A hydrogel tissue adhesive incorporating basic fibroblast growth factor-loaded liposomes accelerates cutaneous wound healing by enhancing cell proliferation, collagen synthesis and angiogenesis.

Abstract

Tissue adhesives have become substitutes or adjuvants for surgical sutures owing to their minimal tissue damage and ease of application. However, limitations remain for existing tissue adhesives, such as weak adhesion strength, potential toxicity, and lack of bioactivities to promote wound healing. Here, we developed an injectable and biocompatible hydrogel tissue adhesive incorporating basic fibroblast growth factor (bFGF)-loaded liposomes for sutureless wound closure and promoting wound healing. The hydrogel, formed by 10 %(w/v) human serum albumin (HSA) and o-phthalaldehyde (OPA)-functionalized four-arm poly(ethylene glycol) (4aPEG-OPA) through irreversible OPA/amine condensation reaction, demonstrated strong tissue adhesion properties, biodegradability (complete degradation in PBS containing 1 U/mL elastase within 10 days), and biocompatibility. The hydrogel incorporating bFGF-loaded liposomes achieved sustained release of bFGF (cumulative release ratio of 65.4 % over 8 days), and promoted cell proliferation, migration, collagen production, and angiogenesis. In rat and porcine full-thickness skin incision models, the hydrogel effectively closed the wounds and facilitated wound healing within 14 days, outperforming commercially available fibrin glue and cyanoacrylate adhesives. RNA sequencing and western blotting analysis demonstrated that the hydrogel stimulated cell proliferation, collagen production, and angiogenesis. Overall, this hydrogel tissue adhesive shows great potential for encouraging wound closure without suture and promoting wound healing. STATEMENT OF SIGNIFICANCE: This study introduces a multifunctional tissue-adhesive hydrogel formed by covalent cross-linking of human serum albumin with o-phthalaldehyde (OPA)-terminated four-arm poly(ethylene glycol), and incorporated with bFGF-loaded liposomes. The catalyst-free OPA/amine reaction used in its synthesis ensures a mild and controllable gelation process, which is beneficial for maintaining the bioactivity of encapsulated growth factors. This composite system exhibited sustained growth factor release profile and remarkable bioactivity in regulating skin cell behaviors, which facilitates easier clinical translation compared to existing approaches. In rat and porcine models, it achieved sutureless wound healing and outperformed commercial adhesives in promoting re-epithelialization and angiogenesis, offering a promising alternative to traditional sutures and commercial adhesives.