Table 2:

Bioengineered vascular disease models using organ-on-a-chip technology

Material	Cell Type(s)	Blood flow conditions	Experiment	Ref.
PDMS	Mouse olfactory harvested arterial segments	Perfusion inlet was subjected to 45 mmHg and the outlet at atmospheric pressure.	Artery segments were reversibly loaded onto device; verified cellular arrangement of artery in chip by staining SMC nuclei, actin, and voltage gated calcium channels; vessel constriction was reduced by 50% after incubating with calcium-blocker nifedipine	Yasotharan et al.[68]
PDMS coated with VWF/fibrinogen	HUVECs	Parallel microchannels with one-side stenosis of 20, 30, 40, 60, or 80 percent lumen reduction; human blood was perfused at 1,000 s⁻¹ input wall shear rates	Stenotic chambers demonstrated enhanced platelet aggregation in 60 – 80% occlusion over a range of input wall shear rates; flow increases EC VWF secretion in stenotic outlet, causing platelet aggregation and post-stenotic thrombus formation	Westein et al.[74]
Gelatin-Agarose IPN	HUVECs, HDMVECs, HLMVECs	Physiologically relevant stiffness ~ 20 kPa (stiffness of healthy arteries between 1 and 35 kPa); Flow velocity in smallest channels set to ~2.8 mm s⁻¹ (corresponding to a wall shear stress ~8.8 dynes cm⁻²)	Stiffer IPNs (~50 kPa) resulted in increased permeability compared to soft devices (~5 kPa); Extracellular haem (haemolytic by-product) induces delayed and reversible EC permeability (dose-dependent manner)	Qui et al.[164]
PDMS and collagen	hBMSCs, hFs, HUVECs, HASMCs	No profusion mentioned	Inflammatory factors (LPS, thrombin, and TNFα) compromises EC barrier function; Simultaneous inhibition of Rac1and activation of RhoA induced loss of HASMC exposure to HUVECs and reduced barrier function; CRISPRmediated knockout of N-cadherin in HASMCs led to loss of barrier function and over expression in HUVECs N-cadherin (validated in mouse model)	Alimperti et al. [165]
PDMS coated with collagen	HUVECs	Perfused human citrated whole blood at a flow rate of 0.29 mL min⁻¹, yielding a shear rate of ~1,000 s⁻¹	SLA printed miniaturized vascular structures that closely mimic stenotic and healthy blood vessel architecture; 15 minutes of blood perfusion revealed induced thrombosis down stream and at the stenotic regions whereas healthy geometries showed no platelet adhesion	Costa et al.[161]
PDMS	Resistance arteries isolated from wile	Harvested arteries were fixed at periphery and subjected to external pressure of 45 mmHg	Developed a microfluidic platform to assess resistance artery structure and function; fully automated acquisition of up to ten does-response sequences of	Gṻnther et al.[166]
	type CD1 mice or CD1 mice expressing Tie2-GFP transgene in ECs	above atmosphere (aligned artery); Disk of sapphire uniformly distributed heat generated by thermoelectric heater; Flow in channels between 0 – 4 mL h⁻¹	intact mouse mesenteric artery segments; Exposure of phenylephrine or acetylcholine yield dose-response relationship identical to human response
PDMS	HUVECs, HMVEC	Citrated human blood was perfused to obtain a wall shear rate of 750 sec⁻¹ (~10 dynes cm⁻² stress); for plateletendothelial dynamics, higher wall shear rate was used (750 sec⁻¹; ~30 dynes cm⁻² stress)	Performed quantitative analysis of organ-level contributions to inflammation-induced thrombosis; LPS endotoxin directly stimulates intravascular thrombosis by activated alveolar epithelium; analyzed inhibition of EC activation and thrombosis due to PAR=1 antagonist	Jain et al.[167]
Fibronectin crosslinked gelatin	iPSC, NRVMs	Bulk elastic modulus of ca 50 – 100 kPa; lower concentrations obtained modulus between 1 and 15 kPa	Micropatterned gelatin hydrogels using laser-etching to obtain surface grooves and pillar structures with a resolution of 15 μm; verified structural organization, contractile function, and long-term viability compared to manually patterned gelatin substrates	Janna et al.[168]
PDMS	HAECs and HASMCs	Vacuum side channels induce cyclic strain of 5 – 8% to mimic stretching and relaxation of the channels; flow in EC chamber produced a wall shear stress of 1 – 1.5 PA	Culture of SMCs and EC with a porous membrane separating the two chambers lead to prolonged viability of cells that exhibited physiological morphology and organization through cell-cell contact;	Engeland et al.[169]

Abbreviations: IPN, inter-penetrating network; HUVECs, human umbilical vein endothelial cells; HDMVECs, human dermal microvascular endothelial cells; HDMVECs, human lung microvascular endothelial cells; PDMS, poly(dimethylsiloxane); hBMSCs, human bone marrow stromal cells; hFs, human lung fibroblasts; HASMCs, human aortic smooth muscle cells; LPS, lipopolysaccharides; HMVEC, human lung microvascular endothelial cells; PAR-1, protease activated receptor-1; iPSC, induced pluripotent stem cells derived cardiomyocytes; NRVMs, neonatal rat ventricular myocytes.