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

Table 4

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

Material	Fabrication method	ID	Mechanical properties	Biological in vitro results	Biological in vivo results	Reference
Fibrin	Two-layer grafts: SMCs embedded in fibrin hydrogel + fibrin layer composed of high concentration fibrinogen	4 mm	After 2 weeks  two layers  UTS ~ 90* kPa, BP = 177 ± 5.3 mmHg; single layer  UTS ~ 65* kPa, BP = 18 ± 7.7 mmHg; UTS calculated from circumferential tensile tests	SMCs isolated from 3-day-old lambs; histological analysis after 2 weeks of culture: SMCs distributed uniformly in the inner layer, SMCs did not migrate into the outer fibrin layer, and SMCs maintained their contractile properties inside gels	—	[39]
Fibrin	nDF entrapment in fibrin gel + static culture for 2 weeks + dynamic bioreactor culture for 5–7 weeks (stimuli: cyclic stretching + luminal, ablumenal, transmural flows)	2.4 mm	After 7–9 weeks  circumferential tensile tests  𝐸∼2500^∗ kPa, UTS ~ 1800* kPa; axial tensile tests  𝐸∼900^∗ kPa, UTS ~ 1200* kPa; ID = 2 mm,  BP = 1366 ± 177 mmHg, SRS = 0.19 ± 0.05 N,  𝐶 ~ 4.5*%/100 mmHg; ID = 4 mm  BP = 1542 ± 188 mmHg, SRS = 1.32 ± 0.58 N (with entrapped PLA cuffs),   𝐶 ~ 2.5*%/100 mmHg; ovine femoral artery  BP = 2297 ± 207 mmHg,   𝐶 ~ 3.25*%/100 mmHg	Histological analysis after 7–9 weeks of static + dynamic culture: circumferential collagen fiber alignment, minor residual fibrin in 2 mm grafts, none evident in 4 mm grafts, and nhDFs evenly distributed across the thickness	—	[40]
Silk fibroin	Electrospinning using a rotating translating mandrel	6 mm	BP = 575.67 ± 17.47 mmHg,   𝐶 = 3.51 ± 0.42%/100 mmHg; circumferential tensile tests  DR = 5 mm/min:  UTS ~ 2.4* N,  𝜀𝑏∼57^∗%;  DR = 25 mm/min:   UTS ~ 1.8* N,   𝜀𝑏∼37^∗%;  DR = 50 mm/min:   UTS ~ 1.2* N, 𝜀𝑏∼34^∗%	MTT assay (7 days): linear increase of NIH/3T3 viability over time; SEM images (7 days): NIH/3T3 attached, spread, and grew; cell motility through matrix	—	[65]
Silk fibroin	Gel spinning	1, 1.5 mm	Silk  𝐸 = 2.20 ± 0.90 MPa, UTS = 0.273 ± 0.11 MPa; native rat aorta  𝐸 = 2.44 ± 0.76 MPa, UTS = 0.519 ± 0.11 MPa; PTFE  𝐸 = 918 ± 52.9 MPa, UTS = 43.4 ± 4.6 MPa	Protein adsorption: lower on silk than PTFE; platelet adhesion and spreading:   silk and PTFE relatively nonthrombogenic; confocal images (overnight incubation): higher HCASMC and HUVEC attachment on silk than PTFE; Pico Green DNA assay (for 14 days): higher rate of HCASMC and HUVEC proliferation on silk than PTFE	Model: rat (4 weeks); no occlusion, clotting, or ischemia; vascular cell remodeling: confluent endothelium, SMCs migration and proliferation	[66]
Silk fibroin + collagen type I	Electrospinning using a rotational mandrel + dynamic dipping	6 mm	BP = 894.00 ± 24.91 mmHg, 𝐶 = 3.24 ± 0.58%/100 mmHg; circumferential tensile tests  DR = 5 mm/min  UTS = 3.17 ± 0.32 N,   𝜀𝑏 = 58.96 ± 4.07%;  DR = 25 mm/min  UTS = 2.76 ± 0.39 N,   𝜀𝑏 = 35.6 ± 2.13%;  DR = 50 mm/min  UTS = 2.5 ± 0.12 N,   𝜀𝑏 = 39.04 ± 5.31%	MTT assay (7 days): linear increase of NIH/3T3 viability over time, collagen increase metabolic activity at the early time points; SEM images (7 days): NIH/3T3 attached, spread, and grew	—	[33]
Hyaff-11 (hyaluronan-based material)	Coating + coagulation bath (ethanol)	4 mm	—	—	Model: porcine (5 months); fibrin glue: sealed anastomotic sites; animal survival: 100%, no signs of vascular insufficiency; 2 grafts completely occluded after 2 and 3 months, 1 graft partially occluded after 4 months, and 7 grafts showed no occlusion or intimal hyperplasia; grafts almost completely degraded; formation of neotissue (SMCs, collagen, elastin fibers organized in layers, complete endothelium)	[28]
Recombinant human tropoelastin^#	Electrospinning using a rotating translating mandrel	4 mm 1 cm	𝐶 = 20.2 ± 2.6%/100 mmHg, BP = 485 ± 25 mmHg; circumferential tensile tests  UTS = 0.34 ± 0.14 MPa,  𝜀𝑏 = 79 ± 6%,  𝐸 = 0.15 ± 0.05 MPa; axial tensile tests  UTS = 0.38 ± 0.05 MPa,  𝜀𝑏 = 75 ± 5%,  𝐸 = 0.15 ± 0.03 MPa; native porcine carotid arteries  𝐶 = 3.4 ± 0.5%/100 mmHg; circumferential tensile tests  UTS = 2.59 ± 0.31 MPa,  𝜀𝑏 = 125 ± 15%,  𝐸 = 0.41 ± 0.09 MPa;   axial tensile tests  UTS = 0.95 ± 0.13 MPa,  𝜀𝑏 = 105 ± 11%,  𝐸 = 0.20 ± 0.06 MPa	Confocal images after 48 h of culture: BMEOCs attached, spread, and grew; cells formed a confluent monolayer	—	[27]

#monomer unit of elastin, cross-linked tropoelastin mimic native elastin fibers.
UTS: ultimate tensile strength; 𝜀_𝑏: strain at break; 𝐸: elastic modulus; 𝐶: compliance; BP: burst pressure; SRS: suture retention strength; DR: deformation rate; *values were graphically read.
nDFs: neonatal human dermal fibroblasts; BMEOCs: porcine bone marrow-derived endothelial outgrowth cells; NIH/3T3: murine fibroblast cell line; HUVECs: human umbilical vein endothelial cells; HCASMCs: human coronary artery smooth muscle cells.