聚内酯是一类具有良好生物相容性的可降解高分子材料，在生物医学领域应用广泛。在骨结核治疗上已有负载抗结核药物的聚内酯载药体系，但仍存在初期爆发释放大，持续释放时间较短，没有骨传导性等缺点，尚不能满足骨结核治疗的长效药物控释同时骨融合的要求。本项目的研究目标是发展多种负载抗结核药物的新型聚内酯载药体系，评估并优化其药物释放和骨融合行为，实现抗结核药的长效局部释放和骨重建修复功能相结合，为临床上骨结核的治疗提供新途径。具体研究手段是设计合成几种多嵌段与支化聚内酯，研究其分子结构与降解/渗透药物释放之间的关系，抑制初期药物暴释行为，延长药物平稳释放周期；合成粗糙表面和介孔的磷酸三钙（TCP）纳米粒子，研究它的形貌结构与不同分子结构和末端基团的聚内酯的掺杂行为和界面结构，以及与药物吸附和释放之间的关系；通过抑菌实验和骨融合实验评估新型聚内酯高分子材料在治疗骨结核上的应用前景。

Polylactones, a kind of biodegradable polymers with good biocompatibility, are widely used in biomedical fields. Some polylactone-based drug systems with loaded anti-tuberculosis (TB) drugs have been developed for treatment of bone tuberculosis. However, due to initial burst release, short sustained release and no bone conduction, these systems cannot meet the requirement of bone TB treatment including long-term drug controlled release and bone fusion. In this proposal, we will develop various novel polylactone-based anti-TB drug systems, evaluate and optimize drug release behaviors and bone fusion, thus realize the combination of long-term local release of anti-TB drugs and bone regeneration, and provide a new way for the clinical treatment of bone tuberculosis. In detail, we design several synthetic multi-block and branched polylactones and study effects of their molecular structures and degradation on permeability and release of drugs to inhibit initial drug burst release and prolong drug release. Then, we synthesize mesoporous TCP nanoparticles (NPs) with rough surfaces, and study relationships of doping behaviors and interface structures between morphologies of TCP NPs and various polylactones with different topologies. Finally, we adopt antibacterial and bone repair experiments to systematically evaluate the effects of bone TB treatments for these novel polylactone-based anti-TB drug systems.