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Showing 1 - 200 of 2351 Journals sorted alphabetically
3D Research     Hybrid Journal   (Followers: 19, SJR: 0.214, h-index: 10)
4OR: A Quarterly J. of Operations Research     Hybrid Journal   (Followers: 10, SJR: 1.073, h-index: 25)
AAPS J.     Hybrid Journal   (Followers: 22, SJR: 1.192, h-index: 74)
AAPS PharmSciTech     Hybrid Journal   (Followers: 7, SJR: 0.718, h-index: 54)
Abdominal Imaging     Hybrid Journal   (Followers: 14, SJR: 0.723, h-index: 60)
Abhandlungen aus dem Mathematischen Seminar der Universitat Hamburg     Hybrid Journal   (Followers: 3, SJR: 0.447, h-index: 12)
Academic Psychiatry     Full-text available via subscription   (Followers: 23, SJR: 0.492, h-index: 32)
Academic Questions     Hybrid Journal   (Followers: 8, SJR: 0.135, h-index: 6)
Accreditation and Quality Assurance: J. for Quality, Comparability and Reliability in Chemical Measurement     Hybrid Journal   (Followers: 26, SJR: 0.378, h-index: 30)
Acoustical Physics     Hybrid Journal   (Followers: 11, SJR: 0.355, h-index: 20)
Acoustics Australia     Hybrid Journal  
Acta Analytica     Hybrid Journal   (Followers: 7, SJR: 0.387, h-index: 6)
Acta Applicandae Mathematicae     Hybrid Journal   (Followers: 1, SJR: 0.624, h-index: 34)
Acta Biotheoretica     Hybrid Journal   (Followers: 4, SJR: 0.419, h-index: 25)
Acta Diabetologica     Hybrid Journal   (Followers: 16, SJR: 1.318, h-index: 46)
Acta Endoscopica     Hybrid Journal   (Followers: 1, SJR: 0.113, h-index: 8)
acta ethologica     Hybrid Journal   (Followers: 4, SJR: 0.465, h-index: 23)
Acta Geochimica     Hybrid Journal   (Followers: 7)
Acta Geodaetica et Geophysica     Hybrid Journal   (Followers: 2, SJR: 0.294, h-index: 13)
Acta Geotechnica     Hybrid Journal   (Followers: 7, SJR: 1.818, h-index: 22)
Acta Informatica     Hybrid Journal   (Followers: 5, SJR: 0.524, h-index: 32)
Acta Mathematica     Hybrid Journal   (Followers: 11, SJR: 8.021, h-index: 47)
Acta Mathematica Hungarica     Hybrid Journal   (Followers: 2, SJR: 0.53, h-index: 29)
Acta Mathematica Sinica, English Series     Hybrid Journal   (Followers: 6, SJR: 0.406, h-index: 30)
Acta Mathematica Vietnamica     Hybrid Journal   (SJR: 0.451, h-index: 5)
Acta Mathematicae Applicatae Sinica, English Series     Hybrid Journal   (SJR: 0.22, h-index: 20)
Acta Mechanica     Hybrid Journal   (Followers: 20, SJR: 0.898, h-index: 52)
Acta Mechanica Sinica     Hybrid Journal   (Followers: 5, SJR: 0.426, h-index: 29)
Acta Metallurgica Sinica (English Letters)     Hybrid Journal   (Followers: 6, SJR: 0.525, h-index: 18)
Acta Meteorologica Sinica     Hybrid Journal   (Followers: 3, SJR: 0.524, h-index: 14)
Acta Neurochirurgica     Hybrid Journal   (Followers: 6, SJR: 0.833, h-index: 73)
Acta Neurologica Belgica     Hybrid Journal   (Followers: 1, SJR: 0.348, h-index: 27)
Acta Neuropathologica     Hybrid Journal   (Followers: 5, SJR: 6.61, h-index: 117)
Acta Oceanologica Sinica     Hybrid Journal   (Followers: 3, SJR: 0.295, h-index: 17)
Acta Parasitologica     Hybrid Journal   (Followers: 10, SJR: 0.581, h-index: 28)
Acta Physiologiae Plantarum     Hybrid Journal   (Followers: 2, SJR: 0.551, h-index: 39)
Acta Politica     Hybrid Journal   (Followers: 13, SJR: 0.658, h-index: 20)
Activitas Nervosa Superior     Hybrid Journal  
adhäsion KLEBEN & DICHTEN     Hybrid Journal   (Followers: 5, SJR: 0.103, h-index: 4)
ADHD Attention Deficit and Hyperactivity Disorders     Hybrid Journal   (Followers: 23, SJR: 0.871, h-index: 15)
Adhesion Adhesives & Sealants     Hybrid Journal   (Followers: 8)
Administration and Policy in Mental Health and Mental Health Services Research     Partially Free   (Followers: 15, SJR: 0.795, h-index: 40)
Adsorption     Hybrid Journal   (Followers: 4, SJR: 0.774, h-index: 52)
Advances in Applied Clifford Algebras     Hybrid Journal   (Followers: 3, SJR: 0.319, h-index: 15)
Advances in Atmospheric Sciences     Hybrid Journal   (Followers: 35, SJR: 0.959, h-index: 44)
Advances in Computational Mathematics     Hybrid Journal   (Followers: 18, SJR: 1.255, h-index: 44)
Advances in Contraception     Hybrid Journal   (Followers: 3)
Advances in Data Analysis and Classification     Hybrid Journal   (Followers: 54, SJR: 1.113, h-index: 14)
Advances in Gerontology     Partially Free   (Followers: 8, SJR: 0.141, h-index: 3)
Advances in Health Sciences Education     Hybrid Journal   (Followers: 25, SJR: 1.397, h-index: 42)
Advances in Manufacturing     Hybrid Journal   (Followers: 3, SJR: 0.2, h-index: 4)
Advances in Polymer Science     Hybrid Journal   (Followers: 43, SJR: 0.637, h-index: 89)
Advances in Therapy     Hybrid Journal   (Followers: 5, SJR: 0.79, h-index: 44)
Aegean Review of the Law of the Sea and Maritime Law     Hybrid Journal   (Followers: 7)
Aequationes Mathematicae     Hybrid Journal   (Followers: 2, SJR: 0.882, h-index: 23)
Aerobiologia     Hybrid Journal   (Followers: 2, SJR: 0.511, h-index: 36)
Aesthetic Plastic Surgery     Hybrid Journal   (Followers: 9, SJR: 0.821, h-index: 49)
African Archaeological Review     Hybrid Journal   (Followers: 16, SJR: 0.612, h-index: 24)
Afrika Matematika     Hybrid Journal   (Followers: 1, SJR: 0.248, h-index: 6)
AGE     Hybrid Journal   (Followers: 7, SJR: 1.358, h-index: 33)
Ageing Intl.     Hybrid Journal   (Followers: 7, SJR: 0.337, h-index: 10)
Aggiornamenti CIO     Hybrid Journal   (Followers: 1)
Aging Clinical and Experimental Research     Hybrid Journal   (Followers: 2, SJR: 0.529, h-index: 55)
Agricultural Research     Hybrid Journal   (Followers: 4)
Agriculture and Human Values     Hybrid Journal   (Followers: 14, SJR: 1.197, h-index: 49)
Agroforestry Systems     Hybrid Journal   (Followers: 19, SJR: 0.64, h-index: 56)
Agronomy for Sustainable Development     Hybrid Journal   (Followers: 11, SJR: 1.732, h-index: 59)
AI & Society     Hybrid Journal   (Followers: 6, SJR: 0.171, h-index: 19)
AIDS and Behavior     Hybrid Journal   (Followers: 13, SJR: 2.006, h-index: 71)
