Poly(lactic acid), PLA, is a viable replacement to petroleum derived polymers due to its renewable feedstock, biodegradability and bioassimilability, yet improvements in its physical, thermal and mechanical properties are required before it can fully enter all commodity markets. This thesis investigates olefin cross-metathesis (CM) as a synthetic strategy to modify the properties of PLA. The use of novel lanthanide and actinide catalysts on the microstructure control of PLA are also explored. The Tebbe reagent was used in a new synthetic strategy to produce a novel olefin derivative of lactide (MML). Olefin CM of MML with hex-1-ene was successful but polymerisation pre- and post-CM was unsuccessful due to monomer instability. CM of another olefin derivative of lactide, 3-methylenated lactide (3-ML) was successful with aliphatic alkenes; hex-1-ene to dodec-1-ene. To overcome competing alcoholysis of the functionalised monomers, which prevented polymerisation, hydrogenation was used to remove the olefin entity followed by successful ring-opening polymerisation (ROP) to produce polymers of low glass-transition temperatures (Tg). Post-polymerisation CM on an olefin containing polymer P(β-heptenolactone) P(β-HL), with methyl acrylate and an epoxide, generated functionalised homopolymers with increased Tg’s. Co-polymerisation of lactide with β-HL generated novel gradient-copolymers. Olefin CM with 15 different cross-partners produced functionalised copolymers with different thermal properties. Based on this route a new methodology was created to introduce two unique functionalities into the polymer backbone by manipulation of the olefin reactivities. Finally, in a collaborative project, uranium and cerium catalysts, Me3SiOU(OArP)3 and Me3SiOCe(OArP)3 - designed out-with the group- were tested and compared as ROP catalysts for lactide. Both catalysts were active in living polymerisations of L-lactide and under immortal conditions the activity and rates of the catalysts were switched, accounted for by a change in the coordination sphere due to ligand displacement. ROP of rac-lactide using the uranium analogue produced heterotactic-biased PLA with a Pr = 0.79.

Yes / Highly oriented poly(lactic acid) (PLA)/thermoplastic polyurethane (TPU) blends were fabricated through solid hot stretching technology in an effort to improve the mechanical properties and blood biocompatibility of PLA as blood-contacting medical devices. It was found that the tensile strength and modulus of the blends can be improved dramatically by stretching. With the increase of draw ratio, the cold crystallization peak became smaller, and the glass transition and the melting peak moved to high temperature, while the crystallinity increased, and the grain size of PLA decreased, indicating of the stress-induced crystallization during drawing. The oriented blends exhibited structures with longitudinal striations which indicate the presence of micro-fibers. TPU phase was finely and homogeneously dispersed in the PLA, and after drawing, TPU domains were elongated to ellipsoid. The introduction of TPU and orientation could enhance the blood compatibility of PLA by prolonging kinetic clotting time, and decreasing hemolysis ratio and platelet activation.

Yes / Highly-oriented poly (lactic acid) (PLA) with bionic fibrillar structure and micro-grooves was fabricated through solid hot drawing technology for further improving the mechanical properties and blood biocompatibility of PLA as blood-contacting medical devices. In order to enhance the melt strength and thus obtain high orientation degree, PLA was first chain branched with pentaerythritol polyglycidyl ether (PGE). The branching degree as high as 12.69 mol% can be obtained at 0.5 wt% PGE content. The complex viscosity, elastic and viscous modulus for chain branched PLA were improved resulting from the enhancement of molecular entanglement, and consequently higher draw ratio can be achieved during the subsequent hot stretching. The stress-induced crystallization of PLA occurred during stretching, and the crystal structure of the oriented PLA can be attributed to the α′ crystalline form. The tensile strength and modulus of PLA were improved dramatically by drawing. Chain branching and orientation could significantly enhance the blood compatibility of PLA by prolonging clotting time and decreasing hemolysis ratio, protein adsorption and platelet activation. Fibrous structure as well as micro-grooves can be observed for the oriented PLA which were similar to intimal layer of blood vessel, and this bionic structure was considered to be beneficial to decrease the activation and/or adhesion of platelets.

