Table 3: Representative studies on cell-based tissue-engineered blood vessels.

Publication yearConstructSourceTechnique appliedReported resultsType of studyReferences

1998Completely biological tissue-engineered human blood vesselSMCs, human fibroblasts, endothelial cells(i) cell culture in a medium with ascorbic acid
(ii) layered SMCs placed in a tubular support to form the media, wrapped with a sheet of fibroblasts to form the adventitia
(iii) after maturation, tubular support was removed and sequentially seeded with endothelial cells in the lumen to form the intima
(1) TEBV displayed well-defined three-layered organization, with numerous ECM proteins including elastin
(2) SMCs reexpressed desmin
(3) endothelium expressed von Willebrand factor, incorporated acetylated LDL, produced PGI, and inhibited platelet adhesion
(4) the grafting in canine model demonstrated good handling and saturability characteristics
in vitro
in vivo  in canine model

2000Tissue-engineered blood vessel from smooth muscles SMCs(i) cell culture in a medium with serum and ascorbic acid(1) TEBV composed of endothelium, media, and adventitia and resembling human artery was produced
(2) serum stimulates cell differentiation and growth and increases cell viability
(3) ascorbic acid induced cohesive cellular sheet organization
in vitro
in vivo  in bovine model
[77, 78]

2001Small-diameter neovesselsEPCs(i) decellularization of porcine iliac vessels
(ii) EPCs were isolated noninvasively from peripheral blood of sheep, expanded ex vivo
(1) endothelial progenitor cell-seeded grafts remained patent for 130 days
(2) nonseeded grafts occluded within 15 days.
(3) explanted grafts exhibited vascular contractile and relaxation activity similar to native arteries
in vitro
in vivo  in sheep model

2005Small-diameter vessel BMCs(i) induction of BMC differentiation into SMCs in vitro
(ii) decellularization of canine artery
(iii) transplantation of grafts in canine carotid artery
(1) vascular grafts seeded with BMCs remained patent for up to 8 weeks
(2) vascular grafts showed regeneration of the 3 vascular layers
(3) the first autologous vessel derived from BMCs
(4) occlusion due to Thrombus formation was evident
in vitro
in vivo  in canine model

2006Human TEBVadult human fibroblasts extracted from skin biopsies(i) sheet-based tissue engineering after vast cell expansion
(ii) fibroblasts were cultured in conditions that promote ECM production
(1) TEBV exhibited properties similar to human blood vessels, without exogenous scaffolding
(2) autologous TEBVs are antithrombogenic and mechanically stable for 8 months in vivo
(3) well-established vasa vasorum, vasa media, and intima
(4) the TEBV was manufactured exclusively from patient’s own cells, completely biological and clinically relevant
in vitro
in vivo  in primate model (rat and mice)

2009Scaffold-free small-diameter vascular constructSMCs and fibroblasts(i) bioprinting using vascular smooth muscle cells and fibroblasts(1) vascular cells which were aggregated into distinct units (spheroids and cylinders) were printed layer-by-layer and molded using agarose rods as templates
(2) engineered vessels were fabricated with distinct shapes and hierarchical trees that combine tubes with distinct diameter
(3) quick and scalable technique
in vitro [80]

2009Scaffold-free arterial mimeticsHuman aortic Endothelial cells and smooth muscle cells (i) ECs and SMCs were co-cultured in platform that mimic either healthy or diseased blood vessels
(ii) incorporation of transforming growth factor (TGF-β) and heparin in culture media to upregulate SMC differentiation markers (α-SMA and calponin)
(1) seeding of near confluent ECs on the scaffold induced increased α-smooth muscle actinin (α-SMA) and calponin Expression
(2) pretreatment of TGF-β and heparin to SMC enhanced α-SMA and calponin levels
(3) EC-SMC co-culture model can mimic either healthy or diseased blood vessels and may be useful in cardio-vascular therapeutics
in vitro [81]

2010Self-assembled microtissue vessel building blocks Human artery-derived fibroblasts and HUVECs
(i) pulsatile and circumferential mechanical stimulation in a bioreactor composed of pulsatile pump, self-assembly device, and medium reservoir(1) significant ECM formation and maturation by the self-assembled microtissues
(2) microtissues displayed prevascularization capacity and can be used as building blocks in generating small TEBV
(3) accumulation of vessel-like tissues occurred within 14 days under static and flow stimulation
(4) no thrombosis and vessel occlusions
in vitro [39]

2011Implantable human arterial graftsHuman dermal fibroblasts (i) fibroblasts seeding on fibrin gel
(ii) direct injection of cell/fibrinogen suspension into glass mandrel tubular molds
(iii) two weeks static culture system
(iv) nine weeks multigraft pulsed flow-stretch culture system in a bioreactor
(v) noninvasive strength monitoring
(1) cells cultured in pulsed-flow bioreactor produced more collagen and with higher burst pressures
(2) the tissue suture retention force was suitable for implantation in rat model and in ovine model using poly(lactic acid) sewing rings
in vitro
in vivo  in rat and ovine model

2012Small-diameter tissue-engineered vascular graft
Marrow-derived mesenchy-mal stem cells (MSCs)(i) cell sheet engineering
(ii) cell sheeting rolling around a mandrel
(iii) graft transplantation
(1) adhesion assay revealed that MSCs share similar EC’s antiplatelet adhesion property
(2) cell sheet layers fully fused in vitro
(3) four weeks after transplantation, TEVG exhibited endothelialization and similar structure of native vessels
(4) the fabricated biological TEVGs are useful for revascularization in humans and may reduce complication with foreign materials
in vitro
in vivo  in rabbit model