Dual photo-enhanced interpenetrating network hydrogel with biophysical and biochemical signals for infected bone defect healing

Abstract The healing of infected bone defects (IBD) is a complex physiological process involving a series of spatially and temporally overlapping events, including pathogen clearance, immunological modulation, vascularization and osteogenesis. Based on the theory that bone healing is regulated by both biochemical and biophysical signals, in this study, we developed a copper doped bioglass (CuBGs)/methacryloyl-modified gelatin nanoparticle (MA-GNPs)/methacrylated silk fibroin (SilMA) hybrid hydrogel to promote IBD healing. This hybrid hydrogel demonstrated a dual-photocrosslinked interpenetrating network mechanism, wherein the photocrosslinked SilMA as the main network ensured structural integrity, and the photocrosslinked MA-GNPs colloidal network increased strength and dissipated loading forces. In an IBD model, the hydrogel exhibited excellent biophysical characteristics, such as adhesion, adaptation to irregular defect shapes, and in situ physical reinforcement. At the same time, by sequentially releasing biological biomimetic signals such as Cu 2+ , Ca 2+ , and Si 2+ ions from CuBGs on demand, the hydrogel spatiotemporally coordinated antibacterial, immunomodulatory and bone remodeling events, efficiently removing infection and accelerating bone repair without the use of antibiotics or exogenous recombinant proteins. Therefore, the hybrid hydrogel can be used as a simple and effective method for the treatment of IBD.