Sacrificial templated grafts to encourage bone healing through mechanotransduction

机械转导促进骨愈合的牺牲性模板移植 项目摘要 大量骨组织的丢失通常是由于创伤或癌症切除造成的。 这种损伤，特别是头部、颌骨和颈部的损伤，对外科医生和长期和短期的 这些患者的并发症以及生活质量通常会因为面部美学的改变而受到影响。 还有五官、言语、咀嚼和呼吸。为了克服这些并发症，目前的临床替代方案 包括具有从次级部位获得的相关维管束的骨移植。所有这些治疗方法 需要多项临床干预，往往会增加患者的疼痛或供区发病率。 在这项研究中，通过控制机械调节的单次手术步骤合成移植物替代品 支架内的顺应性变化以及细胞迁移因子的协同传递以增强骨 大力发展再生能源。因此，这个项目的两个目标是：1)开发一种化学诱导剂 将骨移植替代品与工程降解区结合在一起，同时保持其机械完整性 功能稳定，以及2)在生理相关条件下评估受控的时间退化 成骨和血管生成信号转导的体外条件和机制 钙离子偶联途径。从体外和体内研究中收集的数据将指导这一研究的发展 新型移植物，为研究局部微机械因素的影响和释放提供了一个已建立的平台 补充因素，以促进骨折愈合和骨再生，而不需要广泛的骨固定 仪器仪表。

Sacrificial Templated Grafts to Encourage Bone Healing Through Mechanotransduction Project Summary Loss of large volumes of bone tissue often occurs as a result of traumatic injuries or cancerous resection. Such injuries, especially in the head, jaws, and neck are challenging to surgeons and the long- and short-term complications as well as the quality of life for these patients are often affected due to alteration in facial aesthetics and features, speech, mastication, and breathing. To overcome these complications, current clinical alternatives include grafting of bone with associated vascular bundles obtained from a secondary site. All these treatments require multiple clinical interventions and often result in increased pain or donor site morbidity for the patients. In this study, single-surgical step synthetic graft alternatives with controlled mechano-modulation through compliance changes within the scaffold as well as a concerted delivery of cell migration factors to enhance bone regeneration will be developed. As such, the 2 aims for this project are 1) to develop a chemoattractant incorporated bone graft substitute with engineered degradation zones while retaining its mechanical integrity for functional stabilization, and 2) to assess controlled temporal degradation under physiologically relevant conditions in vitro and mechanisms of osteogenic and angiogenic signaling through mechanotransduction and Ca2+ coupled pathways. Data collected from the in vitro and in vivo studies will guide the development of this novel graft and provide an established platform to study the effects of local micromechanical factors and release of recruitment factors to promote fracture healing and bone regeneration without need for extensive bone fixation instrumentation.