Biomimetic Materials and Bioprocesses for High-Density Cultures of Pancreatic Islets and Tissues

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3.5 million Canadians live with diabetes, with an associated cost of $ 3.4 billion. Beta-cells (cells producing insulin) lost has been observed in both types 1 and 2 diabetes. Pancreatic islet transplantation can restore functional beta-cells to achieve normoglycemia in type 1 diabetics. Islet transplantation has encountered problems including beta-cell apoptosis. Improving the success of islet transplantation has been a target in the research community. Also, the development of therapeutic to treat diabetes has been identified by pharmaceutical companies to be hindered due to a lack of adequate pancreatic tissue models.*** Tissue engineering methods have been applied to encapsulate and culture pancreatic islets and beta-cells in three-dimensional matrices, and using bioreactors. The aim here is to expose cells/tissues to environments mimicking their native ones, so they can behave more physiologically. Encapsulating pancreatic islets could be a solution to protect transplanted islets from host responses. Development in tissue engineering enables the use of decellularized organs and tissues as scaffolds for cell therapies. However, little is known about the mechanisms governing the effects of decellularized matrices on cells.******The LONG-TERM PROGRAM OBJECTIVE is to develop the automated processes to isolate and culture endocrine pancreatic tissues and cells at high density and to adapt the process to other tissues and organs.***The SPECIFIC OBJECTIVES are:***1) To develop a perfusion bioreactor for organ/tissue decellularization and processes for cell/tissue seeding and culture. This reactor will be used to investigate pancreatic islets and beta-cells survival and function in decellularized organs and tissues under perfusion;***2) To study endocrine pancreatic islets/cells survival and function on biomimetic surfaces produced from decellularized tissues/organs;***3) To characterize the co-culture of endocrine pancreatic islets and cells with pancreatic microvessels under bioreactor perfusion.******SIGNIFICANCE AND NOVELTY: 1) Our biomimetic surfaces provide excellent low-fouling coatings allowing studying specific cell responses by eliminating non-specific ones. 2) Knowledge about how biomimetic scaffolds affect islets can support the development of better encapsulation techniques. 3) Understanding how flow conditions affect islet responses allows identifying how transplanted islets are affected by physiological conditions at an implantation site. Developing an automated process to decellularize organs/tissues will be a step to transfer manually-operated laboratory-scale methods to industrial processes for cell therapy products. 4) Finally, little is known about how to re-establish a functional vasculature in isolated islets. We have been the first to isolate pancreatic microvessels. This program will support training of highly qualified personnel.