A bioactive hydrogel patch accelerates revascularization in ischemic lesions for tissue repair

Abstract

Background: Magnesium ions play crucial roles in maintaining cellular functions. Research has shown that Mg²⁺ can promote angiogenesis, indicating its potential for treating cardiovascular ischemic diseases. However, conventional intravenous or oral administration of Mg²⁺ 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 Mg²⁺-releasing adhesive tissue patch (MgAP) that enables the dural release of Mg²⁺ 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 Mg²⁺ 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 in vitro tube formation and in vivo 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 Mg²⁺ 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.

Keywords

Ion therapy / Acute myocardial infarction / Lower limb ischemia / Angiogenesis

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