| Cardiovascular disease is the leading cause of death in the United Sates. When not treated, these diseases which affect the heart and blood vessels end in heart attacks or strokes. Currently, there are around 500,000 coronary artery bypass operations annually. Because of the problems associated with native grafts, synthetic grafts, and prostheses, the creation of a durable small-diameter (<6mm) vascular scaffold is critical to the successful treatment of cardiovascular disease and injury.;Electrospinning technology has been widely used to fabricate three dimension, highly porous, nanofibrous scaffolds that support cellular activities and tissue formation. Nanofibrous scaffolds have been demonstrated as suitable substrates for tissue engineering blood vessels.;In chapter 2, a tubular vascular scaffold has been fabricated by a mixture of Poly (glycolic-co-lactic acid) (PLGA), Collagen Type I and elastin by electrospinning. The scaffold had an inner diameter of 4.75 mm with randomly oriented nano-fibers. The burst pressure of the cross-linked fibers was found to be 12 times systolic pressure. The compliance test showed that there was a higher diameter displacement (12--14%) compared to 9% of the native vessel. The tubular scaffold was biocompatible in vitro and in vivo. Also it was shown to support both smooth muscle cells and endothelial cells growth and proliferation. However, after 1 week of perfusion bioreactor testing, the scaffold failed due to the lack of sufficient elasticity. In chapter 3, another Collagen type I and Poly-epsilon-caprolactone (PCL) scaffold showed better mechanical characteristics compared with PLGA/CollagenlElastin, the scaffold demonstrated a long-term stability under a continuous perfusion bioreactor system for up to 4 weeks. In addition, the composite scaffolds provided a favorable environment that supported the growth of vascular cells as shown in chapter 3. However, the lack of elastin in the composition in the composition was still a big problem in the vascular scaffold design. In addition, the very long degradation time of PCL potentially hinders the new tissue formation when implanted in vivo. Therefore, an elastic material with a controllable degradation rate which can be used as a substitute for elastin should be incorporated into a vascular graft.;In order to fabricate a nanocomposite to stimulate the extracellular matrix (ECM) with viscoelasticity required for artery replacement, Poly (1, 8-octanediol citrate) (POC), a synthetic, biodegradable, elastomeric, and hydrophilic material was used as a substitute for the elastic fiber in artery in chapter 4. Briefly, five nanocomposites were fabricated using electrospinning: Collagen type I; Collagen type I + Collagen type III; Collagen type I + POC; Collagen type I + Collagen type III + POC; and Collagen type I + Decorin + Aggrecan + POC. Scanning electron microscopy images of all the materials had fiber size ranging from 200nm to 600nm with random orientation which mimics the structure of artery ECM. Single fiber mechanical properties were measured by atomic force microscopy. On the average, comparing samples with POC and without POC, elasticity increased 3.2 fold and maximum stress only decreased by 1.3 fold. Fibroblasts in culture had high affinity for all the fibers and proliferate during the 7 days period of study.;The study presented in this dissertation demonstrated the successful incorporation of an elastin substitute, POC in the production of a viscoelastic nanocomposite for vascular grafts and its future applications in the clinic. |
