Development of bio-integrated devices to enhance transplant survival for subcutaneous encapsulated cell therapies

Encapsulated cell therapies (ECT) are attractive therapeutic platforms that involve the housing of collections of transplanted cells capable of secreting therapeutic proteins within polymeric frames. These technologies represent the potential to eliminate patient dependence on complex drug-dosing regimens while maintaining circulating drug levels within healthy, nontoxic therapeutic ranges for diseases ranging from autoimmune disorders to cancer. Transplanted cells are isolated from host immune systems via encapsulation materials and semipermeable, porous polymeric membranes (immunisolation membranes) via size exclusion effects. Despite attracting significant interest, ECT devices have not found widespread clinical translation owing to transplant failure, with low oxygen tension within the transplanted cell microenvironment and fibrosis representing major causes. Size considerations related to cellular packing density represent a further translational challenge. This challenge is particularly acute in subcutaneous (SC) implants owing to the region’s low vascularization and high rates of fibrotic capsule formation. Despite these hurdles, SC implants have attracted considerable attention owing to the minimally invasive surgery requirements and potential for easy device monitoring and retrieval. In this proposal, I will use approaches in microfabrication and bioelectronic device design to improve oxygen tension within the transplanted cell microenvironment in SC-ECT devices. In Aim 1 I will develop advanced multiphysics models to predict and address oxygen need in implanted SC devices. In Aim 2, I will use surface chemical modifications to suppress fibrosis and ensure long-term transplant survival in oxygen-generating bioelectronic ECT implants. In Aim 3, I will pursue system level integration using design principles in flexible bioelectronics, biosensor development and resonant inductive wireless power transfer approaches. If successful, the resulting platform technology will support SC transplanted cell survival long term, with potential applications across cell types and disease models. The work is highly interdisciplinary, incorporating materials science, cell therapies, drug delivery and electronic/electrical engineering. If successful, the work will create a platform technology capable of addressing a wide range of unmet therapeutic needs in minimally invasive implantation sites to de-risk clinical translation. My background is primarily in the physical sciences: through this Fellowship, I will work closely with my co-mentors, Profs. Daniel Anderson and Robert Langer at MIT to develop skills that will allow me to work at the interface between engineering and the life sciences, with a focus on clinical translation.