PLLA/n-Mg-w复合材料制备及其镁腐蚀调控的体内外降解机理研究

In order to solve universal phenomenon of biodegradable aliphatic polyester used in clinic, the strengthening and toughening PLLA/ n-Mg-w composites will be prepared by the mixing between the grafted Magnesium nano-whiskers (n-Mg-w) suspension and poly(L-lactide)(PLLA) solution. The n-Mg-w play a role of controlling degradable rate in two-direction of PLLA matrix by Mg2+ and OH- ions from corroded Mg whiskers in the physiological environment, resulting in appropriate degradable rate matching with new bone growth in host. For increasing the interface bonding strength , the DL- malic acid agents are grafted on the Mg whiskers. The modified Mg whiskers (g-n-Mg-w) can dispersed at the PLLA matrix since the n-Mg-w is not easy to agglomerated again and the silane is well compatible with PLLA matrix. It will be research that the effect of the Preparation Process on the microstructure, mechanical properties and thermal stability, resulting in the mechanism of Strengthening and Toughening by n-Mg-w. The degradable Kinetics of the PLLA/ n-Mg-w composite can be known very well in vitro by analysing the microstructure evolution, the molecular weight and the mechanical properties of the composite as well as the change of pH and Mg2+ ions concentration. During in vivo test, the relations between degration rate of PLLA/ n-Mg-w and new bone groth was quanlificationally analysed by Micro-CT scanning and reconstrut. From the results in vitro and in vivo, the mechanism and modeling of controlling degradation based on the n-Mg-w corrosion. A novel composite with good mechanical and biological compatibility as well as controlled degradation in two-direction not only meet the requirements of internal fixation of bone fractures but also provide scientific introduction for preparing inoganic/oganic composites.

以表面DL-苹果酸改性Mg纳米晶须（n-Mg-w）悬浮液与聚左旋乳酸（PLLA）溶液原位共混，制备PLLA/n-Mg-w复合材料，通过n-Mg-w优先腐蚀释放的Mg2+和OH-离子双向调控PLLA的降解过程，使初期（12周内）降解变慢，后期（12周后）加快，与新生骨生长速率相匹配。其中，n-Mg-w在PLLA基体中的分散通过表面有机物接枝导致的表面能降低和排斥力增大来克服团聚，并增加其与基体的键合及分子链之间的缠绕，实现n-Mg-w与PLLA间良好的界面结合，建立界面模型，丰富和发展晶须增强、增韧复合材料的机理。通过降解过程中复合材料的组织演化、分子量和力学性能的变化、模拟体液pH值和Mg2+离子浓度的变化，掌握复合材料体外降解的动力学规律;通过动物试验，由显微CT扫描和重建,定量分析复合材料体内降解和组织生长的对应关系。由此获得基于n-Mg-w腐蚀调控的PLLA的体内外降解机理和模型。

聚左旋乳酸（PLLA）是可降解骨植入体首选材料，植入初期降解过快、后期过慢，酸性降解物诱发无菌性炎症反应等限制了其临床应用。本研究开发PLLA/MgO晶须或纳米颗粒（MgO-w或MgO-n）复合材料，获得力学性能、生物活性良好，可降解的骨修复材料，造福骨创伤患者，意义重大。. 采用溶液共混法制备复合材料；也尝试原位聚合制备新工艺。通过MgO腐蚀释放的Mg2+、OH-离子调控聚乳酸降解，并由MgO-w（MgO-n）增强增韧PLLA；将其用于生物相容性摩擦纳米发电机（TENG)）制备，取得的创新性研究结果如下：.（1）添加1.0wt%硬脂酸（Sa)改性MgO-w、外消旋苹果酸-低分子量聚乳酸(m)改性MgO-n，有效改善了 MgO晶须或颗粒团聚，增强了MgO的稳定性，使其分散性明显提高。.（2）将Sa-MgO-w或m-MgO-n与PLLA溶液共混，因相似相容而易于形成分散均匀的纳米复合材料，MgO增强相与PLLA基体间形成化学键合及良好的界面状态，可显著增强PLLA的结晶度, 1wt%Sa-MgO-w/PLLA结晶度达到56.52%。.（3）Sa-MgO-w和m-MgO-n均可显著强韧化PLLA基体，0.5wt% m-MgO-n对PLLA的增强效果最显著，拉伸强度增加74%；1wt%Sa-MgO-w提高PLLA塑性最强烈，断裂伸长率可提高9倍。.（4）体内外研究显示，MgO-W降低 PLLA初期降解速率的原因是Sa-MgO-w/PLLA复合材料结晶度的提高、吸水率的下降和MgO 溶解释放OH-离子的中和作用；24周后，复合材料内部孔洞多，吸水量大导致降解速率大于纯PLLA。.（5）PLLA和1wt%Sa-MgO-w（或m-MgO-NPs)/ /PLLA浸提液分别培养2、4d，细胞生存率为84.3%-87.6%和101.4%-103.1， MgO溶解碱性中和降解酸性，复合材料细胞毒性0级。.（6）体内植入前4周1wt%Sa-MgO-w/PLLA弯曲强度下降仅为PLLA的1/2，且成骨活跃，前8周种植体周围新生骨小梁明显较多；24周以后复合材料降解明显加快。.（7）左旋丙交酯单体与MgO-w直接原位聚合，可制备出粘均分子量为36万左右，性能相当的PLLA-MgO-w复合材料。.（8）1wt%Sa-MgO-w/PLLA超高塑性适于生物相容性TENG的制备。