Elastin-like polypeptide-based hydrogel actuator for cardiac tissue engineering

摘要

Cardiac tissue engineering aims to reconstruct functional construction with resembling native tissue to replace damaged myocardium. To mimic native myocardium, cells with phenotypes of mature cardiomyocytes and scaffolds with elastic, electro-conductive, highly porous, and biodegradable plays two major roles. So far, although a number of cell types have been evaluated in the reports of cardiac repair, most of them cannot form functional cardiomyocytes with mature cardiac phenotypes including the formation of the myocytic syncytium with surrounding cardiomyocytes, and expression of cardiac specific proteins in completely organized pattern. The maturation of cardiomyocytes can be achieved by multiple stimuli such as electrical stimulation, mechanical stretching, and chemical stimulation. Therefore, in this study, we aimed to develop a conductive hydrogel actuator based on elastin-like polypeptide (ELP) consisting of repeating elastin-derived sequences Val-Pro-Gly-Ile-Gly (VPGIG), combining near-infrared light (NIR)-induced mechanical stretching and electrical stimulation for the simulation of immature cardiomyocytes. The hydrogel actuator can be fabricated by rapidly crosslinking by tetrakis(hydroxymethyl) phosphonium chloride (THPC) to form a high density porous structure, providing cardiac muscle cell an extracellular matrix (ECM)-like nanostructure with bioactive Arg-Gly-Asp (RGD) peptide. It showed appropriate mechanical strength and sufficient electroactivity, which is suitable for myocardial cell culture system. In addition, the actuation leads a specific and efficient way to regulate activity in cardiac muscle cell by physical cue of the hydrogel. In the future, we expect the ELP-baesd hydrogel actuator to show great potential to be used in the differentiation and maturation of cardiomyocytes.