Surface-Engineering of Pancreatic Islets with Chitosan Microparticles to Inhibit IBMIR in Islet Xenotransplantation

Intraportal islet transplantation is an effective beta-cell replacement therapy for restoring insulin production in patients with type 1 diabetes. However, transplanted islets are rapidly lost due to a strong immediate inflammatory reaction, termed as instant blood-mediated inflammatory reaction (IBMIR). Current preventive therapies for IBMIR face systemic side effects such as bleeding risks. Although surface islet modification with biocompatible polymers or antithrombotic molecules shows promise, the limited anchoring of these molecules on the islet surface, caused by low conjugation efficiency and complex procedures in current methods, often lead to suboptimal outcomes. In this study, a novel islet conjugation platform is presented for effectively delivering heparin (HEP) for overcoming IBMIR. The islet surface is first conjugated with chitosan microparticles (CSMP) via electrostatic interaction. HEP is then absorbed into the conjugated CSMP with a high amount (4.4 ng IEQ^-1). The conjugation system is stable and highly biocompatible with cell viability and functionality in vitro. Importantly, intraportal transplantation of the HEP/CSMP-islets significantly reduces coagulation and complement activation and improves blood glucose levels, thereby achieving a higher survival rate. This strategy can provide a versatile platform to deliver various therapeutic agents, including bioactive anti-inflammatory cytokines and growth factors, leading to enhanced islet transplantation outcomes.