Chitosan and hyaluronic acid based injectable dual network hydrogels - Mediating antimicrobial and inflammatory modulation to promote healing of infected bone defects

Abstract

In bone defects, infections lead to excessive inflammation, increased bacterial, and bone lysis, resulting in irregular wounds that hinder new bone regeneration. Injectable bioactive materials with adequate antimicrobial activity and strong osteogenic potential are urgently required to remedy irregular defects, eradicate bacteria, and facilitate the generation of new bone tissue. In this research, injectable dual-network composite hydrogels consisting of sulfated chitosan, oxidized hyaluronic acid, β-sodium glycerophosphate, and CuSr doped mesoporous bioactive glass loaded with bone morphogenetic protein (CuSrMBGBMP-2) were utilized for the first time to treat infectious bone defects. Initially, the hydrogel was injected into the wound at 37 °C with minimal invasion to establish a stable state and prevent hydrogel loss. Subsequently, sulfated chitosan eliminated bacteria at the wound site and facilitated cell proliferation with oxidized hyaluronic acid. Additionally, CuSrMBGBMP-2 strengthened antibacterial properties, regulated inflammatory reactions, promoted angiogenesis and osteogenic differentiation, addressing the deficiency in late-stage osteogenesis. Specifically, the injectable dual-network hydrogel based on chitosan and hyaluronic acid is minimally invasive, offering antibacterial, anti-inflammatory, pro-angiogenic, and bone regeneration properties. Therefore, this hydrogel with injectable dual network properties holds great promise for the treatment of bone infections in the future.