Table 1.

Currently Existing Vascular Graft Technologies for Anti-Calcification

Mechanism of Action	Base Material	Modifications	Models for Evaluation	Primary Results	Reference
Calcium Deposition Prevention	PU	Coated with PU-PEO-SO3	Canine RV-PA shunt model	Calcium deposition was reduced on PU-PEO-SO3 coated grafts in comparison to untreated PU grafts after 39-day transplantation	(Han et al., 1993)
	Porcine or rabbit vessel	Heparin coupling	Rat subcutaneous implantation	Reduced calcium content at 5 months in heparin-coupled grafts but poor host cell interactions, showed calcification occurs along elastin fibers of bioprosthetic grafts.	(Chanda et al., 1999)
Cell Recruitment & Matrix Remodeling	50:50 PLCL copolymer	PLA nanofiber outer layer (slow degrading) or PLA/PGA nanofiber outer layer (fast degrading)	Mouse infrarenal aortic interposition	No evidence of calcification was present in fast degrading grafts 8 weeks after implantation, while 7/12 slow degradation grafts showed calcification by von Kossa staining. Fast degrading grafts showed more cellular infiltration in outer graft layer compared to slow degrading grafts.	(Sugiura et al., 2017)
	Fast degrading PDO/PLCL (9:1)	N/A	Rat abdominal aortic interposition	Fast degrading grafts showed no calcification at 1 month in contrast to slow degrading grafts (lower PDO/PLCL ratio) that showed calcification in von Kossa staining and polarized light microscopy.	(Fukunishi et al., 2021)
	Large-pore PLA	PLCL coating	Mouse infrarenal aortic interposition	Large-pore PLA-PLCL grafts showed significantly less calcification than small-pore PLA grafts after 12 months of implantation by Alizarin red staining. PLA-PLCL grafts showed more VSMC infiltration (expressing both osteoblast and osteoclast factors) and less macrophage infiltration.	(Tara et al., 2014)
	Electrospun PCL/fibrin	N/A	Rat abdominal aorta interposition	The PCL/fibrin grafts showed higher level of expression of SMC contractile protein, higher microvessel density, and significantly less calcification (by von Kossa staining) than PCL controls at 1, 3, and 9 months.	(Zhao et al., 2021)
	Macro-porous electrospun PCL	N/A	Rat abdominal aorta interposition	No evidence of calcification was shown by von Kossa staining 1 year after implantation.	(Wu et al., 2018)
	Melt-spun/heat treated PCL fiber skeleton	Autologous fibrotic biotube (formed by subcutaneous implantation)	Canine peripheral arterial replacement Sheep arteriovenous graft	Grafts stained negative for calcification with von Kossa stain (along with ePTFE controls) after 7 months in canine study and 3 months in sheep.	(Zhi et al., 2022)
	Heparin-coated porous PGS tube with mesh electrospun PCL sheath	N/A	Rat abdominal aorta interposition	Neoarteries demonstrate rapid remodeling and minimal foreign materials at 3 months without signs of calcification while resembling function, mechanical properties, and ECM organization of native arteries	(Wu et al., 2012)
	Braided PGA	PGS coating	Rat infrarenal abdominal aorta interposition	PGS coating significantly decreased the calcification area in the graft compared to the PGA graft alone at 1, 3, and 6 months after implantation quantified from von Kossa staining.	(Fukunishi et al., 2019)
	Microporous PGS tube reinforced with PCL nanofibers	N/A	Rat abdominal aorta interposition	Patent vessels at 1 year after implantation showed no evidence of calcification by von Kossa staining and some recovered physiological function. Innervation was demonstrated in the adventitial space with similar morphology to native arteries.	(Allen et al., 2014)
	PGS tube reinforced with PCL nanofibers	N/A	Rat carotid artery interposition	PGS/PCL grafts showed no evidence of calcification at 1 year compared to vein grafts which showed sparse mineralization. PGS/PCL grafts also demonstrated innervation and improved contraction function.	(Yang et al., 2019)
	Decellularized rat aorta	Fibronectin (adventitia) and SDF1α (intima) coating	Rat infrarenal implantation	SDF1α-coated grafts improved intimal recellularization at 2 weeks and reduced medial calcification and neointimal hyperplasia at 8 weeks compared to grafts coated with only fibronectin.	(Sugimura et al., 2020)
Immunomodulation	Electrospun PCL	Heparin coating, MSC sEV loading	Rat abdominal aorta interposition (hyperlipidemia model)	Loading with sEV prevented calcification due to heparinization in the PCL graft for 3 months, shown by von Kossa staining and micro-CT.	(Wei et al., 2019)
	PELCL and PELCL-REDV in inner layer, PELCL in middle, and PCL in outer	miR-145 incorporated in middle layer and miR-126 incorporated in inner layer	Rat abdominal aorta interposition	Grafts with miRNA showed no calcification in von Kossa staining at 4 weeks while PELCL/PCL grafts showed extensive calcification. Trilayer grafts with miRNA showed higher M2 and lower M1 expression than PELCL/PCL grafts alone.	(Wen et al., 2020)
	PGS core with PCL/collagen nanofibrous sheath	Rapamycin loading in PCL sheath	Rat abdominal aorta interposition	Rapamycin-loaded grafts showed higher myogenic differentiation of vascular progenitor cells and a reduction in calcification by Alizarin red staining at 6 months in comparison to PBS-treated control or autophagy inhibitor-loaded grafts which demonstrate calcification colocalized with residual PCL.	(Chen et al., 2022)
Antioxidant Activity	Decellularized artery	POCC coating	Rat abdominal aorta interposition	Polymer-ECM grafts showed highest levels of antioxidant activity and lowest levels of calcification by von Kossa and Alizarin red staining (3 months) compared to polymer-ECM-heparin grafts or ECM grafts which showed lower antioxidant activity.	(Jiang et al., 2017)
	Electrospun nitrate-modified PCL	N/A	Rat abdominal aorta interposition	PCL/NO grafts improved cell infiltration and reduced calcification area in von Kossa staining for 3 months compared to PCL.	(Yang et al., 2021)
Mixed Mechanisms	Decellularized swim bladder	GA crosslinking	Rat abdominal aorta interposition	Swim bladder grafts showed no calcification (by von Kossa staining) after 4 weeks of implantation, and in vitro and subcutaneous implantation studies showed lower calcification than bovine pericardium.	(Liu et al., 2020)
	Decellularized fibrotic conduits (autologous)	Heparin chemical conjugation	Rat common carotid artery interposition	Autograft fibrotic conduits showed more M2 macrophages than allografts and no calcification by von Kossa staining at 3 or 6 months after implantation. Both autograft and allograft fibrotic conduits demonstrated better cellular infiltration than decellularized arteries.	(Qiu et al., 2021)