionic current on the wound. Cells in the skin respond to electric current during wound healing processes. A stretchable bioelectric plaster fits to skin and generates ionic current on the wound by enzymatic electrochemical reactions to promote these processes.
      PubDate: 2017-09-20T00:15:41.656635-05:
      DOI: 10.1002/adhm.201700465
  • Fabrication of Trabecular Bone‐Templated Tissue‐Engineered Constructs
           by 3D Inkjet Printing
    • Authors: Joseph P. Vanderburgh; Shanik J. Fernando, Alyssa R. Merkel, Julie A. Sterling, Scott A. Guelcher
      Abstract: 3D printing enables the creation of scaffolds with precisely controlled morphometric properties for multiple tissue types, including musculoskeletal tissues such as cartilage and bone. Computed tomography (CT) imaging has been combined with 3D printing to fabricate anatomically scaled patient‐specific scaffolds for bone regeneration. However, anatomically scaled scaffolds typically lack sufficient resolution to recapitulate the
      PubDate: 2017-09-11T10:40:11.091536-05:
      DOI: 10.1002/adhm.201700369
  • Thermosensitive Hydrogel Containing Doxycycline Exerts Inhibitory Effects
           on Abdominal Aortic Aneurysm Induced By Pancreatic Elastase in Mice
    • Authors: Maomao Yu; Anjie Dong, Cong Chen, Shuxin Xu, Yini Cao, Shu Liu, Qiang Zhang, Rong Qi
      Abstract: Doxycycline (DOX) is reported to exert therapeutic effects against abdominal aortic aneurysm (AAA), a severe degenerative disease. In this study, a DOX hydrogel formulation of DOX/PECTgel is studied, and its phase transition behavior and in vitro release profiles are explored. In addition, the anti‐AAA effects and bioavailability of DOX/PECTgel are evaluated in an elastase induced AAA mouse model. The results show that the phase transition temperature of 30% poly(e‐caprolactone‐co‐1,4,8‐trioxa[4.6]spiro‐9‐undecanone) (PECT) solution is above 34 °C. In vitro release profiles of DOX/PECTgel indicate a fast release of DOX at the first two days, followed by a slow and sustained release for 14 d. In vivo single‐dose single subcutaneous injection of DOX/PECTgel containing 8.4 or 4.2 mg mL−1 DOX presents comparatively preventive effects on AAA, compared to intraperitoneal injections of DOX alone at a dose of 15 mg kg−1 for seven injections, while DOX bioavailability of the DOX/PECTgel treated groups is 1.39 times or 1.19 times of the DOX alone treated group, respectively.A sustained release formulation of doxycycline (DOX) is prepared based on poly(e‐caprolactone‐co‐1,4,8‐trioxa[4.6]spiro‐9‐undecanone) (PECT) hydrogel (DOX/PECTgel). DOX release from the DOX/PECTgel is dose‐dependent and can last for 14 d. One single s.c. injection of the DOX/PECTgel exhibits significant anti‐abdominal aortic aneurysm effects, which is as efficient as seven i.p. injections of DOX alone at an equal dose.
      PubDate: 2017-09-08T07:46:11.168613-05:
      DOI: 10.1002/adhm.201700671
  • An Inexpensive, Point‐of‐Care Urine Test for Bladder Cancer in
           Patients Undergoing Hematuria Evaluation
    • Authors: Abhinav P. Acharya; Kathryn M. Theisen, Andres Correa, Thiagarajan Meyyappan, Abraham Apfel, Tao Sun, Tatum V. Tarin, Steven R. Little
      Abstract: Although hematuria (blood in urine) is the most common symptom of bladder cancer, 70–98% of hematuria cases are benign. These hematuria patients unnecessarily undergo costly, invasive, and expensive evaluation for bladder cancer. Therefore, there remains a need for noninvasive office‐based tests that can rapidly and reliably rule out bladder cancer in patients undergoing hematuria evaluation. Herein, a clinical assay for matrix metalloproteinases (“Ammps”) is presented, which generates a visual signal based on the collagenase activity (in urine of patients) on the Ammps substrates. Ammps substrates are generated by crosslinking gelatin with Fe(II) chelated alginate nanoparticles, which precipitate in urine samples. The cleavage of gelatin‐conjugated alginate (Fe(II)) nanoparticles by collagenases generates free‐floating alginate (Fe(II)) nanoparticles that participate in Fenton's reaction to generate a visual signal. In a pilot study of 88 patients, Ammps had 100% sensitivity, 85% specificity, and a negative predictive value (NPV) of 100% for diagnosing bladder cancer. This high NPV can be useful in ruling out bladder cancer in patients referred for hematuria evaluation.In this work, a novel point‐of‐care urine test for detection of bladder cancer that is low cost (5.5 cents/test), ultrasensitive, provides high negative predictive value (100%, in a pilot study of 88 patients), and aims to improve detection/monitoring for bladder cancer by decreasing costs and possibly reducing the number of necessary invasive procedures (i.e. cystoscopies) is presented for the first time.
