Synthesis and properties of malic acid-containing functional polymers.

Poly-L-lactides containing beta-alkyl alpha-malate-units were prepared by ring-opening copolymerizations of L-lactide with 3-(s)-(benzyloxycarbonyl)methyl]- (BMD) and 3-(s)-(dodecyloxycarbonyl)methyl]-1,4-dioxane-2,5-diones (DMD). The solution-cast films of these copolymers were alkali-treated to form a carboxyl-functionalized surface on which cell-binding Arg-Gly-Asp tripeptide (RGD) was immobilized with dicyclohexylcarbodiimide as coupling agent. For the copolymer of L-lactide and BMD the benzyl groups were removed by catalytic hydrogenolysis to obtain a fully carboxyl-functionalized copolymer (PLGM), and RGD was immobilized on the surface of its cast film. All the RGD-immobilized films thus prepared exhibited improved cell attachment compared with the original films. The cell attachment increased with increasing amount of immobilized RGD, which depended on the composition of the alpha-malate units in the copolymer. The RGD-immobilized PLGM films were degraded rapidly during the cell culture, while the RGD-immobilized films of the beta-alkyl alpha-malate-containing polymers survived the cell culture with little degradation. The rate of hydrolysis increased with increasing content of alpha-malate units for both series, depending on the structure of the protecting groups of the beta-carboxyl. These results suggest that the RGD-immobilized polymers could be a new class of functional bioresorbable polymer having improved cell-attachment and adjustable hydrolysis rate.