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骨组织工程应用中细胞外囊泡整合生物材料:当前进展与未来展望

Extracellular Vesicle-Integrated Biomaterials in Bone Tissue Engineering Applications: Current Progress and Future Perspectives.

作者信息

Huang Yan, Xie Hui

机构信息

Department of Rehabilitation Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430000 People's Republic of China.

Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430000 People's Republic of China.

出版信息

Int J Nanomedicine. 2025 Jun 17;20:7653-7683. doi: 10.2147/IJN.S522198. eCollection 2025.


DOI:10.2147/IJN.S522198
PMID:40546799
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12182063/
Abstract

With an aging population and increased life expectancy, the clinical burden of bone-related disorders, especially large bone defects, continues to grow, underscoring the urgent need for effective regenerative strategies. Effective bone regeneration is essential not only for restoring skeletal structure and function but also for improving patients' quality of life and reducing the socioeconomic burden associated with prolonged recovery or surgical failure. Bone tissue engineering has emerged as a promising approach for healing large bone defects. Traditionally, stem cells, biomaterial scaffolds and growth factors have been considered the three essential elements of bone tissue engineering. However, stem cell-based therapies face several significant challenges, including ectopic tissue formation, malignant transformation, cell embolism, and immune rejection. In recent years, extracellular vesicles (EVs) have gained significant attention as an advanced alternative to stem cells and a novel cell-free therapy for bone regeneration due to their inherent advantages, such as low immune-rejection, excellent biocompatibility, significant bioactivity and high feasibility for carrying bioactive molecules or drugs. This review provides a comprehensive overview of the current state and future potential of EV-based strategies in bone tissue engineering. We first review the sources of parent cells for EVs applied in bone tissue engineering and the roles and potential mechanisms of EVs in bone regeneration. We then discuss the various modification strategies employed to enhance the therapeutic potential of EVs. Additionally, we summarize strategies for integrating EVs with various biomaterial scaffolds, with a specific focus on the latest advances in achieving controlled and sustained release of EVs from scaffolds at bone defect sites. Collectively, this review aims to offer key insights into the translational potential of EV-functionalized biomaterials and guide future directions in the development of next-generation bone regenerative therapies.

摘要

随着人口老龄化和预期寿命的增加,与骨骼相关疾病的临床负担,尤其是大的骨缺损,持续增长,这凸显了对有效再生策略的迫切需求。有效的骨再生不仅对于恢复骨骼结构和功能至关重要,而且对于提高患者的生活质量以及减轻与长期康复或手术失败相关的社会经济负担也至关重要。骨组织工程已成为治疗大骨缺损的一种有前景的方法。传统上,干细胞、生物材料支架和生长因子被认为是骨组织工程的三个基本要素。然而,基于干细胞的疗法面临着几个重大挑战,包括异位组织形成、恶性转化、细胞栓塞和免疫排斥。近年来,细胞外囊泡(EVs)因其固有的优势,如低免疫排斥、优异的生物相容性、显著的生物活性以及携带生物活性分子或药物的高可行性,作为干细胞的一种先进替代物和用于骨再生的新型无细胞疗法而受到了广泛关注。本综述全面概述了基于EVs的策略在骨组织工程中的现状和未来潜力。我们首先回顾了应用于骨组织工程的EVs的母细胞来源以及EVs在骨再生中的作用和潜在机制。然后,我们讨论了为增强EVs的治疗潜力而采用的各种修饰策略。此外,我们总结了将EVs与各种生物材料支架整合的策略,特别关注在骨缺损部位从支架实现EVs的可控和持续释放方面的最新进展。总体而言,本综述旨在提供关于EV功能化生物材料转化潜力的关键见解,并指导下一代骨再生疗法开发的未来方向。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96d9/12182063/992a3fdec7af/IJN-20-7653-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96d9/12182063/02cb7d3f0cfd/IJN-20-7653-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96d9/12182063/cf3db8388cc4/IJN-20-7653-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96d9/12182063/efb285953442/IJN-20-7653-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96d9/12182063/992a3fdec7af/IJN-20-7653-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96d9/12182063/02cb7d3f0cfd/IJN-20-7653-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96d9/12182063/cf3db8388cc4/IJN-20-7653-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96d9/12182063/efb285953442/IJN-20-7653-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96d9/12182063/992a3fdec7af/IJN-20-7653-g0004.jpg

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引用本文的文献

[1]
Extracellular Vesicles in Osteogenesis: A Comprehensive Review of Mechanisms and Therapeutic Potential for Bone Regeneration.

Curr Issues Mol Biol. 2025-8-21

本文引用的文献

[1]
Enhanced Tissue Regeneration Through Immunomodulatory Extracellular Vesicles Encapsulated in Diversified Silk-Based Injectable Hydrogels.

Adv Healthc Mater. 2024-11

[2]
Yoda1 pretreated BMSC derived exosomes accelerate osteogenesis by activating phospho-ErK signaling via Yoda1-mediated signal transmission.

J Nanobiotechnology. 2024-7-10

[3]
Synergistic Interaction between Polysaccharide-Based Extracellular Matrix and Mineralized Osteoblast-Derived EVs Promotes Bone Regeneration via miRNA-mRNA Regulatory Axis.

Biomacromolecules. 2024-7-8

[4]
Extracellular Vesicles Derived from HO-Stimulated Adipose-Derived Stem Cells Alleviate Senescence in Diabetic Bone Marrow Mesenchymal Stem Cells and Restore Their Osteogenic Capacity.

Drug Des Devel Ther. 2024

[5]
Application of Deferoxamine in Tissue Regeneration Attributed to Promoted Angiogenesis.

Molecules. 2024-4-29

[6]
Extracellular Vesicles Derived from Neutrophils Accelerate Bone Regeneration by Promoting Osteogenic Differentiation of BMSCs.

ACS Biomater Sci Eng. 2024-6-10

[7]
Mesenchymal stem cell-derived extracellular vesicles: a regulator and carrier for targeting bone-related diseases.

Cell Death Discov. 2024-5-2

[8]
Bone Tissue Engineering and Nanotechnology: A Promising Combination for Bone Regeneration.

Biology (Basel). 2024-4-2

[9]
An Overview on the Big Players in Bone Tissue Engineering: Biomaterials, Scaffolds and Cells.

Int J Mol Sci. 2024-3-29

[10]
Osteoinductive Dental Pulp Stem Cell-Derived Extracellular Vesicle-Loaded Multifunctional Hydrogel for Bone Regeneration.

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