NEW GENERATION OF POLYANHYDRIDES

生物可蚀聚合物内固定长骨骨折 聚乳酸、聚乙醇酸或聚对二氧环己酮未能 由于生物相容性差、缺乏 足够的机械强度或不可预测的降解问题。为 这些原因导致合成了第一种聚（酸酐-共-酰亚胺）。 然而，这些聚（酸酐-共-酰亚胺）含有酰亚胺环体系， 不是基于生物分子的，这也可能引起生物相容性问题。 因此，本建议的具体目标是：1）综合一个新的 含有生理活性的聚（酸酐-共-酰亚胺）聚合物的制备 基于环系统，如尿嘧啶和胸腺嘧啶的嘧啶环，2） 为了确定聚合物的机械性能，3）研究聚合物的 聚合物在溶液和固体中的降解特性 状态，以及4）确定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 使用嘧啶化学技术和聚合将进行 使用兰格博士以前开发的各种技术， 实验室聚合物机械性能将通过以下表征： 综合强度，抗拉强度，断裂应变，弹性模量 和拉伸-压缩疲劳测试。的稳定性和降解 聚合物将通过凝胶渗透色谱法测定。的 聚合物的生物相容性将使用牛主动脉 培养的内皮细胞和人成纤维细胞。生物侵蚀 用于骨折固定的聚合物具有额外的优点 传统的金属植入物，因为它们可以同时提供 在骨折处注射药物

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.