Sensory Nerve Regulation via H3K27 Demethylation Revealed in Akermanite Composite Microspheres Repairing Maxillofacial Bone Defect

Kaijun Gu; Yu Tan; Sitong Li; Siyue Chen; Kaili Lin; Yanmei Tang; Min Zhu

doi:10.1002/advs.202400242

Advanced Science (Aug 2024)

Sensory Nerve Regulation via H3K27 Demethylation Revealed in Akermanite Composite Microspheres Repairing Maxillofacial Bone Defect

Kaijun Gu,
Yu Tan,
Sitong Li,
Siyue Chen,
Kaili Lin,
Yanmei Tang,
Min Zhu

Affiliations

Kaijun Gu: Center of Craniofacial Orthodontics, Department of Oral and Cranio‐Maxillofacial Surgery, 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 Research Institute of Stomatology Shanghai 200011 China
Yu Tan: Department of Orthodontics, Shanghai Stomatological Hospital and School of Stomatology Fudan University Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, Fudan University Shanghai 200001 China
Sitong Li: Center of Craniofacial Orthodontics, Department of Oral and Cranio‐Maxillofacial Surgery, 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 Research Institute of Stomatology Shanghai 200011 China
Siyue Chen: Center of Craniofacial Orthodontics, Department of Oral and Cranio‐Maxillofacial Surgery, 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 Research Institute of Stomatology Shanghai 200011 China
Kaili Lin: Center of Craniofacial Orthodontics, Department of Oral and Cranio‐Maxillofacial Surgery, 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 Research Institute of Stomatology Shanghai 200011 China
Yanmei Tang: Center of Craniofacial Orthodontics, Department of Oral and Cranio‐Maxillofacial Surgery, 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 Research Institute of Stomatology Shanghai 200011 China
Min Zhu: Center of Craniofacial Orthodontics, Department of Oral and Cranio‐Maxillofacial Surgery, 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 Research Institute of Stomatology Shanghai 200011 China

DOI: https://doi.org/10.1002/advs.202400242
Journal volume & issue: Vol. 11, no. 30
pp. n/a – n/a

Abstract

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Abstract Maxillofacial bone defects exhibit intricate anatomy and irregular morphology, presenting challenges for effective treatment. This study aimed to address these challenges by developing an injectable bioactive composite microsphere, termed D‐P‐Ak (polydopamine‐PLGA‐akermanite), designed to fit within the defect site while minimizing injury. The D‐P‐Ak microspheres biodegraded gradually, releasing calcium, magnesium, and silicon ions, which, notably, not only directly stimulated the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) but also activated sensory nerve cells to secrete calcitonin gene‐related peptide (CGRP), a key factor in bone repair. Moreover, the released CGRP enhanced the osteogenic differentiation of BMSCs through epigenetic methylation modification. Specifically, inhibition of EZH2 and enhancement of KDM6A reduced the trimethylation level of histone 3 at lysine 27 (H3K27), thereby activating the transcription of osteogenic genes such as Runx2 and Osx. The efficacy of the bioactive microspheres in bone repair is validated in a rat mandibular defect model, demonstrating that peripheral nerve response facilitates bone regeneration through epigenetic modification. These findings illuminated a novel strategy for constructing neuroactive osteo‐inductive biomaterials with potential for further clinical applications.

Published in Advanced Science

ISSN: 2198-3844 (Online)
Publisher: Wiley
Country of publisher: Germany
LCC subjects: Science
Website: https://onlinelibrary.wiley.com/journal/21983844

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