Anti‐Inflammatory Peptide‐Conjugated Silk Fibroin/Cryogel Hybrid Dual Fiber Scaffold with Hierarchical Structure Promotes Healing of Chronic Wounds

Abstract Chronic wounds resulting from diabetes, pressure, radiation therapy, and other factors continue to pose significant challenges in wound healing. To address this, this study introduces a novel hybrid fibroin fibrous scaffold (FFS) comprising randomly arranged fibroin fibers and vertically aligned cryogel fibers (CFs). The fibroin scaffold is efficiently degummed at room temperature and simultaneously formed a porous structure. The aligned CFs are produced via directional freeze‐drying, achieved by controlling solution concentration and freezing polymerization temperature. The incorporation of aligned CFs into the expanded fibroin fiber scaffold leads to enhanced cell infiltration both in vitro and in vivo, further elevating the hybrid scaffold's tissue compatibility. The anti‐inflammatory peptide 1 (AP‐1) is also conjugated to the hybrid fibrous scaffold, effectively transforming the inflammatory status of chronic wounds from pro‐inflammatory to pro‐reparative. Consequently, the FFS‐AP1+CF group demonstrates superior granulation tissue formation, angiogenesis, collagen deposition, and re‐epithelialization during the proliferative phase compared to the commercial product PELNAC. Moreover, the FFS‐AP1+CF group displays epidermis thickness, number of regenerated hair follicles, and collagen density closer to normal skin tissue. These findings highlight the potential of random fibroin fibers/aligned CFs hybrid fibrous scaffold as a promising approach for skin tissue filling and tissue regeneration.