Dans cette étude, plusieurs voies ont été explorées dans l’objectif d’utiliser des polyesters aliphatiques issus de ressources oléagineuses comme additifs pour le renfort au choc du poly(L-lactide) (PLLA). Dans un premier temps, des poly(ester-amide)s (PEAs) ont été synthétisés à partir de dérivés de l’huile de ricin. La relation structure-propriétés des PEAs obtenus a été clairement établie. La dispersion des PEAs (à différents taux) par extrusion à l’état fondu dans une matrice de PLLA a ensuite été effectuée, démontrant un accroissement de la résilience de ces mélanges en comparaison au PLLA seul. Une étude systématique reliant la structure d’une large gamme de polyesters aux propriétés des mélanges polyesters/PLLA, a ensuite été réalisée. Une forte dépendance de la résilience des mélanges polyesters/PLLA avec la cristallinité de l’additif polyester a été observée et quantifiée.Une amélioration des propriétés mécaniques du PLLA a également été obtenue par polymérisation par ouverture de cycle du lactide amorcée par un poly(acide ricinoléique) di-hydroxy téléchélique. Les copolymères triblocs ainsi formés ont été caractérisés d’un point de vue morphologique et mécanique.Enfin, un travail exploratoire utilisant l’ADMET comme méthode de polymérisation a été conduit, permettant la synthèse de nouveaux polymères prometteurs pour le renfort au choc du PLLA. Notamment, la copolymérisation de α,ω-diènes bio-sourcés a permis de mimer le polyéthylène basse densité linéaire, couramment employé pour le renfort au choc du PLLA. / The objective of this thesis work, is to promote the use of fatty acid-based aliphatic polyesters as impact modifiers for poly(L-lactide) (PLLA).Firstly, poly(ester-amide)s (PEAs) have been synthesized from castor oil derivatives. The structure-properties relationship of the PEAs so-formed was clearly established. The PEAs were then melt-blended with PLLA by extrusion, yielding blends with improved impact strength compared to neat PLLA.A series of polyesters covering a wide range of thermo-mechanical properties was then employed to evaluate the influence of the polyester morphology on the properties of the blends with PLLA. A strong dependence of the impact strength of the blends was noticed with the crystallinity degree of the polyester additive.An improvement of the mechanical properties of PLLA was also obtained by ring-opening polymerization of lactide initiated by a di-hydroxy telechelic poly(ricinoleic acid). The so-formed triblock copolymers were fully characterized in terms of morphology and mechanical properties.Finally, an exploratory investigation related to the synthesis of PLLA impact modifiers by ADMET was carried out. Particularly, the copolymerization of two bio-based α,ω-dienes yielded a series of “LLDPE like” polyesters, LLDPE being a commonly used impact modifier for PLLA.

L'oxyde d'aluminium anodique poreux (AAO) est formé par anodisationde l'aluminium dans une solution électrolytique acide, sous une tensionconstante et de la température de l'électrolyte. Des techniques spectroscopiquespareilles que la spectroscopie infrarouge FT (ATR-FTIR), diffraction des rayonsX (XRD), spectroscopie Raman, la microscopie à force atomique (AFM) etmicroscopie électronique à balayage (MEB) utilisés pour caractériser la matrice.L'oxydation anodique d'acides L-aminés et des mélanges de monomèrescomprenant 0,1 M aniline et des acides L-aminés dans le milieu aqueux acide deplatine et électrode lisses électrodes Pt modifié (Pt / AAO) est étudié.L'oxydation des acides L-aminés et les électropolymérisation de l'aniline 0,1 Mavec des acides L-aminés tels que la L-alanine, la L-sérine, la L-méthionine,acide L-aspartique, la L-lysine, et phénylalanine en acide le milieu a étéeffectuée par voltammetric cyclique électrochimique couplée à microbalance àcristal de quartz (EQCM). La concentration des acides aminés, le pH del'électrolyte et les effets de balayage de numéros de voltamétrie cyclique ont étéexaminées. L'analyse spectroscopique comme réflectance totale atténuée FTspectroscopie infrarouge (ATR-FTIR), UV-visible, la spectroscopiephotoélectronique à rayons X (XPS), la spectroscopie Raman, et la diffractiondes rayons X (XRD) sont utilisés pour caractériser les couches minces obtenues.Microscopie électronique à balayage (MEB) utilisé pour étudier la morphologiede surface mince de films. La solubilité pour les polymères sont étudiées. Laprésence de liaisons peptidiques est clairement mise en évidence. DFTmodélisation de poly-L-acides aminés volet sur Pt (001) couplée à des mesuresspectroscopiques sont en faveur de L-amino-acides électropolymérisation enacides poly-L-aminés d'une manière irréversible.Les électrosynthèses de poly-L-amino acides, la polyaniline et depolymères ont été utilisées en tant que récepteur de protons à l'état solide pHcapteur solide. / Anodic aluminum oxide porous (AAO) is formed by the anodization ofaluminum in acidic electrolytic solution under at constant voltage and electrolytetemperature. Spectroscopic techniques such as FT infrared spectroscopy (ATRFTIR),X-ray diffraction (XRD), Raman spectroscopy, atomic force microscopy(AFM) and scanning electron microscopy (SEM) used to characterize thetemplate.The anodic oxidation of L-amino acids and monomer mixtures comprising0.1 M aniline and some L-amino acids in acidic aqueous medium on platinumsmooth electrodes and modified Pt electrode (Pt/AAO) is studied. The oxidationof L-amino acids and in presence of aniline 0.1 M with L-amino acids such as Lalanine,L-serine, L-methionine, L-aspartic acid, L-lysine, and L- phenylalaninein acidic media was carried out by cyclic voltammetry coupled withelectrochemical quartz crystal microbalance (EQCM). The Amino acidconcentration, pH of the electrolyte and the scan number effects on cyclicvoltammetry were examined. Spectroscopic analysis such as attenuated totalreflectance FT infrared spectroscopy (ATR-FTIR), UV-Visible, X-rayphotoelectron spectroscopy (XPS), Raman spectroscopy, and X-ray diffraction(XRD) are used to characterize the resulting thin film coatings. Scanningelectron microscopy (SEM) used to study the morphology of thin films surfaceas well as the solubility are studied. The presence of peptide bonds is clearlyhighlighted. DFT modelization of poly-L-amino acids strand on Pt(001) coupledto spectroscopic measurements are in favor of L-amino acidselectropolymerization into poly-L-amino acids in an irreversible way.The electrosynthesis of poly-L-amino acids, polyaniline and polymerswere used as proton receptor for solid state pH solid sensor.

