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和残疾的主要原因。尽管经过数十年的改进，目前的治疗方法（包括自体动脉和静脉移植）仍然存在相当大的局限性。小动脉替代物的两个关键挑战是高顺应性和非血栓形成性。我们的长期目标是创造具有机械性能、非血栓形成和血管反应性的小动脉替代物。该提案的目标是设计具有机械能力的小动脉。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。我们将通过在动态机械条件下在合理设计的弹性支架中培养血管祖细胞来创建模拟血管生成和血管发生的培养条件。这种创新方法可能会在不久的将来实现生理顺应性，并最终实现非血栓形成和血管反应性。在强有力的初步数据的指导下，这一假设将通过追求三个具体目标进行检验。在目标 1 下，我们将用弹性体和刚性生物材料制造管状支架，将其用于目标 2 和 3，以检查支架特性对所得人工动脉的结构和特性的影响。目标 2 和 3 的反馈将指导支架的选择和优化。在目标 2 下，我们将培养循环内皮祖细胞和平滑肌细胞，以设计紧密相互作用的内膜/中膜复合材料，使其具有与天然动脉相匹配的顺应性。目标 3 将侧重于通过添加外膜层来提高结构的强度和稳定性，同时保持内膜/中膜层的高顺应性。目标 1 至 3 的综合工作预计将创建具有机械能力的小动脉，为未来的抗血栓形成和血管反应性研究奠定坚实的基础。这项多学科提案结合了生物材料和再生医学方面的首席研究员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的互补专业知识。成功完成后，拟议的研究预计将代表血管替代品领域的重大进步，并加速组织工程动脉从临床承诺向临床获益的转变。