骨折愈合期可降解镁合金与轴向应力协同作用机理研究

Because of their excellent performances in mechanical-compatibility, biocompatibility and osteoinductivity, bone fixation devices made of biodegradable magnesium alloys get more and more attentions in orthopaedics. At present, bone mass is used to evaluate the level of bone healing. However, there are few reports about the research on bone quality which contribute more to bone mechanical properties. Our prophase research state that preferential biological apatite (BAp) c-axis orientation is a quantitative bone quality parameter and considered to adapt to in vivo stress. Therefore, there is important significance to study the combined effects of biodegradable magnesium alloys and stress during bone fracture healing. However, there is not yet relevant research now. In this project, with the advantage of interdisciplinary combinations, rats are performed with ulnar transverse osteotomy and intramedullary nail fixation, then ulna axial compressive loading model is used to apply stress on right ulnae. The degradation of magnesium alloy and its impact on the healing speed of fracture and preferential BAp c-axis orientation are focused on to build the model of new bone formation with high quality at the nanometer scale, meanwhile, the mechanism of new bone formation with high degree of preferential BAp c-axis orientation is revealed, and ultimately, the quantitative relations of “Magnesium alloy & Stress (strain)—Bone quality (mass)—Bone mechanical properties” are set up, which will promote the development of fracture treatment from experience to theory, fine and quantification and provide the scientific basis for combined application of stress and fixation device of biodegradable magnesium alloys clinically.

可降解镁合金骨固定器件因具有优异的力学与生物相容性，并可诱导新骨生成，在骨科领域越来越受到关注。目前骨康复治疗评价的主要指标是骨量，而决定骨性能的骨质指标却鲜有报道。本课题组前期研究证实骨生物磷灰石（BAp）c轴取向可作为定量评价骨质的指标，且受应力影响。因此，研究骨折愈合期镁合金和应力的协同作用具有重要意义，但目前尚缺乏相关研究。本项目拟利用学科交叉优势，以大鼠为研究对象，行尺骨干中部横行截骨镁合金髓内针固定术，实施轴向应力加载，研究镁合金降解及其在应力加载前后对骨折愈合速度和骨折断端新生骨BAp c 轴取向的影响，在纳米结构级别建立新骨生长模型，揭示镁合金协同应力提高新生骨BAp c 轴取向和骨量机理；利用纳米压痕仪测骨性能，建立“镁合金&应力(应变)—骨质(量)—骨力学性能”的定量关系，促进骨折治疗由经验化向理论化、精细化和定量化方向发展，为镁合金和应力联合应用于临床提供科学依据。

镁合金具有良好的生物相容性、可降解性、避免应力遮挡和骨诱导能力，在骨科领域越来越受到关注。但镁合金在降解过程中力学性能衰减速率和新骨生长速度不匹配一直制约镁合金的发展。本项目引入应力加载和镁合金协同促进骨折更好更快的愈合，缩短镁合金在体内的服役时间，提高骨折愈合速度。. 本项目选取大鼠胫骨作为研究对象，行胫骨干中部横行截骨镁合金髓内针固定术，术后2周开始轴向应力加载直到取出胫骨。为确定镁合金髓内针和新生骨痂的应力分布，对愈合过程中的大鼠胫骨进行了有限元模拟。研究了体内外镁合金的降解产物及降解规律，并对骨折的愈合速度和骨组织形态进行分析。. 随着骨折逐渐愈合，镁合金髓内针的应变值逐渐减小。由于镁合金所产生的应变较小，不影响整体降解速率，但是镁合金髓内针固定骨折断端处所受的应力较大，降解较快。由于新生骨痂逐渐成熟，其应变值逐渐减小。其次，通过对胫骨有限元模型进行实验验证，发现实验值与模拟值吻合。. 镁合金体外浸泡和体内植入在降解形式上不同。体外由于降解速率过快，降解产物层有明显开裂脱落，体内降解速率较慢，无明显的脱落现象。体内降解产物最内层以镁的氧化物或氢氧化物，最外层是钙磷盐。其次，镁合金髓内针体外浸泡的降解速率是其体内降解速率的10倍，其主要原因有两个方面，其一是体内环境存在动态代谢，生理介质离子浓度和酸碱度较为稳定；其二是体内镁合金表面降解层更加致密均匀，且有生物组织覆盖，减缓了镁合金的降解。. 术后10周，镁合金受力组的骨体积分数相比不受力组增加了约10%，且受力组的骨折愈合质量明显优于不受力组。应力的加载使骨细胞形态发生变化，进而影响骨结构，使愈合后的骨组织具有更好的力学性能，为临床骨折治疗提供了新思路。