Promoteur de thèse : Jean-Marie RAQUEZ (UMONS)

Co-promoteur de thèse : Franck MEYER (ULB)

Titre de la dissertation: « Tailoring properties of thermoplastic polyurethanes targeting biomedical applications »

Résumé de la dissertation:

This thesis “Tailoring properties of thermoplastic polyurethanes targeting biomedical applications” is divided into three chapters, Chapter I presents the chemistry of polyurethane where the components involved and the ways of synthesizing are discussed. It further lists the application of polyurethane in the biomedical field. The aim of Chapter II is to synthesis a series of TPU having an antibacterial activity through the incorporation of quaternary onium salts (QOS) for biomedical application. The molar ratios as well as the reaction conditions were varied to study their influence on the TPU properties. Ten samples were thereby studied comprehensively through thermal and mechanical characterization. Subsequently, the polymeric material possessing the most promising physical features was chosen as a potential TPU for catheter fabrication. To this end, the preparation of QOS-containing TPU was carried out in order to provide the polymer with antibacterial properties, without sacrificing its mechanical properties. This chapter will consist of three main parts and some subparts for further clarity. The first part will be devoted to synthesizing plain TPU (TPU-1 to TPU-10); where different reaction conditions will be applied to fully understand the influence on the mechanical and thermal properties of the resulting polymers. More precisely, a study focusing on the synthesis of a series of TPU from MDI, BDO, and PTHF will be held. The molar ratios, as well as the reaction conditions were varied to study their influence on the TPU properties. Ten samples were studied comprehensively through 1H-NMR, GPC, FT-IR, TGA, DSC, DMTA, and tensile testing.

In the second part, the synthesis route of QOS, known to have antibacterial activity, will be discussed. Many approaches were performed for synthesizing quaternary ammonium salts (QAS) and the most promising one was followed to synthesize all the active moieties (QAS and QPS). Several attempts were made using different starting compounds, and the aim of these attempts was to get familiarized with the reactivity of compounds and to result in the most convenient procedure. The resulting active moieties will exhibit different alkyl chain lengths to help understand its influence on antibacterial activity. Then, the minimum inhibitory concentration (MIC) was measured for all these compounds.

Finally, the last part will include the incorporation of the active moieties (from the successful attempt) in TPU and the antibacterial activity and cytotoxicity were studied. A synergistic effect between these QOS was discovered and will be explained thoroughly. The influence of adding the active moieties on the TPU characteristics was also analyzed through several characterization tests. Finally, catheter fabrication was held through extrusion and injection molding.

The aim of Chapter III was to synthesize a degradable PU capable of hosting and proliferating stem cells for tissue engineering purposes. The synthesized TPU must be degraded in a way to allow the detachment of the adhered cells on-demand, without exerting any cytotoxicity. Therefore, adherence, detachment, and compatibility were the key factors. In this respect, these degradable PU containing a soft segment, an adhering entity, and a cleavable segment were designed through a two-step addition method using hexamethylene diisocyanate (HMDI) as a coupling agent. Herein, both PEG and PTHF were used as a soft segment in the synthesized TPU to study the influence of hydrophilicity on cell hosting. Different molecular weights of PEG were investigated to get the best candidate. Disulfide compounds were used to induce the degradation of the final polymer through the cleavage of the disulfide bond using glutathione. 4,4′-Dihydroxydiphenyl disulfide (HPS), 4,4′-diaminodiphenyl disulfide (APS), and bis(2-hydroxyethyl)disulfide) (HEDs) were the disulfide compounds used as a model in terms of reactivity and degradability. To examine the suitable amount of disulfide inside TPU backbone, different molar ratios were incorporated (0, 10, 20, and 40 %-mol). The synthesized QAS-C14 (from chapter II) was used to help adhere the cells to the substrate and different %-molar content (0, 5, and 10 %-mol) was studied to help understand the suitable amount to reach a successful adherence without exerting cytotoxicity. After optimizing the best PU, cells were seeded on films before and after being coated with fibronectin to study the influence on cell adherence. Finally, beads were created to examine the morphology effect on cell proliferation.