功能化外泌体在骨科疾病治疗中的研究进展

doi:10.3969/j.issn.1006-5725.2026.11.008

Abstract

Abstract:

With the continuous development of society and the progress of medical science， the treatments for orthopedic diseases are gradually evolving towards precision medicine. As natural nanovesicles， exosomes possess outstanding biocompatibility and targeting abilities. Through functional modifications including genetic engineering， drug loading， and surface modification， exosomes can precisely facilitate bone regeneration， regulate bone metabolism， and reshape the immune micro-environment. They show remarkable potential in the treatment of orthopedic disorders such as fractures， osteoarthritis， and osteoporosis. Nevertheless， there are still challenges in standardized preparation， efficacy evaluation， safety assessment， and clinical translation. This article systematically reviews the most recent advances in functionalized exosomes for the treatment of orthopedic diseases， encompassing their sources， preparation methods， functionalization strategies， and mechanisms of action. It summarizes the application progress of functionalized exosomes in orthopedic therapy， discusses the current technical challenges and future development directions， and is of great significance for the translation of functionalized exosomes from laboratory research to clinical application in orthopedics.

Key words: fracture, osteoarthritis, osteoporosis, exosomes, miRNA

CLC Number:

R681

Yuele MA,Yan WANG,Hongwei CUI,Hui ZHANG,Yujing CHEN,Benchao DONG,Peichuan YANG,Jianxiong MA. Research advances in functionalized exosomes for orthopedic disease treatment[J]. The Journal of Practical Medicine, 2026, 42(11): 1949-1958.

Figures/Tables 3

Fig.1

Tab.1

Tab.2

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分离方法	原理	成本	优缺点	参考文献
超速离心法	依据密度、大小差异进行差速离心	设备昂贵	分离纯度高，设备依赖性强、耗时长、规模化困难、产率低、易共沉淀杂质及离心过程可能破坏外泌体结构	［8］
超滤法	利用滤膜分离大于孔径的外泌体	低	操作简单、快速、不引入外源性试剂，膜易堵塞、剪切力可能破坏外泌体、纯度一般	［9］
尺寸排阻色谱法	依据粒径大小在凝胶柱中分离	偏高	纯度高，较好保持外泌体生物活性，结构完整，样本处理量小，操作慢，需专业设备	［10］
聚合物沉淀法	改变溶解度，使外泌体共沉淀	低	操作简单、可处理大量样本、回收率高，纯度低，易共沉淀杂质	［11］
免疫亲和捕获法	抗体（如抗CD9/CD63/CD81）特异性结合表面标志物	单次成本高	特异性极高，可获得特定来源或亚型的外泌体，可能破坏膜结构、不能捕获所有外泌体、洗脱困难	［12］
微流控技术	微芯片中利用物理或亲和原理	高	快速、高纯度、自动化、样本需求量极小，设备专业、通量有限、尚处于发展阶段	［13］
商业试剂盒	基于沉淀或亲和原理优化	单次实验成本高	操作最简便、标准化、省时，适合初学者，核心原理不透明、批次间可能有差异、纯度不一	［14］

功能化策略	核心机制	关键技术方法	主要优势	参考文献
基因工程	通过转染供体细胞，使其表达特定的治疗性蛋白或miRNA，从源头改造外泌体的组成与功能	细胞转染、基因编辑	（1）实现源头功能定制，赋予外泌体主动靶向能力；（2）提升生物活性与疾病干预能力；（3）改变外泌体分子组成，强化特定功能	［13］［15］
药物负载	将药物、蛋白质或核酸分子装载入外泌体内部，实现精准递送	共孵育、电穿孔、超声辅助	（1）提高药物的生物利用度与靶向性；（2）克服传统治疗耐药性问题；（3）实现缓释与局部高浓度递送	［16］
表面修饰	在外泌体表面引入靶向配体或识别分子，增强其与目标细胞的结合特异性	化学偶联、生物素-亲和素系统、配体修饰	（1）提升靶向精准性与细胞选择性；（2）可用于骨组织靶向或免疫调控；（3）增强治疗效果并减少脱靶效应	［16］

Research advances in functionalized exosomes for orthopedic disease treatment

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