Influence of Diameter and Cyclic Mechanical Stimulation on the Beating Frequency of Myocardial Cell-Laden Fibers

Abstract

Atrioventricular block (AVB) is a severe disease for pediatric patients. The repetitive operations needed in the case of the pacemaker implantation to maintain the electrical signal at the atrioventricular node (AVN) affect the patient’s life quality. In this study, we present a method of biofabrication of multi-cell-laden cylindrical fibrin-based fibers that can restore the electrical signal at the AVN. We used human umbilical vein smooth muscle cells (HUVSMCs), human umbilical vein endothelial cells (HUVECs) and induced pluripotent stem cell cardiomyocytes (iPSC-CMs) cultivated either statically or dynamically to mimic the native AVN. We investigated the influence of cell composition, construct diameter and cyclic stretch on the function of the fibrin hydrogels in vitro. Immunohistochemistry analyses showed the maturity of the iPSC-CMs in the constructs through the expression of sarcomeric alpha actinin (SAA) and electrical coupling through Connexin 43 (Cx43) signal. Simultaneously, the beating frequency of the fibrin hydrogels was higher and easy to maintain whereas the concentration of iPSC-CMs was higher compared with the other types of cylindrical constructs. In total, our study highlights that the combination of fibrin with the cell mixture and geometry is offering a feasible biofabrication method for tissue engineering approaches for the treatment of AVB.

A Dexamethasone-Loaded Polymeric Electrospun Construct as a Tubular Cardiovascular Implant

“…The medium was changed at day 2, 4, 6, 8, 10, 12, and 14. For the samples containing iPSC-CMs, cylindrical fibrin gels were prepared as previously described [34], and were inserted inside the polymeric tubular structures on day 3, 7, and 10 of the cultivation period.…”

The Challenge of E-Spinning Sub-Millimeter Tubular Scaffolds—A Design-of-Experiments Study for Fiber Yield Improvement

“…Small tubular scaffolds in the sub-millimeter range are highly needed in the development of medicine products, e.g., in nerve [ 1 , 2 ], islet cell [ 3 ], and cardiovascular tissue engineering [ 4 ]. Within tissue engineering, electrospinning has gained significant attention owing to its ability to create highly porous structures characterized with an exceptional surface area to volume ratio and fiber diameters that can mimic the structure of the extracellular matrix (ECM).…”