A Bioinspired Small Diameter Vascular Conduit

描述(由申请人提供)：通过优化动脉生物假体的机械性能以及其他生物相关特性，可以实现临床上耐用的小直径血管移植物。我们认为，天然I型胶原和弹性蛋白纤维组件的分子结构和超分子组织为设计由生物启发的蛋白纤维类似物组成的动脉替代物奠定了重要的范例。具体来说，我们打算： (1)确定影响蛋白质纤维网络的力学行为和物理化学性质的胶原和弹性蛋白纤维类似物的分子水平特征。弹性蛋白和胶原类似物将通过生物合成和化学方案生产，并通过纳米制造技术加工成纤维网络。将使用溶液和固态方法来定义材料结构-性能关系。 (2)确定蛋白质纤维增强生物聚合物复合材料的微观尺度特征，该特征决定了与动脉替代物设计相关的机械响应。在生理相关条件下，通过静态和动态力学试验研究了单组分和多组分纤维网络复合材料的力学行为。在此过程中，将应用本构数学模型来辅助管道设计，以及随后的结构改建分析。 (3)确定胶原纤维和弹性蛋白纤维增强的体内血管构筑的形态和结构重塑。无细胞构建物，以及种植了自体内皮细胞的导管，都将在狒狒动物模型中进行检查。具体地说，将确定当地生物和机械环境对管道短期和长期性能的影响，包括通畅性和生物稳定性。 总结：优化机械和其他生物相关特性可能是开发小直径动脉假体的重要一步，对心脏、整形和血管外科领域至关重要，对人工器官和代谢支持系统的成功植入也是如此。

DESCRIPTION (provided by applicant): A clinically durable small diameter vascular graft may be achievable by optimizing the mechanical properties of an arterial bioprosthesis, as well as other biologically related characteristics. We believe that the molecular structure and supramolecular organization of native type I collagen and elastin fiber assembly establishes an important paradigm for the design of an arterial substitute composed of bio-inspired protein fiber analogues. Specifically, we intend to: (1) Determine the molecular level features of collagen and elastin fiber analogues that influence the mechanical behavior and physiochemical properties of protein-based fiber networks. Elastin and collagen analogues will be produced by biosynthetic and chemical schemes and processed into fiber networks by nanofabrication techniques. Both solution and solid state methodologies will be used to define material structure-property relationships. (2) Identify the micro scale characteristics of a protein fiber reinforced biopolymer composite that dictate mechanical responses relevant to the design of an arterial substitute. The mechanical behavior of both single and multicomponent fiber network composites will be investigated by static and dynamic mechanical testing under physiologically relevant conditions. In the process, constitutive mathematical models will be applied to assist in conduit design, as well as in the subsequent analysis of construct remodeling. (3) Define the morphological and structural remodeling of a collagen and elastin fiber reinforced vascular construct in vivo. Both acellular constructs, as well as conduits seeded with autogenous endothelial cells will be examined in a baboon animal model. Specifically, the effect of the local biological and mechanical environment on short- and long-term conduit properties, including patency and biostability will be defined. Lay summary: Optimizing mechanical and other biologically related properties may be an important step in the development of a small diameter arterial prosthesis critical to the fields of cardiac, plastic, and vascular surgery, as well as to the successful implantation of artificial organs and metabolic support systems.