P41: 4D Manufacturing: Immunoprotective Materials for Islet Tissue Patches in Cell-Based Diabetes Treatments

Abstract

Purpose: In order to cure diabetes on a large scale, researchers are working to develop insulin-producing cells differentiated from human pluripotent stem cells, encapsulating the tissues to protect the cells from immune attack, and implanting the cells for regulated insulin secretion. This project explored the synthesis and in vivo performance of a 4D biomaterial intended to protect implanted insulin-producing cells in the body. 3D printing of insulin-producing cells encapsulated within the biomaterial with additional timed-release anti-inflammatory agents enabled complex, personalized shapes and a 4D functional material. Methods: Anti-inflammatory agents were functionalized with varying permanent and degradable linkages to achieve a range of timed-release therapeutics to prevent immune system-mediated rejection. The molecules were crosslinked with a multi-arm polyethylene glycol (PEG) material in the subcutaneous space of immunocompetent C57BL/6 mice. After 30 days, tissue slices of the explant were examined using H&E staining revealing the thickness of biological encapsulation compared to alginate controls. Results: PEG-based implants with acetal linkages enabling the slow release (~30 days) of anti-inflammatory agents achieved the thinnest layer of biological encapsulation compared to the controls. Summary: Collectively, the described 4D biomaterial with other novel approaches and tools will enable the investigation of survival and function of a stem cell-based therapy for diabetes that could ultimately allow patients to live a diabetes-free lifestyle.