Tissue Engineered Nanofibrous Vascular Graft

组织工程纳米纤维血管移植物

• 批准号: 7294240
• 负责人: Song Li
• 金额: $ 35.66万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-30 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7294240
• 关键词: Address; Allogenic; Aneurysm; Animal Model; Arteries; Atherosclerosis; Autologous; Biocompatible; Biocompatible Materials; Biological Markers; Biomimetics; Blood Vessels; Bone Marrow; Bone Marrow Stem Cell; Bypass; Caliber; Cell Adhesion; Cell Differentiation process; Cells; Collagen; Condition; Development; Endothelial Cells; Engineering; Extracellular Matrix; Facility Construction Funding Category; Failure; Goals; Laboratories; Lead; Liquid substance; Mechanics; Mesenchymal Stem Cells; Molecular Structure; Monitor; Operative Surgical Procedures; Peptides; Personal Satisfaction; Prevention; Procedures; Production; Property; RGD (sequence); Rate; Research; Smooth Muscle Myocytes; Source; Stem cells; Structure; Surface; Technology; Testing; Thrombosis; Tissue Engineering; Tissues; Transforming Growth Factors; Transplantation; Tubular formation; Vascular Diseases; Vascular Graft; Veins; adult stem cell; base; biodegradable polymer; cell type; immunogenic; in vivo; innovative technologies; monolayer; nanofiber; novel; poly(lactic acid); precursor cell; prevent; repaired; response; scaffold; scale up; shear stress; vascular tissue engineering

DESCRIPTION (provided by applicant): Blood vessel replacement is a common treatment for vascular diseases. Tissue engineering is a promising approach to the fabrication of non-thrombogenic and mechanically durable vascular grafts. Our goal is to engineer bone marrow stem cells and electrospun nanofibrous scaffolds to construct tissue-engineered vascular graft (TEVG) that closely matches the composition, structure and mechanical property of native blood vessel. Bone marrow contains vascular endothelial precursor cells (EPCs) and mesenchymal stem cell (MSC). MSC can differentiate into a variety of cell types, including vascular smooth muscle cell (SMC). We hypothesize that: (1) bone marrow stem cells can be used to derive endothelial cells (ECs) and SMCs to construct TEVGs, (2) bioactive nanofibrous scaffolds with aligned nanofibers can promote MSC differentiation, matrix remodeling and the formation of microstructure as in native vessel, and (3) mechanical loading can promote MSC differentiation, matrix remodeling and EC monolayer retention. To test our hypothesis, four Specific Aims are proposed: (1) To engineer bioactive nanofibrous scaffolds and characterize MSC-scaffold interactions; (2) To determine MSC differentiation and matrix remodeling in TEVG in response to mechanical loading; (3) To construct EC monolayer in TEVG using EPCs and determine the effect of flow on EC remodeling; (4) To determine the remodeling and patency of small-diameter TEVGs in vivo. The nanofibers in the tubular scaffolds will be aligned in the circumferential direction to mimic the matrix alignment in native blood vessels and guide the MSC alignment. RGD peptide and TGF-p will be conjugated to the nanofibers to promote matrix remodeling and MSC differentiation into SMC. Mechanical loading will be applied to the tubular scaffolds to further enhance matrix remodeling and MSC differentiation. Bone marrow derived ECs will be cultured as monolayer on the luminal surface of TEVG, and will be pre-conditioned by fluid shear stress. The mechanical property and structure of the TEVGs will be determined. Bypass surgery will be performed in animal model to determine the continued remodeling and patency of small TEVGs. Manufacturing-related issues such as Good Manufacturing Practices, biomarker monitoring, storage and caling-up will be addressed. The accomplishment of this project will lead to the development of innovative technologies to engineer stem cells and nanofibrous scaffolds for the construction of small TEVGs.

描述（由申请人提供）： 血管置换是血管疾病的常见治疗方法。组织工程是一种制造非智能和机械耐用的血管移植物的有前途的方法。我们的目标是设计骨髓干细胞和电纺纳米纤维支架，以构建组织工程的血管移植（TEVG），与天然血管的组成，结构和机械性能紧密匹配。骨髓含有血管内皮前体细胞（EPC）和间质干细胞（MSC）。 MSC可以区分各种细胞类型，包括血管平滑肌细胞（SMC）。 We hypothesize that: (1) bone marrow stem cells can be used to derive endothelial cells (ECs) and SMCs to construct TEVGs, (2) bioactive nanofibrous scaffolds with aligned nanofibers can promote MSC differentiation, matrix remodeling and the formation of microstructure as in native vessel, and (3) mechanical loading can promote MSC differentiation, matrix remodeling和EC单层保留。为了检验我们的假设，提出了四个具体目标：（1）设计生物活性纳米纤维支架并表征MSC-Scaffold相互作用； （2）确定TEVG中的MSC分化和基质重塑，以响应机械负载； （3）使用EPC在TEVG中构建EC单层，并确定流动对EC重塑的影响； （4）确定体内小直径TEVG的重塑和通畅。管状支架中的纳米纤维将沿圆周方向排列，以模仿天然血管中的基质比对并指导MSC比对。 RGD肽和TGF-P将与纳米纤维共轭，以促进基质重塑和MSC分化为SMC。机械载荷将应用于管状支架，以进一步增强基质重塑和MSC分化。骨髓衍生的EC将在TEVG的腔表面上作为单层培养，并将通过流体剪切应力预先调节。将确定TEVG的机械性能和结构。将在动物模型中进行旁路手术，以确定小型TEVG的持续重塑和通畅。将解决与制造有关的问题，例如良好的制造实践，生物标志物监测，存储和平静的问题。该项目的完成将导致开发创新的技术，以设计用于构建小型TEVG的干细胞和纳米纤维支架。