Development of a multifunctional nano-hydroxyapatite platform (nHEA) for advanced treatment of severely infected full-thickness skin wounds

Abstract

The treatment of full-thickness skin injuries complicated by severe infection is hampered by the lack of comprehensive solutions that can regulate the various stages of wound healing. Consequently, there is an urgent need for a multifunctional dressing capable of multi-level regulation. In this study, we propose a novel solution by covalently integrating ε-poly-l-lysine-grafted gallic acid (EG) and in situ bioreduced silver nanoparticles (AgNPs) onto nano-hydroxyapatite (nHAP), thereby developing a multi-layered, multifunctional nanoplatform (nHEA). Cell experiments have shown that, compared to nHAP and nHAP loaded only with EG (nHEG), the addition of AgNPs to nHEA confers excellent antibacterial properties while maintaining optimal biocompatibility. The incorporation of EG onto nHEG and nHEA imparts antioxidation, anti-inflammatory, and pro-angiogenic functions, and the release of Ca2+ and EG further enhances fibroblast migration and collagen secretion. In a rat model of full-thickness skin injury with severe infection, nHEA demonstrates remarkable antibacterial and anti-inflammatory effects, along with promoting collagen remodeling and regeneration. Together, both cell experiments and animal studies confirm the significant potential of this innovative multifunctional nanoplatform in the treatment of full-thickness skin injuries with severe infection. Statement of significanceTreating infected full-thickness skin injuries poses a longstanding challenge due to the lack of comprehensive solutions that can regulate different stages of wound healing. This study introduces a novel multifunctional nanoplatform, nHEA, developed by covalently integrating ε-poly-l-lysine grafted with gallic acid (EG) and in situ bioreduced AgNPs onto nano-hydroxyapatite (nHAP). Cell experiments reveal that the integration of AgNPs enhances nHEA's antibacterial performance while maintaining optimal biocompatibility. The inclusion of EG bestows antioxidant, inflammation-regulating, and angiogenetic properties upon nHEA, and the release of Ca2+ and EG stimulates the migration and collagen secretion of fibroblast cells. Consequently, nHEA exhibits superior antibacterial and inflammation-regulating efficacy, and stimulates collagen remodeling and regeneration in vivo, making it a promising treatment for severely infected skin injuries.