ROS-responsive drug-releasing injectable microgels for ameliorating myocardial infarction

Shuqin Wang; Yuejun Yao; Liang Song; Zihe Zhai; Shifen Li; Zhaolong Wang; Liyin Shen; Yang Zhu; Wenxing Liu; Changyou Gao

doi:10.1016/j.biomaterials.2024.122534

ROS-responsive drug-releasing injectable microgels for ameliorating myocardial infarction

Biomaterials. 2024 Jun:307:122534. doi: 10.1016/j.biomaterials.2024.122534. Epub 2024 Mar 16.

Authors

Shuqin Wang¹, Yuejun Yao¹, Liang Song¹, Zihe Zhai¹, Shifen Li¹, Zhaolong Wang¹, Liyin Shen¹, Yang Zhu², Wenxing Liu³, Changyou Gao⁴

Affiliations

¹ MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310058, China.
² MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310058, China. Electronic address: zhuyang@zju.edu.cn.
³ MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310058, China; Center for Healthcare Materials, Shaoxing Institute, Zhejiang University, Shaoxing, 312099, China. Electronic address: wenxingliu@zju.edu.cn.
⁴ MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310058, China; Center for Healthcare Materials, Shaoxing Institute, Zhejiang University, Shaoxing, 312099, China; Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University, Hangzhou, 310058, China. Electronic address: cygao@zju.edu.cn.

PMID: 38518589
DOI: 10.1016/j.biomaterials.2024.122534

Abstract

Despite of the recent advances in regulatory T cell (Treg) therapy, a limited number of available cells and specificity at the desired tissue site have severely compromised their efficacy. Herein, an injectable drug-releasing (MTK-TK-drug) microgel system in response to in situ stimulation by reactive oxygen species (ROS) was constructed with a coaxial capillary microfluidic system and UV curing. The spherical microgels with a size of 150 μm were obtained. The MTK-TK-drug microgels efficiently converted the pro-inflammatory Th17 cells into anti-inflammatory regulatory T cells (Treg) cells in vitro, and the ROS-scavenging materials synergistically enhanced the effect by modulating the inflammation microenvironment. Thus, the microgels significantly reduced cardiomyocyte apoptosis and decreased the inflammatory response in the early stages of post-myocardial infarction (MI) in vivo, thereby reducing fibrosis, promoting vascularization, and preserving cardiac function. Overall, our results indicate that the MTK-TK-drug microgels can attenuate the inflammatory response and improve MI therapeutic effects in vivo.

Keywords: Microgel; Myocardial infarction; ROS; Regulatory T cells; Th17.

MeSH terms

Humans
Microfluidics
Microgels*
Myocardial Infarction* / drug therapy
Reactive Oxygen Species
T-Lymphocytes, Regulatory

Substances

Microgels
Reactive Oxygen Species