Affiliation:
1. Beijing Institute of Basic Medical Sciences 27 Taiping Rd Beijing 100850 P. R. China
2. The Higher Educational Key Laboratory for Biomedical Engineering of Fujian Province Research Center of Biomedical Engineering of Xiamen Department of Biomaterials College of Materials Xiamen University 422 Siming Nan Road Xiamen 361005 P. R. China
Abstract
AbstractInjectable hydrogels carrying therapeutic factors to modulate the infarct immune microenvironment show great potential in the treatment of myocardial infarction (MI). However, conventional injectable hydrogels release therapeutic factors in an uncontrolled manner, which leads to poor treatment efficacy and acute side effects on normal tissues. In this work, a matrix metalloproteinase (MMP)2/9‐responsive hydrogel system (MPGC4) is developed, considering the characteristics of the post‐MI microenvironment. MPGC4 consists of tetra‐poly(ethylene glycol) (PEG) hydrogels and a composite gene nanocarrier (CTL4) that is composed of carbon dots (CDots) coupled with interleukin‐4 plasmid DNA via electrostatic interactions. MPGC4 can be automatically triggered to release CTL4 on demand after MI to regulate the infarct immune microenvironment. In addition, due to the photoluminescence properties of CDots, a large amount of viscoelastic MPGC4 is found to be retained in situ after injection into the infarct region without leakage. The in vitro results demonstrate that CTL4 promotes proinflammatory M1 macrophage polarization to the anti‐inflammatory M2 subtype and contributes to cardiomyocyte survival through macrophage transition. In a rat model of MI, MPGC4 clears MMPs and precisely targets CTL4 to the infarcted region. In particular, MPGC4 improves cardiac function by modulating macrophage transition to reduce early inflammatory responses and proangiogenic activity.
Funder
National Key Research and Development Program of China
National Natural Science Foundation of China
Subject
Mechanical Engineering,Mechanics of Materials,General Materials Science
Cited by
10 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献