Biodegradable Synthetic Vascular Graft

摘要 这项研究计划建立在先前NIH资助所取得的进展的基础上， 全新的方向下一阶段的研究旨在利用身体自身的愈合 通过创造无细胞的合成移植物，可以迅速重塑宿主的能力。的焦点 上一个资助期是以细胞为中心的动脉体外组织工程。下一步 该项目将完全绕过细胞接种和细胞培养。我们将使用无细胞聚合物支架 直接作为哺乳动物宿主的腹主动脉中的插入移植物。开放多孔移植物将 比目前的高密度血管移植物更有效地充分利用宿主重塑的力量， 并抑制细胞浸润。移植物将立即作为血液的非血栓形成管道发挥作用 在冠状动脉搭桥手术中，隐静脉以类似的方式流动。我们假设 移植物中的大孔将促进宿主细胞浸润 使宿主快速重塑，原位再生动脉。这一假设是基于我们强大的 大鼠主动脉快速宿主细胞浸润和接近完全再生的初步数据3个月 植入后。新生动脉与宿主主动脉同步搏动，具有爆发性 压力和顺应性与天然动脉相当。据我们所知，这种程度的快速宿主 重塑在所报道的血管移植物中是前所未有的。三个具体目标将检验这一假设 未来五年：1。研究了多孔管的结构与 血管移植物的宿主重塑2.确定机械性能的影响 鞘管材料对血管移植物体内性能的影响。和3.调查主机 在细胞水平重塑血管移植物。无细胞组织工程的成功将 加速临床转化，最终使心肌和外周血管疾病患者受益 缺血从这项研究中获得的见解将导致复杂再生的新方法 器官在未来

Abstract This research plan builds upon the progress made with prior NIH funding but strikes out in a brand new direction. The next period of the research aims at harnessing the body’s own healing capacity by creating cell-free synthetic grafts that can be rapidly remodeled by the host. The focus of the last funding period was cell-centered in vitro tissue engineering of arteries. The next stage of this project will completely bypass cell seeding and cell culture. We will use the cell-free polymer scaffolds directly as interposition grafts in abdominal aortas of mammalian hosts. The open porous graft will fully exploit the power of host remodeling more effectively than current vascular grafts that are dense and inhibit cell infiltration. The graft will function immediately as a non-thrombogenic conduit for blood flow in a similar fashion as a saphenous vein in coronary artery bypass surgery. We hypothesize that the extensive pores in the graft will facilitate host cell infiltration and the fast degrading polymer will enable rapid host remodeling to regenerate arteries in situ. This hypothesis is based on our strong preliminary data on rapid host cell infiltration and near complete regeneration of rat aorta 3 month post-implantation. The neo-arteries pulse synchronously with the host aorta and possess burst pressure and compliance comparable to native arteries. To our knowledge, this level of rapid host remodeling is unprecedented in reported vascular grafts. Three specific aims will test this hypothesis in the next five years: 1. Study the relationship between the structure of the porous tube and host remodeling of the vascular grafts. 2. Determine the impact of mechanical properties of sheath material on the performance of the vascular graft in vivo. And 3. Investigate host remodeling of the vascular grafts at the cellular level. Success in cell-free tissue engineering will accelerate clinical translation and ultimately benefit patients suffering myocardial and peripheral ischemia. Insights gained from this research will lead to new approaches in regeneration of complex organs in the future.