3D Printed High-Strength Hydrogel for Dual Release of Cu2+ and Ag+ Ions to Enhance Bone Repair and Antibacterial Properties

en This link goes to a English section zh This link goes to a Chinese section Bone restoration is often hindered by the spatiotemporal dysregulation of immune and regenerative signals. Conventional bio-inert implants, providing only passive support, fail to modulate this microenvironment, leading to infections and poor healing. To achieve proactive regulation of the osteo-immune niche alongside robust antimicrobial defense, we developed a novel 3D-printed, high-strength hydrogel composed of methacrylated silk fibroin (SFMA), copper-epigallocatechin gallate (Cu-EGCG), and silver nanoparticles (AgNPs), characterized by dual-ion release kinetics. A sophisticated staged-release strategy was engineered wherein the rapid initial burst of Cu 2+ establishes an immediate antimicrobial barrier and initiates early immunomodulation, whereas the sustained, long-term release of Ag + ensures continuous pathogen suppression. This “fast-and-slow” synergistic release profile effectively bridges the gap between acute-phase infection control and the requirement for a stable environment during chronic tissue maturation. In vitro studies confirmed that the hydrogel possesses superior mechanical integrity, biocompatibility, and potent antibacterial activity, significantly promoting the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). In vivo results demonstrated robust new bone formation, with near-complete anatomical restoration of critical-size bone defects achieved within 4 weeks in the experimental group. Transcriptomic analysis further elucidated the underlying mechanism, revealing that the SFMA/Cu-EGCG/AgNPs hydrogel significantly reshaped gene expression profiles associated with immunity and osteogenesis. By activating immune-regulatory pathways—specifically IL-17 and TGF-β—the hydrogel successfully orchestrated a pro-regenerative immune microenvironment. Simultaneously, the significant enrichment of Wnt signaling and ossification-related pathways confirmed its dual-functional role in accelerating bone regeneration at the molecular level. In summary, this hydrogel facilitates a synergistic “infection control-immunomodulation-osteogenesis” tripartite repair strategy, offering a highly promising biomimetic approach for the clinical management of complex bone defects. 摘要 en This link goes to a English section zh This link goes to a Chinese section 骨缺损修复过程常受到免疫反应与再生信号时空失调的显著制约。传统生物惰性植入材料仅提供被动结构支撑,难以有效调控局部微环境,易导致感染发生及组织修复不良。针对上述问题,该研究构建了一种新型3D打印高强度水凝胶体系,由甲基丙烯酰化丝素蛋白(SFMA)、铜-表没食子儿茶素没食子酸酯复合物(Cu-EGCG)及银纳米颗粒(AgNPs)组成,具有双离子协同释放特性。通过构建分阶段释放策略,实现了Cu 2+ 与Ag + 的“快-慢协同”调控:初期快速释放的Cu 2+ 可迅速建立抗菌屏障并启动早期免疫调节,而Ag + 的持续释放则维持长期抗菌效应,从而有效衔接急性感染控制与后期组织稳定再生过程。体外实验表明,该水凝胶具有优异的力学性能与生物相容性,并表现出显著的抗菌活性,同时能够促进骨髓间充质干细胞(BMSCs)的增殖与成骨分化。体内实验结果显示,实验组在4周内实现了临界尺寸骨缺损的近完全结构修复。转录组分析进一步揭示其作用机制:SFMA/Cu-EGCG/AgNPs水凝胶显著重塑了与免疫调控及成骨相关的基因表达谱,通过激活IL-17与TGF-β信号通路,构建促再生免疫微环境; 同时,Wnt信号通路及骨形成相关通路的显著富集,证实其在分子水平上具有促进骨再生的双重功能。综上,该水凝胶通过构建“抗感染—免疫调控—成骨再生”协同修复策略,为复杂骨缺损的临床治疗提供了一种具有重要应用前景的仿生材料新方案。