Anti-inflammatory Peptide-Conjugated Silk Fibroin/Cryogel Hybrid Dual Fiber Scaffold with Hierarchical Structure Promotes Healing of Chronic Wounds.

Chronic wounds resulting from diabetes, pressure, radiation therapy, and other factors continue to pose significant challenges in wound healing. To address this, our study introduces a novel hybrid fibroin fibrous scaffold (FFS) comprising randomly arranged fibroin fibers and vertically aligned cryogel fibers (CF). The fibroin scaffold was efficiently degummed at room temperature and simultaneously formed a porous structure. The aligned cryogel fibers were produced via directional freeze-drying, achieved by controlling solution concentration and freezing polymerization temperature. The incorporation of aligned cryogel fibers into the expanded fibroin fiber scaffold led to enhanced cell infiltration both in vitro and in vivo, further elevating the hybrid scaffold's tissue compatibility. We also conjugated the anti-inflammatory peptide 1 (AP-1) 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 demonstrated 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 displayed epidermis thickness, numbers of regenerated hair follicles, and collagen density closer to normal skin tissue. Our findings highlight the potential of random fibroin fibers/aligned cryogel fibers hybrid fibrous scaffold as a promising approach for skin tissue filling and tissue regeneration. This article is protected by copyright. All rights reserved.