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

en This link goes to a English section zh This link goes to a Chinese section 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. 摘要 en This link goes to a English section zh This link goes to a Chinese section 感染性骨缺损具有抗感染与促成骨双重治疗诉求,是临床上的一大挑战。传统的系统性抗生素给药方案往往导致局部药物浓度不足且骨修复延迟。在此,我们构建了一种创新的仿生复合水凝胶平台,该平台利用木质素的生物活性和结构多样性,实现了抗菌与成骨能力的同步增强。该平台的核心特征在于通过反溶剂沉淀自组装策略制备均一分散的载万古霉素木质素纳米颗粒。通过紫外光交联、氯化钙离子交联以及氢氧化钠/冷冻物理交联等多重网络交联策略,并将VCM@KLNPs整合至可注射的聚乙烯醇/海藻酸钠/丙烯酰胺互穿网络水凝胶中,从而有效促进了细胞的粘附与增殖。实验结果表明,该复合凝胶使金黄色葡萄球菌减少了97.8%; 同时,碱性磷酸酶活性提升了4.36倍,矿化结节形成量增加了4.89倍,且成骨相关标记物的表达显著上调。通过大鼠皮肤感染模型和颅骨缺损模型,进一步验证了其体内双重治疗功效。组织学分析证实,在细菌负荷显著降低的同时,形成了结构致密的松质骨。本研究开发了一种极具前景的木质素基微平台,用以克服临床治疗感染性骨缺损的屏障,具有巨大的临床转化潜力。