Improving islet transplantation by developing biomimetic and immune-orchestrating gels for the microencapsulation of islets by microfluidics

Pancreatic islet transplantation in T1D offers the possibility of curing the disease, which is known to reduce life expectancy because exogenous insulin injections cannot fully mimic the fine-tuning of blood glucose levels executed by healthy islets.

However, the clinical success of this strategy is limited because of poor islet survival after transplantation and serious side effects such as the long-term need for immunosuppressive therapies.

Moreover, the extracellular matrix components of islets are degraded during isolation but are critical for islet survival and function.

In this proposal,I design a biomimetic pancreatic islet niche to better support islet survival and function and use a mucin-based immunosuppressive material as the outer layer of islet-laden biomimetic niche to evade the immune response.

I will first synthesize a biomimetic islet niche and immunorchestrating biomaterials and evaluate their functions (Y 1.5).

Second, I will microencapsulate pancreatic islets into synthetic biomimetic niches immunoprivileged by mucin-based materials using a microfluidic device.

The immune responses will be studied in situ using open-trapping microarrays in accordance with 3R principles for animal research (Y 2.5).

Third, I will study the foreign body response, islet cell survival and function, engraftment, and hyperglycemic correction outcome (Y 4). The project would transform islet transplantation for T1D.