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

Table 5

Studies of the scientific literature (2008–2013) on TEVGs fabricated with biodegradable synthetic polymers.

Material	Fabrication method	ID	Mechanical properties	Biological in vitro results	Biological in vivo results	Reference
PCL	Electrospinning of 2 layers with different porosity using a cylindrical rotating translating mandrel; ILLP = inner layer with lower porosity; OLLP = outer layer with lower porosity	2 mm	ILLP UTS = 3.67 ± 0.76 MPa, 𝜀𝑏 = 900 ± 229%, 𝐸 = 8.8 ± 0.9 MPa, BP = 2845 ± 241 mmHg, SRS = 556 ± 47 gf, WL = 33.2 ± 4.6 mL cm^−2 min^−1, BL = 0.25 ± 0.06 mL cm^−2 min^−1; OLLP UTS = 3.66 ± 0.30 MPa, 𝜀𝑏 = 862 ± 142%, 𝐸 = 8.5 ± 0.8 MPa, BP = 2688 ± 192 mmHg, SRS = 490 ± 41 gf, WL = 39.3 ± 2.8 mL cm^−2 min^−1, BL = 0.89 ± 0.39 mL cm^−2 min^−1; UTS, 𝐸, and 𝜀𝑏 calculated from axial tensile tests	—	Model: rat (12 weeks); endothelialization nearly complete; ILLP: allowed good cell invasion from the adventitia; OLLP: inhibits graft cellularization; perfect patency with no thrombosis	[53]
PCL	Electrospinning using a spinning counter electrode	0.7 mm	—	—	Model: rat (18 months); patency = 72.5%; no aneurysm formation; no calcification; scaffolds did not disappear completely; endothelium: complete regeneration; media: partial regeneration	[54]
PCL	Electrospinning using a cylindrical rotating translating mandrel	2 mm	BP = 3280 ± 280 mmHg, SRS = 936 ± 32 g, WL = 32.1 ± 1.3 mL cm^−2 min^−1, BL = 0.87 ± 0.08 mL cm^−2 min^−1; axial tensile tests: UTS = 4.1 ± 0.5 MPa, 𝜀𝑏 = 1092 ± 28%	—	Model: rat (18 months); graft in vivo 𝐶 = 7.8 ± 0.9%/mmHg, proximal native artery in vivo 𝐶 = 21.0 ± 2.8%/mmHg; excellent structural integrity: no aneurysmal dilation, perfect patency with no thrombosis, and limited intimal hyperplasia (maximum 5% lumen loss); promising tissue regeneration until 6 months, after 6 months a clear regression; calcifications: spread transmurally at 18 months; limited vascularization at 18 months	[46]
PGA or PLLA nonwoven felts + PCL/PLA sealant solution	Dual cylinder chamber molding system	PGA-PCL/PLA = 0.9 mm; PLLA-PCL/PLA = 0.7 mm	PGA-PCL/PLA: BP = 2710 ± 282 mmHg, SRS = 3.13 ± 0.72 N, 𝐸 = 33.0 ± 7.0 MPa, UTS = 5.3 ± 0.72 MPa; PLLA-PCL/PLA: BP = 2790 ± 180 mmHg, SRS = 4.37 ± 0.67 N, 𝐸 = 24.0 ± 5.9 MPa, UTS = 3.7 ± 0.53 MPa	MTT after 24 h: no difference in HAoSMC viability between PGA-PCL/PLA, PLLA-PCL/PLA, and TCP; histological analysis after 72 h: HAoSMCs penetrated and adhered to both scaffolds	Model: mice (6 weeks); acellular grafts implanted; foreign body reaction with giant cell formation (at 3 weeks); encapsulation around the external periphery of PLLA-PCL/PLA grafts; no thromboembolic complications or aneurysm formation; organized vascular neotissue (endothelium, media, and collagen)	[57]
