Biodegradable Synthetic Vascular Graft

可生物降解的合成血管移植物

基本信息

批准号：
8706204
负责人：
Yadong Wang
金额：
$ 35.44万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-07-25 至 2017-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8706204
关键词：
Age Animals Anti-Inflammatory Agents Anti-inflammatory Aorta Architecture Arteries Biological Bioreactors Blood Vessels Blood flow Bypass Cell Culture Techniques Cell physiology Cells Clinical Complex Coronary Artery Bypass Coupled Data Developed Countries Disease Elastin Elastomers Employee Strikes Endothelial Cells Extracellular Matrix Feedback Funding Future Gene Expression Goals Grant Healed Histology In Situ In Vitro Infiltration Inflammation Inflammatory Inflammatory Response Ischemia Lead Mechanics Myocardial Natural regeneration Nature Nitric Oxide Pathway Organ Pathway interactions Patients Performance Peripheral Phenotype Physiologic pulse Polymers Porosity Process Property Rattus Reporting Research Residual state Saphenous Vein Seeds Selection Criteria Smooth Muscle Myocytes Source Staging Structure Testing Time Tissue Engineering Translations Transplanted tissue Tube Tubular formation Tunica Adventitia Ultrasonography United States United States National Institutes of Health Vascular Diseases Vascular Endothelial Cell Vascular Graft Wound Healing abdominal aorta aged base cell type cellular transduction clinically relevant crosslink density design disability healing implantation in vivo insight mortality nerve supply novel strategies poly(glycerol-sebacate)polycaprolactone pressure public health relevance scaffold success

项目摘要

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.

该研究计划建立在美国国立卫生研究院先前资助的基础上，但开辟了一个全新的方向。下一阶段的研究旨在通过创建可被宿主快速重塑的无细胞合成移植物来利用人体自身的愈合能力。上一个资助期的重点是以细胞为中心的体外动脉组织工程。该项目的下一阶段将完全绕过细胞接种和细胞培养。我们将直接使用无细胞聚合物支架作为哺乳动物宿主腹主动脉的插入移植物。与目前致密且抑制细胞浸润的血管移植物相比，开放式多孔移植物将更有效地充分利用宿主重塑的力量。移植物将立即作为血流的非血栓形成导管发挥作用，其方式与冠状动脉搭桥手术中的隐静脉类似。我们假设移植物中的大孔将促进宿主细胞浸润，而快速降解的聚合物将使宿主快速重塑以原位再生动脉。这一假设基于我们关于宿主细胞快速浸润和植入后 3 个月大鼠主动脉几乎完全再生的强有力的初步数据。新动脉与宿主主动脉同步搏动，并具有与天然动脉相当的爆破压和顺应性。据我们所知，这种快速宿主重塑水平在报道的血管移植物中是前所未有的。未来五年，三个具体目标将检验这一假设： 1. 研究多孔管结构与血管移植物宿主重塑之间的关系。 2.确定护套材料的机械性能对血管移植物体内性能的影响。 3. 在细胞水平上研究血管移植物的宿主重塑。无细胞组织工程的成功将加速临床转化，并最终使患有心肌和外周缺血的患者受益。从这项研究中获得的见解将在未来带来复杂器官再生的新方法。