Basic Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. May 26, 2024; 16(5): 499-511
Published online May 26, 2024. doi: 10.4252/wjsc.v16.i5.499
Hydrogel loaded with bone marrow stromal cell-derived exosomes promotes bone regeneration by inhibiting inflammatory responses and angiogenesis
Shuai Zhang, Chuan Lu, Sheng Zheng, Guang Hong
Shuai Zhang, Chuan Lu, Guang Hong, Division for International Collaborative and Innovative Dentistry, Tohoku University Graduate School of Dentistry, Sendai 980-8575, Miyagi, Japan
Shuai Zhang, Sheng Zheng, School of Stomatology, Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang Province, China
Author contributions: Zhang S and Hong G contributed to the conception and design; Lu C and Zheng S analyzed and interpreted the data; Zhang S and Lu C drafted the article; Hong G critically revised it for important intellectual content; and all authors approved the final version for publication.
Institutional animal care and use committee statement: This study and the experimental procedures were approved by the Zhejiang Chinese Medical University. All animal experiments were approved by the Animal Care and Use Committee of the Ethical Institution of the Zhejiang Chinese Medical University.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Guang Hong, DDS, MD, PhD, Division for International Collaborative and Innovative Dentistry, Tohoku University Graduate School of Dentistry, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Miyagi, Japan. hong.guang.d6@tohoku.ac.jp
Received: November 30, 2023
Revised: January 17, 2024
Accepted: April 2, 2024
Published online: May 26, 2024
Processing time: 176 Days and 5.5 Hours
ARTICLE HIGHLIGHTS
Research background

Repairing large bone defects is a major challenge for plastic surgeons, and autologous bone transplantation is currently the best treatment option. However, its application is limited due to scarce resources and complications. Exosomes derived from mesenchymal stem cells (MSCs) have shown great potential in bone regenerative medicine, but they face issues such as rapid degradation, short half-life, and unpredictable side effects. Bone marrow stromal cells play a crucial role in bone formation and tissue repair by migrating from their niche to surrounding tissues and promoting regeneration. The interaction between angiogenic factors and bone marrow-derived MSCs (BMSCs) regulates downstream osteogenesis; for example, vascular endothelial growth factor A can stimulate platelet-derived growth factor receptors to modulate the migration and proliferation of BMSCs.

Research motivation

To find a more effective method for bone defect repair to overcome the limitation of autologous bone grafting. Develop and optimize extracellular vesicle technology to improve its usability and safety in clinical practice. To further investigate the role of BMSCS in bone regeneration and explore their wider application in tissue repair. To reveal the mechanism of interaction between angiogenic factors and BMSCS and provide a theoretical basis for future therapeutic strategies.

Research objectives

Bone healing is an intricate physiological process initiated by early inflammatory immune regulation encompassing multiple events, including angiogenesis, osteogenic differentiation, and biommineralization. In this study, we fabricated a BMSC-derived exosomes (BMSC-exos)-loaded hydrogel that dynamically integrates diverse biological functions and thus operates at distinct stages of the fracture healing process.

Research methods

The characterization of hydrogels and loaded BMSC-exo gels was verified to validate their properties. In vitro evaluations were conducted to assess the impact of hydrogels on various stages of the healing process. Hydrogels demonstrated the ability to recruit macrophages and inhibition of inflammatory responses, enhance human umbilical vein endothelial cell angiogenesis, and promote osteogenic differentiation of primary cranial osteoblasts. Furthermore, the effect of hydrogel on fracture healing was confirmed using a mouse fracture model.

Research results

During the initial stage of repair, the hydrogel loaded with BMSC-exos effectively attenuated the inflammatory response. Furthermore, they significantly enhanced vascular migration and angiogenesis. These effects were further corroborated in a fracture model.

Research conclusions

The present study proposes a novel approach for loading BMSC-exos, aiming to optimize patient outcomes by enhancing angiogenesis and bone regeneration capacity in a clinical setting. Simultaneously, continuous development and optimization of extracellular vesicle technology in clinical practice are necessary to improve its usability and safety.

Research perspectives

Further in-depth study of its possible mechanism of action and gradually spread to clinical application.