Self-assembly of chlorogenic acid into hydrogel for accelerating wound healing.

Wound healing remains a considerable challenge due to its complex inflammatory microenvironment. Developing novel wound dressing materials with superior wound repair capabilities is highly required. However, conventional dressing hydrogels for wound healing are often limited by their complex cross-linking, high treatment costs, and drug-related side effects. In this study, we report a novel dressing hydrogel constructed only by the self-assembly of chlorogenic acid (CA). Molecular dynamic simulation studies revealed the formation of CA hydrogel was mainly through non-covalent interactions, such as π-π and hydrogen bond. Meanwhile, CA hydrogel exhibited superior self-healing, injectability, and biocompatibility properties, making it a promising candidate for wound treatment. As expected, in vitro experiments demonstrated that CA hydrogel possessed remarkable anti-inflammatory activity, and its ability to promote the generation of microvessels in HUVEC cells, as well as the promotion of microvessel formation in HUVEC cells and proliferation of HaCAT cells. Subsequent in vivo investigation further demonstrated that CA hydrogel accelerated wound healing in rats through regulating macrophage polarization. Mechanistically, the CA hydrogel treatment enhanced the closure rate, collagen deposition, and re-epithelialization while simultaneously suppressing the secretion of pro-inflammatory cytokines and increasing the production of CD31 and VEGF during the wound healing process. Our findings indicate that this multifunctional CA hydrogel is a promising candidate for wound healing, particularly in cases of impaired angiogenesis and inflammatory responses.