Abstract
Abstract
Background
Ischemic heart disease (IHD) remains a global health challenge, characterized by irreversible cardiomyocyte loss and pathological ventricular remodeling. Myocardial patches provide mechanical support for infarcted myocardium, but conventional biomaterials lack bioactive components to facilitate tissue regeneration. This study introduces a novel therapeutic strategy: a stromal cell-derived factor-1 (SDF-1)-loaded decellularized extracellular matrix (dECM) (SDF-dECM) patch addressing both biological and biomechanical deficiencies in myocardial repair.
Methods
Porcine left ventricular dECM was decellularized, and SDF-1 was loaded to fabricate the SDF-dECM patch. The patch’s physicochemical properties, biocompatibility, and SDF-1 release profile were evaluated via hematoxylin and eosin/4’,6-diamidino-2-phenylindole staining, scanning electron microscopy, cytotoxicity assay, and enzyme-linked immunosorbent assay (ELISA). Transwell assays determined the chemotactic effect of SDF-1 on bone marrow mesenchymal stem cells (BMMSCs) and optimal concentration. Uniaxial tensile testing assessed mechanical properties. A finite element method (FEM) model was established to evaluate the patch’s mechanical support. In vivo, male Sprague-Dawley rats were randomly divided into four groups (
n
= 15 per group): Sham, myocardial infarction (MI), MI + dECM, and MI + SDF-dECM. Echocardiography, histochemical staining, and immunofluorescence staining were used to assess cardiac function, tissue morphology, BMMSCs homing, microvascular regeneration, and cardiomyocyte apoptosis. The paracrine mechanism of BMMSCs was evaluated via ELISA and functional assays.
Results
The SDF-dECM patch achieved successful decellularization, maintained a porous structure (50-150 μm pore size), exhibited favorable biphasic mechanical properties, and exhibited sustained SDF-1 release for 28 days. SDF-1 effectively induced BMMSCs migration via the SDF-1/CXCR4 axis, with 200 ng/mL as the optimal concentration. In vivo, the SDF-dECM patch significantly enhanced endogenous BMMSCs homing to the peri-infarct area, promoted peri-infarct microvascular regeneration, and inhibited cardiomyocyte apoptosis. BMMSCs-conditioned medium contained high levels of vascular endothelial growth factor and hepatocyte growth factor, exerting pro-angiogenic and anti-apoptotic effects. FEM simulations showed the patch reduced infarct zone wall stress and stress concentration. Echocardiography and histological analysis confirmed the SDF-dECM patch significantly improved cardiac function, reduced infarct size and alleviated myocardial fibrosis.
Conclusion
The dual-functional SDF-dECM patch integrates sustained SDF-1 delivery for endogenous BMMSCs mobilization and biomechanical support to mitigate ventricular remodeling. The synergy between biological activity and mechanical stabilization provides a promising therapeutic strategy for IHD, overcoming limitations of conventional biomaterials.