Hydrogel loaded with bone marrow stromal cell-derived exosomes promotes bone regeneration by inhibiting inflammatory responses and angiogenesis

doi:10.4252/wjsc.v16.i5.499

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World Journal of Stem Cells

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1948-0210

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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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

Guang Hong, Sheng Zheng, Chuan Lu, Shuai Zhang

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.

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

Abstract

BACKGROUND

Bone healing is a complex process involving early inflammatory immune regulation, angiogenesis, osteogenic differentiation, and biomineralization. Fracture repair poses challenges for orthopedic surgeons, necessitating the search for efficient healing methods.

AIM

To investigate the underlying mechanism by which hydrogel-loaded exosomes derived from bone marrow mesenchymal stem cells (BMSCs) facilitate the process of fracture healing.

METHODS

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

RESULTS

The hydrogel effectively attenuated the inflammatory response during the initial repair stage and subsequently facilitated vascular migration, promoted the formation of large vessels, and enabled functional vascularization during bone repair. These effects were further validated in fracture models.

CONCLUSION

We successfully fabricated a hydrogel loaded with BMSC-exo that modulates macrophage polarization and angiogenesis to influence bone regeneration.

Keywords: Hydrogel; Bone marrow mesenchymal stem cells; Macrophage polarization; Angiogenesis; Bone regeneration

Core Tip: We adopted a new method to enhance tissue repair and promote bone regeneration through hydrogels loaded with mesenchymal stem cell (MSC) exosomes. This experiment demonstrated that bone marrow-derived MSC (BMSC)-derived exosome (BMSC-exo) hydrogel significantly promoted the proliferation, migration and osteogenesis of mouse osteoblast progenitor cells, and at the same time enhanced the M2 polarization of macrophages in bone marrow, thus translating into accelerated fracture healing and angiogenesis in vivo. In addition, BMSC-exo hydrogels successfully enhance the strength and toughness of regenerated bone, with higher maximum load, stiffness and damage absorption energy.