Journal Article Epublish
PubMed: 40321300 DOI: 10.1093/burnst/tkaf005
A bioactive hydrogel patch accelerates revascularization in ischemic lesions for tissue repair.
Burns Trauma 13:tkaf005
Authors: Zhuo Liu, Kang Wu, Hong Zeng, Wenxin Huang, Xuemeng Wang, Ying Qu, Chuntao Chen, Lei Zhang, Dongpin Sun, Sifeng Chen, Xiao Lin, Ning Sun, Lei Yang, Chen Xu
Affiliations
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, 138 Xueyuan Road, Shanghai 200032, P.R. China.
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, 138 Xueyuan Road, Shanghai 200032, P.R. China. Orthopedic Institute, Department of Orthopedics, The First Affiliated Hospital, Soochow University, 178 East Ganjiang Road, Gusu District, Suzhou 215021, P.R. China.
- China Chemicobiology and Functional Materials Institute, School of Chemistry and Chemical Engineering, Nanjing University of Science and Technology, 200 Xiao Ling Wei Street, Xuanwu District, Nanjing 210094, P.R. China.
- Orthopedic Institute, Department of Orthopedics, The First Affiliated Hospital, Soochow University, 178 East Ganjiang Road, Gusu District, Suzhou 215021, P.R. China.
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, 138 Xueyuan Road, Shanghai 200032, P.R. China. Department of Basic Medicine, Wuxi School of Medicine, Jiangnan University, 1800 Lihu Road, Binhu District, Wuxi, Jiangsu 214122, P.R. China.
- Orthopedic Institute, Department of Orthopedics, The First Affiliated Hospital, Soochow University, 178 East Ganjiang Road, Gusu District, Suzhou 215021, P.R. China. Center for Health Sciences and Engineering (CHSE), Hebei Key Laboratory of Biomaterials and Smart Theranostics, School of Health Sciences and Biomedical Engineering, Hebei University of Technology, 8 Guangrong Road, Hongqiao District, Tianjin 300131, P.R. China.
Abstract
Background
Magnesium ions play crucial roles in maintaining cellular functions. Research has shown that Mg can promote angiogenesis, indicating its potential for treating cardiovascular ischemic diseases. However, conventional intravenous or oral administration of Mg presents several challenges, including the risk of systemic side effects, diminished bioavailability, and a lack of targeted delivery mechanisms. In this study, we designed an Mg-releasing adhesive tissue patch (MgAP) that enables the dural release of Mg ions.
Methods
A novel MgAP was developed on the basis of ionic crosslinking. Fourier transform infrared spectroscopy confirmed the chemical structure, whereas rheological analysis demonstrated stable mechanical properties and adaptability to dynamic loads. Sustained Mg release was quantified over 7 days by inductively coupled plasma-mass spectrometry. In a rat acute myocardial infarction model, we performed echocardiography and strain analysis to assess cardiac function and histological staining to evaluate adverse remodeling. We also verified the proangiogenic effect through tube formation and immunofluorescence assays. Furthermore, transcriptomics and Western blotting were performed to explore the underlying mechanism. Additional assessments were also carried out in a rat model of lower limb ischemia.
Results
Compared with intravenous administration of magnesium chloride, MgAP application effectively improved cardiac function and reduced adverse remodeling in the myocardial infarction rat model. The left ventricular ejection fraction increased by 20.3 ± 6.6%, and the cardiac radial strain improved by 27.4 ± 4.1%. The cardiac fibrosis area and cell apoptosis rate decreased by 10.9 ± 1.2% and 32.1 ± 5.5%, respectively. RNA sequencing analysis also highlighted the upregulation of genes related to cardiac electrophysiological properties, structural and functional intercellular connections, and revascularization. The increased gap junction protein expression and restored local blood supply could contribute to the cardiac repair process posttreatment. The proangiogenic effect of MgAP was also observed in the rat limb ischemia model.
Conclusions
The above results revealed the convincing vascular regeneration effect of an ion therapy-based hydrogel, which enabled the local delivery of Mg to the targeted ischemic tissue, aiding in cardiac and lower limb repair. This study presents a novel strategy and highlights its potential for use across various ischemic conditions.
MeSH
Cells, Genes, Hydrogel, Polyethylene Glycol Dimethacrylate, Hydrogels, Myocardial Infarction, Tissues, Wounds And Injuries, Ischemia