Air Quality, Atmosphere & Health     Hybrid Journal   (Followers: 4, SJR: 0.706, h-index: 19)
Akupunktur & Aurikulomedizin     Full-text available via subscription   (Followers: 1)
Algebra and Logic     Hybrid Journal   (Followers: 4, SJR: 0.566, h-index: 18)
Algebra Universalis     Hybrid Journal   (Followers: 2, SJR: 0.388, h-index: 22)
Algebras and Representation Theory     Hybrid Journal   (Followers: 1, SJR: 0.868, h-index: 20)
Algorithmica     Hybrid Journal   (Followers: 8, SJR: 0.898, h-index: 56)
Allergo J.     Full-text available via subscription   (Followers: 1, SJR: 0.183, h-index: 20)
Allergo J. Intl.     Hybrid Journal   (Followers: 2)
Alpine Botany     Hybrid Journal   (Followers: 5, SJR: 0.729, h-index: 20)
ALTEX : Alternatives to Animal Experimentation     Open Access   (Followers: 3, SJR: 1.392, h-index: 32)
AMBIO     Hybrid Journal   (Followers: 15, SJR: 1.094, h-index: 87)
American J. of Cardiovascular Drugs     Hybrid Journal   (Followers: 16, SJR: 0.864, h-index: 39)
American J. of Community Psychology     Hybrid Journal   (Followers: 26, SJR: 1.237, h-index: 83)
American J. of Criminal Justice     Hybrid Journal   (Followers: 8, SJR: 0.634, h-index: 13)
American J. of Cultural Sociology     Hybrid Journal   (Followers: 15, SJR: 0.283, h-index: 3)
American J. of Dance Therapy     Hybrid Journal   (Followers: 4, SJR: 0.175, h-index: 13)
American J. of Potato Research     Hybrid Journal   (Followers: 3, SJR: 0.558, h-index: 35)
American J. of Psychoanalysis     Hybrid Journal   (Followers: 22, SJR: 0.293, h-index: 13)
American Sociologist     Hybrid Journal   (Followers: 14, SJR: 0.18, h-index: 13)
Amino Acids     Hybrid Journal   (Followers: 8, SJR: 1.362, h-index: 83)
AMS Review     Partially Free   (Followers: 4)
Analog Integrated Circuits and Signal Processing     Hybrid Journal   (Followers: 7, SJR: 0.21, h-index: 37)
Analysis and Mathematical Physics     Hybrid Journal   (Followers: 4, SJR: 0.665, h-index: 7)
Analysis in Theory and Applications     Hybrid Journal   (Followers: 1)
Analysis of Verbal Behavior     Hybrid Journal   (Followers: 5)
Analytical and Bioanalytical Chemistry     Hybrid Journal   (Followers: 31, SJR: 1.096, h-index: 123)
Anatomical Science Intl.     Hybrid Journal   (Followers: 2, SJR: 0.301, h-index: 26)
Angewandte Schmerztherapie und Palliativmedizin     Hybrid Journal  
Angiogenesis     Hybrid Journal   (Followers: 3, SJR: 2.212, h-index: 69)
Animal Cognition     Hybrid Journal   (Followers: 17, SJR: 1.122, h-index: 55)
Annales françaises de médecine d'urgence     Hybrid Journal   (Followers: 1, SJR: 0.156, h-index: 4)
Annales Henri Poincaré     Hybrid Journal   (Followers: 3, SJR: 1.377, h-index: 32)
Annales mathématiques du Québec     Hybrid Journal   (Followers: 4)
Annali dell'Universita di Ferrara     Hybrid Journal   (SJR: 0.504, h-index: 14)
Annali di Matematica Pura ed Applicata     Hybrid Journal   (Followers: 1, SJR: 1.167, h-index: 26)
Annals of Behavioral Medicine     Hybrid Journal   (Followers: 14, SJR: 2.112, h-index: 98)
Annals of Biomedical Engineering     Hybrid Journal   (Followers: 18, SJR: 1.182, h-index: 94)
Annals of Combinatorics     Hybrid Journal   (Followers: 3, SJR: 0.849, h-index: 15)
Annals of Data Science     Hybrid Journal   (Followers: 11)
Annals of Dyslexia     Hybrid Journal   (Followers: 10, SJR: 0.857, h-index: 40)
Annals of Finance     Hybrid Journal   (Followers: 28, SJR: 0.686, h-index: 14)
Annals of Forest Science     Hybrid Journal   (Followers: 6, SJR: 0.929, h-index: 57)
Annals of Global Analysis and Geometry     Hybrid Journal   (Followers: 1, SJR: 1.136, h-index: 23)
Annals of Hematology     Hybrid Journal   (Followers: 16, SJR: 1.117, h-index: 62)
Annals of Mathematics and Artificial Intelligence     Hybrid Journal   (Followers: 12, SJR: 0.593, h-index: 42)
Annals of Microbiology     Hybrid Journal   (Followers: 10, SJR: 0.402, h-index: 26)
Annals of Nuclear Medicine     Hybrid Journal   (Followers: 4, SJR: 0.68, h-index: 45)
Annals of Operations Research     Hybrid Journal   (Followers: 10, SJR: 1.186, h-index: 78)
Annals of Ophthalmology     Hybrid Journal   (Followers: 12)
Annals of Regional Science     Hybrid Journal   (Followers: 8, SJR: 0.405, h-index: 42)
Annals of Software Engineering     Hybrid Journal   (Followers: 13)
Annals of Solid and Structural Mechanics     Hybrid Journal   (Followers: 10, SJR: 0.553, h-index: 8)
Annals of Surgical Oncology     Hybrid Journal   (Followers: 14, SJR: 1.902, h-index: 127)
Annals of Telecommunications     Hybrid Journal   (Followers: 8, SJR: 0.315, h-index: 25)
Annals of the Institute of Statistical Mathematics     Hybrid Journal   (Followers: 1, SJR: 0.931, h-index: 31)
Antonie van Leeuwenhoek     Hybrid Journal   (Followers: 5, SJR: 0.992, h-index: 87)
Apidologie     Hybrid Journal   (Followers: 4, SJR: 1.14, h-index: 57)
APOPTOSIS     Hybrid Journal   (Followers: 8, SJR: 1.554, h-index: 87)
Applicable Algebra in Engineering, Communication and Computing     Hybrid Journal   (Followers: 2, SJR: 0.354, h-index: 27)
Applications of Mathematics     Hybrid Journal   (Followers: 1, SJR: 0.274, h-index: 20)
Applied Biochemistry and Biotechnology     Hybrid Journal   (Followers: 42, SJR: 0.575, h-index: 80)
Applied Biochemistry and Microbiology     Hybrid Journal   (Followers: 16, SJR: 0.267, h-index: 26)
Applied Cancer Research     Open Access  
Applied Categorical Structures     Hybrid Journal   (Followers: 2, SJR: 0.361, h-index: 21)
Applied Composite Materials     Hybrid Journal   (Followers: 48, SJR: 0.705, h-index: 35)
Applied Entomology and Zoology     Partially Free   (Followers: 3, SJR: 0.554, h-index: 34)
Applied Geomatics     Hybrid Journal   (Followers: 4, SJR: 0.323, h-index: 9)
Applied Geophysics     Hybrid Journal   (Followers: 8, SJR: 0.541, h-index: 13)
Applied Intelligence     Hybrid Journal   (Followers: 11, SJR: 0.777, h-index: 43)
Applied Magnetic Resonance     Hybrid Journal   (Followers: 4, SJR: 0.358, h-index: 34)
