Remodeling Electrophysiological Microenvironment for Promoting Bone Defect Repair via Electret Hybrid Electrospun Fibrous Mat

Abstract

Improving the osteogenic properties of bone grafts plays a critical role in the repair and functional restoration of critical-sized bone defects. The endogenous electric field, one of the most crucial physiological signals, has been confirmed to maintain physiological function and reconstruct the structure of bone, which is inadequate in bone defect sites. Strategies for the development of electroactive osteogenic biomaterials arise to remodel and promote the electrophysiological microenvironment. Among the electroactive materials, electret biomaterials can provide a stable and persistent endogenous electrical stimulation, which better conforms to the physiological microenvironment and has long-term effectiveness in the bone repair process. Herein, an electret hybrid electrospun fibrous mat (EHFM) was developed to mimic the structure of the natural extracellular matrix (ECM) with a suitable and persistent electrophysiological microenvironment. The EHFM was constructed with a core–shell structure, in which silicon dioxide electrets were loaded in the core-layer to remodel and maintain the electrical microenvironment over the long term. The EHFM significantly promoted the osteogenesis of bone mesenchymal stem cells (BMSCs) in vitro and showed remarkable ability in bone repair, which was three times better than that of the control group in a critical-sized rat calvarial defect model. Furthermore, it was verified that EHFM-derived osteogenesis was related to the activation of the calcium ion-sensing receptor (CaSR), while increasing intracellular calcium ion concentration of BMSCs. This study puts forward a novel engineering strategy to promote bone defect repair by remodeling a stable and persistent electrophysiological microenvironment, showing potential for clinical applications.

Graphical Abstract

References

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Funding

National Natural Science Foundation of China(52203309); Science and Technology Commission of Shanghai Municipality(21490711700); Cross Disciplinary Research Fund of Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine(JYJC202219); Shanghai's Top Priority Research Center(2022ZZ01017); CAMS Innovation Fund for Medical Sciences(2019-I2M-5-037); Fund of Department of Oral and Maxillofacial Surgery(Department 2022-04); Fundamental Research Funds for the Central Universities(2232022D-09)