Medical Engineering Thesis Defense, Kuang Ming (Allen) Shang

Zoom: https://caltech.zoom.us/j/88340942835

Type 1 diabetes is an autoimmune disease in which immune cells specifically attack and destroy the insulin-producing beta cells in the pancreatic islets that regulate blood glucose levels. Traditionally managed with frequent injections of exogenous insulin, beta cell replacement therapy—also known as islet transplantation—has emerged as an alternative clinical option. Recently, the focus has shifted toward subcutaneous islet transplantation, offering a promising and minimally invasive therapy. However, the survival of transplanted islets has been shown to be significantly challenged by hypoxia-induced graft loss stemming from inadequate oxygen supply.

To address this issue, we have developed innovative hollow mesh devices to enhance oxygen delivery to hypoxic islet grafts. These devices, fabricated using MEMS techniques and biocompatible materials, can draw oxygen from surrounding oxygen-rich tissues or additional oxygen from ambient air. The hollow mesh devices feature a network of air-containing microchannels that utilize the rapid diffusion of oxygen in the air, which is 10,000 times faster than in interstitial fluids. When integrated with islet grafts, these devices redistribute oxygen efficiently throughout the graft, improving local oxygen levels, reducing hypoxia-induced graft loss, and enhancing post-transplant blood glucose control.

In this talk, I will first delve into the physiology of oxygen transport within an islet, establishing the critical oxygen threshold necessary for islet cell survival. I will develop equivalent circuit models for oxygen diffusion and demonstrate how to construct oxygen-regulating hollow mesh MEMS devices based on these models. I will corroborate the effects of oxygenation through both computational models and benchtop experiments. Finally, using our device, I will demonstrate the enhanced survival of islet grafts in diabetic rodent models, successfully achieving a long-term cure for diabetes.

With the preclinical success of this oxygen-regulating hollow mesh in mitigating cellular oxygen deficiency, I will also discuss future pathways toward clinical effectiveness. Together, I hope to convince you that our devices hold significant therapeutic potential to revolutionize clinical outcomes in islet transplantation with the ultimate goal of curing type 1 diabetes.

Advisors: Professor Yu-Chong Tai and Professor Hirotake Komatsu (UCSF)