PurposeThe 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 methodsA 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.ResultsSignificantly 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.ConclusionThe IMC bone scaffold materials significantly enhanced bone regeneration via activation of the Wnt signaling pathway.

Spontaneous bone regeneration could occur to reestablish mandibular bony continuity in patients who underwent partial or total mandibulectomy for tumors with periosteum-preserving. However, scarce data is available related to the precise role of periosteum in this bone regeneration. Therefore we aimed to investigate the gene expression of periosteum that were involved in the mandibular bone regeneration. Mandibular segmental defects were created in six mini-pigs with periosteum preserved. The periosteum of defects and control site were harvested at 1 and 2 weeks. Gene ontology (GO) analysis showed that the mechanisms concerning immature wound healing were clearly up-regulated at week 1. In contrast, by week-2, the GO categories of skeletal development, ossification and bone mineralization were significantly over-represented at week-2 with several genes encoding cell differentiation, extracellular matrix formation, and anatomical structure development. Furthermore, Tgfβ/Bmp, Wnt and Notch signaling were all related to the osteogenic process in this study. Besides osteogenesis, genes related to angiogenesis and neurogenesis were also prominent at week-2. These findings revealed that the gene expression profile of the periosteum’s cells participating in bone regeneration varied in different time points, and numbers of candidate genes that differentially expressed during early healing stages of intramembranous bone regeneration were suggested.

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