Silk Fibroin-zwitterionic Core–shell Hydrogel Microspheres Loaded with Curcumin Micelles for Synergistic Antifouling and Protection of Encapsulated Islets

Abstract

Islet encapsulation is a promising strategy for protecting transplanted islets from immune-mediated damage. Herein, silk fibroin-based hydrogel microspheres with a zwitterionic shell were developed, with or without encapsulation of curcumin-loaded octenyl succinic anhydride starch micelles (OSAS–Cur). All microspheres exhibited favorable mechanical properties and biocompatibility. Curcumin-loaded microspheres showed sustained drug release, which was attributed to micelle-induced β-sheet formation in silk fibroin. Molecular docking and molecular dynamics simulations further revealed strong interactions between curcumin and β-sheet domains, contributing to structural stabilization. Among all formulations, curcumin micelle-loaded silk fibroin–zwitterionic core–shell microspheres (SOCPS) displayed the strongest resistance to protein, polysaccharide, and cell adhesion, while effectively suppressing macrophage activation. In diabetic mice, SOCPS reduced cell adhesion and IL-6-positive cells while increasing CD206-positive cells, indicating the establishment of a more anti-inflammatory microenvironment. Furthermore, SOCPS provided superior protection against hypoxia- and LPS-induced islet apoptosis. Transplantation of SOCPS-encapsulated islets achieved prolonged normoglycemia and improved body weight in diabetic mice. Overall, the combination of zwitterionic antifouling coatings and curcumin offers a promising strategy for improving the immunocompatibility and functional performance of islet encapsulation systems.