Building Blood Vessel Chips with Enhanced Physiological Relevance

Abstract

Due to the bioengineering nature, tissue chips allow the manipulation of cellular composition [11] and a range of biophysical and biochemical environmental cues, including but not limited to cell-ECM interactions, dynamic flows, chemical species gradients, substrate stiffness, [12] and active mechanical stimuli. [13,14] In particular, the on-chip adoption of patients' cells, either primary or induced human pluripotent stem cells (hiPSCs), makes a bespoke and patient-specific tissue model in line with the goal of precision medicine. [15] In contrast, small animal-based models exhibit notable genetic and cellular differences from human physiology, which may lead to biased results regarding disease pathogenesis and therapeutic effects. [16,17] Furthermore, tissue chips can precisely control and decouple multiple experimental factors, beneficial for exploiting the inherently complex human physiology, in contrast to other in vitro models, such as Petri dish-based ones, which are focused on maintaining cell proliferation in vitro. Thus, tissue chips, as a viable alternative to other tissue/disease-modeling approaches, are promising for in vitro recapitulation of the sophisticated human physiology and pathology at the tissue and organ level and are expected to transform the landscapes of fundamental biological research, [18][19][20] drug screening and toxicology, [21][22][23][24] and possibly, clinical trials. [25,26] Tissue chips can construct a broad range of tissue-and organ-analogs in vitro, including the vessel and vascular networks, [27][28][29] muscles, [30][31][32][33] liver, [34][35][36] lung, [37][38][39] brain, [40,41] kidney, [42][43][44][45][46] gut, [47,48] bone marrow, [49] corneal, [50,51] tumor, [52][53][54][55][56] as well as the integrated multiple tissues/organs, [57][58][59] such as liver-kidney, [60][61][62] neuromuscular junction, [63] and a recirculating system with up to 13 organs. [64] Of note, these tissue chips may rely on the same set of technical approaches yet recapitulate the specific tissue (patho)physiology by considering tissue-specific cellular and matrix composition.Among all tissues/organs modeled in the chips, the blood vessel is of particular interest, largely for the following reasons (Figure 1). [65,66] i) The blood vessel exists in all tissues/ organs throughout the body up to the epithelial layer covering surfaces. Thus, the on-chip reconstruction of the vessel or its analog is often a prerequisite for constructing a tissue analog.ii) The blood vessel is both the structural basis of circulating blood flow throughout the body and responsible for many Blood vessel chips are bioengineered microdevices, consisting of biomaterials, human cells, and microstructures, which recapitulate essential vascular structure and physiology and allow a well-controlled microenvironment and spatial-temporal readouts. Blood vessel chips afford promising opportunities to understand molecular and cellular mechanisms underlying a range of vascular diseases. The physiological relevance is key to these ...

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