Modeling and in vitro and in vivo characterization of a tissue engineered pancreatic substitute

Cherie Stabler, C. Fraker, E. Pedraza, I. Constantinidis, A. Sambanis

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)54-73
Number of pages20
JournalJournal of Combinatorial Optimization
Volume17
Issue number1
DOIs
StatePublished - Jan 1 2009

Keywords

  • βTC3 insulinoma cells
  • Agarose
  • Encapsulated cells
  • Pancreatic substitute
  • Tissue construct modeling

ASJC Scopus subject areas

  • Discrete Mathematics and Combinatorics
  • Applied Mathematics
  • Computational Theory and Mathematics
  • Computer Science Applications
  • Control and Optimization

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