Applied Mathematics & Optimization     Hybrid Journal   (Followers: 6, SJR: 0.955, h-index: 33)
Applied Mathematics - A J. of Chinese Universities     Hybrid Journal   (SJR: 0.275, h-index: 8)
Applied Mathematics and Mechanics     Hybrid Journal   (Followers: 5, SJR: 0.37, h-index: 26)
Applied Microbiology and Biotechnology     Hybrid Journal   (Followers: 62, SJR: 1.262, h-index: 161)
Applied Physics A     Hybrid Journal   (Followers: 8, SJR: 0.535, h-index: 121)
Applied Physics B: Lasers and Optics     Hybrid Journal   (Followers: 24, SJR: 0.983, h-index: 104)
Applied Psychophysiology and Biofeedback     Hybrid Journal   (Followers: 8, SJR: 0.677, h-index: 47)
Applied Research in Quality of Life     Hybrid Journal   (Followers: 11, SJR: 0.288, h-index: 15)
Applied Solar Energy     Hybrid Journal   (Followers: 18, SJR: 0.251, h-index: 6)
Applied Spatial Analysis and Policy     Hybrid Journal   (Followers: 5, SJR: 0.351, h-index: 9)
Aquaculture Intl.     Hybrid Journal   (Followers: 22, SJR: 0.613, h-index: 40)
Aquarium Sciences and Conservation     Hybrid Journal   (Followers: 1)
Aquatic Ecology     Hybrid Journal   (Followers: 32, SJR: 0.646, h-index: 44)
Aquatic Geochemistry     Hybrid Journal   (Followers: 4, SJR: 0.764, h-index: 39)
Aquatic Sciences     Hybrid Journal   (Followers: 13, SJR: 1.172, h-index: 53)
Arabian J. for Science and Engineering     Hybrid Journal   (Followers: 5, SJR: 0.345, h-index: 20)
Arabian J. of Geosciences     Hybrid Journal   (Followers: 1, SJR: 0.417, h-index: 16)
Archaeological and Anthropological Sciences     Hybrid Journal   (Followers: 23, SJR: 1.056, h-index: 15)
Archaeologies     Hybrid Journal   (Followers: 12, SJR: 0.397, h-index: 13)
Archiv der Mathematik     Hybrid Journal   (Followers: 1, SJR: 0.597, h-index: 29)
Archival Science     Hybrid Journal   (Followers: 56, SJR: 0.804, h-index: 22)
Archive for History of Exact Sciences     Hybrid Journal   (Followers: 8, SJR: 0.28, h-index: 15)
Archive for Mathematical Logic     Hybrid Journal   (Followers: 1, SJR: 0.946, h-index: 23)
Archive for Rational Mechanics and Analysis     Hybrid Journal   (SJR: 4.091, h-index: 66)
Archive of Applied Mechanics     Hybrid Journal   (Followers: 5, SJR: 0.865, h-index: 40)
Archives and Museum Informatics     Hybrid Journal   (Followers: 142)
Archives of Computational Methods in Engineering     Hybrid Journal   (Followers: 5, SJR: 2.841, h-index: 40)
Archives of Dermatological Research     Hybrid Journal   (Followers: 7, SJR: 0.9, h-index: 65)
Archives of Environmental Contamination and Toxicology     Hybrid Journal   (Followers: 13, SJR: 0.846, h-index: 84)
Archives of Gynecology and Obstetrics     Hybrid Journal   (Followers: 16, SJR: 0.695, h-index: 47)
Archives of Microbiology     Hybrid Journal   (Followers: 8, SJR: 0.702, h-index: 85)
Archives of Orthopaedic and Trauma Surgery     Hybrid Journal   (Followers: 8, SJR: 1.039, h-index: 56)
Archives of Osteoporosis     Hybrid Journal   (Followers: 2, SJR: 1.092, h-index: 13)
Archives of Sexual Behavior     Hybrid Journal   (Followers: 10, SJR: 1.198, h-index: 74)
Archives of Toxicology     Hybrid Journal   (Followers: 17, SJR: 1.595, h-index: 76)
Archives of Virology     Hybrid Journal   (Followers: 5, SJR: 1.086, h-index: 90)
Archives of Women's Mental Health     Hybrid Journal   (Followers: 14, SJR: 1.264, h-index: 50)
Archivio di Ortopedia e Reumatologia     Hybrid Journal  
Archivum Immunologiae et Therapiae Experimentalis     Hybrid Journal   (Followers: 2, SJR: 1.2, h-index: 42)
ArgoSpine News & J.     Hybrid Journal   (SJR: 0.102, h-index: 3)
Argumentation     Hybrid Journal   (Followers: 5, SJR: 0.295, h-index: 18)
Arid Ecosystems     Hybrid Journal   (Followers: 3)
Arkiv för Matematik     Hybrid Journal   (Followers: 1, SJR: 0.948, h-index: 22)
Arnold Mathematical J.     Hybrid Journal   (Followers: 1)
Arthropod-Plant Interactions     Hybrid Journal   (Followers: 2, SJR: 0.797, h-index: 17)
Arthroskopie     Hybrid Journal   (Followers: 1, SJR: 0.145, h-index: 8)
Artificial Intelligence and Law     Hybrid Journal   (Followers: 11, SJR: 0.288, h-index: 25)
Artificial Intelligence Review     Hybrid Journal   (Followers: 14, SJR: 0.948, h-index: 48)
Artificial Life and Robotics     Hybrid Journal   (Followers: 8, SJR: 0.231, h-index: 14)
Asia Europe J.     Hybrid Journal   (Followers: 5, SJR: 0.247, h-index: 9)
Asia Pacific Education Review     Hybrid Journal   (Followers: 12, SJR: 0.371, h-index: 17)
Asia Pacific J. of Management     Hybrid Journal   (Followers: 16, SJR: 1.676, h-index: 50)
Asia-Pacific Education Researcher     Hybrid Journal   (Followers: 12, SJR: 0.353, h-index: 13)
Asia-Pacific Financial Markets     Hybrid Journal   (Followers: 2, SJR: 0.19, h-index: 15)
Asia-Pacific J. of Atmospheric Sciences     Hybrid Journal   (Followers: 20, SJR: 1.006, h-index: 14)
Asian Business & Management     Hybrid Journal   (Followers: 8, SJR: 0.41, h-index: 10)
Asian J. of Business Ethics     Hybrid Journal   (Followers: 8)
Asian J. of Criminology     Hybrid Journal   (Followers: 5, SJR: 0.263, h-index: 8)
AStA Advances in Statistical Analysis     Hybrid Journal   (Followers: 2, SJR: 0.681, h-index: 15)
AStA Wirtschafts- und Sozialstatistisches Archiv     Hybrid Journal   (Followers: 5, SJR: 0.195, h-index: 5)
ästhetische dermatologie & kosmetologie     Full-text available via subscription  

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Journal Cover Annals of Biomedical Engineering
  [SJR: 1.182]   [H-I: 94]   [18 followers]  Follow
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
   ISSN (Print) 1573-9686 - ISSN (Online) 0090-6964
   Published by Springer-Verlag Homepage  [2351 journals]
  • Biomechanical Characterisation of Bone-anchored Implant Systems for
           Amputation Limb Prostheses: A Systematic Review
    • Authors: Alexander Thesleff; Rickard Brånemark; Bo Håkansson; Max Ortiz-Catalan
      Pages: 377 - 391