Yes / Highly-oriented poly (lactic acid) (PLA) with bionic micro-grooves was fabricated through solid hot drawing technology for further improving the mechanical properties and blood biocompatibility of PLA. In order to enhance the melt strength and thus obtain high orientation degree, long chain branched PLA (LCB-PLA) was prepared at first through a two-step ring-opening reaction during processing. Linear viscoelasticity combined with branch-on-branch (BOB) model was used to predict probable compositions and chain topologies of the products, and it was found that the molecular weight of PLA increased and topological structures with star like chain with three arms and tree-like chain with two generations formed during reactive processing, and consequently draw ratio as high as1200% can be achieved during the subsequent hot stretching. With the increase of draw ratio, the tensile strength and orientation degree of PLA increased dramatically. Long chain branching and orientation could significantly enhance the blood compatibility of PLA by prolonging clotting time and decreasing platelet activation. Micro-grooves can be observed on the surface of the oriented PLA which were similar to the intimal layer of blood vessel, and such bionic structure resulted from the formation of the oriented shish kebab-like crystals along the draw direction.

Yes / By controlling the crystallization behavior of poly(lactic acid) (PLA) in the presence of a hydrazide nucleating agent (HNA), PLA-HNA foams with enhanced microcellular structures were prepared via supercritical CO2 foaming. It was found that HNA can self-assemble into fibrillar networks, inducing the crystallization of PLA on their surface, and "shish-kebab"crystalline structures with high crystallinity formed, which can be maintained during the whole foaming process. Incorporation of HNA promoted the formation of gt conformers, improved the amount of dissolved CO2, hindered the escape of CO2, and increased the viscoelasticity of PLA. Compared with neat PLA foam, for PLA-HNA foam, the average cell diameter decreased obviously, from 64.39 to 6.59 μm, while the cell density increased up to nearly three orders of magnitudes, from 6.82 × 106 to 4.44 × 109 cells/cm3. Moreover, lots of fibrillar structures appeared and entangled with each other on the cell wall of the foam. By forming such dense micropores and enhanced fibrillar structures, PLA foam was highly reinforced with significantly improved compressive strength. / This research was financially supported by National Natural Science Foundation of China (grant no. 51773122) and State Key Laboratory of Polymer Materials Engineering (grant no. sklpme2019-2-21).

