Kenyon, N. S.1; Pedraza, E.2; Berman, D. M.2; Brady, A. C.2; Willman, M.2; Latta, P.2; Ricordi, C.3; Stabler, C.2 Author Information
1Diabetes Research Institute, University of Miami, Miami/FL/UNITED STATES OF AMERICA, 2Diabetes Research Institute, University of Miami School of Medicine, Miami/UNITED STATES OF AMERICA, 3Miller School Of Medicine, University of Miami, Miami/UNITED STATES OF AMERICA, 4Biomedical Engineering/diabetes Research Institute, University of Miami, Miami/FL/UNITED STATES OF AMERICA
In designing appropriate devices for the development of a functional pancreatic substitute, computational models capable of accurately predicting cellular behavior constitute a critical aspect. This study investigated the model-based design, fabrication and in vitro and in vivo experimental characterization of a pancreatic substitute consisting of mouse insulinoma cells encapsulated in agarose in a disk-shaped construct. Two construct prototypes were examined: (i) a single disk construct comprised of agarose and βTC3 cells; and (ii) a buffered disk construct, consisting of agarose and βTC3 cells, coated with an additional layer of pure agarose. Diffusional studies of glucose and insulin were performed to characterize the transport properties of the material. Three dimensional oxygen diffusion-reaction models were used to predict the appropriate cell loadings for the two construct prototypes under varying external oxygen tensions. In vitro and in vivo experiments found the overall viable cell number for each construct prototype plateaued to the same value, regardless of the initial cell seeding number, when constructs were placed under identical environmental conditions. Furthermore, mathematical model calculations correlated well with experimental in vitro and in vivo results of cell viability, indicating oxygen tension to be the dominating factor in establishing total viable cell number in these constructs. These results indicate that the development of a computational model capable of accurately predicting overall cell viability is useful for the development of tissue engineered constructs, when permissive matrices and continuous cell lines are used. The applicability of this modeling and experimental methodology in the development of agarose-based constructs for use as a bioartificial pancreas is discussed.
Cherie Stabler合作论文数J. Crayton Pruitt Family Department of Biomedical Engineering, Herbert Wertheim College of Engineering, University of Florida;Diabetes Institute, School of Medicine, University of Florida;Department of Biomedical Engineering, University of Miami5
Camillo Ricordi合作论文数Division of Cellular Transplantation, DeWitt Daughtry Family Department of Surgery, Miller School of Medicine, University of Miami3
Dora M. Berman合作论文数2Norma S. Kenyon合作论文数Diabetes Research Institute;University of Miami;School of Medicine2L. Garcia-Covarrubias合作论文数1M. Willman合作论文数1E. Margolles-Clark合作论文数1M.A. Willman合作论文数1N. M. Kenyon合作论文数1I Castro合作论文数1Sambanis Athanassios合作论文数1
Maria M. Coronel合作论文数Diabetes Research Institute and;College of Engineering, University of Miami;College of Engineering, University of Miami1Antonello Pileggi合作论文数1
Peter Buchwald合作论文数Department of Molecular & Cellular Pharmacology, Miller School of Medicine, University of Miami;Diabetes Research Institute, Miller School of Medicine, University of Miami1Christopher Fraker合作论文数Diabetes Research Institute, University of Miami School of Medicine1Ioannis Constantinidis合作论文数1
