Yang Jianqiu, Du Lei, Du Hui, Yang Ganghua, Fu Weicong, Zhai Liang, Yang Zhuoyuan, Chen Shixuan, Yang Qining, Wan Wenbing
Department of Orthopaedic Surgery, Institute of Orthopedics of Jiangxi Province and Jiangxi Provincial Key Laboratory of Spine and Spinal Cord Disease, the Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330006, China.
Zhejiang Engineering Research Center for Tissue Repair Materials, Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, Zhejiang, 325000, China.
Adv Mater. 2025 Jul 2:e2502919. doi: 10.1002/adma.202502919.
Bone regeneration remains a significant clinical challenge due to the complexity of the bone healing process and the need for biomaterials that provide both structural support and immunomodulatory functions. Here, a bioinspired immunomodulatory scaffold is developed, composed of mineralized decellularized lotus stalks (MDL) integrated with manganese carbonyl (MnCO)-loaded mesoporous polydopamine (mPDA) microspheres (MM@MDL3). This scaffold mimics the hierarchical architecture of natural bone while offering controlled CO and Mn release, promoting M2 macrophage polarization, reducing inflammation, and enhancing osteogenesis. In vitro studies demonstrate that MM@MDL3 effectively promotes mesenchymal stem cell (MSC) differentiation by activating the BMP2/SMAD/RUNX2 pathway. In vivo rat calvarial defect models confirm significant bone regeneration, with increased bone volume, enhanced vascularization, and reduced osteoclastogenesis. These results demonstrate MM@MDL3 as a promising strategy for large-segment bone defect repair by integrating a biomimetic structure with immunomodulatory and osteogenic properties. The proposed scaffold has great potential for treating clinical large-segment bone defects.
由于骨愈合过程的复杂性以及对既能提供结构支持又具有免疫调节功能的生物材料的需求,骨再生仍然是一项重大的临床挑战。在此,开发了一种受生物启发的免疫调节支架,它由矿化脱细胞莲茎(MDL)与负载羰基锰(MnCO)的介孔聚多巴胺(mPDA)微球(MM@MDL3)整合而成。这种支架模仿天然骨的分层结构,同时实现可控的CO和Mn释放,促进M2巨噬细胞极化,减轻炎症并增强成骨作用。体外研究表明,MM@MDL3通过激活BMP2/SMAD/RUNX2途径有效促进间充质干细胞(MSC)分化。体内大鼠颅骨缺损模型证实了显著的骨再生,骨体积增加、血管生成增强且破骨细胞生成减少。这些结果表明,MM@MDL3通过将仿生结构与免疫调节和成骨特性相结合,是修复大段骨缺损的一种有前景的策略。所提出的支架在治疗临床大段骨缺损方面具有巨大潜力。