      Abstract: Bone-anchored limb prostheses allow for the direct transfer of external loads from the prosthesis to the skeleton, eliminating the need for a socket and the associated problems of poor fit, discomfort, and limited range of movement. A percutaneous implant system for direct skeletal attachment of an external limb must provide a long-term, mechanically stable interface to the bone, along with an infection barrier to the external environment. In addition, the mechanical integrity of the implant system and bone must be preserved despite constant stresses induced by the limb prosthesis. Three different percutaneous implant systems for direct skeletal attachment of external limb prostheses are currently clinically available and a few others are under investigation in human subjects. These systems employ different strategies and have undergone design changes with a view to fulfilling the aforementioned requirements. This review summarises such strategies and design changes, providing an overview of the biomechanical characteristics of current percutaneous implant systems for direct skeletal attachment of amputation limb prostheses.
      PubDate: 2018-03-01
      DOI: 10.1007/s10439-017-1976-4
      Issue No: Vol. 46, No. 3 (2018)
  • Cell Migration in 1D and 2D Nanofiber Microenvironments
    • Authors: Horacio M. Estabridis; Aniket Jana; Amrinder Nain; David J. Odde
      Pages: 392 - 403
      Abstract: Understanding how cells migrate in fibrous environments is important in wound healing, immune function, and cancer progression. A key question is how fiber orientation and network geometry influence cell movement. Here we describe a quantitative, modeling-based approach toward identifying the mechanisms by which cells migrate in fibrous geometries having well controlled orientation. Specifically, U251 glioblastoma cells were seeded onto non-electrospinning Spinneret based tunable engineering parameters fiber substrates that consist of networks of suspended 400 nm diameter nanofibers. Cells were classified based on the local fiber geometry and cell migration dynamics observed by light microscopy. Cells were found in three distinct geometries: adhering two a single fiber, adhering to two parallel fibers, and adhering to a network of orthogonal fibers. Cells adhering to a single fiber or two parallel fibers can only move in one dimension along the fiber axis, whereas cells on a network of orthogonal fibers can move in two dimensions. We found that cells move faster and more persistently in 1D geometries than in 2D, with cell migration being faster on parallel fibers than on single fibers. To explain these behaviors mechanistically, we simulated cell migration in the three different geometries using a motor-clutch based model for cell traction forces. Using nearly identical parameter sets for each of the three cases, we found that the simulated cells naturally replicated the reduced migration in 2D relative to 1D geometries. In addition, the modestly faster 1D migration on parallel fibers relative to single fibers was captured using a correspondingly modest increase in the number of clutches to reflect increased surface area of adhesion on parallel fibers. Overall, the integrated modeling and experimental analysis shows that cell migration in response to varying fibrous geometries can be explained by a simple mechanical readout of geometry via a motor-clutch mechanism.
      PubDate: 2018-03-01
      DOI: 10.1007/s10439-017-1958-6
      Issue No: Vol. 46, No. 3 (2018)
  • The Advantages of Viscous Dissipation Rate over Simplified Power Loss as a
           Fontan Hemodynamic Metric
    • Authors: Zhenglun Alan Wei; Michael Tree; Phillip M. Trusty; Wenjun Wu; Shelly Singh-Gryzbon; Ajit Yoganathan
      Pages: 404 - 416
      Abstract: Flow efficiency through the Fontan connection is an important factor related to patient outcomes. It can be quantified using either a simplified power loss or a viscous dissipation rate metric. Though practically equivalent in simplified Fontan circulation models, these metrics are not identical. Investigation is needed to evaluate the advantages and disadvantages of these metrics for their use in in vivo or more physiologically-accurate Fontan modeling. Thus, simplified power loss and viscous dissipation rate are compared theoretically, computationally, and statistically in this study. Theoretical analysis was employed to assess the assumptions made for each metric and its clinical calculability. Computational simulations were then performed to obtain these two metrics. The results showed that apparent simplified power loss was always greater than the viscous dissipation rate for each patient. This discrepancy can be attributed to the assumptions derived in theoretical analysis. Their effects were also deliberately quantified in this study. Furthermore, statistical analysis was conducted to assess the correlation between the two metrics. Viscous dissipation rate and its indexed quantity show significant, strong, linear correlation to simplified power loss and its indexed quantity (p < 0.001, r > 0.99) under certain assumptions. In conclusion, viscous dissipation rate was found to be more advantageous than simplified power loss as a hemodynamic metric because of its lack of limiting assumptions and calculability in the clinic. Moreover, in addition to providing a time-averaged bulk measurement like simplified power loss, viscous dissipation rate has spatial distribution contours and time-resolved values that may provide additional clinical insight. Finally, viscous dissipation rate could maintain the relationship between Fontan connection flow efficiency and patient outcomes found in previous studies. Consequently, future Fontan hemodynamic studies should calculate both simplified power loss and viscous dissipation rate to maintain ties to previous studies, but also provide the most accurate measure of flow efficiency. Additional attention should be paid to the assumptions required for each metric.
