Piezoelectric stimulation enhances bone regeneration in alveolar bone defects through metabolic reprogramming of macrophages
Baiyan Sui,
Tingting Ding,
Xingyi Wan,
Yuxiao Chen,
Xiaodi Zhang,
Yuanbo Cui,
Jie Pan,
Linlin Li,
Xin Liu
Affiliations
Baiyan Sui
Department of Dental Materials Shanghai Biomaterials Research and Testing Center Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology Shanghai China
Tingting Ding
Department of Dental Materials Shanghai Biomaterials Research and Testing Center Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology Shanghai China
Xingyi Wan
Beijing Institute of Nanoenergy and Nanosystems Chinese Academy for Sciences Beijing China
Yuxiao Chen
Department of Dental Materials Shanghai Biomaterials Research and Testing Center Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology Shanghai China
Xiaodi Zhang
Institute for Cell Engineering Department of Neurology Johns Hopkins University School of Medicine Baltimore Maryland USA
Yuanbo Cui
Leavey School of Business Santa Clara University Santa Clara California USA
Jie Pan
Department of Orthodontics, Shanghai Stomatological Hospital and School of Stomatology Fudan University Shanghai China
Linlin Li
Beijing Institute of Nanoenergy and Nanosystems Chinese Academy for Sciences Beijing China
Xin Liu
Department of Dental Materials Shanghai Biomaterials Research and Testing Center Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology Shanghai China
Abstract Immunomodulation has emerged as a promising strategy for promoting bone regeneration. However, designing osteoimmunomodulatory biomaterial that can respond to mechanical stress in the unique microenvironment of alveolar bone under continuous occlusal stress remains a significant challenge. Herein, a wireless piezoelectric stimulation system, namely, piezoelectric hydrogel incorporating BaTiO3 nanoparticles (BTO NPs), is successfully developed to generate piezoelectric potentials for modulating macrophage reprogramming. The piezoelectric stimulation reprograms macrophages towards the M2 phenotype, which subsequently induces osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). RNA sequencing analysis reveals that piezoelectricity‐modulated macrophage M2 polarization is closely associated with metabolic reprogramming, including increased amino acid biosynthesis and fatty acid oxidation. The composite hydrogel with excellent biocompatibility exhibits immunomodulatory and osteoinductive activities. In a rat model of alveolar bone defects, the piezoelectric hydrogel effectively promotes endogenous bone regeneration at the load‐bearing sites. The piezoelectric‐driven osteoimmunomodulation proposed in this study not only broadens understanding of the mechanism underlying piezoelectric biomaterials for tissue regeneration but also provides new insights into the design and development of next‐generation immunomodulatory biomaterials.
