Biodegradable Synthetic Vascular Graft

这项研究计划建立在先前NIH资助所取得的进展基础上，但在一个全新的方向上取得了进展。下一阶段的研究旨在通过创造无细胞合成移植物来利用人体自身的愈合能力，这种移植物可以被宿主迅速重塑。上一个资助期的重点是以细胞为中心的动脉体外组织工程。该项目的下一阶段将完全绕过细胞接种和细胞培养。我们将使用无细胞的聚合物支架直接作为插入移植物在哺乳动物宿主的腹部动脉。开放多孔移植物将比目前致密并抑制细胞浸润的血管移植物更有效地充分利用宿主重塑的力量。移植物将立即作为用于血液流动的非血栓形成管道，其方式与冠状动脉旁路手术中的隐静脉类似。我们推测移植物中广泛的孔隙将促进宿主细胞浸润，快速降解的聚合物将使宿主快速重塑以原位再生动脉。该假设基于我们关于植入后3个月大鼠主动脉快速宿主细胞浸润和几乎完全再生的强有力的初步数据。新生动脉与宿主主动脉同步脉动，并且具有与天然动脉相当的爆破压和顺应性。据我们所知，这种快速的宿主重塑水平在报道的血管移植物中是前所未有的。在未来五年内，三个具体目标将检验这一假设：1。研究多孔管的结构与移植血管的宿主重塑的关系。2.确定鞘管材料的机械性能对体内血管移植物性能的影响。和3.在细胞水平上研究移植血管的宿主重塑。无细胞组织工程的成功将加速临床转化，并最终使心肌和外周缺血患者受益。从这项研究中获得的见解将导致未来复杂器官再生的新方法。

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 polyer 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 o 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.