      PubDate: 2017-09-08T07:45:34.520474-05:
      DOI: 10.1002/adhm.201700808
  • Densification of Type I Collagen Matrices as a Model for Cardiac Fibrosis
    • Authors: Logan J. Worke; Jeanne E. Barthold, Benjamin Seelbinder, Tyler Novak, Russell P. Main, Sherry L. Harbin, Corey P. Neu
      Abstract: Cardiac fibrosis is a disease state characterized by excessive collagenous matrix accumulation within the myocardium that can lead to ventricular dilation and systolic failure. Current treatment options are severely lacking due in part to the poor understanding of the complexity of molecular pathways involved in cardiac fibrosis. To close this gap, in vitro model systems that recapitulate the defining features of the fibrotic cellular environment are in need. Type I collagen, a major cardiac extracellular matrix protein and the defining component of fibrotic depositions, is an attractive choice for a fibrosis model, but demonstrates poor mechanical strength due to solubility limits. However, plastic compression of collagen matrices is shown to significantly increase its mechanical properties. Here, confined compression of oligomeric, type I collagen matrices is utilized to resemble defining hallmarks seen in fibrotic tissue such as increased collagen content, fibril thickness, and bulk compressive modulus. Cardiomyocytes seeded on compressed matrices show a strong beating abrogation as observed in cardiac fibrosis. Gene expression analysis of selected fibrosis markers indicates fibrotic activation and cardiomyocyte maturation with regard to the existing literature. With these results, a promising first step toward a facile heart‐on‐chip model is presented to study cardiac fibrosis.New collagen matrices are fabricated that are densified to mimic excess matrix accumulation observed in cardiac fibrosis. The densification process also allows for the easy seeding of cells, leading to strong beating abrogation of cardiomyocytes, and fibrotic activation. It is anticipated that this densification process presents a promising first step toward a facile heart‐on‐chip model to study cardiac fibrosis.
      PubDate: 2017-09-07T11:31:52.446927-05:
      DOI: 10.1002/adhm.201700114
  • Injectable Mussel‐Inspired Immobilization of Platelet‐Rich Plasma on
           Microspheres Bridging Adipose Micro‐Tissues to Improve Autologous Fat
           Transplantation by Controlling Release of PDGF and VEGF, Angiogenesis,
           Stem Cell Migration
    • Authors: Shaolong Zhou; Qiang Chang, Feng Lu, Malcolm Xing
      Abstract: Platelets‐rich plasma (PRP) can produce growth factors (GFs) to improve angiogenesis. However, direct injection of PRP does not lead to highly localized GFs. The current study employs a mussel‐inspired polydopamine to immobilize PRP on gelatin microspheres (GMs) with the purpose of bridging adipose micro‐tissues to help implanted fat survive (GM‐pDA‐PRP). Enhanced PRP adhesion leads to a prolonged and localized production of GFs, which is verified by platelet counting and by ELISA of vascular endothelial growth factors (VEGFs) and of platelet derived growth factors (PDGFs). The GM‐pDA‐PRP “hatches” a microenvironment for the proliferation of adipose‐derived stem cells. After the adipose micro‐tissue has bridged with GM‐pDA‐PRP after 16 weeks, triple‐fluorescence staining reveals that the mature adipocytes, blood vessels, and capillaries are arranged like in normal adipose tissue. The survival fat increases significantly compared to that in control, PRP, and GM‐PRP groups (84.8 ± 11.4% versus 47.8 ± 8.9%, 56.9 ± 9.7%, and 60.2 ± 10.5%, respectively). Both histological assessments and CD31 immunofluorescence indicate that the improvement of angiogenesis in GM‐pDA‐PRP is higher than in the fat graft group (6.4‐fold in quantitative CD31 positive cells). The CD34 positive cells in the GM‐pDA‐PRP group are around 3.5‐fold the amount in the fat graft group, which suggests that more stem cells migrate to the implant area. Cell proliferation staining shows that the number of Ki67 positive cells is around five times as high as that in the fat graft group.A facile strategy to immobilize platelets‐rich plasma (PRP) on gelatin microspheres is achieved with mussel‐inspired polydopamine adhesion. This reinforced platelets adhesion and release system leads to a prolonged and localized production of growth factors, and hatches a microenvironment for chemotaxis and proliferation of adipose‐derived stem cells. The PRP improves angiogenesis and enhances the final autologous fat transplantation survival.