Submitted by Sara Ribeiro (sara.ribeiro@ucb.br) on 2018-06-06T14:01:03Z No. of bitstreams: 1 ThaisDuarteCostaDissertacao2018.pdf: 3076865 bytes, checksum: 13af7d694f07d7e2dcc9281907285b62 (MD5) / Approved for entry into archive by Sara Ribeiro (sara.ribeiro@ucb.br) on 2018-06-06T14:01:33Z (GMT) No. of bitstreams: 1 ThaisDuarteCostaDissertacao2018.pdf: 3076865 bytes, checksum: 13af7d694f07d7e2dcc9281907285b62 (MD5) / Made available in DSpace on 2018-06-06T14:01:33Z (GMT). No. of bitstreams: 1 ThaisDuarteCostaDissertacao2018.pdf: 3076865 bytes, checksum: 13af7d694f07d7e2dcc9281907285b62 (MD5) Previous issue date: 2018-04-03 / Polyethylene terephthalate (PET) based plastics are serious environmental problem due to long decomposition periods and petroleum-dependent origin. Therefore, bioplastics are a promising alternative as their synthesized by the polimerization of renewable raw materials, yeilding biodegradable and environmental-friendly products. One of the most relevant polymers in this scenario is the poly lactic acid (PLA) formed from lactic acid monomers. The main characteristics of PLA are low toxicity to humans due to high biocompatibility, for example in biomedical materials, and biodegradability, which reduces their time in landfills due to the faster decomposition process. These properties provide wide applicability of this polymer in various areas such as packaging, textiles and biomedical materials. Commonly, the chemical polymerization process of PLA can be carried out in two ways, (1) ring opening for further polymerization or (2) condensation of the lactic acids. In both cases, the presence of metal catalysts such as zinc, aluminum and magnesium is required. These, in addition to being toxic, hinder the use of the polymer, for instance, in the biomedical area, for generating metallic waste. An alternative to such catalysts is the use of biocatalysts. Polyhydroxyalkanoate synthase (phaC) has been previously used for the polymerization of lactic acid produced in recombinant strains of Escherichia coli. Thus, within the lactic acid production platform in recombinant Komagataella phaffi strains, the objective of this work is to produce the phaC enzyme with point mutations at the S325N and Q481I sites. These residue changes provide a greater specificity of the enzyme-substrate complex to act as a biocatalyst in the polymerization of lactic acid in Komagataella phaffi. In this study, three cloning strategies were performed between the phaCPs insert and pGAPZ??B vector. To date, there have been no transformants in any of the strategies. However, Strategy C has not yet been fully implemented, which also results in the possibility of cloning between phaCPs insert and pGAPZ??B expression vector with the correct sequence. It is expected that successful cloning, recombinant DNA sequencing and plasmid insertion into Komagataella phaffii genome can be performed to conclude this study. / Os problemas ambientais gerados por pl??sticos ?? base de tereftalato de polietileno (PET) se devem ao extenso tempo de decomposi????o desses materiais no meio ambiente e a sua fonte de origem que ?? dependente de petr??leo. Diante disso, biopl??sticos t??m sido uma alternativa promissora devido ao fato de serem biologicamente degrad??veis, al??m de terem como origem mat??rias-primas renov??veis, o que os tornam sustent??veis. Um dos pol??meros mais relevantes desse cen??rio ?? o poli (??cido l??tico) (PLA) formado a partir de mon??meros de ??cido l??tico. As principais caracter??sticas do PLA s??o baixa toxicidade aos humanos devido ?? alta biocompatibilidade, como por exemplo em mat??rias biom??dicos, e biodegradabilidade, o que reduz seu tempo em aterros devido ao processo mais r??pido de decomposi????o. Essas propriedades proporcionam uma ampla aplicabilidade deste pol??mero em diversas ??reas como embalagens, ??reas t??xteis e materiais biom??dicos. Comumente, o processo qu??mico de polimeriza????o do PLA pode ser realizado por meio de duas formas, (1) abertura do anel para posterior polimeriza????o ou (2) por condensa????o dos ??cidos l??ticos. Nos dois casos, ?? necess??ria a presen??a de catalisadores met??licos como zinco, alum??nio e magn??sio. Estes, al??m de serem t??xicos atrapalham na utiliza????o do pol??mero, por exemplo, na ??rea biom??dica, por gerar res??duos met??licos. Uma alternativa a esses catalisadores ?? a utiliza????o de biocatalisadores, como a polihidroxialcanoato sintase (phaC), j?? foi previamente utilizada para polimeriza????o de ??cido l??tico produzido em cepas recombinantes de Escherichia coli. Assim, dentro da plataforma de produ????o de ??cido l??tico, em cepas de Komagataella phaffii recombinantes, o objetivo deste trabalho ?? referente ?? produ????o da enzima phaC com muta????es pontuais nos s??tios S325N e Q481I, pois essas altera????es proporcionam uma maior especificidade do complexo enzima-substrato, para que atue como biocatalisador na polimeriza????o de ??cido l??tico em Komagataella phaffi. Neste estudo, foram realizadas tr??s estrat??gias de clonagem entre o inserto phaCPs e vetor pGAPZ??B. At?? o presente, n??o houve transformantes em nenhuma das estrat??gias. Entretanto, a Estrat??gia C ainda n??o foi executada completamente, o que resulta ainda na possibilidade de clonagem entre inserto phaCPs e vetor de express??o pGAPZ??B com a sequ??ncia correta. A expectativa deste estudo ?? a conclus??o da clonagem, verifica????o da sequ??ncia correta do DNA recombinante atrav??s do resultado do sequenciamento e inser????o do plasm??deo ao genoma da levedura Komagataella phaffii.

