Single-cell RNA-sequencing-guided reactive oxygen species-scavenging hydrogel design for regeneration of osteoporotic bone

The pathological microenvironment of osteoporosis poses a substantial clinical challenge for bone defect regeneration. Through single-cell RNA-sequencing (scRNA-seq) analysis, we identified a reactive oxygen species (ROS)-overloading osteoblast subpopulation as a critical pathological feature of osteoporotic niches. Guided by scRNA-seq analysis, we engineered a microenvironment-adaptive hydrogel system through precise integration of antioxidant curcumin-encapsulated zeolitic imidazolate framework-8 nanoparticles (CCM@ZIF-8 NPs) within photo-crosslinkable alginate methacrylate (AlgMA) hydrogel (AlgMA/CCM@ZIF-8). This engineered design exhibited dual functions: effectively scavenging ROS in bone marrow-derived mesenchymal stem cells (BMSCs) while simultaneously suppressing osteoclast differentiation. The osteo-regenerative superiority of the AlgMA/CCM@ZIF-8 nanocomposite hydrogel was conclusively demonstrated in bone defect models of osteoporotic mice. This scRNA-seq-informed engineering strategy offers a promising approach for developing pathophysiology-adapted biomaterials to promote regenerative repair in osteoporotic bone defects. 骨质疏松症的特殊病理微环境为骨缺损再生带来了巨大的临床挑战。通过单细胞转录组测序技术本研究发现活性氧（ROS）过载的成骨细胞亚群是骨质疏松微环境的关键病理特征。在此基础上，本研究将姜黄素包裹的沸石咪唑酯框架-8（CCM@ZIF-8）纳米颗粒整合到光交联甲基丙烯酰化海藻酸盐（AlgMA）水凝胶中，构建了一种微环境自适应水凝胶系统（AlgMA/CCM@ZIF-8）。该设计展现出有效清除骨髓间充质干细胞ROS过载和抑制破骨细胞分化的双重功能，且其骨再生优势在骨质疏松小鼠骨缺损模型中得到明确验证。这种基于单细胞转录组测序分析的工程策略为开发适配病理生理学特征的生物材料以促进骨质疏松性骨缺损的再生修复，创立了极具前景的新方法。