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 the 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 14-3-3f–c-Src–integrin-β3 complex, holds significant potential in inhibiting IBMIR without causing significant bleeding. This study introduces a novel surface modification technique using 3,4-dihydroxy-L-phenylalanine (L-DOPA) conjugated with KF7 to enhance the engraft-ment 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 normoglyce-mia in diabetic mice, and survival time was significantly longer compared with the 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, a compos-ite 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.