Recreating Physiological Environments In Vitro: Design Rules for Microfluidic‐Based Vascularized Tissue Constructs

Vascularization of engineered tissue constructs remains one of the greatest unmet challenges to mimicking the native tissue microenvironment in vitro. The main obstacle is recapitulating the complexity of the physiological environment while providing simplicity in operation and manipulation of the model. Microfluidic technology has emerged as a promising tool that enables perfusion of the tissue constructs through engineered vasculatures and precise control of the vascular microenvironment cues in vitro. The tunable microenvironment includes i) biochemical cues such as coculture, supporting matrix, and growth factors and ii) engineering aspects such as vasculature engineering methods, fluid flow, and shear stress. In this systematic review, the design considerations of the microfluidic‐based in vitro model are discussed, with an emphasis on microenvironment control to enhance the development of next‐generation vascularized engineered tissues. Tissue perfusion is essential for the survival of the tissue inner core and can be achieved through perfusable vascular networks constructed by employing microfluidic technology. However, there are still challenges in recreating a physiologically realistic microenvironment system in vitro. The biochemical and engineering aspects of the tissue microenvironment that regulate vasculature formation on a microfluidic platform are discussed.