An all-in-one “multifunctional hydrogel”: Through antibacterial, anti-inflammatory, and angiogenic to promoting MRSA-infected bone defect repair

Abstract

Recently, in situ injectable hydrogels have emerged as a promising approach for bone defect healing. However, bone defect healing involves immunomodulation, angiogenesis, and osteogenic differentiation. Furthermore, the repair process is complicated by bacterial infections. Therefore, integrated treatment strategies are urgently needed to attain satisfactory therapeutic outcomes. This study presents an all-in-one multifunctional in situ injectable hydrogel (C/O/Sr/MA hydrogel) designed to repair MRSA-infected bone defects. Notably, carboxymethylated chlorogenic acid insect chitosan (ECCS-CA) exhibited an inhibitory effect on MRSA growth and formed complexes with Sr²⁺ through metal–ligand bonding. This interaction resulted in a notable reduction in inflammation, accompanied by a shift in macrophage polarization towards the M2 phenotype and enhanced vascularization and bone regeneration. Moreover, ECCS-CA was crosslinked with methacrylic anhydride-oxidized chondroitin sulfate (OCS-MA) via dynamic Schiff base. The cross-linking process enabled the C/O/Sr/MA hydrogel to effectively fill irregularly shaped bone defect sites upon injection and further improved its mechanical properties following UV curing. In rat models of MRSA-infected bone defects, the C/O/Sr/MA hydrogel demonstrated remarkable therapeutic efficacy, promoting bone regeneration, angiogenesis, and collagen deposition while inhibiting inflammatory responses. Overall, this all-in-one multifunctional hydrogel shows excellent promise for bone defect healing.