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

描述(申请人提供)：组织工程血管移植物(TEVGs)可以在传统假体不可用或失败时提供血管替代。研究人员正在采取多种方法来制造可行的TEVG，包括开发设计师脚手架。合理的TEVG支架设计的一个主要限制是在特定支架属性和由此产生的平滑肌细胞(SMC)行为之间缺乏相关关系。我们建议开发材料性能可调的新型PDMSstar-PEO水凝胶，以便系统地评估支架性能对SMC行为和终点TEVG力学性能的影响。这项研究设计的另一个新元素是我们关注支架属性对内部细胞信号的影响，而不仅仅是细胞外基质的合成。具体地说，除了细胞外基质的产生和组织，我们还将研究与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。ECM合成/组织和基因表达的独特签名将产生，并将作为初始支架属性和终点TEVG机械性能之间的预测性链接，显著促进合理的TEVG支架设计。公共卫生相关性：组织工程血管移植物(TEVGs)的成功在很大程度上是由于长期机械性能不足，这是由于不适当的细胞反应造成的。在拟议的研究中，我们将准备一个由疏水和亲水大分子形成的新型杂化支架的文库，其性质也可以在广泛的范围内进行系统的调节。然后，我们将探索支架特性的系统性变化对平滑肌细胞行为和长期TEVG力学特性的影响，以期建立可用于合理的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.