Engineering challenges in microphysiological systems

Modeling human physiology with the microphysiological systems In humans, tissues and organs are made of hierarchically assembled structures of mul tiple compositions to achieve biological func tions. The different tissues and organs are then organized in a specific order enabled by a circuitry of vascular network, further achieving physiological interactions. On the one hand, many of these complex elements cannot be readily reproduced on the con ventional planar, static cell culture systems already used in biology and medicine for over a century [1]. On the other hand, while pre clinical animal models are both biologically and physiologically capable, their relevancy to the human system remains question able, often leading to inaccurate clinical translation of assay results [2]. To this end, microphysiological systems, which are miniaturized biomimetic in vitro human tissue and organ models built from a combination of biological and engineering approaches, usually feature much higher per formance in recapitulating the functions of their in vivo counterparts [3–7]. A microphysio logical system usually consists of three main aspects: the organoid that is biologically relevant, often generated through principles including developmental biology [8], tissue engineering [9], bioreactor designs [10,11] and their combinations; the biophysical cues that represent the local niches, such as the sup porting matrix with tissuematching proper ties [12], shear stress/interstitial pressure [13] and biomechanical strains [14]; and the cir culatory system that brings in physiological relevance, to enable communications among different organoids [5]. The ability to interconnect multiple organ oids together in a fashion so that the integral platforms reproduce their desired human physiology, forms the unique strength of the microphysiological systems. This is because of the fact that in the human body no single tissue or organ is isolated, where the function and behavior of one is closely dependent on the others through biophysical and biochem ical interactions. Sung and Shuler piloted the micro cell culture analog devices where up to ten types of organs were integrated to study their interactions [15]. Wikswo proposed the microphysiological systems with builtin valves to control the ‘blood flow’ among dif ferent organs [4]. More recently, a platform was developed to support longterm cocul ture of multiple human organoids [16], and a portable, reconfigurable multiorgan system with onboard microfluidic flow control has been reported [17]. Further development of Engineering challenges in microphysiological systems