Micro-Thickness Collagen Membranes in Tissue Engineering

组织工程中的微厚胶原膜

• 批准号: 7267956
• 负责人: ROBERT B VERNON
• 金额: $ 22.21万
• 依托单位: BENAROYA RESEARCH INST AT VIRGINIA MASON
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7267956
• 关键词: Acetylcholine; Address; Adult; Apoptosis; Arteries; Arteriosclerosis; Atherosclerosis; Basement membrane; Bathing; Biocompatible; Biocompatible Materials; Biological Assay; Blood Vessel Tissue; Blood Vessels; Caliber; Cell Count; Cell Density; Cell Differentiation process; Cell Survival; Cells; Clinic; Collagen; Collagen Type I; Collagen Type IV; Condition; Contracts; Coronary Arteriosclerosis; Coronary Artery Bypass; Coronary artery; Data; Deposition; Development; Dyes; Elasticity; Elastin; Endothelial Cells; Excision; Exhibits; Exploratory/Developmental Grant; Extracellular Matrix; Facility Construction Funding Category; Fibrillar Collagen; Fibrin; Fibronectins; Foreign-Body Reaction; Foundations; Goals; Graft Rejection; Guidelines; Health; Histologic; Human; Hydrogels; Immunohistochemistry; In Vitro; Laminin; Left; Legal patent; Light; Liquid substance; Measures; Mechanics; Medial; Mediating; Membrane; Microscopic; Monitor; Necrosis; Numbers; Nutrient; Outcome; Patients; Personal Satisfaction; Population; Population Dynamics; Procedures; Production; Property; Proteins; Proteoglycan; Pulsatile Flow; Purpose; Rate; Rattus; Relative (related person); Research; Research Personnel; Scanning; Simulate; Smooth Muscle Myocytes; Stainless Steel; Stenosis; Stress; Structure; Surface; Techniques; Technology; Testing; Thick; Time; Tissue Engineering; Transmission Electron Microscopy; Tube; Tubular formation; Vascular Graft; Vasodilation; Viral; Week; Work; base; dacron; day; density; improved; interest; interstitial; monolayer; mortality; mouse Smc1l1 protein; mouse Smc1l2 protein; new technology; novel; novel strategies; programs; resilience; response; scaffold; shear stress; technique development; vascular smooth muscle cell proliferation; vector; versican

DESCRIPTION (provided by applicant): A major problem in coronary bypass treatment for arteriosclerosis is the lack of suitable autogenous replacement vessels in many patients. This proposal explores new technologies to create tissue-engineered blood vessels (TEBVs) that can serve as readily available replacements for coronary arteries. The bulk of the thickness of an artery wall (the media) is comprised of vascular smooth muscle cells (VSMCs) arranged in concentric layers that provide mechanical strength and contractility. In Aim 1, we will construct TEBV media that incorporate a novel, biocompatible, collagen membrane (CM) scaffold that we developed recently. The CMs' high intrinsic strength and capacity to prealign VSMCs in vitro (via microgrooving) could dramatically shorten TEBV fabrication times to a matter of days, rather than the weeks or months required by other methods. CMs populated with confluent, aligned human coronary artery SMCs (HCASMCs) will be wrapped around a mandrel to form a multilamellar tube. Following removal of the mandrel, the TEBV lumen will be seeded with human coronary artery endothelial cells and the TEBV subsequently grown in a bath of nutrient fluid with nutrient fluid also circulated through the TEBV lumen. After specific intervals of culture, the TEBVs will be evaluated for: (i) deposition of extracellular matrix (ECM) by the VSMCs, (ii) structural changes in the CM scaffolds, (iii) survival, orientation and state of differentiation of the VSMCs, (iv) functional endothelialization of the lumen, and (v) mechanical (burst) strength. The resilient protein elastin is abundant in normal artery walls and its absence in most TEBVs results in a lack of elasticity and excessive proliferation of VSMCs which narrows the TEBV lumen. Ultimately, it would be desirable to use the patient's own VSMCs to limit graft rejection. Unfortunately, adult VSMCs synthesize little or no elastin. To address this problem, Aim 2 evaluates ECM deposition, cell survival and orientation, and mechanical properties (burst-strength, stress/strain response) of TEBVs that incorporate adult rat aortic SMCs that produce elevated levels of elastin as a consequence of expression (via viral transduction) of the proteoglycan versican 3. This proposal seeks to develop new approaches and technologies and apply them to an important problem in human health (coronary artery disease). Moreover, data from this work will serve as a foundation for further development of TEBVs. Accordingly, this application is well suited to the purpose of the R21 mechanism.

描述（由申请人提供）：冠状动脉硬化治疗的主要问题是许多患者缺乏合适的自源替代血管。该提案探讨了新技术，以创建组织工程的血管（TEBV），可以作为冠状动脉动脉的可用替代品。动脉壁（培养基）的大部分厚度由血管平滑肌细胞（VSMC）组成，这些肌肉细胞（VSMC）以同心层排列，提供机械强度和收缩力。在AIM 1中，我们将构建TEBV介质，该媒体结合了我们最近开发的一种新型，生物相容性的胶原膜（CM）支架。 CMS的高内在强度和在体外进行预先VSMC的能力（通过微骨干）可能会大大缩短TEBV制造时间，而不是几天，而不是其他方法所需的几周或几个月。用汇合，对齐的人冠状动脉SMC（HCASMC）填充的CM将包裹在曼德尔周围，形成多层管。去除曼德斯后，TEBV管腔将用人体冠状动脉内皮细胞接种，随后将TEBV种植在养分液中，并在营养液中也通过TEBV管腔循环。经过特定的培养间隔后，将评估TEBV：（i）VSMCS的细胞外矩阵（ECM）沉积，（ii）CM支架的结构变化，（iii）VSMCS的生存，定向和状态VSMCS的生存，方向和状态，（（IV）函数式内皮化的强度，以及（V）爆发（v）（v）（v）usherial and（v）。弹性蛋白弹性蛋白在正常的动脉壁中丰富，并且在大多数TEBV中的缺失导致VSMC缺乏弹性和过度增殖，从而缩小了TEBV腔。最终，希望使用患者自己的VSMC限制移植物的拒绝。不幸的是，成年VSMC几乎没有或没有弹性蛋白。为了解决这个问题，目标2评估ECM沉积，细胞存活和取向以及TEBV的机械性能（爆发力，压力/应变响应），这些特性融合了成年大鼠主动脉smc，从而产生弹性蛋白水平升高的结果（通过病毒转化）的结果（通过病毒转导）的蛋白质cans versican 3的健康方法（通过病毒转移），以实现新的措施和技术（旋转的方法）（统治着新的方法），而技术和技术（技术和技术）的措施（技术和技术）（技术和技术）的方法（技术和技术）（技术和技术）（技术和技术）的技术（技术）（技术）（技术和技术）（技术和技术）（技术和技术）的技术（技术）。动脉疾病）。此外，这项工作的数据将成为进一步发展TEBV的基础。因此，该应用非常适合R21机制。