      PubDate: 2018-03-01
      DOI: 10.1007/s10439-017-1950-1
      Issue No: Vol. 46, No. 3 (2018)
  • Blood Pump Design Variations and Their Influence on Hydraulic Performance
           and Indicators of Hemocompatibility
    • Authors: L. Wiegmann; S. Boës; D. de Zélicourt; B. Thamsen; M. Schmid Daners; M. Meboldt; V. Kurtcuoglu
      Pages: 417 - 428
      Abstract: Patients with ventricular assist devices still suffer from high rates of adverse events. Since many of these complications are linked to the flow field within the pump, optimization of the device geometry is essential. To investigate design aspects that influence the flow field, we developed a centrifugal blood pump using industrial guidelines. We then systematically varied selected design parameters and investigated their effects on hemodynamics and hydraulic performance using computational fluid dynamics. We analysed the flow fields based on Eulerian and Lagrangian features, shear stress histograms and six indicators of hemocompatibility. Within the investigated range of clearance gaps (50–500 µm), number of impeller blades (4–7), and semi-open versus closed shroud design, we found association of potentially damaging shear stress conditions with larger gap size and more blades. The extent of stagnation and recirculation zones was reduced with lower numbers of blades and a semi-open impeller, but it was increased with smaller clearance. The Lagrangian hemolysis index, a metric commonly applied to estimate blood damage, showed a negative correlation with hydraulic efficiency and no correlation with the Eulerian threshold-based metric.
      PubDate: 2018-03-01
      DOI: 10.1007/s10439-017-1951-0
      Issue No: Vol. 46, No. 3 (2018)
  • Mechanical Characterization and Material Modeling of Diabetic Aortas in a
           Rabbit Model
    • Authors: Jianhua Tong; F. Yang; X. Li; X. Xu; G. X. Wang
      Pages: 429 - 442
      Abstract: Diabetes has been recognized as a major risk factor to cause macrovascular diseases and plays a key role in aortic wall remodeling. However, the effects of diabetes on elastic properties of aortas remain largely unknown and quantitative mechanical data are lacking. Thirty adult rabbits (1.6–2.2 kg) were collected and the type 1 diabetic rabbit model was induced by injection of alloxan. A total of 15 control and 15 diabetic rabbit (abdominal) aortas were harvested. Uniaxial and biaxial tensile tests were performed to measure ultimate tensile strength and to characterize biaxial mechanical behaviors of the aortas. A material model was fitted to the biaxial experimental data to obtain constitutive parameters. Histological and mass fraction analyses were performed to investigate the underlying microstructure and dry weight percentages of elastin and collagen in the control and the diabetic aortas. No statistically significant difference was found in ultimate tensile strength between the control and the diabetic aortas. Regarding biaxial mechanical responses, the diabetic aortas exhibited significantly lower extensibility and significantly higher tissue stiffness than the control aortas. Notably, tissue stiffening occurred in both circumferential and axial directions for the diabetic aortas; however, mechanical anisotropy does not change significantly. The material model was able to fit biaxial experimental data very well. Histology showed that a number of isolated foam cells were embedded in the diabetic aortas and hyperplasia of collagen was identified. The dry weight percentages of collagen within the diabetic aortas increased significantly as compared to the control aortas, whereas no significant change was found for that of elastin. Our data suggest that the diabetes impairs elastic properties and alters microstructure of the aortas and consequently, these changes may further contribute to complex aortic wall remodeling.
      PubDate: 2018-03-01
      DOI: 10.1007/s10439-017-1955-9
      Issue No: Vol. 46, No. 3 (2018)
  • Engineering Analysis of Tricuspid Annular Dynamics in the Beating Ovine
    • Authors: Manuel K. Rausch; Marcin Malinowski; Penny Wilton; Asghar Khaghani; Tomasz A. Timek
      Pages: 443 - 451
      Abstract: Functional tricuspid regurgitation is a significant source of morbidity and mortality in the US. Furthermore, treatment of functional tricuspid regurgitation is suboptimal with significant recurrence rates, which may, at least in part, be due to our limited knowledge of the relationship between valvular shape and function. Here we study the dynamics of the healthy in vivo ovine tricuspid annulus to improve our understanding of normal annular deformations throughout the cardiac cycle. To this end, we determine both clinical as well as engineering metrics of in vivo annular dynamics based on sonomicrometry crystals surgically attached to the annulus. We confirm that the tricuspid annulus undergoes large dynamic changes in area, perimeter, height, and eccentricity throughout the cardiac cycle. This deformation may be described as asymmetric in-plane motion of the annulus with minor out-of-plane motion. In addition, we employ strain and curvature to provide mechanistic insight into the origin of this deformation. Specifically, we find that strain and curvature vary considerable across the annulus with highly localized minima and maxima resulting in aforementioned configurational changes throughout the cardiac cycle. It is our hope that these data provide valuable information for clinicians and engineers alike and ultimately help us improve treatment of functional tricuspid regurgitation.
      PubDate: 2018-03-01
      DOI: 10.1007/s10439-017-1961-y
      Issue No: Vol. 46, No. 3 (2018)
  • AngleNav: MEMS Tracker to Facilitate CT-Guided Puncture
    • Authors: Rui Li; Sheng Xu; William F. Pritchard; John W. Karanian; Venkatesh P. Krishnasamy; Bradford J. Wood; Zion Tsz Ho Tse
      Pages: 452 - 463
      Abstract: As a low-cost needle navigation system, AngleNav may be used to improve the accuracy, speed, and ease of CT-guided needle punctures. The AngleNav hardware includes a wireless device with a microelectromechanical (MEMS) tracker that can be attached to any standard needle. The physician defines the target, desired needle path and skin entry point on a CT slice image. The accuracy of AngleNav was first tested in a 3D-printed calibration platform in a benchtop setting. An abdominal phantom study was then performed in a CT scanner to validate the accuracy of the device’s angular measurement. Finally, an in vivo swine study was performed to guide the needle towards liver targets (n = 8). CT scans of the targets were used to quantify the angular errors and needle tip-to-targeting distance errors between the planned needle path and the final needle position. The MEMS tracker showed a mean angular error of 0.01° with a standard deviation (SD) of 0.62° in the benchtop setting. The abdominal phantom test showed a mean angular error of 0.87° with an SD of 1.19° and a mean tip-to-target distance error of 4.89 mm with an SD of 1.57 mm. The animal experiment resulted in a mean angular error of 6.6° with an SD of 1.9° and a mean tip-to-target distance error of 8.7 mm with an SD of 3.1 mm. These results demonstrated the feasibility of AngleNav for CT-guided interventional workflow. The angular and distance errors were reduced by 64.4 and 54.8% respectively if using AngleNav instead of freehand insertion, with a limited number of operators. AngleNav assisted the physicians to deliver accurate needle insertion during CT-guided intervention. The device could potentially reduce the learning curve for physicians to perform CT-guided needle targeting.