During this project, photocatalytic material, nano sized titanium dioxide, was introduced into poly (lactic acid) to produce functional surface capable of self-cleaning property. Samples containing 0%, 5%, 10%, 15% and 20% titanium dioxide were prepared and etched with proteinase K to expose the nano particles on the surface. It was shown that the nano titanium dioxide could dispersed in the polymer matrix pretty well, it was also found that the nano particles affected the thermal and mechanical properties of the polymer matrix differently , due to difference in concentrations of nano filler. The self-cleaning property was evaluated by decolouration of stains caused by coffee and red wine, also by detecting degradation of methylene blue via a UV-vis spectrophotometer. By measuring changes in absorbance of light at 664nm wavelength after a maximum of 24h UV irradiation, it was possible to measure the degradation property of the samples. / Program: Masterutbildning i textilteknik

<div>Wounds are created in soft and hard tissue through surgery or disease. As the wound heals, the tissue is held in place using sutures or staples for soft tissue or plates, pins, or screws for hard tissues. These fixation methods inherently damage the surrounding healthy tissue. Surgical adhesives are a non-damaging alternative to these methods. In order to be effective, surgical adhesives must be biocompatible,</div><div>adhere strongly in a moist environment, and have mechanical properties similar to those of the native tissue.</div><div><br></div><div><div>To address the design criteria for surgical adhesives, we look to nature to find inspiration from compounds that provide these properties. Mussels use catechol-based</div><div>molecules to adhere to surfaces in wet and turbulent environments. Incorporating catechols into polymer systems can provide adhesion even in moist biological environments.</div><div>Mimics of elastomeric proteins from soft tissue can be used as backbones for soft and flexible adhesive systems. In particular, elastin-inspired proteins have a well-defined modular sequence that allows for a range of design choices. In this work, we explored the behavior of elastin- and mussel-inspired natural and synthetic polymers in biologically relevant environments.</div></div><div><br></div><div><div>First, the cytocompatibility of a catechol-containing poly(lactic acid) (cPLA) hard tissue adhesive was studied. The cPLA polymer was reacted with iron- or periodatebased</div><div>crosslinkers and compared to PLA. Fibroblasts grown directly on cPLA or cultured with leachate from cPLA had high viability but slower growth than cells on PLA. The periodate crosslinker was significantly cytotoxic, and cells grown on cPLA crosslinked with periodate had reduced metabolism and slowed growth. Cells grown on or in leachate from iron-crosslinked cPLA had similar viability, metabolism, and growth to cells on or in leachate from cPLA. The iron-crosslinked cPLA is a promising</div><div>cytocompatible adhesive for hard tissue applications.</div></div><div><br></div><div><div>Second, two elastin-like proteins (ELP) were developed that had pH-sensitive properties in solution and when crosslinked into hydrogels. Both ELPs had a large number of ionizable tyrosine and lysine residues, and one design also had a large number of ionizable histidine and aspartic acid residues. The stiffness of the hydrogels was maximized at pH values near the isoelectric point of the protein. The stoichometric ratio of crosslinker used affected hydrogel stiffness but did not significantly alter the pH-sensitivity of the gel. The crosslinked gel shrank when swelled at physiological pH. The pH-sensitive mechanical properties of hydrogels made from the two ELPs did not vary significantly. The tyrosine and lysine residues in one ELP were also</div><div>chemically blocked through acetylation to lower the isolectric point of the protein. The acetylated hydrogels had maximum stiffness at a pH near the isoelectric point of the acetylated ELP. The stiffness of both the native and acetylated gels were within the range of soft tissue. Through a combination of crosslinker ratio and chemical modification, the pH-responsive properties of the elastin-inspired hydrogels could be tuned.</div></div><div><br></div><div><div>Finally, adhesive proteins were created that were inspired by both elastin and mussels. An ELP was modified to include catechol groups (mELP). The ELP and mELP were optimized for adhesive use in a soft tissue system. A warm and humid environment was used to study the adhesion of these proteins on pig skin. Iron and (hydroxymethyl) phosphine crosslinkers increased the adhesive strength of both proteins, and periodate increased the adhesive strength of mELP. The adhesive strengths of the proteins were maximized when mELP was mixed with iron or when either protein were mixed with (hydroxymethyl)phosphine crosslinkers. These maximized adhesives were 12-17 times stronger than a commercially available sealant. In addition,</div><div>the iron and mELP adhesive formulation achieved high adhesive strengths even when cured for only ten minutes. This adhesive formula shows promise for adhesive</div><div>applications on soft tissue.</div></div>

