Vascular Tissue Engineering: Recent Advances in Small Diameter Blood Vessel Regeneration

Table 3

Studies of the scientific literature (2008–2013) on decellularized matrices for vascular tissue engineering.

Organ/material	Decellularization method	Decellularization results	ID	Mechanical results	Biological in vitro results	Biological in vivo results	Reference
Bovine jugular vein	Multistep detergent enzymatic process + photooxidatively crosslinking	Integrity of collagen fibrils and elastic fibers	Patch	UTS~6* MPa significant higher than native bovine veins (~5* MPa)	Coating with fibronectin, gelatin, and collagen IV; SEM images and histological analysis (7 days): confluent layer of HUVECs	Model: rat (12 weeks); implanted subcutaneously; graft stability; chronic inflammatory response	[59]
Rat aortic conduit graft	Detergent-based protocol	—	—	—	—	Model: rat (8 weeks); fibronectin-coated grafts (on both graft surfaces); fibronectin surface coating persistent for at least 8 weeks; luminal endothelialization accelerated by fibronectin; local myofibroblast hyperplasia increased by fibronectin; cell invasion from the adventitial layer into the media increased by fibronectin; enhanced matrix metalloproteinase activity by fibronectin; no inflammatory cell markers; no signs of thrombosis	[60]
Urinary bladder	Soaking in saline + mechanical delamination + soaking in phosphate-buffered saline [61]	Intact basement membrane; bimodal surface	Patch	1 layer:  UTS = 1.9–2.3 MPa, 𝜀𝑏 = 38–40%; 4 layers:   UTS = 21–30 MPa, 𝜀𝑏 = 38–40%	SEM and confocal microscope images (5 days): excellent adhesion, spread, and proliferation with phenotype preservation of HAoECs and HAoSMCs	—	[62]
Porcine abdominal aorta and carotid	Detergent-enzymatic process	Preserved ECM structure with no residual cells; removal of the majority of DNA content	2–11 mm	Circumferential tensile tests  𝐸 = 0.22^a MPa, UTS = 2.01^a MPa,  𝜀𝑏 = 1.35^a,  𝐶=2.27×10^−3a 1/mmHg, BP = 2560^a mmHg, SRS = 732^a g;	—	—	[18]
				stress-relaxation tests   𝜎residual = 0.78%; similar to native porcine arteries (except 𝜀𝑏, 𝜎residual):  𝐸 = 0.19^a MPa, UTS = 1.55^a MPa,  𝜀𝑏 = 1.83^a,  𝐶 = 2.61×10^−3a 1/mmHg, BP = 2331^a mmHg, SRS = 882^a kPa, 𝜎residual = 0.58%
Porcine abdominal aorta	Nonionic detergent process + lyophilization	Intact collagen and elastin	7-8 mm	—	Smooth muscle-like and endothelial-like cells differentiated in vitro from autologous BMMNCs (3 weeks)	Model: pig (18 weeks); before implant: seeding of SMCs and ECs on grafts (1 week of culture); no sign of thrombus formation, dilatation, or stenosis; regeneration of endothelium, tunica media, and adventitia; presence of collagen and elastin; growth potential	[63]
Human umbilical artery	Detergent process	Integrity of extracellular collagenous matrix; maybe partial reduction of elastin	1.5 mm	BP = 840.37 ± 114.67 mmHg, UTS = 1618.21 ± 691.26 kPa,  𝐸 = 7.41 ± 3.85 MPa,  𝐶 = 4.26 ± 2.96%/100 mmHg; similar to native human umbilical arteries:   BP = 969.66 ± 154.42 mmHg, UTS = 1372.23 ± 809.30 kPa, 𝐸 = 13.33 ± 6.85 MPa,  𝐶 = 5.84 ± 3.10%/100 mmHg	—	Model: rat (8 weeks); acellular grafts implanted; 5 rats died within few hours after implantation due to thrombosis; other 6 TEVGs remained patent; thrombosis at the proximal anastomosis; no rupture or aneurysm formation	[64]
PGA tubular scaffold cultured with human allogeneic or canine SMCs using a bioreactor (7–10 weeks)	Detergent process	—	3,4 mm canine TEVG  6 mm human TEVG	Canine TEVGs  BP = 1618 ± 67^b mmHg; human TEVGs  SRS = 178 ± 11^b g; BP = 3337 ± 343^b mmHg; C = 3.3 ± 0.8^b%/100 mmHg; similar to native human blood vessels	Canine TEVGs  before implantation: culture with autologous ECs; ~21 days for EC expansion and 2 days for seeding and preconditioning in a bioreactor	Canine TEVGs for coronary artery bypass  model: dog (12 months); excellent long-term patency, and no stenosis or dilatation, and no intimal hyperplasia; 1 animal died with a patent graft; 1 TEVG occluded at 1 week; canine TEVGs for peripheral artery bypass model: dog (1 month); only 1 animal died with a patent TEVG (1 day);   human TEVGs for arteriovenous access for hemodialysis;    model: baboon (6 months); patency: 88% (7 of 8); 1 TEVG with thrombosis at 3 months; no aneurysmal dilatation, and no calcification, and no substantial intimal hyperplasia	[23]

UTS: ultimate tensile strength; 𝜀_𝑏: strain at break; 𝐸: elastic modulus; BP: burst pressure; 𝐶: compliance; SRS: suture retention strength; *values were graphically read; ^amedian; ^bmean ± standard error of the mean; 𝜎: stress.
HUVECs: human umbilical vein endothelial cells; HAoSMCs: human aortic smooth muscle cells; HAoECs: human aortic endothelial cells; BMMNCs: bone marrow mononuclear cells.