Novel Biodegradable Materials for Tissue Engineering

近年来，生物材料工程的重点已从生物稳定材料转向生物可降解材料 在生理条件下可降解为无毒产品的材料。乳酸和 乙醇酸及其共聚物聚（丙交酯-共-乙交酯）（PLAGA）是一些最常用的 用于医疗应用的生物可降解聚合物。所有这些聚合物都有一些局限性， 这就要求寻找生物相容性和生物响应性的新型生物可降解材料。 聚磷腈是近年来发展起来的一类具有生物降解潜力的无机高分子材料 成为各种生物医学应用的理想候选者，由于其前所未有的合成 灵活性和多功能性。PI先前已经表明，将聚磷腈与PLAGA混合， 可以显著地阻止PLAGA的酸性降解产物和相关的 炎症反应，同时可以显着改善其机械性能， 骨传导性我们相信，聚磷腈的合成灵活性将允许设计新颖的 大分子，其可与PLAGA形成可混溶的共混物并增加生物活性。这些新颖 共混物由于其良好的生物降解性、机械和生物性能， 骨完整性可以满足骨科的各种需求。这一目标将通过以下方式实现： 具体目标：具体目标1：设计、合成和表征新型可生物降解的 聚磷腈可与PLAGA形成混溶性共混物，作为骨组织的候选材料 工程.具体目标2：构建聚磷腈与PLAGA的新型共混物， 对这些共混物的优化研究集中在物理化学性质的改进上， 机械性能、体外降解、体外矿化和骨传导性。具体目标3： 使用体内动物模型对聚磷腈与PLAGA的新型共混物进行生物学评价。

In recent years emphasis in biomaterial engineering has shifted from biostable materials to biodegradable materials that can degrade to non-toxic products under physiological conditions. Polymers of lactic and glycolic acid and their copolymers poly(lactide-co-glycolide), (PLAGA) are some of the most commonly used biodegradable polymers for medical applications. All these polymers are associated with some limitations, which demand the search for novel biodegradable materials that are biocompatible and bioresponsive. Biodegradable polyphosphazenes, a unique class of inorganic polymer developed recently have the potential to become ideal candidates for various biomedical applications due to their unprecedented synthetic flexibility and versatile properties. PI had previously shown that blending polyphosphazenes with PLAGA can significantly preclude the accumulation of acidic degradation products of PLAGA and associated inflammatory reponses, at the same time can significantly improve their mechanical properties and osteoconductivity. We believe that the synthetic flexibility of polyphosphazenes will allow the design of novel macromolecules, which can for miscible blends with PLAGA and increase the bioactivity. These novel blends due to their well-tuned biodegradability, mechanical and biological properties combined with osteointegrity can serve a variety of needs in orthopaedics. This goal will be achieved via the following specific aims: Specific Aim 1: To design, synthesize and characterize novel biodegradable polyphosphazenes, which can form miscible blends with PLAGA as candidate materials for bone tissue engineering. Specific Aim 2: To construct novel blends of polyphosphazenes with PLAGA and perform optimization studues with these blends focusing on improvements in physico-chemical properties, mechanical properties, in vitro degradation, in vitro mineralization and osteoconductivity. Specific Aim 3: To perform biological evaluation of novel blends of polyphosphazenes with PLAGA using in vivo animal models.