La conception de nanoparticules (NPs) polymériques pour le transport de médicaments dans la peau repose sur la compréhension du rôle de leurs compositions chimiques sur leurs interactions avec la peau, notamment la peau pathologique. Ce travail s'est attaché à définir le rôle de la composante hydrophile des NPs sur l'administration cutanée d'un principe actif lipophile modèle (cholécalciférol). Il a été remarqué que la composition hydrophile de polymères amphiphiles à base de PLA conditionnait les propriétés physicochimiques des NPs, notamment la taille, la surface, et la structure, tout comme la protection du cholécalciférol. Concernant l'absorption cutanée sur peau intacte, la composante hydrophile de NPs de 100 nm a eu peu d'influence. Une absorption cutanée du cholécalciférol légèrement plus importante a toutefois été obtenue à partir des NPs très riches en PEG hydrophile en comparaison aux NPs peu PEGylées. A l'inverse sur peau lésée, les NPs hydrophobes et négativement chargées de PLA seul ont permis la meilleure absorption du cholécalciférol. D'une part, la dynamique de la structure des NPs très PEGylées a permis une meilleure mouillabilité de la peau et une possible extraction de lipides cutanés, pouvant faciliter l'absorption sur peau intacte. D'autre part, la composition de la peau a conditionné la structure des NPs, puisque, sur peau lésée, les espèces ioniques libérées de la peau ont déstabilisé les NPs peu ou non PEGylées. Par adhésion à la surface de la peau, les agrégats de PLA ont pu ainsi faciliter l'absorption sur peau lésée.Lors du développement de formulations de NPs, leur composition chimique est donc à optimiser selon l'état pathologique de la peau / The design of clinically efficient polymeric nanoparticles (NPs) for skin drug delivery is based on the understanding of the influence of NPs chemical composition on their interactions with the skin tissue, notably the pathological skin. The aim of this work was to determine the influence of the hydrophilic component of polymeric NPs on the delivery of a lipophilic model drug (cholecalciferol).It was noticed that the polymeric hydrophilic composition of amphiphilic PLA-based NPs conditioned the NPs physico-chemical properties, notably in terms of size, surface properties, structure and drug protection. With regard to absorption into intact skin, the hydrophilic composition of 100 nm NPs had little impact. Only a slightly greater skin absorption was obtained from NPs with high hydrophilic PEG content compared to weakly PEGylated NPs. On the contrary in impaired skin, hydrophobic and negatively charged non-PEGylated NPs (PLA NPs) provided the best drug absorption. On the one hand, the dynamic structure of highly PEGylated NPs providing better skin wettability and potential skin lipids extraction may have contributed for increased absorption in intact skin. On the other hand, skin condition altered the NPs structure since it was observed that a non-negligible quantity of ionic species was released from impaired skin, triggering the destabilization of weakly or non-PEGylated charged NPs. However, only PLA aggregates sedimented/adhered onto the skin surface, which could have facilitated absorption in impaired skin. The polymeric hydrophilic composition of NPs and the pathological skin condition are therefore essential points to consider when designing nanoformulations

The master's thesis focuses on preparation of blown films from polylactid acid (PLA) which was blended with selected polyesteres – poly(butylene adipate-co-terephtalate) (PBAT), polycaprolactone (PCL) and polybutylene succinate (PBS) – and thermoplastic starch (TPS) in amount of 30% in order to soften PLA films. The influence of the aditives on static and mechanical tensile properties, on structure, morphology and thermal properties of the films was determined and the obtained parameters were compared to properties of films prepared from neat PLA and high density polyethylene (HDPE). The results showed that the additives increased crystalinity of PLA and thus significantly influenced the properties of the films. In contrast to the film from neat PLA, softening in terms of lowering glass transition temperature occured only by adding PBS and TPS, in terms of increasing ductility only by adding PBAT. All PLA films showed nearly constant elastic modulus up to the beginning of glass transition enabling their potential application till 50 °C. Preparation of the film with TPS was problematic and the film showed the worst mechanical properties. Preparation of other films was without any problems. The most promising additive from the tested ones was PBAT which showed comparable mechanical properties as the film from HDPE.