Biomimetic peptide dynamic hydrogel inspired by humanized defensin nanonets as the wound-healing gel coating

Abstract

Clinical treatment of chronic wounds, particularly those prone to relapse, has been hampered by the regeneration, infection complications, and malignant transformation of disordered tissue adhesions. At the surface of intestinal endothelial, human defensins self-assemble into higher-order nanonets that defend host cells, fight inflammation and promote wound healing. Inspired by this antimicrobial nanostructured network, we herein attempted to construct an antimicrobial nanonet with hemostatic function integrated as wound dressing. Aiding by molecular docking and dynamics analysis, we designed a hemostatic nanogel called ACFP, which was constructed by spontaneously assembling two RADA16-based hydrogelators with one θ-defensin-derived peptide motif. As expected, ACFP possesses antimicrobial properties derived from the nanonet structure of defensin, as well as the ability to prevent bleeding and effectively promote wound healing. As an injectable biocompatible hydrogel, ACFP successfully treated chronic epidermal wounds associated with multiple bacterial infections, and promoted healing of a complicated intraperitoneal wound involving the cecum and adjacent abdominal walls while preventing tissue adhesion. In addition to providing a comprehensive therapeutic approach with tremendous clinical potential for chronic wound therapy, ACFP may encourage the development of biomimetic peptide hydrogels with multiple functions against a wide range of human diseases.