超声响应聚合物微粒在骨修复领域的研究进展

Research Progress of Ultrasound-Responsive Polymeric Microparticles in the Field of Bone Repair

摘要: 骨修复过程复杂，需要先进的药物递送系统来满足骨微环境的复杂性、精准治疗和多阶段治疗的需求。传统缓释系统存在药物突释与后期释放不足的矛盾，且缺乏对修复过程中动态生物学需求的响应能力。刺激响应型药物载体为解决这些问题提供了新思路，其中超声触发系统因具有非侵入性、深层组织穿透性和精确时空控制特性而备受关注。低强度脉冲超声(LIPUS)不仅能促进骨愈合，还在软组织再生方面有一定效果，但单独使用治疗深部病变存在局限性。聚合物基药物递送系统可实现药物靶向递送和可控释放，聚合物微粒在药物递送中具有诸多优势。超声介导的药物递送增强效应源于力学效应与热效应，涉及微气泡、纳米气泡、聚合物囊泡/胶束、聚合物水凝胶和压电聚合物基复合材料等多种载体。目前超声响应材料在药物/基因递送中的研究多处于体外和动物实验阶段，未来需更多临床试验进行验证，超声控释与压电结合也为智能响应材料局部疗法的精细控制开辟了新方向。

Abstract: Drug delivery systems are designed to meet the needs of the complexity of the bone microenvironment, precise treatment, and multi-stage treatment. Traditional sustained-release systems have the contradiction of rapid drug release at the beginning and insufficient release in the later stage, and lack the ability to respond to the dynamic biological needs during the repair process. Stimuli-responsive drug carriers provide new ideas for solving these problems. Among them, the ultrasound-triggered system has attracted much attention due to its non-invasive nature, deep tissue penetration, and precise spatiotemporal control characteristics. Low-intensity pulsed ultrasound (LIPUS) can not only promote bone healing but also has certain effects in soft tissue regeneration. However, its use alone has limitations in treating deep-seated lesions. Polymeric drug delivery systems can achieve targeted drug delivery and controlled release, and polymeric microparticles have many advantages in drug delivery. The enhanced effect of ultrasound-mediated drug delivery originates from its mechanical and thermal effects, involving various carriers such as microbubbles, nanobubbles, polymeric vesicles/micelles, polymeric hydrogels, and piezoelectric polymer-based composites. Currently, the research on ultrasound-responsive materials in drug/gene delivery is mostly at the in vitro and animal experiment stages. More clinical trials are needed for verification in the future. The combination of ultrasound-controlled release and piezoelectricity also opens up a new direction for the fine control of local therapies with intelligent responsive materials.