We believe that the distinctive hierarchical assembly of collagen and elastin fiber networks within the arterial wall provides a rational design strategy for the development of a small diameter arterial conduit. We hypothesize that the generation of protein polymers that mimic native structural proteins, and the assembly of these recombinant proteins either alone or in combination with naturally occurring matrix proteins, provides an opportunity to optimize the mechanical properties of an arterial bioprostheses, as well as other biologically related characteristics. 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. Recombinant elastin analogues will be synthesized and along with purified native type I collagen processed into nanofibers and fiber networks. Both solution and solid state methodologies will be used to define material structure-property relationships. (2) Identify the microscale characteristics of a protein fiber reinforced biopolymer composite that dictates the mechanical and biological 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 defined 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. Direct in vivo implant studies will be performed in a baboon animal model to determine the effect of the local biological and mechanical environment on short- and long-term conduit properties. Specifically, construct biostability as well as collagen and elastin network remodeling, and tissue infiltration will be investigated in arterial implantation sites. In addition, graft thrombogenicity and patency will be characterized.
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