Compliant and strong small arteries engineered in vitro

体外工程设计的顺应且坚固的小动脉

• 批准号: 7657297
• 负责人: Yadong Wang
• 金额: $ 36.64万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-25 至 2011-12-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7657297
• 关键词: Arteries; Autologous; Biocompatible Materials; Biomechanics; Biomimetics; Blood; Blood Vessels; Caliber; Cell Proliferation; Cell physiology; Cells; Cellular biology; Clinical; Coculture Techniques; Collaborations; Collagen; Coronary Arteriosclerosis; Coronary Artery Bypass; Data; Developed Countries; Development; Effectiveness; Elastin; Elastin Fiber; Elastomers; Endothelial Cells; Engineering; Environment; Extracellular Matrix; Fibroblasts; Foundations; Future; Goals; Hyperplasia; In Vitro; Interfacial Phenomena; Investigation; Laboratories; Lead; Mechanical Stimulation; Mechanics; Medial; Methods; Modeling; Outcome; Papio; Phenotype; Physiological; Polymers; Principal Investigator; Production; Property; Regenerative Medicine; Regulation; Research; Research Personnel; Shunt Device; Smooth Muscle Myocytes; Solid; Staging; Stem cells; Structure; Teflon; Testing; Tissue Engineering; Translations; Tubular formation; Tunica Adventitia; United States; Ursidae Family; Veins; Work; angiogenesis; base; conditioning; crosslink; dacron; design; disability; elastomeric; experience; graft failure; implantation; improved; in vivo; innovation; intima media; migration; mortality; multidisciplinary; programs; protein expression; scaffold; vasculogenesis

DESCRIPTION (provided by applicant): Coronary artery disease is the leading cause of mortality and disability in the US. Current treatment methods including autologous artery and vein grafts have considerable limitations despite decades of refinement. Two critical challenges in small artery substitutes are high compliance and nonthrombogenicity. Our long-term goal is to create mechanically competent, nonthrombogenic and vasoresponsive small artery substitutes. The objective of this proposal is to engineer mechanically competent small arteries. The central hypothesis of this application is that a biomimetic culture environment will facilitate the formation of small arteries with structure and properties representative of the native vessels. We will create a culture condition that mimics angiogenesis and vasculogenesis by cultivating vascular progenitor cells in rationally-designed elastomeric scaffolds under dynamic mechanical conditions. This innovative approach may lead to physiological compliance in the near future, and nonthrombogenicity and vasoresponsiveness ultimately. Guided by strong preliminary data, this hypothesis will be tested by pursuing three specific aims. Under aim 1, we will fabricate tubular scaffolds from elastomeric and stiff biomaterials that will be used in aims 2 and 3 to examine the effects of scaffold properties on the structure and properties of the resultant artificial arteries. The feedbacks from aims 2 and 3 will guide the selection and optimization of the scaffolds. Under aim 2, we will culture circulating endothelial progenitor cells with smooth muscle cells to engineer closely interacting intima/media composites with compliance matching native arteries. Aim 3 will focus on increasing the strength and stability of the constructs by adding an adventitia layer while maintaining the high compliance of the intima/media layer. The combined work in aims 1 to 3 is expected to create mechanically competent small arteries that provides a solid foundation for future investigations in antithrombogenicity and vasoresponsiveness. This multidisciplinary proposal combines the complementary expertise of the Principal Investigator in biomaterial and regenerative medicine, and the Collaborators in vascular cell biology, biomechanics, and blood-material interfacial phenomenon. When successfully completed, the proposed research is expected to represent a significant advance in the field of blood vessel substitutes and accelerate the translation of tissue-engineered arteries from benchside promise to bedside benefit.

描述（由申请人提供）：冠状动脉疾病是美国死亡率和残疾的主要原因。尽管精致数十年，包括自体动脉和静脉移植物在内的当前治疗方法仍存在相当大的局限性。小动脉替代品的两个关键挑战是高依从性和非平稳性。我们的长期目标是创建机械胜任，非平稳性和血管措施的小动脉替代物。该提案的目的是设计机械胜任的小动脉。该应用的中心假设是，仿生培养环境将促进具有代表天然血管的结构和特性的小动脉的形成。我们将创建一种培养条件，通过在动态机械条件下在合理设计的弹性型支架中培养血管生成和血管生成。这种创新的方法可能会在不久的将来导致生理依从性，并最终非表现和血管调查。在强大的初步数据的指导下，该假设将通过追求三个具体目标来检验。在AIM 1下，我们将制造来自弹性和僵硬生物材料的管状支架，这些支架将用于AIM 2和3中，以检查支架特性对所得人造动脉结构和特性的影响。 AIM 2和3的反馈将指导脚手架的选择和优化。在AIM 2下，我们将用平滑肌细胞培养循环内皮祖细胞，以与符合天然动脉相匹配的互动内膜/培养基复合材料进行工程。 AIM 3将专注于通过添加Addeditia层来增强构建体的强度和稳定性，同时保持Intima/Media层的高依从性。 AIM 1至3中的合并工作预计将创造机械胜任的小动脉，为未来的抗巩膜性和血管备份研究提供了坚实的基础。这项多学科的建议结合了生物材料和再生医学主要研究者的互补专业知识，以及血管细胞生物学，生物力学和血液材料界面现象方面的合作者。成功完成后，预计拟议的研究将代表血管替代品领域的重大进展，并加速从板凳上的组织工程动脉的翻译，承诺对床旁益处。