NEW GENERATION OF POLYANHYDRIDES

基于生物可腐蚀聚合物的长骨骨折内固定 聚乳酸、聚乙醇酸或聚对二氧六环 由于生物相容性差、缺乏 足够的机械强度或不可预测的退化问题。为 这些原因导致了第一个聚(酸酐-共酰亚胺)的合成。 然而，这些聚(酸酐-共酰亚胺)含有亚胺环体系， 不是基于生物分子的，这也可能引起生物兼容性的担忧。 因此，这一提议的具体目标是：1)合成一种新的 含生理成分的聚(酸酐-共亚胺)聚合物的合成 基环系统，如尿嘧啶和胸腺嘧啶的嘧啶环，2) 测定聚合物的力学性能；3)研究聚合物的力学性能 聚合物在溶液和固体中的降解特性 状态，以及4)确定其初始生物相容性特征 这些聚合物在体外。将进行单体的合成 将使用嘧啶化学技术和聚合 使用兰格博士之前开发的各种技术 实验室。聚合物的力学性能将通过以下方式进行表征 综合强度、抗拉强度、断裂应变、弹性模数 和拉压疲劳试验。的稳定性和降解性 聚合物将通过凝胶渗透色谱进行测定。这个 聚合物的生物相容性将用牛主动脉进行测定。 培养中的内皮细胞和人成纤维细胞。生物可腐蚀性 用于骨折固定的聚合物有一个额外的优点 传统的金属植入物，它们可以同时提供 把药物送到骨折处。

Internal long hone fracture fixation using bioerodible polymers based on polylactic acid, polyglycolic acid or poly-p-dioxanon have failed to provide adequate results due to either poor biocompatility, lack of adequate mechanical strength or unpredictable degradation concerns. For these reasons the first poly(anhydride-co-imides) were synthesized. However, these poly(anhydride-co-imides) contained imide ring systems that weren't biomolecule based which may also raise biocompatibility concerns. Therefore, the specific aims of this proposal are to: 1) synthesize a new generation of poly(anhydride-co-imide) polymers containing physiologically based ring systems, such as the pyrimidine rings of uracil and thymine, 2) to determine the mechanical properties of the polymers, 3) to study the degradation characteristics of the polymers in solution and in the solid state, and 4) to determine the initial biocompatibility characteristics of these polymers in vitro. The synthesis of the monomers will be conducted using pyrimidine chemistry techniques and polymerizations will be carried out using variations of techniques previously developed in Dr. Langer's laboratory. The polymer mechanical properties will be characterized by comprehensive strength, tensile strength, fracture strain, elastic moduli and tension-compression fatigue testing. The stability and degradation of the polymers will be determined by gel permeation chromatography. The biocompatibility of the polymers will be determined using bovine aortic endothelial cells and human fibroblast cells in culture. Bioerodible polymers for fracture fixation have an additional advantage over traditional metallic implants in that they could simultaneously deliver drugs to the fracture site.