Objectives: To investigate the effects of inferior alveolar nerve on new bone formation in rabbit mandibular distraction osteogenesis.

Bone defects caused by various factors may cause morphological and functional disorders that can seriously affect patient’s quality of life. Autologous bone grafting is morbid, involves numerous complications, and provides limited volume at donor site. Hence, tissue-engineered bone is a better alternative for repair of bone defects and for promoting a patient’s functional recovery. Besides good biocompatibility, scaffolding materials represented by hydroxyapatite (HA) composites in tissue-engineered bone also have strong ability to guide bone regeneration. The development of manufacturing technology and advances in material science have made HA composite scaffolding more closely related to the composition and mechanical properties of natural bone. The surface morphology and pore diameter of the scaffold material are more important for cell proliferation, differentiation, and nutrient exchange. The degradation rate of the composite scaffold should match the rate of osteogenesis, and the loading of cells/cytokine is beneficial to promote the formation of new bone. In conclusion, there is no doubt that a breakthrough has been made in composition, mechanical properties, and degradation of HA composites. Biomimetic tissue-engineered bone based on vascularization and innervation show a promising future.

The present study evaluated the effects of calcitonin gene‑related peptide (CGRP) on bone marrow mesenchymal stem cells (BMMSCs) in vitro and in a rat model of mandibular distraction osteogenesis (MDO). Rat BMMSCs were isolated then treated with CGRP or CGRP antagonist (CGRP8‑37). The proliferation and migration ability of BMMSCs was determined using 5‑bromo‑2'‑deoxyuridine and Transwell assays, respectively. Osteogenic‑related gene expression was analyzed with reverse transcription‑quantitative polymerase chain reaction. For the in vivo analysis, thirty MDO rats were randomly assigned to control, CGRP or CGRP8‑37 groups. To evaluate the mobilization of BMMSCs, nestin and stromal cell‑derived factor 1 (SDF‑1) were detected by immunohistochemistry and ELISA. Rats were sacrificed following 14 days and new bone formation was assessed by histological and micro‑computed tomography analysis. In the in vitro results, the CGRP group demonstrated significantly higher migration and proliferation, as well as enhanced alkaline phosphatase and runt‑related transcription factor 2 expression compared with the control. In the in vivo experiments, bone mineral density of the newly formed bone in the CGRP group was significantly higher than controls. The nestin and SDF‑1 expression in the CGRP group was also significantly upregulated. In conclusion, the present study demonstrated that CGRP administration increased new bone formation, possibly via enhancing BMMSC migration and differentiation in MDO rats.

Distraction osteogenesis (DO) is a widely used self-tissue engineering. However, complications and discomfort due to the long treatment period are still the bottleneck of DO. Novel strategies to accelerate bone formation in DO are still needed. P38 is capable of regulating the osteogenic differentiation of both mesenchymal stem cells (MSCs) and osteoblasts, which are crucial to bone regeneration. However, it is not clear whether targeting p38 could regulate bony formation in DO. The purpose of the current work was to investigate the effects of local application of either p38 agonist anisomycin or p38 inhibitor SB203580 in a rat model of DO. 30 adult rats were randomly divided into 3 groups: (A) rats injected with DMSO served as the control group; (B) rats injected with p38 agonist anisomycin; (C) rats injected with p38 inhibitor SB203580. All the rats were subjected to mandibular distraction and the injection was performed daily during this period. The distracted mandibles were harvested on days 15 and 30 after surgery and subjected to the following analysis. Micro-computed tomography and histological evaluation results showed that local application of p38 agonist anisomycin increased new bone formation in DO, whereas p38 inhibitor SB203580 decreased it. Immunohistochemical analysis suggested that anisomycin promoted MSC recruitment in the distraction gap. In conclusion, this study demonstrated that local application of p38 agonist anisomycin can increase new bone formation during DO. This study may lead to a novel cell-based strategy for the improvement of bone regeneration.