Endogenous Metal Ion‐Enriched Immunostimulating Biomimetic Scaffold Improves In Situ Bone Regeneration
Abstract
ABSTRACT Effective in situ regeneration and functional reconstruction of large‐scale bone defects remain a formidable clinical challenge. The endogenous metal ions have been shown to critically regulate immune responses and bone remodeling, but methods for precisely regulating the spatiotemporal recruitment dynamics of endogenous ions are still lacking. Here, we develop a novel endogenous metal ion‐enriched immunostimulation‐amplified bone biomimetic scaffold (emia‐BBS) based on the hierarchical multi‐level assembly of nano‐hydroxyapatites (nHAs), collagen fibrils, and mussel adhesion proteins (MAPs). The emia‐BBS not only mimics the nanostructure and mechanical properties of native bone, but notably, the assembled MAPs endow emia‐BBS with abundant lysine and dopamine chemical structures, enabling efficient capture of endogenous metal ions to amplify ion‐mediated immunomodulation. Functionally, in large‐scale mandibular defects, emia‐BBS‐induced enrichment of endogenous metal ions could recruit and reprogram macrophages, thereby enhancing the innate immune response. These M2 macrophages, recruited by the emia‐BBS‐metal ion complex, in turn, facilitate the recruitment and osteogenic activation of endogenous LepR⁺ skeletal stem cells via the CCL5/CCR5/STAT3 axis. This study introduces an immunomodulatory strategy that harnesses endogenous ion dynamics to amplify regenerative signals, providing a precisely guided and clinically applicable approach for critical‐sized bone defect repair.
Article Details
Authors (16)
Min Yu
Liyuan Chen
School of Chemistry and Chemical Engineering Chongqing University Chongqing 401331 P. R. China
Xinjia Cai
Shengjie Cui
Department of General Dentistry Peking University School and Hospital for Stomatology Beijing P. R. China
Zixin Li
College of Chemistry and Materials
Chengye Ding
Central Laboratory, Department of Orthodontics Peking University School and Hospital for Stomatology, National Center for Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing Key Laboratory of Digital Stomatology, Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health, NMPA Key Laboratory for Dental Materials, National Engineering Research Center of Oral...
He Zhang
Hangbo Liu
Chang Li
Shiying Zhang
School of Chemical Sciences
Xinmeng Shi
Central Laboratory, Department of Orthodontics Peking University School and Hospital for Stomatology, National Center for Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing Key Laboratory of Digital Stomatology, Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health, NMPA Key Laboratory for Dental Materials, National Engineering Research Center of Oral...
Ting Zhang
Yunsong Liu
Department of Prosthodontics Peking University School and Hospital for Stomatology, National Center for Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing Key Laboratory of Digital Stomatology, Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health, NMPA Key Laboratory for Dental Materials, National Engineering Research Center of Oral Biomaterials and...
Dan Luo
Power Battery & Systems Research Center, State Key Laboratory of Catalysis
Yan Liu
Yongsheng Zhou
Department of Prosthodontics Peking University School and Hospital for Stomatology, National Center for Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing Key Laboratory of Digital Stomatology, Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health, NMPA Key Laboratory for Dental Materials, National Engineering Research Center of Oral Biomaterials and...