      PubDate: 2017-09-07T11:31:07.02689-05:0
      DOI: 10.1002/adhm.201700131
  • Rational Design of Glucose-Responsive Insulin Using Pharmacokinetic
    • Authors: Naveed A. Bakh; Gili Bisker, Michael A. Lee, Xun Gong, Michael S. Strano
      Abstract: A glucose responsive insulin (GRI) is a therapeutic that modulates its potency, concentration, or dosing of insulin in relation to a patient's dynamic glucose concentration, thereby approximating aspects of a normally functioning pancreas. Current GRI design lacks a theoretical basis on which to base fundamental design parameters such as glucose reactivity, dissociation constant or potency, and in vivo efficacy. In this work, an approach to mathematically model the relevant parameter space for effective GRIs is induced, and design rules for linking GRI performance to therapeutic benefit are developed. Well-developed pharmacokinetic models of human glucose and insulin metabolism coupled to a kinetic model representation of a freely circulating GRI are used to determine the desired kinetic parameters and dosing for optimal glycemic control. The model examines a subcutaneous dose of GRI with kinetic parameters in an optimal range that results in successful glycemic control within prescribed constraints over a 24 h period. Additionally, it is demonstrated that the modeling approach can find GRI parameters that enable stable glucose levels that persist through a skipped meal. The results provide a framework for exploring the parameter space of GRIs, potentially without extensive, iterative in vivo animal testing.This paper combines pharmacokinetic models of glucose–insulin metabolism with mathematical models of glucose-responsive insulins to explore the effective parameter space of these new types of therapeutics. The model reveals that there is a range of parameter values that can maintain glycemic control over a 24 h period, from a single bolus over a wide range of conditions.
      PubDate: 2017-08-25T11:23:55.118633-05:
      DOI: 10.1002/adhm.201700601
  • 3D Bioprinting for Cartilage and Osteochondral Tissue Engineering
    • Authors: Andrew C. Daly; Fiona E. Freeman, Tomas Gonzalez-Fernandez, Susan E. Critchley, Jessica Nulty, Daniel J. Kelly
      Abstract: Significant progress has been made in the field of cartilage and bone tissue engineering over the last two decades. As a result, there is real promise that strategies to regenerate rather than replace damaged or diseased bones and joints will one day reach the clinic however, a number of major challenges must still be addressed before this becomes a reality. These include vascularization in the context of large bone defect repair, engineering complex gradients for bone-soft tissue interface regeneration and recapitulating the stratified zonal architecture present in many adult tissues such as articular cartilage. Tissue engineered constructs typically lack such spatial complexity in cell types and tissue organization, which may explain their relatively limited success to date. This has led to increased interest in bioprinting technologies in the field of musculoskeletal tissue engineering. The additive, layer by layer nature of such biofabrication strategies makes it possible to generate zonal distributions of cells, matrix and bioactive cues in 3D. The adoption of biofabrication technology in musculoskeletal tissue engineering may therefore make it possible to produce the next generation of biological implants capable of treating a range of conditions. Here, advances in bioprinting for cartilage and osteochondral tissue engineering are reviewed.In this paper, advances in 3D bioprinting for articular cartilage and osteochondral tissue engineering are reviewed. An overview of the field and a description of the current state of the art are provided for the first time. Then, future research directions are discussed and a description of how emerging bioprinting strategies could be used to engineer functional implants for joint regeneration is given.
