NEW GENERATION OF POLYANHYDRIDES

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Internal long hone fracture fixation using bioerodible polymers based on polylactic acid, polyglycolic acid or poly-p-dioxanon have failed to provide adequate results due to either poor biocompatility, lack of adequate mechanical strength or unpredictable degradation concerns. For these reasons the first poly(anhydride-co-imides) were synthesized. However, these poly(anhydride-co-imides) contained imide ring systems that weren't biomolecule based which may also raise biocompatibility concerns. Therefore, the specific aims of this proposal are to: 1) synthesize a new generation of poly(anhydride-co-imide) polymers containing physiologically based ring systems, such as the pyrimidine rings of uracil and thymine, 2) to determine the mechanical properties of the polymers, 3) to study the degradation characteristics of the polymers in solution and in the solid state, and 4) to determine the initial biocompatibility characteristics of these polymers in vitro. The synthesis of the monomers will be conducted using pyrimidine chemistry techniques and polymerizations will be carried out using variations of techniques previously developed in Dr. Langer's laboratory. The polymer mechanical properties will be characterized by comprehensive strength, tensile strength, fracture strain, elastic moduli and tension-compression fatigue testing. The stability and degradation of the polymers will be determined by gel permeation chromatography. The biocompatibility of the polymers will be determined using bovine aortic endothelial cells and human fibroblast cells in culture. Bioerodible polymers for fracture fixation have an additional advantage over traditional metallic implants in that they could simultaneously deliver drugs to the fracture site.