PGA nonwoven mesh + PCL porous sheet + PGA nonwoven mesh	PGA and PCL seeded with SMCs + after 4 days SMC-PGA wound around a silicone tube + after 3 days SMC-PCL wound around SMC-PGA + after 3 weeks PGA seeded with fibroblasts + after 2 days fibroblast-PGA wound around SMC-PCL (2 days) + silicone tube removed + seeding of ECs in the lumen + static culture (2 days) + pulsatile bioreactor (14 days)	6 mm	Circumferential tensile tests after 14 days of culture: UTS = 827 ± 155 kPa, 𝐸 of collagen region = 3.75 ± 0.78 MPa, 𝐸 of elastin region ~0.1* MPa, 𝜀𝑏∼0.42^∗; only polymeric scaffolds: UTS = 91 ± 21 kPa, 𝜀𝑏∼0.6^∗; bovine native arteries: UTS = 882 ± 133 kPa, 𝐸 in collagen region = 3.31 ± 0.56 MPa, 𝐸 in elastin region ~0.075* MPa, 𝜀𝑏∼0.6^∗	SMCs, fibroblasts, and ECs isolated from calf; histological analysis (after 14 days in the bioreactor): formation of 3 layers, luminal area: presence of ECs, middle layer: presence of abundant elastin, well-organized dense collagen ECM, SMCs, and PCL, outer region: presence of loose collagen ECM	—	[55]
Heparin-coated PGS porous tube wrapped with a PCL thin electrospun layer	Salt fusion method + electrospinning	720 μm	PGS + PCL SRS = 0.45 ± 0.031 N, 𝐸 = 536 ± 119 kPa, UTS = 3790 ± 1450 kPa; PGS SRS = 0.11 ± 0.0087 N, 𝐸 = 243 ± 71.8 kPa, UTS = 76.6 ± 15.7 kPa; 𝐸, UTS calculated from circumferential tensile tests; neoartery BP = 2360 ± 673^a mmHg, 𝐶 = 11 ± 2.2^a%/100 mmHg; native aorta	—	Model: rat (3 months); no aneurysm and stenosis; regular, strong, and synchronous pulsation of grafts; confluent endothelium, contractile smooth muscle layers, and coexpression of elastin, collagen, and GAG;	[56]
			BP = 3415 ± 529^a mmHg, 𝐶 = 6.7 ± 2.3^a%/100 mmHg		graft extensive degradation + ECM synthesization within 14 days; remodeling still active at 3 months
PCL/PLA	Patient-specific scaffolds: rapid prototyping (using radiographic X-ray slices) + lost wax + dip coating + selective dissolution + salt leaching	>1 mm	𝐸 = 0.6 to 5.2 MPa; higher 𝐸 for lower porosity and higher concentration	PCL/PLA scaffolds coated with collagen; fluorescent images (4 days): HUVEC attachment; material biocompatibility confirmed	—	[58]
PGA nonwoven mesh	Seeding of SMCs + culture for 7 days in static condition + mesh wound around a silicone tube + pulsatile bioreactor (8 weeks)	4 mm	After 8 weeks of culture UTS = 0.62 × 10^6 Pa, 𝐸 = 10.5 ± 1.25 MPa, SRS = 1.26 ± 0.16 N, BP ~ 1.2* MPa; ~50–60% of those of human saphenous veins: UTS ~ 0.95 × 10^6* Pa, 𝐸∼14.5^∗ MPa, SRS ~ 2.25* N, BP ~ 1.2* MPa; UTS, 𝐸 calculated from circumferential tensile tests	SMCs differentiated from hASC (7 days); histological analysis (after 8 weeks in the bioreactor): no remnant of undegraded PGA fibers, dense structure with well-populated SMCs, SMCs orientated in layers, and no elastic fibers	—	[67]

PCL/PLA: 50 : 50 copolymer of 𝜀-caprolactone and L-lactide.
UTS: ultimate tensile strength; 𝐸: elastic modulus; 𝜀_𝑏: strain at break; SRS: suture retention strength; BP: burst pressure; 𝐶: compliance; WL: water leakage at 120 mmHg; BL: blood leakage at 120 mmHg; *values were graphically read; ^amean ± standard error of the mean.
hASCs: human adipose-derived stem cells; HAoSMCs: human aortic smooth muscle cells; HUVECs: human umbilical vein endothelial cells; GAG: glycosaminoglycan; TCP: tissue culture plastic.