      PubDate: 2018-03-01
      DOI: 10.1007/s10439-017-1968-4
      Issue No: Vol. 46, No. 3 (2018)
  • A Robotic Flexible Drill and Its Navigation System for Total Hip
    • Authors: Ahmad Nazmi Bin Ahmad Fuad; Hariprashanth Elangovan; Kamal Deep; Wei Yao
      Pages: 464 - 474
      Abstract: This paper presents a robotic flexible drill and its navigation system for total hip arthroplasty (THA). The new robotic system provides an unprecedented and unique capability to perform curved femoral milling under the guidance of a multimodality navigation system. The robotic system consists of three components. Firstly, a flexible drill manipulator comprises multiple rigid segments that act as a sheath to a flexible shaft with a drill/burr attached to the end. The second part of the robotic system is a hybrid tracking system that consists of an optical tracking system and a position tracking system. Optical tracking units are used to track the surgical objects and tools outside the drilling area, while a rotary encoder placed at each joint of the sheath is synchronized to provide the position information for the flexible manipulator with its virtual object. Finally, the flexible drill is integrated into a computer-aided navigation system. The navigation system provides real time guidance to a surgeon during the procedure. The flexible drill system is then able to implement THA by bone milling. The final section of this paper is an evaluation of the flexible and steerable drill and its navigation system for femoral bone milling in sawbones.
      PubDate: 2018-03-01
      DOI: 10.1007/s10439-017-1959-5
      Issue No: Vol. 46, No. 3 (2018)
  • SpinoBot: An MRI-Guided Needle Positioning System for Spinal Cellular
    • Authors: Alexander Squires; John N. Oshinski; Nicholas M. Boulis; Zion Tsz Ho Tse
      Pages: 475 - 487
      Abstract: The neurodegenerative disease amyotrophic lateral sclerosis (ALS) results in the death of motor neurons in voluntary muscles. There are no cures for ALS and few available treatments. In studies with small animal models, injection of cellular therapeutics into the anterior horn of the spinal cord has been shown to inhibit the progression of ALS. It was hypothesized that spinal injection could be made faster and less invasive with the aid of a robot. The robotic system presented—SpinoBot—uses MRI guidance to position a needle for percutaneous injection into the spinal cord. With four degrees of freedom (DOF) provided by two translation stages and two rotational axes, SpinoBot proved capable of advanced targeting with a mean error of 1.12 mm and standard deviation of 0.97 mm in bench tests, and a mean error of 2.2 mm and standard deviation of 0.85 mm in swine cadaver tests. SpinoBot has shown less than 3% signal-to-noise ratio reduction in 3T MR imaging quality, demonstrating its compliance to the MRI environment. With the aid of SpinoBot, the length of the percutaneous injection procedure is reduced to less than 60 min with 10 min for each additional insertion. Although SpinoBot is designed for ALS treatment, it could potentially be used for other procedures that require precise access to the spine.
      PubDate: 2018-03-01
      DOI: 10.1007/s10439-017-1960-z
      Issue No: Vol. 46, No. 3 (2018)
  • Trunk Reaction Time and Kinematic Changes Following Slip Perturbations in
           Subjects with Recurrent Low Back Pain
    • Authors: Paul S. Sung; Pamela Danial
      Pages: 488 - 497
      Abstract: Postural responses following slip perturbations are critical to fall prevention strategies. It is unclear how postural reactions with a handheld task can validly be transferred to treadmill-induced slip perturbations in subjects with recurrent low back pain (LBP). The purpose of this study was to investigate trunk reaction times and trunk flexion angle as well as velocity following the slips between subjects with and without LBP. There were 29 subjects with LBP and 40 control subjects who participated in the study. Three levels of consecutive treadmill-induced slip perturbations were introduced at level 1 (duration: 0.10 s, velocity: 0.24 m/s, displacement: 1.20 cm), level 2 (0.12 s, 0.72 m/s, 4.32 cm), and level 3 (0.12 s, 1.37 m/s, 8.22 cm). The trunk reaction time, swing/step times, and trunk flexion angle as well as velocity at heel strike/toe-off were compared between the groups. There were significantly longer trunk reaction times (t = − 2.03, p = 0.04), swing times (t = − 2.63, p = 0.01), and step times (t = − 2.53, p = 0.01) in the LBP group at the level 1 slip perturbation. The groups demonstrated a significant interaction between the levels and trunk flexion angles (F = 4.72, p = 0.03), but there was no interaction between the levels and trunk flexion velocities (F = 0.07, p = 0.79). The LBP group demonstrated longer reaction times at the level 1 perturbation due to a possible pain recurrence. However, this compensatory tolerance was limited at the level 3 perturbation due to increased trunk flexion angle at heel strike and toe-off in the LBP group. Clinicians may consider a compensatory strategy to improve reaction time and minimize trunk flexion following slip perturbations in patients with LBP.
      PubDate: 2018-03-01
      DOI: 10.1007/s10439-017-1972-8
      Issue No: Vol. 46, No. 3 (2018)
  • Airflow Simulations in Infant, Child, and Adult Pulmonary Conducting
    • Authors: Jessica M. Oakes; Steven C. Roth; Shawn C. Shadden
      Pages: 498 - 512
      Abstract: The airway structure continuously evolves from birth to adulthood, influencing airflow dynamics and respiratory mechanics. We currently know very little about how airflow patterns change throughout early life and its impact on airway resistance, namely because of experimental limitations. To uncover differences in respiratory dynamics between age groups, we performed subject-specific airflow simulations in an infant, child, and adult conducting airways. Airflow throughout the respiration cycle was calculated by coupling image-based models of the conducting airways to the global respiratory mechanics, where flow was driven by a pressure differential. Trachea diameter was 19, 9, and 4.5 mm for the adult (36 years, female), child (6 years, male), and infant (0.25 years, female), respectively. Mean Reynolds number within the trachea was nearly the same for each subject (1100) and Womersley number was above unity for all three subjects and largest for the adult, highlighting the significance of transient effects. In general, air speeds and airway resistances within the conducting airways were inversely correlated with age; the 3D pressure drop was highest in the infant model. These simulations provide new insight into age-dependent flow dynamics throughout the respiration cycle within subject-specific airways.
