Dual‐Bioactive Lignin‐Based Microcarrier Hydrogel Platform via Metal Salt Crosslinking for Synchronized Infection Eradication and Bone Regeneration

ABSTRACT Infected bone defects represent a dual therapeutic challenge demanding concurrent infection inhibition and osteogenesis promotion. Systemic antibiotic administration is taken as a classical treatment protocol but often yields inadequate local antibiotic concentrations and delayed bone repair. Herein, we introduce a pioneering biomimetic composite hydrogel platform that exploits the bioactivity and structural versatility of lignin to deliver simultaneous enhanced antimicrobial and osteogenic capacity. This platform features self‐assembled monodisperse vancomycin‐loaded lignin nanoparticle (VCM@KLNPs), engineered via a solvent temporal self‐assembly strategy. Integration of VCM@KLNPs into injectable polyvinyl alcohol/acrylamide interpenetrating hydrogel based on multiple strategies, via UV photo‐crosslinking, CaCl 2 ionically‐crosslinking, and NaOH/Freezing physical crosslinking, enabling promoted cellular adhesion and proliferation. The resulting composite gel exhibits 97.8% reduction of Staphylococcus aureus , while a 4.36‐fold elevation in alkaline phosphatase activity, 4.89‐fold mineralized nodule formation, and upregulated expression of osteogenesis‐related markers ( p < 0.01). The dual in vivo therapeutic efficacy was further validated using infected skin wounds and critical‐sized calvarial defect models. Histological analyses confirmed the emergence of robust trabecular bone with a marked reduction in bacterial burden. Our work develops a promising lignin‐based micro‐platform to overcome the barriers in managing infected bone defects, with great potential for clinical translation.