Development and assessment of a natural bio scafold for vascular reconstruction

用于血管重建的天然生物支架的开发和评估

基本信息

批准号：
8234075
负责人：
Peter Stuart McFetridge
金额：
$ 35.19万
依托单位：
UNIVERSITY OF FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-03-01 至 2014-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8234075
关键词：
Adhesions Adopted Agonist Biological Bioreactors Blood Platelets Blood Vessels Caliber Cardiac Cell Proliferation Cell physiology Cell surface Cells Chemicals Clinical Collagen Complex Computers Contracts Coronary artery Development E-Selectin Endothelial Cells Endothelium Ensure Environment Event Failure Frequencies Goals Growth Human Hydrogels Hyperplasia Hypoxia Implant Industry Inflammatory Inflammatory Response Investigation Laboratories Lead Legal patent Leukocytes Liquid substance Measures Mechanical Stimulation Mechanics Modeling Natural regeneration Oxygen measurement, partial pressure, arterial Performance Perfusion Peripheral Phenotype Physiologic pulse Process Property Protein C Pulsatile Flow Reaction Seeds Series Side Signal Transduction Smooth Muscle Myocytes Sterility Stimulus Surface System Techniques Technology Testing Thromboplastin Thrombosis Time Tissue Engineering Tissues Tubular formation Umbilical cord structure Umbilical vein Vascular Graft Veins Work Wound Healing conditioning density graft failure immunogenic implant material implantation improved in vivo in vivo Model innovation migration reconstruction regenerative response scaffold tissue regeneration

项目摘要

DESCRIPTION (provided by applicant): Numerous factors have contributed to the failure to produce a successful small diameter vascular graft. It is clear that a working graft must include a cellular component since inert materials are unable to interact appropriately with the surrounding tissue. The body responds to implanted materials by initiating a complex series of biological reactions, broadly grouped as thrombotic, immunogenic and hyperplastic responses. In fact, even with grafts that include a cellular component, these negative biological responses occur leading to graft failure. It is our hypothesis that it is the inability of the cellular component of a tissue engineered vascular graft to respond appropriately that leads to graft failure. Therefore it is essential to define and measure specific aspects of endothelial and smooth muscle cell (SMC) function that are required to improve graft performance. Over the last several years, our laboratory has developed several innovative approaches for the development of a small diameter tissue engineered blood vessel. We use a decellurized human umbilical vein (HUV) as a remodelable scaffold. This scaffold is mechanically isolated from the tissue resulting in a long, tubular scaffold with uniform mechanical properties. We have developed a hydrogel 'shrink-wrapping' technique for rapidly seeding high densities of human SMC onto the abluminal surface of the vessel. These preliminary investigations have shown the HUV scaffold to have an excellent capacity to remodel. Our goal with this project is to fully develop the HUV as a small diameter blood vessel, then characterize and define conditions leading to a cell phenotype that minimizes inappropriate responses to thrombogenic and inflammatory signals. Our specific aims are 1) comprehensively assess the human umbilical vein (HUV) scaffold as an environment favorable for early regenerative events of smooth muscle cells. 2) Identify conditions promoting attachment, growth, and function (in vivo-like) of human endothelial cells on the lumen of the HUV scaffold. 3) Test the hypothesis that details of the fluid mechanical environment are critical in causing endothelial cells to adopt a phenotype that minimizes thrombosis and an inflammatory response. 4) Test the hypothesis that exposing the smooth muscle cells to hypoxic conditions does not severely impair the function of the fully oxygenated endothelial cells Narrative Our aim to develop functional blood vessels for cardiac and peripheral vascular reconstruction. A unique approach is taken using a bioscaffold derived from the human umbilical veins that have been ¿machined¿ from umbilical cords to yield a mechanically uniform, biologically compatible material. The investigations proposed herein aim to defined conditions that promote regeneration of the vascular wall to confer biological functionality. Further, we will investigate parameters that modulate undesirable cell function, such as wound healing We believe, this unique approach using the human umbilical vein in concert with technologies described herein, a viable alternative can be developed to alleviate this clinical demand.

描述（通过应用程序证明）：众多因素导致无法产生dyct材料的不合时宜的材料对内部的构成都不是对植入的材料的反应。那些不符合的成分，这些负面的生物反应发生了，这是组织工程的血管移植物的细胞成分无法适当的响应，从而导致移植物。在最后一个断裂中改善移植的肌肉细胞（SMC）功能已形成了断断续续的OD血管的断断续续性。在这些预动作调查中，在血管的表面上，具有良好的重塑能力。平滑肌细胞的环境福利。细胞采用表型可最大程度地减少脑栓塞，并炎症的重生。我们的目的是开发用于心脏和周围血管重构的功能性血管。使用源自已经曾经的人脐静脉的生物肉饼。机加工从脐带具有机械统一的生物学兼容材料此处的目的是定义促进血管壁再生以结合生物学功能的条件。此外，我们将研究调节不良细胞功能的参数，例如伤口愈合WEE 相信，这种独特的方法使用人类脐静脉与此处描述的技术共同可以开发可行的替代方案来减轻这一临床需求。

项目成果

期刊论文数量（24）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Adaptation of endothelial cells to physiologically-modeled, variable shear stress.

DOI：
10.1371/journal.pone.0057004
发表时间：
2013
期刊：
PloS one
影响因子：
3.7
作者：
Uzarski JS;Scott EW;McFetridge PS
通讯作者：
McFetridge PS

Pilot assessment of a human extracellular matrix-based vascular graft in a rabbit model.

DOI：
10.1016/j.jvs.2016.02.046
发表时间：
2017-03
期刊：
JOURNAL OF VASCULAR SURGERY
影响因子：
4.3
作者：
Amensag, Salma;Goldberg, Leslie A.;O'Malley, Kerri A.;Rush, Demaretta S.;Berceli, Scott A.;McFetridge, Peter S.
通讯作者：
McFetridge, Peter S.

Preimplantation processing of ex vivo-derived vascular biomaterials: effects on peripheral cell adhesion.