Physiologically relevant platform for an advanced in vitro model of the vascular wall: focus on in situ fabrication and mechanical maturation.

Abstract

The mechanical stimulation applied on engineered vascular constructs in perfusion bioreactors has been shown to be beneficial for their maturation. The level of mechanical stimulation applied on these constructs depends on the flow parameters of the circuit (e.g., fluid viscosity, flow rate, frequency, and pressure). As a group, these parameters are often overlooked in the literature, and they rarely meet the physiological values of the blood flow. For this reason, the level of circumferential stretching and shear stress that blood vessels experience in the human body are rarely reproduced. In this work, we reported the development of a physiologically relevant platform for (1) the in situ fabrication of vascular wall models based on collagen gel, and (2) their maturation under physiological levels of mechanical stimulation in a perfusion bioreactor (pulsatile flow rate of 100 mL/min, frequency of 1 Hz, pressure of 80-120 mmHg, and viscosity of 4 cP). One week of dynamic maturation oriented the seeded cells into the circumferential direction, increased the deposition of collagen and key elastin fiber-related proteins, and improved the mechanical properties in terms of tensile equilibrium elastic modulus (by 110%) and strength at break (by 63%) when compared to the static condition. In addition to the maturation study under selected physiologically relevant mechanical stimulation (such as adult, fetal, child, and hypertension conditions), the platform might also be used as a relevant in vitro testing system for new drugs or pro-active coating to medical devices (such as stents, endografts, and vascular prostheses) expected to trigger specific mechanisms or activities in vascular cells composing the arterial wall.