In order to replace or repair small diameter arteries in patients suffering from peripheral vascular disease, for example, for coronary artery bypass or below the knee femoral/popliteal bypass, the current "gold standard" for the choice of material involves the patient’s own tissue such as the internal mammary artery/or saphenous vein. However, there are certain shortcomings with these autologous vessels, such as problems of inappropriate size for certain procedures, unacceptable varicosities for different veins and unavailability of supply in chronic patients. Current synthetic polymer graft materials, such as poly(ethyleneterephthalate)(polyester-PET) or expanded polytetrafluoroethylene (ePTFE-Goretex(?)), inevitably fail due to thrombosis (clot formation) or intimal hyperplasia most likely caused by compliance mismatch. Natural polymers, such as silk fibroin, have long been used as implantable surgical sutures, and recent reports from our group and others have demonstrated that it has acceptable mechanical properties and patency rates for use as a vascular substitute in animal models. However, fibroin is believed to contribute to the damage of red blood cells, and in order to be used as an implantable vascular prosthesis its hemocompatibility needs to be improved. This study has taken two sequential steps to address this problem. First, in order to create a positively charged surface on the clean silk fibroin fabric (SFF), a3and5layers of polyelectrolyte surface deposition layer-by-layer technique was used with the positive counterion poly(allylamine hydrochloride)(PAH) and the negative counterion poly(acrylic acid)(PAA). Second, negatively charged low molecular weight heparin (LMWH) with and without activation with1-ethyl-3-(dimethylaminopropyl) carbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS) was then immobilized on these positively charged self-assembled surfaces.The effectiveness of the alkali degumming treatment for raw silk fabric was confirmed qualitatively using picric acid and carmine staining (PACS). Fibroin selectively adsorbs picric acid molecules in alkaline solution, generating a yellow color, whereas, both carmine (red color) and picric acid (yellow color) adhere to sericin producing a deep red identifiable coloration. In addition, the accumulation of sericin gum on the virgin silk fabric surface was readily visualized by SEM micrographs compared to the SFF which showed a smooth surface which confirmed the effectiveness of the degumming process. Additional gravimetric measurements, representing a quantitative assessment of the degumming process, attributed a weight loss of25.5%to the degummed silk fabric.The presence of heparin was confirmed with Alcian Blue staining, a toluidine blue assay, energy dispersive X-ray analysis and XPS (X-ray photoelectron spectroscopy) analysis.Surface modified and immobilized silk fibroin fabrics showed an evident difference and uniformity in color under light microscopy between the untreated and modified samples when stained with of Alcian Blue solution. This result confirmed the presence of an active glycosaminoglycan (GAG), namely heparin, and indicated that it was uniformly distributed over the surface of the modified fibroin fabrics.According to the toluidine blue assay, the average heparin content was found to lie in the range10.65μg/cm2to15.34μg/cm2. In order to confirm the presence of heparin molecule on the modified SFF surfaces, both sulfur (S) and sodium (Na) peaks were identified by XPS and EDX analyses.Increased roughness and hydrophilicity of the modified surfaces were characterized by scanning electron microscopy (SEM), atomic force microscopy (AFM) and water contact angle measurements. SEM microphotographs confirmed that the surface of the control silk fibroin fibers appeared to be smooth with axially aligned striations. On the other hand, the surfaces of the modified fibroin fibers changed from being smooth to being irregular and rough. The3and5layers of polyelectrolyte deposition and heparin immobilization added a raised globular appearance on the fibroin fiber surface. The irregular distribution of discrete "hills and valleys" suggests that the polyelectrolyte distribution was not applied evenly across the whole fiber surface. In some areas the discrete globular regions combined and fused together to form a more extensive modified surface.AFM analysis showed that before modification, the top view of the fibroin fiber surface appeared to be comparatively smooth. However, after modification, the fiber surfaces became more uneven with many convex protrusions separated by pits or valleys, suggesting that the polyelectrolyte deposition created irregular clusters of condensation on the fibers’ surface. The contact angle test results indicated ensured that the modified SFFs had significantly increased hydrophilicity. The mechanical properties in terms of bursting strength test and the thermal performance as measured by thermogravimetric analysis (TGA) revealed that the modification process caused no reduction in bursting strength and resulted in a marginally higher thermal stability.The polyelectrolytes deposition and heparin immobilization surface treatment also generated improvements in the biological performance. The modified SFF surfaces were found to have a negligible hemolytic effect, reduced protein adsorption and platelet adhesion and a higher concentration of free hemoglobin measured by a kinetic clotting time test. Furthermore, the surface treated with the5layer deposition procedure gave an enhanced performance compared to the3layer self-assembly technique. Given the success of these preliminary results, it is anticipated that this novel approach to surface modification and heparin immobilization will demonstrate long term patency in during in vivo animal trials of small caliber silk fibroin vascular grafts.