Liu Zhuo, Wu Kang, Zeng Hong, Huang Wenxin, Wang Xuemeng, Qu Ying, Chen Chuntao, Zhang Lei, Sun Dongpin, Chen Sifeng, Lin Xiao, Sun Ning, Yang Lei, Xu Chen
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.
Burns Trauma. 2025 May 2;13:tkaf005. doi: 10.1093/burnst/tkaf005. eCollection 2025.
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.
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.
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.
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.
镁离子在维持细胞功能方面发挥着关键作用。研究表明，镁可促进血管生成，这表明其在治疗心血管缺血性疾病方面具有潜力。然而，传统的静脉注射或口服镁存在诸多挑战，包括全身副作用风险、生物利用度降低以及缺乏靶向递送机制。在本研究中，我们设计了一种能实现硬膜释放镁离子的镁释放黏附组织贴片（MgAP）。
基于离子交联开发了一种新型MgAP。傅里叶变换红外光谱证实了其化学结构，而流变学分析表明其具有稳定的力学性能以及对动态负荷的适应性。通过电感耦合等离子体质谱法对7天内镁的持续释放进行了定量分析。在大鼠急性心肌梗死模型中，我们进行了超声心动图和应变分析以评估心脏功能，并通过组织学染色评估不良重塑情况。我们还通过管腔形成和免疫荧光测定验证了促血管生成作用。此外，进行了转录组学和蛋白质印迹分析以探索潜在机制。在大鼠下肢缺血模型中也进行了额外评估。
与静脉注射氯化镁相比，应用MgAP可有效改善心肌梗死大鼠模型的心脏功能并减少不良重塑。左心室射血分数增加了20.3±6.6%，心脏径向应变改善了27.4±4.1%。心脏纤维化面积和细胞凋亡率分别降低了10.9±1.2%和32.1±5.5%。RNA测序分析还突出了与心脏电生理特性、细胞间结构和功能连接以及血管再生相关基因的上调。间隙连接蛋白表达的增加和局部血供的恢复可能有助于治疗后的心脏修复过程。在大鼠肢体缺血模型中也观察到了MgAP的促血管生成作用。
上述结果揭示了基于离子疗法的水凝胶具有令人信服的血管再生作用，该水凝胶能够将镁局部递送至靶向缺血组织，有助于心脏和下肢修复。本研究提出了一种新策略，并突出了其在各种缺血性疾病中的应用潜力。
