中国组织工程研究

工程化外泌体修复组织损伤：应用潜力及优异的生物稳定性和靶向特异性

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罗文彬 ¹ , 李若云 ¹ , 潘超凡 ¹ , 罗长江 ²

中国组织工程研究 | 2026,30(1): 204-217

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中国组织工程研究 2026 , 30 (1) : 204 -217

工程化外泌体修复组织损伤：应用潜力及优异的生物稳定性和靶向特异性

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罗文彬¹, 李若云¹, 潘超凡¹, 罗长江²

作者信息

^1.州大学第二临床医学院，甘肃省兰州市 730030

^2.州大学第二医院疝与腹壁外科，甘肃省兰州市 730030

Engineered exosomes for repairing tissue damage: application potential, excellent biological stability, and targeting specificity

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出版时间: 2026-01-08 doi: 10.12307/2025.543

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摘要

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背景：外泌体是各种类型细胞都可分泌的一种纳米级细胞外囊泡，具有高生物利用度、低毒性、低免疫原性及良好的生物相容性等优点。然而，天然外泌体在临床治疗上存在一定的局限性，通过生物工程技术对外泌体进行改造修饰，得到的工程化外泌体在改善其原本治疗效果的同时，展现出优异的生物稳定性和靶向特异性，在组织修复领域展现出巨大的应用潜力。目的：总结工程化外泌体的不同策略，包括功能装载和表面修饰，概述工程化外泌体在不同组织修复中的研究进展，探讨工程化外泌体在组织修复中的治疗潜力。方法：检索PubMed 数据库中2010-2024年发表的相关文献，检索词为“engineered exosomes，tissue repair，biomaterials，tissue engineering，wound healing，parenchyma，bone regeneration，cartilage，neural，myocardial，hepatic”，排除研究内容与文章主题关系不大、文献质量较差、重复及内容陈旧文献，共115篇文献符合纳入标准。结果与结论：①功能负载通过将治疗性分子与外泌体相结合令外泌体获得额外的特性或是增强原本生理功能，其中超声处理和挤出法在操作简单的同时能获得更高的载药量。②表面修饰可令外泌体表达所需要的蛋白或增强其靶向性，包括基因工程和化学修饰，基因工程操作复杂、可重复性差，且最终产物可控性差；化学修饰则相对简单通用，更适合用于设计高度靶向和特定功能的工程化外泌体。③在预处理细胞以获得工程化外泌体的技术中，缺氧预处理操作简单且机制较明确故而应用较广，其既可激活糖酵解来促细胞增殖、还可通过生成缺氧诱导因子来调节血管内皮生长因子受体信号通路以促进血管生成。④外泌体自身功能受细胞来源、细胞状态、合成过程和细胞外环境等多种因素影响，如工程化策略复杂，最终工程化外泌体更难确保功能一致性，因此采用相对简单可靠的工程化策略更适合临床应用。⑤工程化外泌体结合生物材料或支架可用于治疗皮肤软组织的复杂创伤，如感染性伤口和糖尿病性溃疡，这种方法能够提高外泌体的递送量并控制其释放，促进组织修复，控制感染，并调节伤口局部微环境。⑥由于骨组织损害的特殊性，单一机制的工程化外泌体常治疗效果不明显，故而需要双重甚至多重功能工程化外泌体来促进骨折修复的同时抗炎或是重塑血管系统。⑦外泌体的来源对神经组织修复作用的影响明显，不同神经细胞来源的外泌体通过不同的作用促进神经修复。此外，支架联合工程化外泌体用于创伤性脑损伤有明显优势，支架自身提供止血和支持作用，联合工程化外泌体的促修复作用，能获得更好的治疗效果。⑧对于心脏组织和肝组织的修复，更需要开发抗纤维化的工程化外泌体以抵抗心脏组织和肝组织自身的损伤后异常修复，此方面未来还需进一步研究。

