Synthetic Pathways to Aliphatic Polyesters and Scaffold Design

Abstract: As the field of tissue engineering progresses, a continuous development of scaffold fabrication techniques and suitable degradable materials is required to obtain scaffolds with tunable characteristics. This thesis has focused on the development of pathways to synthesize degradable aliphatic polyesters and on the design of highly porous scaffolds from this class of materials.Porous scaffolds aimed for tissue engineering applications were successfully created from poly(L-lactide-co-trimethylene carbonate) copolymers, with an emphasis on obtaining highly porous scaffolds, possessing well interconnected pores throughout the scaffold structure. To obtain the porous structures, sugar templates were used in a combined phase separation and porogen leaching scaffold fabrication technique. The technique developed for these materials was simple and versatile and scaffolds of up to 55 mol% TMC were effectively produced.Poly(p-dioxanone) (PPDX) is a degradable polyether-ester with a comparatively short degradation time, making it useful for many biomedical applications. A synthetic route to PPDX polymers was developed using the cyclic tin (IV) alkoxide initiator 1-di-n-butyl-1-stanna-2,5-dioxacyclopentane. Our work demonstrated that the polymerization route with this initiator is indeed a promising alternative to the more commonly used stannous octoate. Under the appropriate reaction conditions, PPDX polymers with inherent viscosities over 1 dL/g and promising mechanical properties were synthesized.The design of functional materials is an important step towards fulfilling the material demands within tissue engineering. The free radical ring-opening polymerization of the cyclic ketene acetal monomer 2-methylene-1,3-dioxe-5-pene was developed. As a first step towards the creation of a new multifunctional polyester, the reaction mechanism and the reaction products at different reaction temperatures were mapped. At higher reaction temperatures, the main reaction product was the cyclic ester 3-vinyl-1,4-butyrolactone. At lower reaction temperatures, low molecular weight oligomeric products of both ring-opened and ring-retained repeating units were formed.Combining scaffold design with sugar templates and the synthesis of functional polyesters led to the creation of highly porous functional scaffolds. Both functional scaffolds and functional films were obtained from poly(ɛ-caprolactone) and poly(L-lactide), synthesized using multifunctional poly(but-2-ene-1,4-diyl malonate) and stannous octoate as initiating system. The mechanical characteristics of the cross-linkable scaffolds and films were evaluated by cyclic compression test under physiological conditions and by cyclic tensile tests.