Physicochemically Cross-linked Injectable Hydrogel: an Adhesive Skin Substitute for Burned Wound Therapy

Burns carry a large surface area, varying in shapes and depths, and an elevated risk of infection. Regardless of the underlying etiology, burns pose significant medical challenges and a high mortality rate. Given the limitations of current therapies, tissue-engineering-based treatments for burns are inevitable. Herein, we developed a natural physicochemically cross-linked adhesive injectable skin substitute (SS) comprising chitosan (Ch) and silk fibroin (SF), cross-linked with tannic acid (TA) through hydrogen bonding, and incorporated with fresh platelet-rich fibrin (FPRF). SF was also chimerically cross-linked with riboflavin (RF) under visible light to ensure desirable biodegradability rate and nontoxicity. Double cross-linked SS exhibited a semibilayer (SBSS) structure with smaller pores in the upper layer. In the CaCl₂-treated FPRF, the activated platelets augmented vascular endothelial growth factor (VEGF) and platelet-derived GF (PDGF) release. The resultant SBSS possessed optimal adhesion, hemocompatibility, and significant antibacterial and antioxidant activities (P ≤ 0.05). The rat liver injury model confirmed the rapid hemostatic effect of SBSS. Furthermore, the bottom layer of SBSS promoted L929 fibroblast growth, proliferation, and migration. SBSS-treated wounds showed lower inflammatory cells, earlier epithelialization, significant angiogenesis, and faster healing. The proposed SBSS could be an ideal remedy for burn wound therapy.