Synthesis and characterization of dendritic poly(L-lysine) based polymers for use in tissue engineering

The design and synthesis of dendritic poly(L-lysine) based materials will be presented. The poly(L-lysine) was built on a monomethoxy poly(ethylene glycol) support through generation six and were further functionalized by addition of glycolic acid residues at the termini. These dendritic polymers were then used to initiate ring opening polymerization to yield star polymers with arms of either poly(&egr;-caprolactone) or poly(lactic-co-glycolic acid). The dendrimers as well as the star polymers were tested for their ability to make films alone and in the presence of hydroxyapatite. Further, the poly(&egr;-caprolactone) star polymers were used during an in-situ synthesis of hydroxyapatite, yielding films with better mechanical properties than their linear counterparts. Since these materials are to be used for tissue engineering applications, cell adhesion studies and degradation studies were also performed. The materials presented a surface that encouraged cell adhesion. The degradation studies utilized trypsin, which was unable to degrade the polymer over the eight week study. However, these materials present potential for their use as scaffolds in tissue engineering.; Finally, the poly(L-lysine) dendrimer was used to synthesize a targeted delivery system. The monomethoxy poly(ethylene glycol) support incorporated a nine amino acid sequence for plasminogen activator inhibitor type 2, before attachment of the dendrimer. This sequence is able to form fusion proteins with fibrin by transglutaminase catalysis. The synthesis of the material was successful, yielding the nine amino acid sequence attached to the generation four poly(L-lysine) dendrimer. This material, therefore, holds promise as a generic delivery vehicle, able to target active molecules located on the dendrimer periphery to fibrin.