Biomimetic intrafibrillar mineralized collagen promotes bone regeneration via activation of the Wnt signaling pathway

Abstract

Zhen Zhang,1, Zheyi Li,2,3, Chengyao Zhang,1 Jiannan Liu,1 Yuxing Bai,2 Song Li,2 Chenping Zhang1 1Department of Oral & Maxillofacial-Head & Neck Oncology, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai Key Laboratory of Stomatology & Shanghai Research, Institute of Stomatology and National Clinical Research Center of Stomatology, Shanghai, China; 2Department of Orthodontics, School of Stomatology, Capital Medical University, Beijing, China; 3Institute for Clinical Research and Application of Sunny Dental, Beijing, China Purpose: The purpose of this study was to assess the effects of biomimetic intrafibrillar mineralized collagen (IMC) bone scaffold materials on bone regeneration and the underlying biological mechanisms.Materials and methods: A critical-sized bone defect in the rat femur was created; then IMC, extrafibrillar mineralized collagen, and nano-hydroxyapatite bone scaffold materials were grafted into the defect. Ten weeks after implantation, micro-computed tomography and histology were applied to evaluate the bone regeneration. Furthermore, microarray technology was applied for transcriptional profile analysis at two postoperative time points (7 and 14 days). Subsequently, the critical genes involved in bone regeneration identified by transcriptional analysis were verified both in vivo through immunohistochemical analysis and in vitro by quantitative real-time transcription polymerase chain reaction evaluation.Results: Significantly increased new bone formation was found in the IMC group based on micro-computed tomography and histological evaluation (P<0.05). Transcriptional analysis revealed that the early process of IMC-guided bone regeneration involves the overexpression of genes mainly associated with inflammation, immune response, skeletal development, angiogenesis, neurogenesis, and the Wnt signaling pathway. The roles of the Wnt signaling pathway-related factors Wnt5a, β-catenin, and Axin2 were further confirmed both in vivo and in vitro.Conclusion: The IMC bone scaffold materials significantly enhanced bone regeneration via activation of the Wnt signaling pathway. Keywords: mineralized collagen, bone defects reconstruction, bone regeneration, transcriptional analysis, Wnt signaling pathway

Keywords

• mineralized collagen
• bone defects reconstruction
• bone regeneration
• transcriptional analysis
• Wnt signaling pathway