Table 1.

Summary of the extensively used PDMS surface modification treatment for improving cell adhesion.

Method	Hydrophilicity of PDMS	Type of Cell Used	Adhesion of Cells	Flow Conditions	Pros	Cons	References
Plasma Treatment	Increases as WCA decreases by approximately 30°	Human primary pulmonary arterial endothelial cells	100% confluency was achieved after 3 days on plasma treated PDMS surface	Confluency was equivalent in both static and flow condition	Relatively inexpensive Easy to perform. Time efficient.	The hydrophilicity of the oxygen plasma treated PDMS surface is temporary and gradual hydrophobic recovery is shown over time. It is not suitable for long term cell adhesion.	[32,33,34]
Collagen	Type I Collagen increases the hydrophilicity to the greatest extent among extracellular matrix (ECM)proteins	Human umbilical vein endothelial cells (HUVECs)	Both cell lines were able to attach and proliferate after initial seeding	Stable under static conditions for a few days	Good adsorption of collagen onto PDMS among ECM proteins Good modulation of ECs morphology Increases the hydrophilicity of PDMS to one of the greatest extents amongst reagents Exhibits good adhesion of ECs	Cell detachment occurs after a few days due to the formation of cell clusters Type IV Collagen is a poor reagent for seeding EC Might not be stable under high flow rates as ECs begin to detach at flow rates above 10 μL/min	[35,36,37,38,39,40,41,42,43]
		Endothelial cells derived from Human induced pluripotent stem cells (iPSC-ECs)		More cell activity than HUVEC under flow conditions of 10 μL/min
		Human dermal microvascular endothelial cells	Confluent layer formed	Not specified
		HUVECs	Good adhesion as confluency achieved after an hour	Cells were stable at flow rates of 5–10 μL/min
Gelatin	Increases the hydrophilicity by increasing the surface roughness	Sheep Carotid Arterial endothelial cells	Poor adhesion of endothelial cells (ECs) as compared to other ECM proteins	Cells were adherent when exposed to the shear stress of 1 dyne/cm2	Able to maintain the activity of cells for the longest duration	Cell aggregation A high tendency for cells to dissociate from PDMS	[44,45,46,47,48,49,50]
		HUVECs,	Good adhesion
Fibronectin	Hydrophilicity increases significantly	Sheep Carotid Arterial ECs	Good adhesion	Adhesion lasts for a few days without exposure to flow.	Second among the ECM proteins in seeding ECs The highest rate of reagent adsorption onto PDMS	Fibronectin is an ECM protein that can lead to cell dissociation	[19,38,48,51,52,53,54,55]
		HeLa ECs	Better than gelatin in terms of adhesion
		Human aortic ECs	Unable to reach confluency
		HUVECs	The same extent of adhesion as oxygen-fibronectin	Stable to flow rates at 7.5 mL/min
		Bovine Aortic ECs	The same extent of adhesion as oxygen-fibronectin	95% detachment after 2 weeks under static flow
Laminin	Increases but not as much as ECM protein.	HUVECs	Poor adhesion of ECs as compared to ECM protein.	Stable under flow at 5 dyne/cm2	Good adhesion	Spreading of cells over laminin-modified surface is slow. Might change the cell morphology.	[56]
APTES ((3-aminopropyl) triethoxysilane)	Increases as WCA decreases by approximately 70°	HUVECs	Cells proliferated with the increase in incubation time	Good stability and adhesion under shear stress (0.5 mm/s)	Chemical treatment is not prone to degradation Forms amine groups, which is suitable for HUVECs adhesion	Weaker increase in hydrophilicity as compared to ECM proteins	[57,58,59,60]
		Vascular ECs	Cell adhesion observed
PDA (Polydopamine)	Increases as WCA decreases by 50%	Vascular ECs Human cerebral microvascular ECs	Improved adhesion and proliferation for both cell lines	Poorer response when exposed to flow compared to fibronectin	Significant increase in hydrophilicity Non-toxic to cells Long term stability for cell culture	Effect of PDA on cells is poorly understood Seldom used in ECs seeding	[49,52,61,62,63]
PEG (Poly (ethylene glycol))	Increases as WCA decreases by approximately 57°	HUVECs	Adhesion was similar to non-modified PDMS.	Poor cell adhesion under flow	Stable for long term culture when used to encapsulate cells	Poor adhesion when used as a coating reagent	[40,64,65]
		(iPSC-ECs)	When encapsulated with PEG, cells were stable for at least 2 weeks
Silica-Titanium	Increases but less than ECM proteins	HUVECs	Good adhesion of cells	Not specified	Does not degrade easily as ECM proteins	Certain combinations of silica-titanium could present a hostile environment for cells	[66,67]
Oxygen Plasma + Fibronectin	Increases as WCA decreases by approximately 80°	HUAECs	The same extent of adhesion as fibronectin Confluency reached	Stable adhesion at physiological flow rate (0.5 mm/s)	Increases the hydrophilicity of PDMS to a huge extent	Cell dissociation in long term cell culture	[19,37]
PEG + RGDS (Arg–Gly–Asp–Ser) peptides	Increases	HUVECs	87% of cells coverage observed	Stable at low flow rates of 0.3 µL/min	Good adhesion of cells Cells increase with increasing RGDS density	The combination is not commonly used as ECM proteins	[64,68]
TEOS (tetraethylorthosilane) + Fibronectin	Increases	Primary Pulmonary Artery ECs	Adhesion of cells was achieved	Stable under low flow rates of 0.1 mL/h	Good adhesion of cells	The detachment of cells might occur at high flow rates	[66]