Aliphatic Polyesters for Soft Tissue Engineering : Development from Conventional Organometallic to Novel Enzymatic Catalysis

Abstract: The development of macromolecules with defined structure and properties, aimed specifically for biomedical applications, has resulted in diverse biodegradable polymers with advanced architectures. Among them, aliphatic polyesters synthesized by ring-opening polymerization (ROP) of lactones and lactides have a leading position due to their good mechanical properties, hydrolyzability and biocompatibility. To achieve tailored properties and controlled architecture, the technique for ROP of lactones and lactides has been continuously refined in the past years. Enzyme-catalyzed ROP is one of the most promising tools, which avoids the use of toxic organometallic catalysts and brings a “green-chemistry” appeal with it. In the work described in this thesis, enzyme-catalyzed ROP of 1,5-dioxepan-2-one (DXO), ε-caprolactone (CL) and lactides (L-, D- and D,L-lactide) was performed in bulk using Lipases from different sources. The effects of enzyme concentration, polymerization temperature and reaction water content on the monomer conversion and the polymer molecular weight during DXO polymerization were studied, and the role of water as initiator was confirmed. Terminal functionalized, block, comb and star polymers were synthesized using different alcohols as initiator in the enzyme-catalyzed ROP of DXO, CL or lactides under strictly anhydrous conditions. The effect of simultaneous and sequential copolymerization of DXO and CL on the micro-block structure of the copolymers was studied and the reactivity ratios of DXO and CL were determined under Lipase catalysis. High molecular weight copolymers of DXO and CL thus obtained were fabricated into porous scaffolds for tissue implant applications. Enzymatic degradation and alkaline hydrolysis of lactides was performed to study the effect of molecular branches and the stereochemistry of the monomer on the degradation profile. In another approach, cross-linked films of DXO and CL were prepared using 2,2´-bis-(ε-caprolactone-4-yl) propane (BCP) as the cross-linking agent and Sn(Oct)2 as the catalyst. The networks obtained thereof were elastomeric materials, easy to cast and remove from the mould.