Novel Biodegradable Materials for Tissue Engineering

描述（由申请人提供）：近年来，生物材料工程的重点已经从生物稳定材料转移到生物可降解材料，可以在生理条件下降解成无毒产品。乳酸和乙醇酸聚合物及其共聚物聚（乳酸-共乙醇酸）（PLAGA）是医疗应用中最常用的生物可降解聚合物。所有这些聚合物都有一定的局限性，这就要求寻找具有生物相容性和生物反应性的新型可生物降解材料。可生物降解聚磷腈是最近开发的一类独特的无机聚合物，由于其前所未有的合成灵活性和多用途特性，有可能成为各种生物医学应用的理想候选者。PI之前的研究表明，聚磷腈与PLAGA混合可以显著阻止PLAGA酸性降解产物的积累和相关的炎症反应，同时可以显著改善其力学性能和骨导电性。我们相信，聚磷腈的合成灵活性将允许设计新的大分子，可以与PLAGA混溶，提高生物活性。这些新型混合物由于其良好的生物降解性、机械和生物特性以及骨完整性，可以满足骨科的各种需求。该目标将通过以下具体目标实现：具体目标1：设计、合成和表征新型可生物降解聚磷腈，其可与PLAGA形成混溶物，作为骨组织工程的候选材料。具体目标2：构建聚磷腈与PLAGA的新型共混物，并对这些共混物进行优化研究，重点关注其物理化学性能、机械性能、体外降解、体外矿化和骨导电性的改善。具体目标3：使用体内动物模型对聚磷腈与PLAGA的新型混合物进行生物学评估。

DESCRIPTION (provided by applicant): 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.