logo SBA


Digital archive of theses discussed at the University of Pisa


Thesis etd-10172007-135158

Thesis type
Tesi di dottorato di ricerca
Thesis title
Synthesis and Characterization of Novel Biodegradable Polyesters Tailored for Biomedical Applications
Academic discipline
Course of study
Relatore Prof. Solaro, Roberto
  • Biomedical
  • Polyesters
  • Synthesis
Graduation session start date
In the last decades, biomaterial science experienced enormous expansion because of its peculiar connections with other scientific, medical, and engineering disciplines, including molecular and cell biology, human physiology, and materials science. The continuous flow of knowledge among these fields, and the constant demand for new supplies and solutions is driving biomaterial science to be one of the most promising and intriguing scientific fields. In particular, two major applications of biomaterial science, that is tissue engineering and controlled drug delivery, attracted attention and dedication from many branches of academic and industrial entities. Tissue engineering is aimed at creating partial or complete bioartificial organs by exploiting the synergistic interactions of living cells and synthetic materials. Controlled drug delivery technology also represents one of the most rapidly advancing areas of biomaterial science. With respect to conventional dosage forms, delivery systems offer several advantages, including improved efficacy, reduced toxicity, better patient compliance, and convenience.
Recently, the combination of drug delivery and tissue engineering techniques has been proposed, to afford systems that not only constitute a supportive scaffold for cell proliferation, but also guide cell development and organization by progressive and controlled release of cell growth and differentiating factors. Aliphatic polyesters are generally considered to be well–suited for applications as polymer–based biomaterials due to their demonstrated biocompatibility and biodegradability, because of the wide range of properties that can be attained by careful modulation of their chemical structure. The present work was aimed at the development of bioactive polymeric materials to be used for the targeted delivery of proteic drug and for applications in the tissue engineering field. The proposed strategy was based on the design of special polymer classes whose structures and functionality could be easily modified by finely tuning the adopted synthetic procedures. Polymalolactonate and other polyesters containing side chain primary hydroxyl groups were chosen as promising materials for the proposed applications.
Initially, polyesters containing pendant primary hydroxyl groups were synthesized by polyaddition of oxetanes and carboxylic anhydrides catalyzed by quaternary onium halides. The polyaddition of bis(oxetane) with different dicarboxylic acids in the presence of the same catalysts was also investigated. In all cases, the oxetane monomers contained one hydroxyl functionality either free or protected by a benzyl group. The yield and the molecular weight of soluble polymer are good when aromatic anhydrides were used. In all other cases low conversions or no polymerization at all were obtained. On the other hand, readily available alcoholic derivatives were successfully employed to synthesize a series of á,á’,â–trisubstituted â–lactone monomers displaying a wide range of physical–chemical derivatives. The preparations were carried out according to established synthetic routes, in five steps starting from diethyl oxalpropionate. Final yields were related to the preparation method as well as to the nature of the monomer side chain, and were comprised in the 53–63% range as based on the precursor alcohol. The purity of all synthesized monomers and intermediates were assessed by chromatographic techniques whereas their structural features were confirmed by FT–IR and 1H–NMR spectroscopy.
In the presence of catalytic amounts of quaternary ammonium salts, the synthesized functional lactones underwent anionic ring opening polymerization leading to the corresponding homopolymers and copolymers in fairly good yields. The prepared polymeric materials were extensively characterized by spectroscopic techniques, gel permeation chromatography, and thermal analysis. Thermogravimetric analysis evidenced materials stability up to 190–240 °C, the actual values being fairly dependent on the nature of pendant groups in the polymers. Preliminary biological tests performed on thin polymer films indicated that the polymer surface did not promote cell adhesion, although no significant toxic effect was detected. These data suggest that the synthesized, poly(alkyl malolactonate)s are better suited for drug delivery than for tissue engineering applications.