Enhancing Chronic Wound Healing through Engineering Mg2+-Coordinated Asiatic Acid/Bacterial Cellulose Hybrid Hydrogels

Infectious chronic wounds have gradually become a major clinical problem due to their high prevalence and poor treatment outcomes. The urgent need for wound dressings with immune modulatory, antibacterial, and angiogenic properties has led to the development of innovative solutions. Asiatic acid (AA), derived from herbs, has demonstrated excellent antibacterial, anti-inflammatory, and angiogenic effects, making it a promising candidate for incorporation into hydrogel carriers for wound healing. However, there is currently no available report on AA-based self-assembled hydrogels. Here, a novel hybrid hydrogel dressing consists of interpenetrating polymer networks composed of self-assembled magnesium ion (Mg2+) coordinated asiatic acid (AA-Mg) and bacterial cellulose (BC) is developed to promote infected chronic wound healing. A natural carrier-free self-assembled AA-Mg hydrogel with good injectable and self-healing properties could maintain the sustained release of AA and Mg2+ over an extended period. Notably, the introduction of Mg2+ boosted some pharmacological effects of self-assembled hydrogels due to its excellent anti-inflammatory and angiogenesis. In vitro studies confirmed the exceptional biocompatibility, antibacterial efficacy, and anti-inflammatory potential of the AA-Mg/BC hybrid hydrogel, which also exhibited a commendable mechanical strength. Furthermore, in vivo biological results displayed that the hybrid hydrogel significantly accelerated the wound healing process by boosting dense and organized collagen deposition and the granulation tissue and benefiting revascularization. The introduced self-assembled AA-Mg-based hydrogel offers a promising solution for the effective management of chronic wounds. This universal strategy for the preparation of self-assembled hydrogels modulated with bioactive divalent metal ions is able to excavate more herbal small molecules to construct new self-assembled biomaterials.