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The Study of NapFFGRGD Surface Modified with Electrospun PCL as a Small Diameter Vascular Graft

Author: WangZhiHong
Tutor: KongDeLing
School: Nankai University
Course: Biochemistry and Molecular Biology
Keywords: endothelization small-diameter vascular graft surface modification biomaterial diabetes
CLC: R318.08
Type: PhD thesis
Year: 2013
Downloads: 19
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Abstract

Nowadays, suitable small-diameter vascular grafts are a pressing clincal need for disease coronary and peripheral arteries. More than500,000coronary artery bypass procedures are performed every year, reported by the American Heart Association in2012. In addition, over1million vascular grafts per year are required for lower limb revascularization and hemodialysis. As we know, the gold standard for bypass surgery is autologous vein, but the resource limited its use. Current vascular grafts, such as expanded polytetrafluoroethylene (ePTFE), which has been used as large-diameter vascular prostheses for decades, have been proved unsatisfactory in small-diameter graft (ID<6mm) applications due to acute thrombus formation and intimal hyperplasia.Rapid endothelization of the vascular graft is the key to solve this problem. The discovery of circulating endothelial progenitor cells (EPCs) in1997brought new perspectives for the endothelialization of blood contacting materials. The strategy is: synthetic graft surfaces modified with specific molecules binding to endogenous EPCs can capture circulating EPCs directly from blood stream after implantation. And then these cells with high proliferation potential can cover the graft with non-thrombogenic endothelium, which maintains optimal haemostasis and minimizes the risk of restenosis.s-caprolactone (PCL) has been investigated as small-diameter vascular grafts. Especially compared with other polymers, PCL has its advantages including good biocompatibility, biodegradability with longer degradation time and FDA approval. However, it lacks functional groups for covalent linkage and its hydrophobic surface is disadvantageous to cell adhesion and proliferation. To overcome the deficiency, many approaches have been developed to improve properties of PCL by surface modification with bioactive molecules. Various groups immobilized RGD sequence onto the materials. They have demonstrated that RGD peptides directly immobilized onto materials can improve ECs attachment, spread and proliferation. However, conventional chemical reactions applied in surface modification often weaken the mechanical properties of the scaffolds and inactivated the biomolecules. A simple surface functionalization approach without damage to the bulk properties or the introduced biomolecules is still needed.In the present study, a new molecular, Nap-FFGRGD, was synthesized. The small molecular is amphibilic and contains RGD motif. We found that it can self-assemble and form small molecular hydrogels. Herein, we hypothesized that PCL fibers can be modified by Nap-FFGRGD through self-assembly and this modification method can improve the hydrophilicity, biocompatibility and blood compatibility of PCL scaffolds. Our data showed that Nap-FFGRGD modification changed the PCL surface from hydrophobic into hydrophilic, improved anticoagulation and endothelial cell adhesion. The results of in vivo implantation showed that RGD modification improved the patency of the grafts and enhanced the formation of endothelium and regeneration of smooth muscle cells. These indicated that Nap-FFGRGD was a useful molecule for surface modification of vascular materials.In clinical, patients who need artificial vascular graft usually are complicated. They usually have other diseases at the same time, for example, type2diabetes mellitus. Data from "the clinical report of cardiovascular disease in China "showed that about30%of patients who need by-pass surgery are complicated with diabetes. In America one-third of old patients undergoing PCI have diabetes, and a study showed that diabetes was independently and strongly associated with increased long-term adverse events after both DES and BMS implantation.Thus it is crucial to test the remodeling of the vascular grafts in animal model of diseases before its use in clinical. Herein, we further investigate the performance of PCL and PCL-RGD in the rat model of type2diabetes mellitus. Our data showed that rats with diabetes had higher major adverse evens rates than non-diabetics, including slowly endothelization, inflammatory, early calcification and platelet adhesion. Thus, take consideration of diabetic environment, development of an improved vascular graft designed to promote the endothelization would be an important advance in the translation of this from bench to bedside.In all, we offered a surface modification method by molecular self-assembly, which is simple and stable to generate a bioactive surface for PCL films prepared by electrospinning. Further, we fabricated a small diameter vascular graft with this method, which could realize the rapid endothelization in rat model as a substitute for abdominal artery. Third, our data from the performance of this material in rat model of type2diabetes mellitus gave an important clue that the high glycemic niche or internal environment affects the rapid endothelization and tissue regeneration, which require a dedicated work to develop the materials for clinic use.

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CLC: > Medicine, health > Basic Medical > Medical science in general > Biomedical Engineering > General issues > Biomaterial
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