Injectable High-Adhesion Fibrinogen-Silk Fibroin Hydrogel Loaded with Curcumin Accelerates Pterygium Repair via Dual Anti-Inflammatory/Antiproliferative Mechanisms

Pterygium is a common ocular surface lesion, and postoperative recurrence remains a major challenge due to insufficient therapeutic strategies targeting fibroblast proliferation and inflammation. Fibrinogen hydrogel (Fibrin glue, FG), a bioadhesive hydrogel, is widely used in pterygium surgery to secure conjunctival autografts. However, its low adhesion often leads to graft detachment, hindering effective repair. To overcome this limitation, we developed an injectable high-adhesion fibrin-silk glue (FG-GP-SF-Cur) by genipin-cross-linking silk fibroin (SF) into FG, enabling sustained release of the anti-inflammatory/antiproliferative drug curcumin (Cur). The material exhibited enhanced shear/tensile adhesion and prolonged Cur release (>10 days) in vitro, supported by FTIR and SEM analyses of its cross-linked structure. In primary pterygium fibroblasts, FG-GP-SF-Cur suppressed migration and proliferation by downregulating α-SMA, FN1, and COL3A1 while reducing VEGF/MMP2 via GSK3β/β-catenin pathway inhibition. Flow cytometry revealed its ability to promote anti-inflammatory M2 macrophage polarization, elevating IL-4/IL-10 and suppressing IL-1β/TNFα. In a corneal alkali burn model, FG-GP-SF-Cur effectively inhibited neovascularization and sustained M2 polarization, correlating with reduced inflammation and fibrosis. This study demonstrates FG-GP-SF-Cur as a dual-functional, high-adhesion biomaterial combining mechanical stability with controlled anti-inflammatory and antiproliferative drug delivery, offering a promising strategy to minimize pterygium recurrence and enhance surgical outcomes.