ELECTROSPUN FUCOIDAN LOADED PCL/PEO NANOFIBER SCAFFOLDS FOR SMALL DIAMETER VASCULAR GRAFTS

Abstract

The prime stumbling block for achieving prolonged patency of SDVG (<6 mm in diameter) is to forgo the high incidence of arteriosclerosis, thrombosis and re-stenosis, specially its major pathology, arterial intimal hyperplasia. Intimal hyperplasia arises from migration and proliferation of vascular smooth muscle cells (VSMCs). Intimal hyperplasia accounts for around 40% (late implantation) failure of the SDVG (small diameter vascular graft). Though there have been well established results for the potential of Fucoidan as a drug for intimal hyperplasia there has not been any attempt to impregnate Fucoidan into the vascular stents which can thereby aid in successful long term patency of SDVG. Hence, in this work Fucoidan is sought after for its potential in improving SDVG patency by inculcating it in PEO/PCL nanofiberous scaffold of SDVG. Fucoidan, a sulfated polysaccharide is now a well established drug with anti-coagulant, anti-complimentary, anti-oxidant, anti-tumor, anti-viral properties, apart from this the therapeutic potential of Fucoidan being effectuated is reduction of neo-intimal hyperplasia. At first, Fucoidan is extracted from the brown sea weed Sargassum wightii by slight modification of acid hydrolysis method. The extracted Fucoidan was confirmed by FTIR and APTT assay. After which, the PEO/PCL blend composition, and the operating parameters of electrospinning for producing uniform PEO/PCL nanofiberous scaffold were established by Taguchi (Orthogonal array) DOE. The parameters thus obtained were then adopted for fabricating First and Second layer of hi-layered graft like conduit, the intermediate layer (i.e. one between first and second) of the graft is a Fucoidan loaded PEO/PCL layer, formed by electrospraying Fucoidan loaded PEO/PCL polymer blend. Thus, the conduit fabricated is a bi-layered graft, in which a Fucoidan loaded PEO/PCL layer sandwiched between two layers of PEO/PCL nanofibers. The Fucoidan release profile from the bi-layered vascular conduit was monitored in vitro. The Fucoidan release profile depicted a sustained and uniform release profile after a small initial burst; hence it was established that this system can serve the purpose of delivering drugs in latter phase of SDVG implantation. To establish the significance of drug loading in the intermediate layer drug release profile from Fucoidan loaded monolayered conduit is also monitored. The comparison of which indicated that the release profile of the graft fabricated can be tuned according to the requirement by varying the depth of drug loaded layer across the conduit cross-sectional thickness. Once the Fucoidan loaded nanofiberous scaffold attains the mechanical compliance and cell compatibility it would of critical importance in SDVG fabrication.