Biodegradable polymetric scaffolds and tissue engineeri*

可生物降解的聚合物支架和组织工程*

• 批准号: 6768633
• 负责人: LARRY V. MC INTIRE
• 金额: $ 20.2万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-30 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6768633
• 关键词: bioengineering /biomedical engineering; biomaterial development /preparation; biomimetics; blood vessel transplantation; cardiovascular prosthesis; combinatorial chemistry; extracellular matrix; laboratory mouse; metalloendopeptidases; tissue engineering; tissue support frame; vascular smooth muscle

DESCRIPTION (provided by applicant): Tissue engineered blood vessels may potentially revolutionize vascular replacement surgery by providing viable alternatives for often unavailable autologous grafts. Vascular constructs tissue engineered using natural components offer the potential to mimic the responsive nature of native arteries. However in spite of much progress in the field those developed so far have insufficient strength or require an extremely long time of growth in vitro to achieve it. From our own recent efforts to optimize development of vascular grafts tissue engineered using vascular smooth muscle cells (SMC) seeded collagen, we learned that loss of mechanical properties of such constructs is associated with premature scaffold degradation by enzymes released by SMC, called matrix metalloproteinases (MMPs). Blocking MMPs however, proved to also prevent SMC capacity to assemble matrix, process essential for proper construct organization and function. We are proposing to explore a potential construct design improvement, which would preserve the advantageous MMP remodeling functions while preventing premature failure, by providing additional mechanical support during the in vitro assembly through the addition of a biodegradable scaffold. The innovative aspect of this idea is that we seek to identify a scaffold that, in addition to providing mechanical support, will also optimize the characteristics of natural components that have been associated with enhanced mechanical properties of tissue engineered constructs: cell viability and appropriate turn-over and organization of the natural matrix components. For this purpose we will use a novel rational combinatorial approach, which allows testing of a large number of potential chemical and physical characteristics of the biodegradable scaffold. We will also assess whether the synthetic scaffold is susceptible to degradation by MMPs, which would modify its properties and may be related to the body reaction following construct implantation in vivo. For these experiments we will use SMC that we isolate from the arteries of genetically engineered MMP knock-out or transgenic mice, which will allow the specific testing of the role of these enzymes. Our studies should contribute to the improvement of vascular grafts tissue engineered using natural components. We plan to use the gained information to optimize the future design of hybrid grafts containing human vascular smooth muscle and endothelial cells.

描述（由申请人提供）： 组织工程血管可能会为通常无法获得的自体移植物提供可行的替代方案，从而可能彻底改变血管置换手术。使用天然成分进行组织工程的血管构建体具有模拟天然动脉反应性质的潜力。然而，尽管在该领域取得了很大进展，但迄今为止开发的那些支架强度不足或需要极长的体外生长时间才能实现。从我们自己最近优化使用血管平滑肌细胞（SMC）接种胶原的血管移植物组织工程化的开发的努力中，我们了解到这种构建物的机械性能的丧失与SMC释放的酶导致的支架过早降解有关，称为基质金属蛋白酶（MMPs）。然而，阻断MMPs被证明也阻止了SMC组装基质的能力，这是正确构建组织和功能所必需的过程。我们建议探索一种潜在的结构设计改进，通过添加可生物降解的支架在体外组装期间提供额外的机械支撑，从而在防止过早失效的同时保留有利的MMP重塑功能。这个想法的创新方面是，我们试图确定一个支架，除了提供机械支持，还将优化与组织工程构建体的机械性能增强相关的天然成分的特性：细胞活力和适当的周转和组织的天然基质成分。为此，我们将使用一种新的合理的组合方法，它允许测试大量的潜在的化学和物理特性的可生物降解的支架。我们还将评估合成支架是否易受基质金属蛋白酶降解的影响，这将改变其性质，并可能与体内植入结构后的身体反应有关。对于这些实验，我们将使用我们从遗传工程MMP敲除或转基因小鼠的动脉中分离的SMC，这将允许对这些酶的作用进行特异性测试。我们的研究将有助于改善使用天然成分的组织工程血管移植物。我们计划利用所获得的信息来优化含有人血管平滑肌和内皮细胞的混合移植物的未来设计。