Tissue Engineering Plant-based Vascular Grafts

组织工程植物血管移植物

• 批准号: 10439063
• 负责人: Nicholas J. Merna
• 金额: $ 39.54万
• 依托单位: HOFSTRA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10439063
• 关键词: Affect; American; Animals; Arteries; Autologous; Biochemical; Biological Assay; Biomedical Engineering; Bioreactors; Blood Vessels; Blood flow; Bypass; Caliber; Career Choice; Cell Adhesion; Cell-Matrix Junction; Cells; Cellulose; Cessation of life; Clinical; Coronary heart disease; Custom; DNA; Deposition; Detergents; Egtazic Acid; Endothelial Cells; Endothelium; Engraftment; Environment; Excision; Extracellular Matrix; Extracellular Matrix Proteins; Feasibility Studies; Fluorescence Microscopy; Future; Goals; Histology; Hyperplasia; Image Analysis; Immune response; Implant; Laboratories; Legal patent; Liquid substance; Mechanics; Mesenchymal Stem Cells; Methods; Modeling; Monitor; Muscle Tonus; Myocardial Infarction; Operative Surgical Procedures; Patients; Performance; Perfusion; Peripheral arterial disease; Plant Leaves; Plants; Play; Property; Proteins; Pump; Rattus; Research; Research Personnel; Risk; Role; Saphenous Vein; Scanning Electron Microscopy; Smooth Muscle; Smooth Muscle Myocytes; Specialist; Surgeon; Suspensions; Syringes; Testing; Thinness; Thrombosis; Time; Tissue Engineering; Tissues; Transplantation; Trypsin; Ultrasonography; United States; Universities; Validation; Vascular Graft; Vascular Smooth Muscle; Vascular blood supply; Work; animal tissue; base; common treatment; conditioning; experimental study; fluorescence imaging; hands on research; implantation; improved; in vivo; insight; mechanical properties; ocular surface; preconditioning; pressure; prevent; public health relevance; reconstruction; recruit; repaired; scaffold; shear stress; skills; stem cell differentiation; success; thrombogenesis; undergraduate student; vascular tissue engineering

Abstract Coronary heart disease and peripheral artery disease affects millions of Americans each year, and is often treated with bypass surgery to reroute the blood supply around a blocked artery. However, patients do not always have a saphenous vein suitable for an arterial bypass graft. The structural similarities between animals and plants inspired a more recent strategy of decellularizing plants in order to generate perfusable scaffolds. Unlike animal tissue, plants are primarily composed of cellulose which can offer a promising, nonthrombogenic alternative capable of promoting cell attachment and redirecting blood flow. The immediate goal of this project is to succeed in tissue engineering and testing a patent, nonthrombogenic vessel for engraftment that mimics the mechanical and structural properties of native vessels. We hypothesize that the mechanical and biochemical microenvironment provided by the decellularized plant leaves will promote initial endothelial cell and vascular smooth muscle cell adhesion, maintain vessel patency, and that the addition of fluid shear stress preconditioning will promote long-term endothelialization of the scaffold and minimize early graft occlusions in vivo. Based on our preliminary pressure tests and cell adhesion assays showing that decellularized plant leaves maintain their mechanical properties and promote endothelial cell adhesion, we believe this work will provide a useful method of decellularizing plants and pre-conditioning of cells into a natural scaffold capable of successful engraftment. The proposed project will also enhance the research environment at Hofstra University by allowing undergraduate students to plan, execute and perform analysis of authentic hands-on research. This would allow them to acquire a broad range of skills in biomedical engineering that they would otherwise not have access to and is expected to have a significant impact on their future studies and career choices.

摘要 冠心病和外周动脉疾病每年影响数百万美国人，而且 通常接受搭桥手术，以改变阻塞动脉周围的血液供应。然而，患者并不是这样 总要有适合动脉搭桥术的大隐静脉。动物之间的结构相似之处 植物启发了一种更新的策略，即脱细胞植物，以产生可循环使用的支架。 与动物组织不同，植物主要由纤维素组成，它可以提供一种有希望的、不会导致血栓形成的 能够促进细胞附着和重定向血液流动的替代品。这个项目的近期目标是 是在组织工程学和测试一种专利的、非血栓形成的血管植入方面取得成功，这种血管可以模仿 天然血管的机械和结构特性。我们假设机械和生物化学 脱细胞植物叶片提供的微环境将促进初始内皮细胞和血管 平滑肌细胞黏附，维持血管通畅，并加入流体切应力预适应 将促进支架的长期内皮化，并最大限度地减少体内早期移植物闭塞。基于 我们的初步压力测试和细胞黏附分析表明，脱细胞的植物叶片保持了它们的 力学性能和促进内皮细胞黏附，我们相信这项工作将提供一种有用的方法 对植物进行脱细胞处理，并将细胞预调节为能够成功植入的天然支架。 拟议的项目还将改善霍夫斯特拉大学的研究环境， 本科生计划、执行和分析真实的实践研究。这将允许 让他们获得生物医学工程方面的广泛技能，否则他们将无法获得这些技能 并有望对他们未来的学习和职业选择产生重大影响。