Question

4. For the bioartificial pancreas case study we had in class: (1) Write a problem statement. (2) Describe one non-tissue engineering treatment option. What is the main limitation for this treatment? (3) Propose your tissue engineering design for bioartificial pancreas.

Answer 1

1) Islet transplantation has been shown to be a viable treatment option for patients afflicted with Type 1 diabetes. However, the severe shortage of human pancreas and the need to use risky immunosuppressive drugs to prevent transplant rejection remain two major obstacles to routine use of islet transplantation in diabetic patients. Successful development of a bioartificial pancreas using the approach of microencapsulation with perm-selective coating of islets in hydrogels for graft immunoisolation holds tremendous promise for diabetic patients because it has great potential to overcome these two barriers.

2) The artificial pancreas is a technological development to enable Type 1 diabetic patients to automatically control their blood glucose, acting in essence like a healthy pancreas. The goals of the artificial pancreas are: i) to improve presently popular but inefficient insulin therapy to attain a better glycemic control, thus avoiding the complications due to blood glucose fluctuations, and ii) to mimic normal stimulation of the liver by the pancreas and to normalize carbohydrate and lipid metabolism.

Bioengineering approach

The bioengineering approach to designing a bioartificial pancreas has generally involved the development of either microcapsules, or macrocapsules, or other devices such as biocompatible sheet of encapsulated islets. When implanted, these constructs would substitute for the defective native endocrine pancreas. However, this review will focus on the microencapsulated islet construct, as it has advanced into the stage of clinical trials and has significant promise to be a good alternative to pancreas transplantation. Using alginate as the encapsulation polymer, the concept of islet immunoisolation is illustrated in below figure, which essentially incorporates a semipermeable membrane into the process because alginate does not have any appreciable perm-selectivity towards immune cells and other immunological factors such as antibodies that can potentially destroy the encapsulated cells.

Limitation: The bioartificial pancreas encapsulating pancreatic islets in immunoprotective hydrogel is a promising therapy for Type 1 diabetes. As pancreatic islets are highly metabolically active and exquisitely sensitive to hypoxia, maintaining O₂ supply after transplantation remains a major challenge.

3) Design of Bioartificial Pancreas:

A new design of a bioartificial pancreas comprising islets co-encapsulated with angiogenic protein in permselective multilayer alginate-poly-L-ornithine-alginate microcapsules and transplanted in an omentum pouch is described. The multilayer alginate-poly-L-ornithine-alginate microcapsules are made with ultrapure alginate using poly-L-ornithine as a semipermeable membrane separating the 2 alginate layers. The inner alginate layer is used to encapsulate the islets, and the outer layer is used to encapsulate angiogenic protein, which would induce neovascularization around the graft within the omentum pouch. Both the wild-type and the heparin-binding growth-associated molecule (HBGAM)-fibroblast growth factor-1 chimera can be encapsulated and released in a controlled and sustained manner from the outer alginate layer with a mean diameter in the range of 113 to 164 µm when 1.25% high guluronic acid alginate is used to formulate this outer layer. In vivo experiments to determine the ability of angiogenic proteins released from this outer layer to induce neovascularization around the grafts in the omentum pouch are needed.