      PubDate: 2018-03-01
      DOI: 10.1007/s10439-017-1971-9
      Issue No: Vol. 46, No. 3 (2018)
  • Using a Teaching Intervention and Calibrated Peer Review™ Diagnostics to
           Improve Visual Communication Skills
    • Authors: Ann Saterbak; Anoosha Moturu; Tracy Volz
      Pages: 513 - 524
      Abstract: Rice University’s bioengineering department incorporates written, oral, and visual communication instruction into its undergraduate curriculum to aid student learning and to prepare students to communicate their knowledge and discoveries precisely and persuasively. In a tissue culture lab course, we used a self- and peer-review tool called Calibrated Peer Review™ (CPR) to diagnose student learning gaps in visual communication skills on a poster assignment. We then designed an active learning intervention that required students to practice the visual communication skills that needed improvement and used CPR to measure the changes. After the intervention, we observed that students performed significantly better in their ability to develop high quality graphs and tables that represent experimental data. Based on these outcomes, we conclude that guided task practice, collaborative learning, and calibrated peer review can be used to improve engineering students’ visual communication skills.
      PubDate: 2018-03-01
      DOI: 10.1007/s10439-017-1946-x
      Issue No: Vol. 46, No. 3 (2018)
  • Robot-Assisted Fracture Surgery: Surgical Requirements and System Design
    • Authors: Ioannis Georgilas; Giulio Dagnino; Payam Tarassoli; Roger Atkins; Sanja Dogramadzi
      Abstract: The design of medical devices is a complex and crucial process to ensure patient safety. It has been shown that improperly designed devices lead to errors and associated accidents and costs. A key element for a successful design is incorporating the views of the primary and secondary stakeholders early in the development process. They provide insights into current practice and point out specific issues with the current processes and equipment in use. This work presents how information from a user-study conducted in the early stages of the RAFS (Robot Assisted Fracture Surgery) project informed the subsequent development and testing of the system. The user needs were captured using qualitative methods and converted to operational, functional, and non-functional requirements based on the methods derived from product design and development. This work presents how the requirements inform a new workflow for intra-articular joint fracture reduction using a robotic system. It is also shown how the various elements of the system are developed to explicitly address one or more of the requirements identified, and how intermediate verification tests are conducted to ensure conformity. Finally, a validation test in the form of a cadaveric trial confirms the ability of the designed system to satisfy the aims set by the original research question and the needs of the users.
      PubDate: 2018-03-09
      DOI: 10.1007/s10439-018-2005-y
  • A Novel Role of Id1 in Regulating Oscillatory Shear Stress-Mediated Lipid
           Uptake in Endothelial Cells
    • Authors: Kang Zhang; Yidan Chen; Tian Zhang; Lu Huang; Yi Wang; Tieying Yin; Juhui Qiu; Hans Gregersen; Guixue Wang
      Abstract: Inhibitor of DNA binding 1 (Id1) has been shown to be involved in adipogenesis and metabolism, which may contribute to atherosclerotic progression. However, it remains unclear how Id1 regulates endothelial cell functions and atherosclerosis in response to oscillatory shear stress. The current study aims to evaluate the effects of oscillatory shear stress on LDL uptake by endothelial cells and to delineate the roles of Id1 in this process. Using an in vivo ligation model of ApoE−/− mice and applying low and oscillatory shear stress (OSS) in vitro, we found that OSS can effectively promote lipid uptake. In vivo en face staining results showed that OSS down-regulated Id1 expression. In vitro, OSS activated Id1 transiently but eventually inhibited its expression with time. Overexpression of Id1 can abolish OSS-mediated lipid uptake in ECs. In addition, Id1 overexpression and knockdown experiments demonstrated that Id1 can regulate LDLR expression to influence lipid uptake. Immunoprecipitation and subcellular localization results further suggested that Id1 can combine with sterol regulatory element-binding protein1 (SREBP1), which may be related to the Id1-mediated LDLR down-expression. Our study shows a biomechanical role of Id1 in endothelial cells’ uptake of lipid by down-regulating LDLR, which could help understand how oscillatory flow affects atherosclerotic development.
      PubDate: 2018-03-05
      DOI: 10.1007/s10439-018-2000-3
  • Development of an In Vitro 3D Brain Tissue Model Mimicking In Vivo -Like
           Pro-inflammatory and Pro-oxidative Responses
    • Authors: Hyung Joon Cho; Scott S. Verbridge; Rafael V. Davalos; Yong W. Lee
      Abstract: To analyze complex inflammatory responses in an in vitro system, we constructed a new 3D in vitro brain tissue model that exhibits in vivo-like tissue responses (e.g. immune cell phenotypes, and molecular response) to inflammatory stimuli. Finite element modeling of oxygen diffusion and cellular oxygen consumption predicted the oxygen profile within 3D structures, consisting of Type I collagen hydrogel embedded with murine microglia. Viability and cytotoxicity analyses supported the mathematical analysis, determining optimal cell growth conditions for 3D construct development. Real-time RT-PCR and ELISA demonstrated significant up-regulation of pro-inflammatory mediators, such as TNF-α, MCP-1, IL-6 and IL-1β, in lipopolysaccharide (LPS)-stimulated in vitro cell culture (2D and 3D) and in vivo mouse model systems. Interestingly, levels of inflammatory responses from the in vitro 3D model system were more similar to in vivo than in vitro 2D. Additionally, in situ dihydroethidium (DHE) assay and immunofluorescence staining revealed that levels of LPS-stimulated reactive oxygen species (ROS) generation and microglial activation from in vitro 3D model system were closer to in vivo than in vitro 2D. These results demonstrated that an in vitro 3D model provides more physiologically relevant pro-oxidative and pro-inflammatory environments in brain than an in vitro 2D model.
      PubDate: 2018-03-02
      DOI: 10.1007/s10439-018-2004-z
  • Spheroid Culture System Confers Differentiated Transcriptome Profile and
           Functional Advantage to 3T3-L1 Adipocytes
    • Authors: Paul A. Turner; Michael R. Garrett; Sean P. Didion; Amol V. Janorkar
      Abstract: This study highlights functional differences between 2-D monolayer and 3-D spheroid 3T3-L1 adipocyte culture models and explores the underlying genomic mechanisms responsible for the different phenotypes present. The spheroids showed higher triglyceride accumulation than the monolayer culture and further increase with larger spheroid size. Whole transcriptome analysis indicated significant differential expression of genes related to adipogenesis, including adipocytokine signaling, fatty acid metabolism, and PPAR-γ signaling. Spheroids also showed downregulation of matrix metalloproteinases (MMPs), integrin, actin-cytoskeleton associated genes, and Rho/GTPase3 expression relative to 2-D monolayer, indicating suppression of the Rho-ROCK pathway and thereby promoting adipogenic differentiation. When exposed to linoleic acid (500 μM) and TNF-α (125 ng/mL) to promote chronic adiposity, linoleic acid treatment resulted in increased intracellular triglycerides and subsequent TNF-α treatment resulted in significantly altered adipocytokine signaling, fatty acid metabolism, and PPAR signaling, in addition to upregulation of multiple MMPs in spheroids vs. monolayer. Overall, 3-D spheroids showed enhanced adipogenic phenotype as indicated by triglyceride synthesis and transcriptome changes while retaining sensitivity to a pro-inflammatory stimulus. The 3-D spheroid culture thus may provide a simple, convenient, and sensitive in vitro model to study adipocyte response to metabolic stresses relevant to clinical pathologies.
