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A Hydrogel Construct and Fibrin-based Glue Approach to Deliver Therapeutics in a Murine Myocardial Infarction Model.
Published on: June 14, 2015
Biomimetic oriented nanofiber-reinforced conductive cardiac patch for enhanced cardiac repair after myocardial
Zheng Cao1,2,3, Dong He1,2,3, Linjie Zhong4
1School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou 511442, China.
Abstract:
The myocardium is a highly organized, multilayered anisotropic tissue in which the extracellular matrix (ECM) provides structural guidance for cardiomyocyte alignment, enabling synchronized contraction and efficient electrical conduction. Following myocardial infarction (MI), however, this intricate architecture and electrical integrity are severely disrupted, leading to impaired cardiac function and limited self-repair capacity. Consequently, engineering bio-inspired, multi-strata electroactive scaffolds capable of mimicking the essential architectural and physiological properties of natural heart tissue represents a vital strategy for successful cardiac repair. In this study, we constructed a biomimetic oriented nanofiber-reinforced conductive cardiac patch by integrating dopamine-polypyrrole (DA-PPy) with a GelMa hydrogel matrix. In vitro, the presence of multi-strata oriented nanofibers conferred directional electrical properties to the hydrogel while orchestrating the orderly arrangement of cardiomyocytes. This architecture ensured that cellular alignment followed the fiber axis within each layer, displaying a seamless transition across the stacked interfaces. In a rat MI model, the implanted cardiac patch exhibited remarkable therapeutic effects, including significant improvement of cardiac function, attenuation of ventricular wall thinning and fibrosis, reduced cardiomyocyte apoptosis and oxidative stress, and enhanced angiogenesis within the infarcted region. Furthermore, seeding cardiomyocytes onto the cardiac patch before implantation further amplified these reparative outcomes. Taken together, this work highlights the indispensable nature of re-establishing both the ECM's structural integrity and its electrical properties to foster myocardial regrowth, while positioning our biomimetic conductive cardiac patch as a highly viable therapeutic modality for MI intervention.

