Heparin-modified small-diameter nanofibrous vascular grafts.

Department of Bioengineering, University of California, Berkeley, CA 94720USA.
IEEE transactions on nanobioscience (Impact Factor: 1.71). 03/2012; 11(1):22-7. 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.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Tissue-engineered vascular grafts (TEVGs) offer an alternative to synthetic grafts for the surgical treatment of atherosclerosis and congenital heart defects, and may improve graft patency and patient outcomes after implantation. Electrospinning is a versatile manufacturing process for the production of fibrous scaffolds. This review aims to investigate novel approaches undertaken to improve the design of electrospun scaffolds for TEVG development. The review describes how electrospinning can be adapted to produce aligned nanofibrous scaffolds used in vascular tissue engineering, while novel processes for improved performance of such scaffolds are examined and compared to evaluate their effectiveness and potential. By highlighting new drug delivery techniques and porogenic technologies, in addition to analyzing in vitro and in vivo testing of electrospun TEVGs, it is hoped that this review will provide guidance on how the next generation of electrospun vascular graft scaffolds will be designed and tested for the potential improvement of cardiovascular therapies.
    Expert Review of Cardiovascular Therapy 06/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Hemocompatibility of tissue-engineered vascular grafts remains a major hurdle to clinical utility for small-diameter grafts. Here we assessed the feasibility of using autologous blood outgrowth endothelial cells to create an endothelium via lumenal seeding on completely biological, decellularized engineered allografts prior to implantation in the sheep femoral artery. The 4-mm-diameter, 2- to 3-cm-long grafts were fabricated from fibrin gel remodeled into an aligned tissue tube in vitro by ovine dermal fibroblasts prior to decellularization. Decellularized grafts pre-seeded with blood outgrowth endothelial cells (n = 3) retained unprecedented (>95 %) monolayer coverage 1 h post-implantation and had greater endothelial coverage, smaller wall thickness, and more basement membrane after 9-week implantation, including a final week without anti-coagulation therapy, compared with contralateral non-seeded controls. These results support the use of autologous blood outgrowth endothelial cells as a viable source of endothelial cells for creating an endothelium with biological function on decellularized engineered allografts made from fibroblast-remodeled fibrin.
    Journal of Cardiovascular Translational Research 01/2014; · 3.06 Impact Factor
  • Source
    [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.
    Acta biomaterialia 01/2014; · 5.68 Impact Factor


Available from