Currently, there is often a lack of suitable small-caliber graft vessels for treating cardiovascular diseases because of thrombosis and intimal hyperplasia. Tissue engineered vascular grafts (TEVGs) promise a potential solution to this issue. Acellular vascular matrix with good mechanical properties and biocompatibility is commonly used as a tissue engineered scaffold. In this study, acellular rat aortas were preloaded with heparin and hepatocyte growth factor (HGF) to fabricate small diameter TEVGs. In terms of the biomechanical properties, this scaffold was similar to native rat aortas. We implanted this scaffold into a rat abdominal aorta, and the acellular aorta with heparin only was used as control. The patency at 6 months of the two groups was 100%. At 1 month, a complete layer of endothelial cells could be seen on the surface of the vascular lumen of the scaffold with heparin and HGF. The results also showed that the intimal thickness was significantly reduced in the grafts coated with HGF compared to the control grafts. In conclusion, the small-diameter TEVGs constructed by acellular vascular scaffolds coated with heparin and HGF have a promising clinical application prospect.
GregoryARGeorgeAMCatherineOJ, et al. Global burden of cardiovascular diseases and risk factors, 1990–2019: update from the GBD 2019 study. J Am Coll Cardiol2020; 76(25): 2982–3021.
SalacinskiHJGoldnerSGiudiceandreaA, et al. The mechanical behavior of vascular grafts: a review. J Biomater Appl2001; 15(3): 241–278.
4.
RathoreAClearyMNaitoY, et al. Development of tissue engineered vascular grafts and application of nanomedicine. Wiley Interdiscip Rev Nanomed Nanobiotechnol2012; 4(3): 257–272.
5.
XuLVarkeyMJorgensenA, et al. Bioprinting small diameter blood vessel constructs with an endothelial and smooth muscle cell bilayer in a single step. Biofabrication2020; 12(4): 045012.
6.
WeiYWangFGuoZ, et al. Tissue-engineered vascular grafts and regeneration mechanisms. J Mol Cell Cardiol2022; 165: 40–53.
WangXNChenCZYangM, et al. Implantation of decellularized small-caliber vascular xenografts with and without surface heparin treatment. Artif Organs2010; 31(2): 99–104.
9.
StephenFBDonaldOFThomasWG. Extracellular matrix as a biological scaffold material: structure and function. Acta Biomater2009; 5(1): 1–13.
10.
Da PalmaRKNonakaPNCampilloN, et al. Behavior of vascular resistance undergoing various pressure insufflation and perfusion on decellularized lungs. J Biomech2016; 49(7): 1230–1232.
11.
ConklinBSRichterERKreutzigerKL, et al. Development and evaluation of a novel decellularized vascular xenograft. Med Eng Phys2002; 24(3): 173–183.
12.
SchwartzSMCampbellGRCampbellJH.Replication of smooth muscle cells in vascular disease. Circ Res1986; 58(4): 427–444.
13.
MaHCalderonTMFallonJT, et al. Hepatocyte growth factor is a survival factor for endothelial cells and is expressed in human atherosclerotic plaques. Atherosclerosis2002; 164(1): 79–87.
14.
HaradaMTakenagaHIkenagaS, et al. Hepatocyte growth factor prevents intimal hyperplasia in rabbit carotid expanded polytetrafluoroethylene grafting. J Vas Surg2002; 35(4): 786–791.
15.
SmithPKMalliaAKHermansonGF.Colorimetric method for the assay of heparin content in immobilized heparin preparations. Anal Biochem1980; 109(2): 466–473.
16.
WangXLinPYaoQ, et al. Development of small-diameter vascular grafts. World J Surg2007; 31: 682–689.
17.
TillmanBWYazdaniSKLeeSJ, et al. The in vivo stability of electrospun polycaprolactone-collagen scaffolds in vascular reconstruction. Biomaterials2009; 30(4): 583–588.
18.
West-LivingstonLJuYMLeeH, et al. Antibody-conjugated electrospun vascular scaffolds to enhance in situ endothelialization. ACS Appl Bio Mater2020; 3(7): 4486–4494.
19.
CrapoPMGilbertTWBadylakSF.An overview of tissue and whole organ decellularization processes. Biomaterials2011; 32: 3233–3243.
20.
LinCHHsiaKMaH, et al. In vivo performance of decellularized vascular grafts: a review article. Int J Mol Sci2018; 19(7): 2101.
21.
FitzpatrickJCClarkPMCapaldiFM, et al. Effect of decellularization protocol on the mechanical behavior of porcine descending aorta. Int J Biomater. Epub ahead of print 4 July 2010. DOI: 10.1155/2010/620503.
22.
FleischerSTavakolDNVunjak-NovakovicG.From arteries to capillaries: approaches to engineering human vasculature. Adv Funct Mater2020; 30(37): 1910811.
23.
McClureMJSellSASimpsonDG, et al. A three-layered electrospun matrix to mimic native arterial architecture using polycaprolactone, elastin, and collagen: a preliminary study. Acta Biomater2010; 6(7): 2422–2433.
TeebkenOEHaverichA.Tissue engineering of small diameter vascular grafts. Eur J Vasc Endovasc2002; 23(6): 475–485.
26.
NovakPKruppaGH.Intra-molecular cross-linking of acidic residues for protein structure studies. Eur J Mass Spectrom2008; 14(6): 355–365.
27.
JeongJOJuYMKangHW, et al. Biofunctionalized electrospun vascular scaffolds for enhanced antithrombotic properties and in situ endothelialization. ACS Appl Mater Interfaces2023; 15(45): 52313–52323.
28.
AslaniSKabiriMHosseinzadehS, et al. The applications of heparin in vascular tissue engineering. Microvasc Res2020; 131: 104027.
29.
CapilaILinhardtRJ.Heparin-protein interactions. Angew Chem Int Ed Engl2002; 41(3): 391–412.
30.
WangWLiuDLiD, et al. Nanofibrous vascular scaffold prepared from miscible polymer blend with heparin/stromal cell-derived factor-1 alpha for enhancing anticoagulation and endothelialization. Colloids Surf B Biointerfaces2019; 181: 963–972.
31.
AsaharaTBautersCPastoreC, et al. Local delivery of vascular endothelial growth factor accelerates reendothelialization and attenuates intimal hyperplasia in balloon-injured rat carotid artery. Circulation1995; 91: 2793–2801.
32.
MorishitaRAokiMNakamuraS, et al. Potential role of a novel vascular modulator, hepatocyte growth factor (HGF), in cardiovascular disease: characterization and regulation of local HGF system. J Atheroscler Thromb1997; 4(1): 12–19.
33.
MatsumotoKNakamuraT.Roles of HGF as a pleiotropic factor in organ regeneration. EXS1993; 65: 225–249.
34.
MontesanoRSorianoJVMalindaKM, et al. Differential effects of hepatocyte growth factor isoforms on epithelial and endothelial tubulogenesis. Cell Growth Differ1998; 9: 355–365.
35.
YasudaSNoguchiTGohdaM, et al. Single low-dose administration of human recombinant hepatocyte growth factor attenuates intimal hyperplasia in a balloon-injured rabbit iliac artery model. Circulation2000; 101(21): 2546–2549.
36.
ChangHKKimPHKimDW, et al. Coronary stents with inducible VEGF/HGF-secreting UCB-MSCs reduced restenosis and increased re-endothelialization in a swine model. Exp Mol Med2018; 50(9): 1–14.
