Endothelialization and Flow Conditioning of Fibrin-Based Media-Equivalents

Abstract

It is generally accepted that endothelialization and subsequent development of a functional endothelium are of paramount importance to the success of any bioartificial artery. In this study, we aimed to assess the ability of smooth muscle cell-remodeled, fibrin-based media-equivalents (MEs) to be endothelialized, examine the morphological changes of endothelial cells (ECs) associated with exposure to physiologically-relevant shear stress in a custom-built bioreactor, and determine if adherent ECs are capable of withstanding average physiological shear stresses. It was found that MEs could be readily endothelialized with surface coverages of 98.8 +/- 0.9% after two days, and the ECs expressed von Willebrand factor. Furthermore, EC retention remained high (steady: 96.5 +/- 4.4%, pulsatile: 94.3 +/- 4.3%) under exposure to physiologically relevant shear stresses for 48 h. The results indicate that these MEs are conducive to generating an EC monolayer, with the ECs possessing adhesion strength sufficient to withstand physiological shear stress and maintain a normal phenotype.

A fibrinogen-based precision microporous scaffold for tissue engineering

“…They have been investigated for the development of many tissues including cartilage, [15] heart valves, [9] and bioartificial arteries. [10,23] However, the mechanical strength of fibrin hydrogel constructs is initially weak. Promising in-vitro studies performed by Jockenhoevel et al using typical fibrin hydrogels in cardiovascular tissue engineering have been conducted, however, disadvantages were noted.…”

Vascularization Strategies for Tissue Engineering

“…Vascular perfusion bioreactors typically focus on producing a tissue-engineered blood vessel, not on vascularizing another tissue type. Using pulsatile conditions typically found in vivo, functional arteries may be grown in vitro [83][84][85][86][87] Only recently have vessels been used as a means of perfusing a larger tissue, such as the abdominal aorta of a rat as a core perfusion element within an artificial myocardial matrix of collagen and neonatal rat cardiomyocytes. 88 The perfused tissues displayed enhanced cell viability and increased metabolic activity when compared to nonperfused controls.…”

A thermoresponsive, microtextured substrate for cell sheet engineering with defined structural organization

“…Attempts to specifically engineer such organization into tissue engineered arteries have met with differing degrees of success. While biopolymer-based tissues have been shown to possess the proper alignment of matrix components [9][10][11] and exhibit mechanical anisotropy [12], their overall mechanical properties are not sufficient for implantation [13]. On the other hand, tissue engineered grafts made solely from cell-secreted ECM, using a "self-assembly" or cell sheet-based approach, could support high burst pressures and have shown success in vivo, yet lacked the desired organization [14].…”