Tianqi Shi,Penghui Wang,Yanhan Ren,Wenjie Zhang,Juping Ma,Shuang Li,Xiaoyan Tan,Bo Chi
Remodeling the conductive zone to assist normal myocardial contraction and relaxation during myocardial fibrosis has become the primary concern of myocardial infarction (MI) regeneration. Herein, we report an unbreakable and self-recoverable hyaluronic acid conductive cardiac patch for MI treatment, which can maintain structural integrity under mechanical load and integrate mechanical and electrical conduction and biological cues to restore cardiac electrical conduction and diastolic contraction function. Using the free carboxyl groups and aldehyde groups in the hydrogel system, excellent adhesion properties are achieved in the interface between the myocardial patch and the tissue, which can be closely integrated with the rabbit myocardial tissue, reducing the need for suture. Interestingly, the hydrogel patch exhibits sensitive conductivity (ΔR/R0 ≈ 2.5) for 100 cycles and mechanical stability for 500 continuous loading cycles without collapse, which allows the patch to withstand mechanical damage caused by sustained contraction and relaxation of the myocardial tissue. Moreover, considering the oxidative stress state caused by excessive ROS in the MI area, we incorporated Rg1 into the hydrogel to improve the abnormal myocardial microenvironment, which achieved more than 80% free radicalscavenging efficiency in the local infarcted region and promoted myocardial reconstruction. Overall, these Rg1-loaded conductive hydrogels with highly elastic fatigue resistance have great potential in restoring the abnormal electrical conduction pathway and promoting the myocardial microenvironment, thereby repairing the heart and improving the cardiac function.
Although hydrogel-based patches have shown promising therapeutic efficacy in myocardial infarction (MI), synergistic mechanical, electrical, and biological cues are required to restore cardiac electrical conduction and diastolic–systolic function. Here, an injectable mechanical–electrical coupling hydrogel patch (MEHP) is developed via dynamic covalent/noncovalent cross-linking, appropriate for cell encapsulation and minimally invasive implantation into the pericardial cavity. Pericardial fixation and hydrogel self-adhesiveness properties enable the MEHP to highly compliant interfacial coupling with cyclically deformed myocardium. The self-adaptive MEHP inhibits ventricular dilation while assisting cardiac pulsatile function. The MEHP with the electrical conductivity and sensitivity to match myocardial tissue improves electrical connectivity between healthy and infarcted areas and increases electrical conduction velocity and synchronization. Overall, the MEHP combined with cell therapy effectively prevents ventricular fibrosis and remodeling, promotes neovascularization, and restores electrical propagation and synchronized pulsation, facilitating the clinical translation of cardiac tissue engineering.
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