Vascular Tissue Engineering: Recent Advances in Small Diameter Blood Vessel Regeneration
Table 7
Studies of the scientific literature (2008–2013) on TEVG development without the use of scaffolds.
Fabrication method
Cell type
ID
Mechanical properties
Biological in vivo results
Reference
In vivo bioreactor approach: device implanted in the peritoneal cavity to attract cells around a tubular scaffold; scaffold = stretchable urethane + silicone with a coating of nonadhesive material
Model: sheep;
device implantation for 10 days: many porous spaces in neotissue; some contractile protein expression; no production of collagen bundles and elastin;
carotid artery interposition: quick rupture;
patches in carotid artery (2 weeks): 1 graft failed after 1 week; other graft remained patent; aneurysm formation in both cases
Cell ring-based approach: seeding of cells into annular agarose wells + cell aggregation + formation of thick tissue rings (static culture); tissue rings could be fused to generate tubular constructs
Rat aortic SMCs
2, 4, and 6 mm
Circumferential tensile tests ID 2 mm day 8: UTS = 169 ± 45 kPa,
= 0.81 ± 0.28 MPa, ;
day 14: UTS = 97 ± 30 kPa,
= 0.50 ± 0.09 MPa, ;
ID 4 mm day 8: UTS = 339 ± 131 kPa,
= 1.21 ± 0.46 MPa, ;
day 14: UTS = 201 ± 63 kPa,
= 0.71 ± 0.20 MPa, ;
ID 6 mm day 8: UTS = 503 ± 76 kPa,
= 1.98 ± 0.4 MPa, ;
day 14: UTS = 302 ± 42 kPa,
= 1.08 ± 0.14 MPa,
Cell sheet-based approach: production of a completely autologous TEVG (7 months) + air-dried devitalization + freezing + storing for 5 months at −80°C + seeding with autologous ECs (culture for 4 days)
Autologous fibroblasts and ECs isolated from skin and vein biopsies
Clinical trial (1 patient); reduction of the production time (~2 weeks versus ~6–9 months); implanted without complication; no evidence of leakage at anastomoses; at 8 weeks: no complication; graft patency; stable diameter; no adverse reactions
Cell sheet-based approach (single step method): tunica media and adventitia produced by rolling a tissue sheet containing both cell types contiguously (SMCs grew beside fibroblasts in the same culture dish)
SMCs isolated from human umbilical cord; TEVMA produced by SMCs and either DFs (TEVMA-DF) or SVFs (TEVMA-SVF)
4.5 mm
TEVMA-DF BP ~ 1000* mmHg;
circumferential tensile tests: UTS ~ 2.1* MPa, MPa,
~ 30*%;
stress-relaxation tests:
N, N; TEVMA-SVF BP ~ 250* mmHg;
circumferential tensile tests: UTS ~ 0.8* MPa, MPa,
%;
stress-relaxation tests:
N, N
Cell sheet-based approach (single step method): tunica media and adventitia produced by rolling a tissue sheet containing both cell types contiguously (SMCs grew beside fibroblasts in the same culture dish)
SMCs and fibroblasts isolated from 3 distinct human umbilical cords; aTEVMA-arterial TEVMA; vTEVMA-venous TEVMA
Cell sheet-based approach + decellularization (dTEVM): sheet from fibroblasts (21 days) + decellularization by osmotic shock + seeding of SMCs + culture for 7 days + cellular sheet rolled on a mandrel + culture for 21 days
Human arterial SMCs isolated from an umbilical cord; DFs obtained from a reductive breast surgery;
dTEVM-DF obtained from DFs;
dTEVM-SVF obtained from SVFs;
TEVM standard cell-sheet grafts (no decellularization), produced by SMCs
Microtissue self-assembly approach: microtissues produced higher amounts of ECM + bioreactor to assemble microtissues in a tubular shape + dynamic culture for 14 days (pulsatile flow and circumferential mechanical stimulation)
Microtissues composed of myofibroblasts and ECs; HAFs and HUVECs used for microtissue generation
Scaffold-free rapid prototyping bioprinting approach: cells aggregated into cylinders + bioprinting of cell cylinders using agarose rods as molding template + 2–4 days in the mold (fusion period) + maturation in a perfusion bioreactor
