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
Abstract
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.
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    • "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). "
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