Surface Modification of Islets with L-DOPA-KF7 Enhances Islet Survival by Inhibiting IBMIR in Intrahepatic Islet Transplantation

Intrahepatic islet transplantation is followed by islet loss due to instant blood-mediated inflammatory response (IBMIR), in which platelet activation plays a key role. The KEATSTF-fragment (KF7), a newly discovered platelet inhibitor that interferes with the formation of the 14-3-3z–c-Src–integrin-β3 complex, holds significant potential in inhibiting IBMIR without causing significant bleeding. This study introduces a novel surface modification technique using L-DOPA (3,4-Dihydroxy-L-phenylalanine) conjugated with KF7 to enhance the engraftment of transplanted islets in a syngeneic marginal mass model. KF7 loaded with L-DOPA(L-DOPA-KF7) formed a protective coating on the surface of islets without interfering with their viability and functionality. Islets coated with L-DOPA-KF7 restored normoglycemia in diabetic mice, and survival time was significantly longer compared to control group. Transplantation of L-DOPA-KF7 coated islets was associated with reduced blood clot formation and decreased infiltration of CD11b+ cells and platelets. In conclusion, composite L-DOPA-KF7 coating significantly prolongs the survival of transplanted islets by providing a robust IBMIR -isolation barrier, thereby enhancing the overall success of islet transplantation in preclinical models.