关键词

工程化外泌体 / 工程化策略 / 组织修复 / 组织工程 / 生物材料 / 皮肤软组织 / 骨组织 / 神经组织 / 心脏组织 / 肝组织 / 再生医学

Abstract

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BACKGROUND: Exosomes are nanoscale extracellular vesicles secreted by various types of cells, with advantages such as high bioavailability, low toxicity, low immunogenicity, and good biocompatibility. However, natural exosomes have certain limitations in clinical therapy. By using bioengineering techniques to modify and engineer exosomes, the engineered exosomes not only improve their original therapeutic effects but also exhibit excellent biostability and targeting specificity, showing great potential for application in the field of tissue repair. OBJECTIVE: To summarize the various strategies for engineering exosomes, including functional loading and surface modification, outline the research progress of engineered exosomes in different tissue repairs, and explore the therapeutic potential of engineered exosomes in tissue repair. METHODS: PubMed database was searched for relevant literature published between 2010 and 2024 using the search terms “engineered exosomes, tissue repair, biomaterials, tissue engineering, wound healing, parenchyma, bone regeneration, cartilage, neural, myocardial, hepatic.” Studies that were not closely related to the article’s theme, of poor quality, repetitive, or outdated were excluded. A total of 115 articles met the inclusion criteria. RESULTS AND CONCLUSION: (1) Functional loading is used to combine therapeutic molecules with exosomes to obtain additional properties or to enhance the original physiological function of the exosome, among which ultrasonication and extrusion are simple to operate and can obtain higher drug loading capacity at the same time. (2) Surface modification can make exosomes express desired proteins or enhance their targeting, including genetic engineering and chemical modification. Genetic engineering is complicated, poorly reproducible, and the end product is poorly controllable. Chemical modification, on the other hand, is relatively simple and versatile, and is more suitable for designing highly targeted and functionally specific engineered exosomes. (3) Among the techniques for pre-treating cells to obtain engineered exosomes, hypoxic pre-treatment is more widely used because of its simplicity and clearer mechanism, which can activate glycolysis to promote cell proliferation, and regulate the vascular endothelial growth factor receptor signaling pathway through the generation of hypoxia-inducible factors to promote angiogenesis. (4) The function of exosomes is affected by various factors such as cell source, cell state, synthesis process, and extracellular environment. If the engineering strategy is complicated, it is more difficult to ensure the functional consistency of the final engineered exosomes, so the relatively simple and reliable engineering strategy is more suitable for its clinical application. (5) Engineered exosomes combined with biomaterials or scaffolds can be used to treat complex wounds of skin soft tissue, such as infected wounds and diabetic ulcers. This approach enhances exosome delivery and controls their release, promotes tissue repair, controls infection, and regulates the local microenvironment of the wound. (6) A single mechanism of engineered exosomes is often ineffective due to the specificity of the bone tissue fracture, so dual or even multi-functional engineered exosomes are needed to promote fracture repair while anti-inflammatory or remodeling the vascular system. (7) The source of exosomes has a significant impact on neural tissue repair. Exosomes derived from different neural cells promote neural repair through different effects. In addition, the combination of stents and engineered exosomes for traumatic brain injury has obvious advantages, the stent itself provides hemostasis and support, combined with the engineered exosomes itself to promote the repair effect, can obtain better therapeutic effect. (8) In cardiac and hepatic tissue repair, it is needed to develop anti-fibrotic engineered exosomes to resist the abnormal repair of cardiac and hepatic tissues themselves, which will require further research in the future.

Key words

engineered exosome / engineering strategies / tissue repair / tissue engineering / biomaterial / skin soft tissue / bone tissue / neural tissue / heart tissue / liver tissue / regenerative medicine

引用本文

罗文彬, 李若云, 潘超凡, 罗长江. 工程化外泌体修复组织损伤：应用潜力及优异的生物稳定性和靶向特异性. 中国组织工程研究, 2026 , 30 (1) : 204 -217 . DOI: 10.12307/2025.543

. Engineered exosomes for repairing tissue damage: application potential, excellent biological stability, and targeting specificity[J]. Chinese Journal of Tissue Engineering Research, 2026 , 30 (1) : 204 -217 . DOI: 10.12307/2025.543

基金

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甘肃省自然科学基金项目

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2026年第30卷第1期

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doi: 10.12307/2025.543

首发时间：2025-05-30
出版时间：2026-01-08

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录用日期：2024-09-13

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甘肃省自然科学基金项目

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^1.州大学第二临床医学院，甘肃省兰州市 730030

^2.州大学第二医院疝与腹壁外科，甘肃省兰州市 730030

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2种不同金属材料的力学参数

科 Family	属数 Number of genus	种数 Number of species	占总种数比例 Percentage of total species (%)	属 Genus	种数 Number of species	占总种数比例 Percentage of total species (%)
鹅膏菌科Amanitaceae	2	11	5.26	鹅膏菌属 Amanita	10	4.78
小菇科 Mycenaceae	2	12	5.74	丝盖伞属 Inocybe	5	2.39
多孔菌科 Polyporaceae	8	14	6.70	蜡蘑属 Laccaria	5	2.39
红菇科 Russulaceae	3	23	11.00	小皮伞属 Marasmius	6	2.87
				小菇属 Mycena	11	5.26
				光柄菇属 Pluteus	5	2.39
				红菇属 Russula	17	8.13
				栓菌属 Trametes	5	2.39

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