Exosome-mimetic vesicles derived from fibroblasts carrying matrine for wound healing

Author:

Zhang Xinyue12,Huang Jiahua34,Zhao Jing56,Li Lisha12,Miao Fengze12,Zhang Tingrui12,Chen Zhongjian12,Zhou Xing78,Tai Zongguang12ORCID,Zhu Quangang12

Affiliation:

1. Shanghai Skin Disease Hospital, School of Medicine, Tongji University , 1278 Baode Road, Shanghai 200443 , China

2. Shanghai Engineering Research Center for Topical Chinese Medicine , 1278 Baode Road, Shanghai 200443 , China

3. Department of Neurology , Shanghai Public Health Clinical Center, , 2901 Caolang Road, Shanghai 201500 , China

4. Fudan University , Shanghai Public Health Clinical Center, , 2901 Caolang Road, Shanghai 201500 , China

5. The Central Hospital of Wuhan , Tongji Medical College, , 26 Shengli Street, Wuhan 430014, Hubei , China

6. Huazhong University of Science and Technology , Tongji Medical College, , 26 Shengli Street, Wuhan 430014, Hubei , China

7. Yunnan Key Laboratory of Stem Cell and Regenerative Medicine , Science and Technology Achievement Incubation Center, , 1168 Chunrong West Road, Kunming 650500, Yunnan , China

8. Kunming Medical University , Science and Technology Achievement Incubation Center, , 1168 Chunrong West Road, Kunming 650500, Yunnan , China

Abstract

Abstract Background Chronic skin wounds are a leading cause of hospital admissions and reduced life expectancy among older people and individuals with diabetes. Delayed wound healing is often attributed to a series of cellular abnormalities. Matrine, a well-studied component found in Sophora flavescens, is recognized for its anti-inflammatory effects. However, its impact on wound healing still remains uncertain. This study aims to explore the potential of matrine in promoting wound healing. Methods In this study, we utilized gradient extrusion to produce fibroblast-derived exosome-mimetic vesicles as carriers for matrine (MHEM). MHEM were characterized using transmission electron microscopy and dynamic light scattering analysis. The therapeutic effect of MHEM in wound healing was explored in vitro and in vivo. Results Both matrine and MHEM enhanced the cellular activity as well as the migration of fibroblasts and keratinocytes. The potent anti-inflammatory effect of matrine diluted the inflammatory response in the vicinity of wounds. Furthermore, MHEM worked together to promote angiogenesis and the expression of transforming growth factor β and collagen I. MHEM contained growth factors of fibroblasts that regulated the functions of fibroblasts, keratinocytes and monocytes, which synergistically promoted wound healing with the anti-inflammatory effect of matrine. Conclusions MHEM showed enhanced therapeutic efficacy in the inflammatory microenvironment, for new tissue formation and angiogenesis of wound healing.

Funder

National Natural Science Foundation of China

Science and Technology Commission of Shanghai Municipality

Shanghai Municipal Health Commission

Publisher

Oxford University Press (OUP)

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