Mechanical stimulation of autogenous growth factors and neo-vascularization after bony reconstruction of mandibular segmental defects in a goat model

自体骨移植重建下颌骨的连续性缺陷作为金标准仍然有很大的失败率。目前正在研究的外源生长因子如rhBMP-2和VEGF的应用，可能会产生有益的结果，主要是由于间充质干细胞的活化。此外，骨的机械刺激，例如在愈合阶段使用体外冲击波（ESW），可能通过干扰间充质干细胞的迁移和分化以及促进新血管形成，以积极的方式影响骨愈合过程。与应用外部生长因子重建下颌骨相比，机械刺激尚未在大于大鼠的动物或人类颅面区域进行过研究。尽管如此，最初的结果是有希望的，因为ESW代表了一种生物物理刺激，不需要合并有潜在副作用的药物，它可能是一种有价值的替代或额外的技术。下颌骨重建中体外刺激骨生长的关键问题可能为更好的愈合开辟新的途径。因此，本研究项目的目的是评估山羊部分下颌骨切除术后可能加速骨生长的动物模型。所有动物将接受左下颌骨“临界尺寸”连续切除，并从下颌骨对侧角度用双皮质骨重建。在第1组，将不进行进一步的程序。第二组在自体骨移植的基础上，通过ESW进行低剂量的机械刺激。在第三组，移植骨将采用高剂量的esw治疗。我们假设通过机械刺激诱导各种自体宿主因子，如BMP-2和VEGF，可能导致骨生长增加并改善血液供应。

Autogenous transfer of bone for reconstruction of continuity defects of the mandible as the gold standard still yields a substantial failure rate. The application of exogenous growth factors such as rhBMP-2 and VEGF, which is under current research, may lead to a beneficial result, mostly because of activation of mesenchymal stem cells. Moreover, mechanical stimulation of the bone, for example with extracorporeal shock waves (ESW) during the healing phase may affect the bone healing process in a positive way by interference with migration and differentiation of mesenchymal stem cells and promotion of neo-vascularization. In contrast to the application of external growth factors for the reconstruction of the mandible, mechanical stimulation has not been examined in the craniofacial area in animals bigger than rats nor in humans before. Though, the first results are promising and as ESW represents a biophysical stimuli and does not need the incorporation of medication with potential adverse effects, it could be a valuable alternative or additional technique. The crucial question of an extracorporal stimulation of bone growth in reconstruction of the mandible may open a new way for a better healing. Therefore, the objective of this research project is an evaluation of the possible acceleration of bone growth after partial mandibulectomy in an animal goat model. All animals will receive a ¿critical size¿ continuity resection of the left mandible with reconstruction with bicortical bone from the contralateral angle of the mandible. In group 1, no further procedures will be conducted. Group 2 will receive, next to the autogenous bone transfer, a low-dose mechanical stimulation via ESW. In group 3, the transplanted bone will be treated with a high-dose ESW-therapy. We hypothesize that the induction of various autogenous host-factors such as BMP-2 and VEGF by mechanical stimulation may lead to an increased bone growth with an improvement in blood supply.