Photo-crosslinking modified gelatin-silk fibroin hydrogel for accelerating wound repair of open abdomen

Abstract

Open abdomen (OA), a major advance in modern trauma surgery, enables the treatment of severe abdominal trauma, infections, and hypertension by temporarily closing the abdominal cavity without suturing. Although OA can reduce mortality rates, it also presents challenges such as disruption of the abdominal environment, intestinal exposure, and impaired wound healing. Current temporary abdominal closure (TAC) techniques using polypropylene (PP) mesh are susceptible to abrasion and rupture of the intestine, leading to adhesions and serious complications such as intestinal fistulas and chronic wounds. These complications seriously impact outcomes due to mesh rigidity and its incompatibility with surrounding tissues. In this study, we designed a multifunctional hydrogel composed of GelMA (Gelatin Methacryloyl) and SilMA (Silk Fibroin Methacryloyl) as a promising solution for open abdominal wound repair. In vitro experiments confirmed the biocompatibility, self-healing properties, pro-angiogenic effects, and promotion of macrophage polarization. In vivo studies revealed that the GelMA-SilMA hydrogel could enhance abdominal wall tissue thickness and integrity via isolating the peritoneal cavity, protecting the intestinal tract, polarizing macrophages, promoting collagen formation, inducing neovascularization, inhibiting oxidative stress, and suppressing inflammation. Furthermore, immunofluorescence, immunohistochemistry, and RNA sequencing were employed to evaluate the wound healing mechanisms of GelMA-SilMA hydrogels. The results demonstrated that the hydrogels can promote angiogenesis, inhibit inflammation and immune responses, and enhance wound healing by activating the HIF-a-VEGF signaling pathway, RAP1 signaling pathway, and PI3K-AKT signaling pathway. Hence, the multifunctional GelMA-SilMA hydrogel has tremendous potential for clinical use in open abdominal wound repair.