Hierarchical Intrafibrillarly Mineralized Collagen Membrane Promotes Guided Bone Regeneration and Regulates M2 Macrophage Polarization

Yaowei Xuan; Lin Li; Muzhi Ma; Junkai Cao; Zhen Zhang

doi:10.3389/fbioe.2021.781268

Hierarchical Intrafibrillarly Mineralized Collagen Membrane Promotes Guided Bone Regeneration and Regulates M2 Macrophage Polarization

Front Bioeng Biotechnol. 2022 Jan 26:9:781268. doi: 10.3389/fbioe.2021.781268. eCollection 2021.

Authors

Yaowei Xuan^{1

2}, Lin Li^{1

2}, Muzhi Ma³, Junkai Cao², Zhen Zhang³

Affiliations

¹ Medical School of Chinese PLA, Beijing, China.
² Department of Stomatology, The First Medical Centre, Chinese PLA General Hospital, Beijing, China.
³ Department of Oral and Maxillofacial-Head and Neck Oncology, 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

Mineralized collagen has been introduced as a promising barrier membrane material for guided bone regeneration (GBR) due to its biomimetic nanostructure. Immune interaction between materials and host significantly influences the outcome of GBR. However, current barrier membranes are insufficient for clinical application due to limited mechanical or osteoimmunomodulatory properties. In this study, we fabricated hierarchical intrafibrillarly mineralized collagen (HIMC) membrane, comparing with collagen (COL) and extrafibrillarly mineralized collagen (EMC) membranes, HIMC membrane exhibited preferable physicochemical properties by mimicking the nanostructure of natural bone. Bone marrow mesenchymal stem cells (BMSCs) seeded on HIMC membrane showed superior proliferation, adhesion, and osteogenic differentiation capacity. HIMC membrane induced CD206+Arg-1+ M2 macrophage polarization, which in turn promoted more BMSCs migration. In rat skull defects, HIMC membrane promoted the regeneration of new bone with more bone mass and more mature bone architecture. The expression levels of Runx2 and osterix and CD68 + CD206 + M2 macrophage polarization were significantly enhanced. HIMC membrane provides an appropriate osteoimmune microenvironment to promote GBR and represents a promising material for further clinical application.

Keywords: guided bone regeneration; macrophage polarization; mineralized collagen membrane; nanostructure; osteoimmunomodulation.