      PubDate: 2018-03-02
      DOI: 10.1007/s10439-018-1993-y
  • The Importance of the Scalp in Head Impact Kinematics
    • Authors: Antonia Trotta; Dimitris Zouzias; Guido De Bruyne; Aisling Ní Annaidh
      Abstract: The best way to reduce the risk of head injury (up to 69% reduction) is to wear a helmet. In recent years, the improvement of helmet standard tests focused on reproducing realistic impact conditions and including the effect of rotational acceleration. However, less importance has been given to the development of a realistic headform. The goal of this work was to evaluate the role of scalp tissue in head impact kinematics; both with respect to its mechanical properties and with respect to its sliding properties. An EN960 and HIII headform were subjected to linear and oblique impacts, respectively, both with and without porcine scalp attached. Different speeds, impact locations and impact surfaces were tested. Standard linear drop tests (EN960) showed that the scalp reduced the impact energy by up to 68.7% (rear impact). Oblique head impact tests showed how the headform-anvil friction coefficient changes when the HIII is covered with scalp, affecting linear and rotational accelerations. Therefore, the scalp plays an important role in head impacts and it should be realistically represented in headforms used for impact tests and in numerical models of the human head.
      PubDate: 2018-03-01
      DOI: 10.1007/s10439-018-2003-0
  • A Novel Plasma-Based Fluid for Particle Image Velocimetry (PIV): In-Vitro
           Feasibility Study of Flow Diverter Effects in Aneurysm Model
    • Authors: Johanna Clauser; Marius S. Knieps; Martin Büsen; Andreas Ding; Thomas Schmitz-Rode; Ulrich Steinseifer; Jutta Arens; Giorgio Cattaneo
      Abstract: Particle image velocimetry (PIV) is a commonly used method for in vitro investigation of fluid dynamics in biomedical devices, such as flow diverters for intracranial aneurysm treatment. Since it is limited to transparent blood substituting fluids like water-glycerol mixture, the influence of coagulation and platelet aggregation is neglected. We aimed at the development and the application of a modified platelet rich plasma as a new PIV fluid with blood-like rheological and coagulation properties. In standardized intracranial aneurysm silicone models, the effect of this new PIV plasma on the fluid dynamics before and after flow diverter implantation was evaluated and compared with water-glycerol measurements. The flow diverting effect was strongly dependent on the used fluid, with considerably lower velocities achieved using PIV plasma, despite the same starting viscosity of both fluids. Moreover, triggering coagulation of PIV plasma allowed for intra-aneurysmal clot formation. We presented the first in vitro PIV investigation using a non-Newtonian, clottable PIV plasma, demonstrating a mismatch to a standard PIV fluid and allowing for thrombus formation.
      PubDate: 2018-02-27
      DOI: 10.1007/s10439-018-2002-1
  • Variable Cell Line Pharmacokinetics Contribute to Non-Linear Treatment
           Response in Heterogeneous Cell Populations
    • Authors: Matthew T. McKenna; Jared A. Weis; Vito Quaranta; Thomas E. Yankeelov
      Abstract: We develop a combined experimental–mathematical framework to investigate heterogeneity in the context of breast cancer treated with doxorubicin. We engineer a cell line to over-express the multi-drug resistance 1 protein (MDR1), an ATP-dependent pump that effluxes intracellular drug. Co-culture experiments mixing the MDR1-overexpressing line with its parental line are evaluated via fluorescence microscopy. To quantify the impact of population heterogeneity on therapy response, these data are analyzed with a coupled pharmacokinetics/pharmacodynamics model. The proliferation and death rates of each line vary with co-culture condition (the relative fraction of each cell line at the time of seeding). For example, the death rate in the parental line under low-dose doxorubicin treatment is increased from 0.64 (± 0.22) × 10−2 to 1.46 (± 0.58) × 10−2 h−1 with increasing fractions of MDR1-overexpressing cells. The growth rate of the MDR1-overexpressing line increases 29% as its relative fraction is decreased. Simulations of the pharmacokinetics/pharmacodynamics model suggest increased efflux from MDR1-overexpressing cells contributes to the increased death rate in the parental cells. Experimentally, the death rate of parental cells is constant across co-culture conditions under co-treatment with an MDR1 inhibitor. These data indicate that intercellular pharmacokinetic variability should be considered in analyzing treatment response in heterogeneous populations.
      PubDate: 2018-02-26
      DOI: 10.1007/s10439-018-2001-2
  • Solid Stress Facilitates Fibroblasts Activation to Promote Pancreatic
           Cancer Cell Migration
    • Authors: Maria Kalli; Panagiotis Papageorgis; Vasiliki Gkretsi; Triantafyllos Stylianopoulos
      Abstract: Pancreatic fibroblasts are continuously gaining ground as an important component of tumor microenvironment that dynamically interact with cancer cells to promote tumor progression. In addition, these tumor-infiltrated fibroblasts can acquire an activated phenotype and produce excessive amounts of extracellular matrix creating a highly dense stroma, a situation known as desmoplasia. Desmoplasia, along with the uncontrolled proliferation of cancer cells, leads to the development of compressive forces within the tumor, generating the so-called solid stress. Solid stress is previously shown to affect cancer cell proliferation and migration, however there is no pertinent study taking into account the effects of solid stress on fibroblasts and whether these effects contribute to tumor progression. In this work, we applied a defined compressive stress on pancreatic fibroblasts, similar in magnitude to that experienced by cells in native pancreatic tumors. Our results suggest that solid stress stimulates fibroblasts activation and strongly upregulates Growth Differentiation Factor-15 (GDF15) expression. Moreover, co-culture of compression-induced activated fibroblasts with pancreatic cancer cells significantly promotes cancer cell migration, which is inhibited by shRNA-mediated silencing of GDF15 in fibroblasts. Conclusively, our findings highlight the involvement of biophysical factors, such as solid stress, in tumor progression and malignancy revealing a novel role for GDF15.
      PubDate: 2018-02-22
      DOI: 10.1007/s10439-018-1997-7
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