碱土金属催化脂肪族聚酯的缩聚合成及其在组织诱导再生术中的应用研究

The performance enhancement and functionalization of traditional polymeric materials is one of the key problems in polymer science. This project will develop a new synthetic method for the high performance aliphatic polyesters based on the new polycondensation catalysts, endowing the traditional aliphatic polyesters with new functionalities and expanding their application in the new fields. Non-toxic alkaline earth metal compounds with osteogenic activity will be designed and synthesized as catalysts for polycondensation to in situ synthesize alkaline earth metal containing aliphatic polyesters with high molecular weight, controllable composition and material properties. This new synthetic strategy provides a thorough solution for the problems of the toxic catalyst residue and the phase separation of bioactive inorganic compounds in aliphatic polyesters for biomedical applications. Such polyesters with osteogenic activity also can be used to prepare membranes for the study and application in guided tissue regeneration. In the meantime, aliphatic polyesters synthesized by polycondensation have controllable mechanical strength and degradation rate to meet the requirements of guided tissue regeneration. Furthermore, the residue alkaline earth metal catalyst will be slowly released with the degradation of aliphatic polyester, which can promote the growth of osteoblast and accelerate the bone regeneration. The investigation on the osteogenic activity of the membranes and the evaluation of potential clinical applications are also planned.

传统高分子材料的高性能化和功能化是高分子科学领域的关键问题之一。本项目基于新缩聚催化剂，研究开发高性能脂肪族聚酯的新合成方法，赋予传统脂肪族聚酯新功能，开拓其新应用。项目提出设计合成无毒且具有成骨活性的碱土金属化合物用于催化缩合聚合，原位合成高分子量、组成和性能可控的含碱土金属脂肪族聚酯。这种基于新催化剂的新合成方法可以从根本上解决传统脂肪族聚酯有毒催化剂残留、及其与生物活性无机物难相容的问题，使其能够更好地被应用于生物医学领域。将这种具有成骨活性的新型脂肪族聚酯制备成薄膜，用于组织诱导再生术的应用研究。缩聚合成的脂肪族聚酯具有可调控的力学强度和降解速度，能够满足组织再生术的应用需求；残留的碱土金属离子能够随着脂肪族聚酯的降解而缓慢释放，可以促进成骨细胞的生长，加速骨缺损的修复。项目拟初步评价采用含碱土金属脂肪族聚酯制备的组织诱导再生膜的成骨活性，考察其临床应用潜力。

脂肪族聚酯由于其良好的生物可降解性、生物相容性以及可调控的力学性能，被广泛应用于生物医学工程领域。熔融缩聚是规模化合成脂肪族聚酯的主要途径，但是传统的聚酯缩聚合成催化剂，如锑、锗、锡等催化剂，都具有一定的生物毒性，所合成的脂肪族聚酯需要完全去除催化剂方能作为生物医用材料。同时，脂肪族聚酯本身不具有生物活性，需要另外添加生物活性物质以满足生物医用领域的需求。针对上述问题，本项目设计合成了一系列无毒且具有生物活性的碱土金属化合物用于催化脂肪族二元醇和二元羧酸的缩合聚合，原位合成高分子量、组成和性能可控的含碱土金属脂肪族聚酯。催化剂研究表明原位生成的二羧酸碱土金属盐是缩合聚合的真实催化剂，不仅能够有效催化缩聚反应，还具有很高的生物活性。将这种原位缩聚合成的生物活性聚酯制备成薄膜，应用于组织诱导再生术的应用研究。体内外评价结果表明基于含碱土金属脂肪族聚酯制备的组织诱导再生膜具有良好的成骨活性和抗炎性能，能够在16周内有效地修复骨缺损，修复效果显著强于商品化的聚乳酸薄膜。本项目的成果提供了一种低成本、规模化制备生物活性可降解材料的新途径，有望应用于生物医学领域。