Heparin-Modified Small-Diameter Nanofibrous Vascular Grafts

ArticleinIEEE transactions on nanobioscience 11(1):22-7 · March 2012with23 Reads
DOI: 10.1109/TNB.2012.2188926 · Source: PubMed
Due to high incidence of vascular bypass procedures, an unmet need for suitable vessel replacements exists, especially for small-diameter vascular grafts. Here we produced 1-mm diameter vascular grafts with nanofibrous structure via electrospinning, and successfully modified the nanofibers by the conjugation of heparin using di-amino-poly(ethylene glycol) (PEG) as a linker. Antithrombogenic activity of these heparin-modified scaffolds was confirmed in vitro. After 1 month implantation using a rat common carotid artery bypass model, heparin-modified grafts exhibited 85.7% patency, versus 57.1% patency of PEGylated grafts and 42.9% patency of untreated grafts. Post-explant analysis of patent grafts showed complete endothelialization of the lumen and neovascularization around the graft. Smooth muscle cells were found in the surrounding neo-tissue. In addition, greater cell infiltration was observed in heparin-modified grafts. These findings suggest heparin modification may play multiple roles in the function and remodeling of nanofibrous vascular grafts, by preventing thrombosis and maintaining patency, and by promoting cell infiltration into the three-dimensional nanofibrous structure for remodeling.
    • "However, the incorporation of growth factors has numerous limitations, due to: (i) the sensitivity of growth factors to chemical solvents; (ii) the short half-life of growth factors in vivo; and (iii) the limited control over the spatial and temporal distribution of growth factors throughout the scaffolds. Since heparin can bind to many growth factors, more attention has been focused on heparin-mediated recruitment of vascular endothelial growth factor (VEGF), which has been shown to enhance neovascu- larization40414243444546. It can be seen inFig. "
    [Show abstract] [Hide abstract] ABSTRACT: Silk fibroin (SF) scaffolds have been designed and fabricated for multiple organ engineering owing to the remarkable mechanical property, excellent biocompatibility and biodegradability, as well as its low immunogenicity. In this study, an easy-to-adopt and mild approach based on modified freeze-drying method was developed to fabricate a highly interconnected porous SF scaffold. Physical properties of the SF scaffold, including pore morphology, pore size, porosity and compressive modulus could be adjusted by the amount of added ethanol, freezing temperature and the concentration of SF. Fourier transform infrared (FTIR) illustrated that treatment of the lyophilized scaffolds with 90% methanol led to a structure transition of SF from silk I (random coil) to silk II (beta-sheet) which stabilized the SF scaffolds in water. We also incorporated heparin during fabrication to obtain a heparin-loaded scaffold which possessed excellent anticoagulant property. Heparin which was incorporated in SF scaffolds could be released in a sustain manner for approximately 7 days, inhibiting in vitro human smooth muscle cells (hSMCs) proliferation within the scaffold while promoting neovascularization in vivo. We therefore propose that the SF porous scaffold fabricated here may be an attractive candidate to be used as potential vascular graft for implantation based on its high porosity, excellent blood compatibility and mild fabrication process.
    Full-text · Article · Jan 2014
    • "Electrospun nanofibers with tunable nanometer size, surface functionality, mechanical properties (Su and Mo, 2011a) find extensive applications in drug delivery, health supplement delivery (Azarbayjani et al., 2010; Ngawhirunpat et al., 2011) and cosmetics applications (Fathi-Azarbayjani et al., 2010; Opanasopit et al., 2008). As wound dressing materials (Chen et al., 2012; Grewal et al., 2012; Jannesari et al., 2011), drug eluting stents (Yoo et al., 2012), transdermal drug delivery patches (Taepaiboon et al., 2007; Ngawhirunpat et al., 2009; Wu et al., 2010) and as blood vessels (Janairo et al., 2012) nanofibers have shown their marked uniqueness. The co-axial electrospinning methodology rendered a sustained mode of delivery of encapsulated drugs through slow degradation of shell polymer (Zhang et al., 2006; Su and Mo, 2011b). "
    [Show abstract] [Hide abstract] ABSTRACT: Biocompatible PCL polymer nanofiber mediated sustained release of hydrophilic drug and applicability as transdermal delivery system is attempted. This new attempt to investigate water soluble vitamin delivery with hydrophobic polymer nanofiber sustained the release of the vitamin and the method is suited for the transdermal patch applications. The drug loaded fibers were characterised with SEM for morphology, porometer for pore size measurements, mechanical strength calculation and FT-IR for drug load characterisation. The contact angle measurement showed surface wettability and controlled release of drug was quantified with UV absorption measurements. To further enhance the release of vitamin, the polymer fiber was plasma treated at different time intervals and made hydrophilic gradually. Since the increased surface area and drug encapsulation in nano-reservoirs can able to release drug in small quantities and in a sustained manner we attempted the release of the energy supplement with nanofibrous delivery mode.
    Article · Jan 2013
  • [Show abstract] [Hide abstract] ABSTRACT: Prosthetic vascular grafts do not mimic the antithrombogenic properties of native blood vessels and therefore have higher rates of complications that involve thrombosis and restenosis. We developed an approach for grafting bioactive heparin, a potent anticoagulant glycosaminoglycan, to the lumen of ePTFE vascular grafts to improve their interactions with blood and vascular cells. Heparin was bound to aminated poly(1,8-octanediol-co-citrate) (POC) via its carboxyl functional groups onto POC-modified ePTFE grafts. The bioactivity and stability of the POC-immobilized heparin (POC-Heparin) were characterized via platelet adhesion and clotting assays. The effects of POC-Heparin on the adhesion, viability and phenotype of primary endothelial cells (EC), blood outgrowth endothelial cells (BOECs) obtained from endothelial progenitor cells (EPCs) isolated from human peripheral blood, and smooth muscle cells were also investigated. POC-Heparin grafts maintained bioactivity under physiologically relevant conditions in vitro for at least one month. Specifically, POC-Heparin-coated ePTFE grafts significantly reduced platelet adhesion and inhibited whole blood clotting kinetics. POC-Heparin supported EC and BOEC adhesion, viability, proliferation, NO production, and expression of endothelial cell-specific markers von Willebrand factor (vWF) and vascular endothelial-cadherin (VE-cadherin). Smooth muscle cells cultured on POC-Heparin showed increased expression of α-actin and decreased cell proliferation. This approach can be easily adapted to modify other blood contacting devices such as stents where antithrombogenicity and improved endothelialization are desirable properties.
    Full-text · Article · Oct 2012
Show more