Small diameter (<5 mm) vascular grafts exhibit low success rates. Failure of these devices has been attributed to the difference in mechanical properties between the graft and the natural vessel, and the inability of the synthetic material to support an endothelial monolayer. With these shortcomings in mind, the aim of this proposal is to design and synthesize an elastic and bioactive material for vascular grafts that will have long-term efficacy. In order to achieve this objective, the material will possess the following qualities: (i) a flexible hydrocarbon backbone assembled from a new class of functionalized trans-cyclooctene monomers (ii) elasticity similar to that of natural vessels through either block copolymers that function based on the aggregation of elastin-like peptide sequences or crosslinked polymer networks (iii) ligands containing an integrin binding motif that promotes selective adhesion of endothelial cells. Ring-opening metathesis polymerization (ROMP) has emerged as a unique method that allows for a high degree of control over a polymer's mechanical properties. Ruthenium catalysts for ROMP show excellent activity in the presence of polar functional groups and have been employed in the synthesis of polymers with impressive bioactive components. The modularity of the process thus allows for access to a variety of polymer scaffolds in which the elasticity of the polymer can be tailored and bioactive ligands can be introduced. A set of functionalized trans-cyclooctene monomers is proposed that contain either the elastin sequence Val-Pro-Gly-Val-Gly or an analog thereof for the synthesis of a material that exhibits strong interchain aggregation effects in an aqueous environment. Conditions for polymerization are presented through which the elasticity may be adjusted by varying block size. Alternatively, random copolymers will be made that contain reactive moieties at the termini of the polymer chain for crosslinking to form a network. The elasticity and water content of the network may be adjusted by varying the distance between crosslinks. These materials could have great impact on millions of surgeries that are performed every year on patients that are victims of accidents, cardiovascular disease, diabetes and other afflictions.
Small and medium sized artificial blood vessels often fail in less than six months and rarely last beyond two years. In order to increase the health and lifetime of patients in need of these prostheses, the aim of this research is to design a new material for application in artificial blood vessels that addresses the deficiencies of the current technology.
| Walker, Ron; Conrad, Rosemary M; Grubbs, Robert H (2009) The Living ROMP of trans-Cyclooctene. Macromolecules 42:599-605 |
| Conrad, Rosemary M; Grubbs, Robert H (2009) Tunable, temperature-responsive polynorbornenes with side chains based on an elastin peptide sequence. Angew Chem Int Ed Engl 48:8328-30 |
