High Strength Bioresorbable PLA/CaP Composites

描述（由申请人提供）：由可降解聚合物和生物活性磷酸钙制成的生物可吸收复合材料在临床上适用于骨固定和修复，因为它们不必在骨愈合后通过二次手术取出。然而，目前生物可吸收聚乳酸/磷酸钙（PLA/CaP）复合材料在骨固定中更广泛和更成功使用的关键障碍是其较弱的机械性能。本项目的目标是开发一种新技术，以提高PLA/CaP复合材料的机械强度，使其与天然骨的机械强度相匹配，从而使其能够在承重部位得到更广泛的应用。由于复合材料中PLA基质和CaP填料之间的界面粘合至关重要，因此该策略是开发一种技术，该技术有效地将核-壳有机-无机杂化结构与特殊的膦酸螯合剂和表面引发聚合相结合，以在PLA基质和CaP填料之间建立直接的化学键。基于改进的界面，我们的目标是将生物可吸收复合材料的机械强度提高到天然骨的平均值（例如，100 MPa作为拉伸强度的目标值）。此外，通过额外优化一些关键变量（例如，CaP相、粒度、PLA分子量（MW）和CaP/PLA质量比），我们试图将PLA/CaP复合材料的机械强度调节到宽范围（例如，拉伸强度50 - 100 MPa），使得它们能够最好地匹配来自不同位置的天然骨的那些。本研究将对复合材料的初始机械强度、降解相关的机械强度以及生物相互作用进行研究。这项研究的成功将产生生物可吸收复合材料，具有改善的生物相容性和高的可调节的机械强度，可以很好地匹配新骨的生长。这将允许这种生物可吸收材料更广泛和成功地应用于骨固定和修复，特别是用于承重区域，通过在骨愈合期间保持足够的强度，消除应力屏蔽，并避免临床不良炎症效应。在临床上，使用这种生物可吸收材料代替目前的不可吸收金属器械将对患者有很大的益处，因为避免了对诊断仪器（例如计算机断层扫描（CT））的干扰，消除了在骨愈合后可能进行的第二次手术以移除器械，并降低了总治疗成本。 公共卫生相关性：将核-壳有机-无机杂化结构与现代表面引发聚合有效结合的技术将被开发以改善生物可吸收复合材料的机械强度以良好地匹配骨。这将使这些材料能够成功地用于承重部位的骨固定，并消除了在骨愈合后进行第二次手术将其取出的情况，如目前的不可吸收金属植入物。

DESCRIPTION (provided by applicant): Bioresorbable composites made from degradable polymers and bioactive calcium phosphates are clinically desirable for bone fixation and repair, because they do not have to be removed by second surgery after bone heals. However, a critical barrier to wider and more successful use of current bioresorbable polylactide/calcium phosphate (PLA/CaP) composites to bone fixation is their weak mechanical properties. The goal of this project is to develop a new technology to improve the mechanical strength of PLA/CaP composites to match that of natural bone, so that they can have wider application in load-bearing locations. Due to the critical importance of the interfacial adhesion between the PLA matrix and CaP filler within the composites, the strategy is to develop a technology that effectively combines a core-shell organic-inorganic hybrid structure with a special phosphonic chelating agent and surface initiated polymerization to establish direct chemical bonds between the PLA matrix and CaP filler. Based on the improved interface, we target to improve the mechanical strengths of the bioresorbable composites to the average value of natural bone (e.g. 100 MPa as the target value of the tensile strength). Moreover, by additional optimizing a number of critical variables (e.g. CaP phase, particle size, PLA molecular weight (MW) and CaP/PLA mass ratio), we seek to adjust the mechanical strength of PLA/CaP composites into a wide range (e.g. tensile strength 50 - 100 MPa), so that they can best match those of natural bones from varied locations. Both of the initial mechanical strength and the degradation dependent mechanical strength as well as biological interaction of the composites will be studied in the proposed research. Success of the proposed research will produce bioresorbable composites with improved biocompatibility and high and adjustable mechanical strength which can well match new bone growth. This will allow such bioresorbable materials to be more widely and successfully applied to bone fixation and repair, particularly for the load-bearing areas, by maintaining sufficient strength during bone healing, eliminating stress-shielding, and avoiding the clinical adverse inflammatory effects. Clinically, using such bioresorbable materials instead of current non-resorbable metallic devices would be of great benefit to patients, by avoiding the interference with diagnostic instruments (e.g. computed tomography (CT)), eliminating the possible second surgery to remove the device after bone heals, and reducing the total treatment cost. PUBLIC HEALTH RELEVANCE: A technology that effectively combines a core-shell organic-inorganic hybrid structure with modern surface initiated polymerization will be developed to improve the mechanical strength of bioresorbable composites to well match bone. This will allow such materials to be successfully used for bone fixation in load-bearing locations, and eliminate second surgery to remove them after bone heals as that for current non-resorbable metallic implants.