      PubDate: 2017-08-14T02:19:27.990847-05:
      DOI: 10.1002/adhm.201700298
  • Silicone-Based Adhesives with Highly Tunable Adhesion Force for
           Skin-Contact Applications
    • Authors: Bong Kuk Lee; Jin Hwa Ryu, In-Bok Baek, Yarkyeon Kim, Won Ick Jang, Sang-Hyeob Kim, Yong Sun Yoon, Seung Hwan Kim, Seong-Gu Hong, Sangwon Byun, Han Young Yu
      Abstract: A fundamental approach to fabricating silicone-based adhesives with highly tunable adhesion force for the skin-contact applications is presented. Liquid blends consisting of vinyl-multifunctional polydimethylsiloxane (V-PDMS), hydride-terminated PDMS (H-PDMS), and a tackifier composed of a silanol-terminated PDMS/MQ resin mixture and the MQ resin are used as the adhesive materials. The peel adhesion force of addition-cured adhesives on the skin is increased by increasing the H-PDMS molecular weights and the tackifier content, and decreasing the H-PDMS/V-PDMS ratio. There is an inverse relationship between the adhesion force and the Young's modulus. The low-modulus adhesives with a low H-PDMS/V-PDMS ratio exhibit enhanced adhesion properties. The low-modulus adhesives with the high MQ resin content show significantly enhanced adhesion properties. These adhesives exhibit a wide range of modulus (2–499 kPa), and their adhesion force (0.04–5.38 N) is superior to commercially available soft silicone adhesives (0.82–2.79 N). The strong adhesives (>≈2 N) provide sufficient adhesion for fixing the flexible electrocardiogram (ECG) device to the skin in most daily activity. The human ECG signals are successfully recorded in real time. These results suggest that the silicone-based adhesives should be useful as an atraumatic adhesive for the skin-contact applications.A fundamental approach to fabricating silicone-based adhesives with highly tunable adhesion is presented for the skin-contact applications. By adjusting the molecular weight of PDMSs and the concentration of PDMSs and MQ resin, the adhesion force of adhesives is highly controlled. The Young's modulus and silanol functionalities of the adhesives are the two main factors governing the adhesion to the skin.
      PubDate: 2017-08-10T01:30:41.617899-05:
      DOI: 10.1002/adhm.201700621
  • Edible Electrochemistry: Food Materials Based Electrochemical Sensors
    • Authors: Jayoung Kim; Itthipon Jeerapan, Bianca Ciui, Martin C. Hartel, Aida Martin, Joseph Wang
      Abstract: This study demonstrates the first example of completely food-based edible electrochemical sensors. The new edible composite electrodes consist of food materials and supplements serving as the edible conductor, corn, and olive oils as edible binders, vegetables as biocatalysts, and food-based packing sleeves. These edible composite electrodes are systematically characterized for their attractive electrochemical properties, such as potential window, capacitance, redox activity using various electrochemical techniques. The sensing performance of the edible carbon composite electrodes compares favorably with that of “traditional” carbon paste electrodes. Well defined voltammetric detection of catechol, uric acid, ascorbic acid, dopamine, and acetaminophen is demonstrated, including sensitive measurements in simulated saliva, gastric fluid, and intestinal fluid. Furthermore, successful biosensing applications are realized by incorporating a mushroom and horseradish vegetable tissues with edible carbon pastes for imparting biocatalytic activity toward the biosensing of phenolic and peroxide compounds. The attractive sensing performance of the new edible sensors indicates considerable promise for physiological monitoring applications and for developing edible and ingestible devices for diverse biomedical applications.This study first demonstrates the first example of edible electrochemical sensors made solely of food materials, offering digestive and innocuous platform. Various types of food materials are demonstrated and their electroanalytical behaviors are characterized. For biomedical monitoring applications, several (bio)markers are detected in artificial biofluids, indicating that the developed edible sensors can be expanded to monitor healthcare status following gastrointestinal tract.
      PubDate: 2017-08-07T12:31:55.206632-05:
      DOI: 10.1002/adhm.201700770
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