In this study, we fabricated native tissue mimicking a bilayered small-diameter vascular graft based on PEGylated chitosan (PEG–CS) and poly(l-lactic acid-co-ε-caprolactone) (PLCL). PEG–CS possesses good hemocompatibility, and as the inner layer of a vascular graft, it is more likely to swell and deform to debris, causing a blood clot, so the PLCL was added to stabilize it. In order to optimize the performance of the inner layer, PEG–CS blends with different ratios of PLCL (P/C:PLCL) casting films were fabricated, and endothelial cell compatibility and hemocompatibility were tested. The outer layer of the graft was fabricated via electrospinning with PLCL blends with different ratios of water-soluble polyethylene glycol. After water treatment, we tested smooth muscle cell penetration. Designing a two-layer vascular graft structure with an inner layer of P/C:PLCL = 1:6 and an outer layer being composed of a PLCL blend with 12% polyethylene glycol offers very good hemocompatibility and fast cell growth and also reserves well mechanical properties with good cell infiltration. Therefore, this kind of graft has a high potential to be used as an artificial blood vessel.
YinAZhangKMcClureMJ, et al.
Electrospinning collagen/chitosan/poly(l-lactic acid-co-ε-caprolactone) to form a vascular graft: mechanical and biological characterization. J Biomed Mater Res2013;
101: 1292–1301.
2.
IsenbergBCWilliamsCTranquilloRT.Small-diameter artificial arteries engineered in vitro. Circ Res2006;
98: 25–35.
3.
de ValenceSTilleJCGilibertoJP, et al.
Advantages of bilayered vascular grafts for surgical applicability and tissue regeneration. Acta Biomater2012;
8: 3914–3920.
4.
de ValenceSTilleJCMugnaiD, et al.
Long term performance of polycaprolactone vascular grafts in a rat abdominal aorta replacement model. Biomaterials2012;
33: 38–47.
5.
WangZCuiYWangJ, et al.
The effect of thick fibers and large pores of electrospun poly(ε-caprolactone) vascular grafts on macrophage polarization and arterial regeneration. Biomaterials2014;
35: 5700–5710.
6.
HongYYeSHNieponiceA, et al.
A small diameter, fibrous vascular conduit generated from a poly(ester urethane)urea and phospholipid polymer blend. Biomaterials2009;
30: 2457–2467.
7.
StankusJJSolettiLFujimotoK, et al.
Fabrication of cell microintegrated blood vessel constructs through electrohydrodynamic atomization. Biomaterials2007;
28: 2738–2746.
8.
MoXMXuCYKotakiM, et al.
Electrospun P(LLA-CL) nanofiber: a biomimetic extracellular matrix for smooth muscle cell and endothelial cell proliferation. Biomaterials2004;
25: 1883–1890.
9.
XuC.Aligned biodegradable nanofibrous structure: a potential scaffold for blood vessel engineering. Biomaterials2004;
25: 877–886.
10.
VaquetteCKahnCFrochotC, et al.
Aligned poly(l-lactic-co-ε-caprolactone) electrospun microfibers and knitted structure: a novel composite scaffold for ligament tissue engineering. J Biomed Mater Res A2010;
94: 1270–1282.
11.
TaraSKurobeHRoccoKA, et al.
Well-organized neointima of large-pore poly(l-lactic acid) vascular graft coated with poly(l-lactic-co-ε-caprolactone) prevents calcific deposition compared to small-pore electrospun poly(l-lactic acid) graft in a mouse aortic implantation model. Atherosclerosis2014;
237: 684–691.
12.
YangGLiXHeY, et al.
From nano to micro to macro: electrospun hierarchically structured polymeric fibers for biomedical applications. Prog Polym Sci2018;
81: 80–113.
13.
PengSJinGLiL, et al.
Multi-functional electrospun nanofibres for advances in tissue regeneration, energy conversion & storage, and water treatment. Chem Soc Rev2016;
45: 1225–1241.
14.
WuJWangNZhaoY, et al.
Electrospinning of multilevel structured functional micro-/nanofibers and their applications. J Mater Chem A2013;
1: 7290–7305.
15.
DuFWangHZhaoW, et al.
Gradient nanofibrous chitosan/poly 3-caprolactone scaffolds as extracellular microenvironments for vascular tissue engineering. Biomaterials2012;
33: 762–770.
16.
HashiCKDeruginNJanairoRR, et al.
Antithrombogenic modification of small-diameter microfibrous vascular grafts. Arterioscler Thromb Vasc Biol2010;
30: 1621–1627.
17.
SolettiLNieponiceAHongY, et al.
In vivo performance of a phospholipid-coated bioerodable elastomeric graft for small-diameter vascular applications. J Biomed Mater Res A2011;
96: 436–448.
18.
MaharaASomekawaSKobayashiN, et al.
Tissue-engineered acellular small diameter long-bypass grafts with neointima-inducing activity. Biomaterials2015;
58: 54–62.
19.
HeiseMSchmidmaierGHusmannI, et al.
PEG-hirudin/iloprost coating of small diameter ePTFE grafts effectively prevents pseudointima and intimal hyperplasia development. Eur J Vasc Endovasc Surg2006;
32: 418–424.
20.
LiangYKiickKL.Heparin-functionalized polymeric biomaterials in tissue engineering and drug delivery applications. Acta Biomater2014;
10: 1588–1600.
21.
YaoYWangJCuiY, et al.
