Novel Star-PDMS/PEO Hydrogel Scaffolds with Tunable Properties for TEVG

描述（由申请人提供）：当传统假体不可用或失效时，组织工程血管移植物（TEVG）可提供血管置换。研究人员正在采取多种方法来制造可行的TEVG，包括开发设计支架。合理的TEVG支架设计的一个主要限制是缺乏特定支架特性和所产生的平滑肌细胞（SMC）行为之间的相关关系。我们提出开发具有可调材料特性的新型PDMSstar-PEO水凝胶，以系统评估支架特性对SMC行为和终点TEVG机械特性的影响。这项研究设计的另一个新元素是我们关注支架特性对内部细胞信号传导的影响，而不是单独对ECM合成的影响。具体来说，我们将研究与SRF途径相关的一系列基因的表达，SRF途径是SMC表型的关键调控途径，此外还有ECM的产生和组织。ECM合成/组织加上基因表达的独特特征将产生并将用作初始支架特性和终点TEVG机械特性之间的预测性联系，显著推进合理的TEVG支架设计。公共卫生相关性：组织工程血管移植物（TEVG）的成功一直受到限制，主要是由于不适当的细胞反应导致的长期力学性能不足。在拟议的研究中，我们将准备一个新的混合支架库形成的疏水性和亲水性大分子单体，其性能也可以在很宽的范围内系统地调整。然后，我们将探索支架特性的系统性改变对平滑肌细胞行为和长期TEVG机械特性的影响，以建立可用于合理TEVG支架设计的预测关系。

DESCRIPTION (provided by applicant): Tissue engineered vascular grafts (TEVGs) may provide vessel replacements when conventional prostheses are unavailable or fail. Researchers are taking multiple approaches toward fabricating viable TEVGs, including the development of designer scaffolds. A major limitation to rational TEVG scaffold design is the absence of correlative relationships between specific scaffold properties and resulting smooth muscle cell (SMC) behavior. We propose the development of novel PDMSstar-PEO hydrogels with tunable material properties to enable the systematic evaluation of scaffold property impact on SMC behavior and endpoint TEVG mechanical properties. Another novel element of this research design is our focus on the effects of scaffold properties on internal cellular signaling rather than on ECM synthesis alone. Specifically, we will examine the expression of an array of genes associated with the SRF pathway, a key regulatory pathway of SMC phenotype, in addition to ECM production and organization. A unique signature of ECM synthesis/organization plus gene expression will result and will serve as a predicative link between initial scaffold properties and endpoint TEVG mechanical properties, significantly advancing rational TEVG scaffold design. PUBLIC HEALTH RELEVANCE: The success of tissue engineering vascular grafts (TEVGs) has been limited largely due to insufficient long term mechanical properties, which results from inappropriate cell responses. In the proposed research we will prepare a library of novel hybrid scaffolds formed from hydrophobic and hydrophilic macromers whose properties may also be systematically tuned over a broad range. We will then explore the effects of systematic alterations in scaffold properties on smooth muscle cell behavior and long term TEVG mechanical properties toward the development of predictive relationships that can be used for rational TEVG scaffold design.