Synthetic Strategies for Biomedical Polyesters Specialties

Abstract

Aliphatic polyesters are biocompatible and biodegradable polymers exhibiting good mechanical properties and hydrolyzability. They are among the best characterized and most studied biodegradable systems for temporary biomedical applications such as drug delivery systems, resorbable implants or tissue engineering scaffolds. Properties such as hydrophilicity and biodegradation can be tailored by the introduction of biologically relevant functional groups in the polymer. This chapter examines critically the various strategies implemented for this purpose. Polyesters can be synthesized by polycondensation (step growth polymerization) or by ring opening polymerization (chain growth polymerization). A specific functionality can be introduced via these polymerizations using functionalized monomers or functionalized initiators. The presence of functional groups such as hydroxyls for instance can be detrimental for both polymerization methods, leading to deactivation and/or undesirable crosslinking reactions. Protection/deprotection chemistries are thus usually applied prior and after polymerization. These strategies will be presented and illustrated by relevant examples. Such multistep approaches provide interesting and sophisticated materials but require long production times and high production costs. For practical applications however, biomedical materials must also be cost-effective, introducing a balance between sophistication and ease of production. Recent advances enabling a one pot approach for each strategy are of particular interest (Zinck 2009) and are further presented and discussed in this frame. The polyesters classically used for biomedical applications are poly(e-caprolactone), poly(lactic acid), poly(glycolic acid) (Fig. 1) and their copolymers, and in a lesser extent, poly(3-hydroxybutyrate) and polyorthoesters. This chapter focuses essentially on the first three polyesters, with some extensions to other polyesters when the synthetic strategy or functionalization concept is judged relevant. These polyesters can be synthesized by the ring-opening polymerization of the corresponding cyclic ester (e-caprolactone, lactide and glycolide, respectively, the two latter being dimers) and by polycondensation of the corresponding ω-hydroxyacid (6-hydroxyhexanoic, lactic and glycolic acids respectively). 6hydroxyhexanoic acid is scarcely isolable, and the polycondensation route for the formation of poly(e-caprolactone) is rarely used. Lactic acid has a stereocenter, and can be found as Llactic acid, D-lactic acid or a racemic mixture of both forms. The lactide dimer exhibits thus