Effect of sustained heparin release from PCL/chitosan hybrid small-diameter vascular grafts on anti-thrombogenic property and endothelialization. Acta Biomater2014;
10(6): 2739–2749.
22.
SeibFPHerklotzMBurkeKA, et al.
Multifunctional silk-heparin biomaterials for vascular tissue engineering applications. Biomaterials2014;
35: 83–91.
23.
ChenSAnJWengL, et al.
Construction and biofunctional evaluation of electrospun vascular graft loaded with selenocystamine for in situ catalytic generation of nitric oxide.Mater Sci Eng C Mater Biol Appl2014;
45: 491–496.
24.
TeichmannJMorgensternASeebachJ, et al.
The control of endothelial cell adhesion and migration by shear stress and matrix-substrate anchorage. Biomaterials2012;
33: 1959–1969.
25.
ShinYMLeeYBKimSJ, et al.
Mussel-inspired immobilization of vascular endothelial growth factor (VEGF) for enhanced endothelialization of vascular grafts. Biomacromolecules2012;
13: 2020–2028.
26.
KhanMYangJShiC, et al.
Surface tailoring for selective endothelialization and platelet inhibition via a combination of SI-ATRP and click chemistry using Cys–Ala–Gly-peptide. Acta Biomater2015;
20: 69–81.
27.
CichaISinghRGarlichsCD, et al.
Nano-biomaterials for cardiovascular applications: clinical perspective. J Control Release2016;
229: 23–36.
28.
FrostMCReynoldsMMMeyerhoffME.Polymers incorporating nitric oxide releasing/generating substances for improved biocompatibility of blood-contacting medical devices. Biomaterials2005;
26: 1685–1693.
29.
TziampazisEKohnJMoghePV.PEG-variant biomaterials as selectively adhesive protein templates: model surfaces for controlled cell adhesion and migration. Biomaterials2000;
21: 511–520.
30.
JainSBajpaiAK.Designing polyethylene glycol (PEG) – plasticized membranes of poly(vinyl alcohol-g-methyl methacrylate) and investigation of water sorption and blood compatibility behaviors. Design Monomers Polym2013;
16: 436–446.
BaiLZhaoJLiQ, et al.
Biofunctionalized electrospun PCL-PIBMD/SF vascular grafts with PEG and cell-adhesive peptides for endothelialization. Macromol Biosci2019;
19: e1800386.
33.
LiuGLuoQWangH, et al.
In situ synthesis of multidentate PEGylated chitosan modified gold nanoparticles with good stability and biocompatibility. RSC Adv2015;
5: 70109–70116.
34.
SzentivanyiAChakradeoTZernetschH, et al.
Electrospun cellular microenvironments: understanding controlled release and scaffold structure. Adv Drug Deliv Rev2011;
63: 209–220.
35.
YangSFLeongKFDuZH, et al.
The design of scaffolds for use in tissue engineering. Part 1: traditional factors. Tissue Eng2001;
7: 679–689.
36.
ZhangYOuyangHLimCT, et al.
Electrospinning of gelatin fibers and gelatin/PCL composite fibrous scaffolds. J Biomed Mater Res Part B Appl Biomater2005;
72: 156–165.
37.
BakerBMGeeAOMetterRB, et al.
The potential to improve cell infiltration in composite fiber-aligned electrospun scaffolds by the selective removal of sacrificial fibers. Biomaterials2008;
29: 2348–2358.
38.
YinABowlinGLLuoR, et al.
Electrospun silk fibroin/poly (l-lactide-ε-caplacton) graft with platelet-rich growth factor for inducing smooth muscle cell growth and infiltration. Regen Biomater2016;
3: 239–245.
ZhouXZhangTGuoD, et al.
A facile preparation of poly(ethylene oxide)-modified medical polyurethane to improve hemocompatibility. Colloids Surf A: Physicochem Eng Aspects2014;
441: 34–42.
41.
NaguraMNomuraYGotokY, et al.
Anti-thrombogenicity of styrene-butadiene-styrene triblock copolymer grafted with poly(ethylene glycol)s. J Appl Polym Sci2009;
113: 2462–2476.
42.
WangDJiJGaoC, et al.
Surface coating of stearyl poly(ethylene oxide) coupling-polymer on polyurethane guiding catheters with poly(ether urethane) film-building additive for biomedical applications. Biomaterials2001;
22: 1549–1562.
43.
JuYMChoiJSAtalaA, et al.
Bilayered scaffold for engineering cellularized blood vessels. Biomaterials2010;
31: 4313–4321.
44.
MuruganRRamakrishnaS.Nano-featured scaffolds for tissue engineering: a review of spinning methodologies. Tissue Eng2006;
12: 435–447.
45.
PhamQPSharmUMikosAG.Electrospun poly(ε-caprolactone) microfiber and multilayer nanofiber/microfiber scaffolds: characterization of scaffolds and measurement of cellular infiltration. Biomacromolecules2006;
7: 2796–2805.
46.
SunXLangQZhangH, et al.
Electrospun photocrosslinkable hydrogel fibrous scaffolds for rapid in vivo vascularized skin flap regeneration. Adv Funct Mater2017;
27: 1604617.
47.
XuCInaiRKotakiM, et al.
Electrospun nanofiber fabrication as synthetic extracellular matrix and its potential for vascular tissue engineering. Tissue Eng2004;
10: 1160–1168.
48.
BergmeisterHSchreiberCGraslC, et al.
Healing characteristics of electrospun polyurethane grafts with various porosities. Acta Biomater2013;
9: 6032–6040.
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