Les matières premières biosourcées s'avèrent être une possibilité de substitution du pétrole de plus en plus prisée dans le domaine des matériaux. De plus, l'utilisation de procédé propre limitant l'impact environnemental du développement de matériau est aujourd'hui incontournable. Dans ce contexte, l'acide aminé L-lysine, un nouveau synthon issu des biotechnologies blanches peu étudié dans le domaine de la chimie des matériaux, a été retenu. Ce synthon sera modifié pour la conception de macromonomères polymérisables sous irradiation UV. En effet, la technique de photopolymérisation est un procédé propre en plein essor, et qui permet le développement de revêtement.La L-lysine étant peu soluble dans les milieux organiques classiques, une étape de transformation est nécessaire pour améliorer sa processabilité. Ainsi, la polycondensation en masse de la L-lysine a conduit à des oligomères de poly-L-lysine de faibles masses molaires. La détermination de la structure obtenue a été réalisée par différentes techniques d'analyses. Ces oligomères sont alors greffés par des fonctions photopolymérisables dans des conditions douces. Le choix s'est porté sur des fonctions accepteur et donneur d'électron. Enfin, l'étude de la photopolymérisation des oligomères de L-lysine greffés accepteurs donneurs a été effectuée par la technique UV aqueuse, une technique innovante et respectueuse de l'environnement, dans différentes conditions pour en optimiser le système. / Biobased raw materials are an interesting and promising option for the substitution of fossil resources in material design. Moreover, using green processes which limit environmental impact of the material conception can't be avoided nowadays. In this context, the L-lysine amino acid, a building block made by white biotechnologies and poorly described in material field has been evaluated. As photopolymerization is a green process in great expansion and allowing coating design, this building block has been modified into a photocurable macromonomer.L-lysine is hardly soluble in usual organic solvents, a transformation step is necessary in order to improve its processability. Thus, L-lysine polycondensation has been tackled and led to oligomers of poly-L-lysine with low molar mass and improved solubility. In addition, the structure determination has been undertaken by different analytic technics. These oligomers can thus be grafted with photocurable functional groups in mild conditions. The chosen photocurable functional groups are donor acceptor of electron. At last, the photopolymerization of L-lysine based oligomers grafted with donor acceptor functional groups has been done by UV waterborne technic which is innovative and environmentally friendly. The photopolymerization has been carried out in different conditions in order to optimize the process.

A mist reactor was used to study plant growth and development under various environmental conditions towards the production of healthy plantlets ready for soil transplant in one step from inoculation. In addition, a 3D type of cultivation via surface attachment of explants to vertically hanging strips inside the mist reactor was also investigated to maximize productivity with minimal footprint. Using carrot as the model species, pre-embryogenic cell suspensions were successfully spray-inoculated onto hanging poly-L-lysine (PLL)-coated nylon mesh to which they then attached and remained for several weeks while they developed into rooted plantlets. To study single step micropropagation from shoot explants to fully acclimatized plantlets, Artemisia annua was used as the model species. Nodal cuttings of A. annua were inoculated onto PLL-coated mesh strips by briefly immersing the strips in the suspension of nodal cuttings. Investigation of medium, phytohormones, CO2, ventilation level and humidity ensued resulting in selection of a preferred final process that reduced physiological aberrations like hyperhydricity and was time efficient. The nodal cuttings that attached to the strips were first misted with half strength shooting medium for 7 days to develop new shoots. Then the new shoots were misted with the rooting medium supplemented with NAA for 12 days to develop roots. Rooted plantlets were acclimatized in the same rooting medium for 9 days to acquire fully functional stomata prior to planting into soil. Taken together this study suggested that fully developed plantlets ready for planting into soil could be obtained in a single step in a bioreactor from embryogenic cells or from nodal explants.

In the field of maxillofacial surgery, the treatment for the recovery of the fracture at condyle region of the mandible has been carried out using Bio-metals such as Titanium, Cobalt, Stainless-Steel because they were considered the standard materials for Implant plate devices for fracture fixation. Using these materials have led to undesired disturbances where the patient must undergo secondary surgery after recovery leading to exposure of the fracture site to the surrounding, metal-ion release into the human system, stress-shielding and interruption during imaging i.e. (Computerized tomography scans). The healing of the mandible requires a delicate and stable fixation procedure for the bone structure to heal. Bio-resorbable materials are the renovation for substituting metals for recovery of the fracture. The main dis-advantage using resorbable plates is absence of mechanical strength and stability. Bio-composites are the innovation for the treatment of the fractures the main study for this thesis is comparing the combination bio-ceramic and bio-resorbable materials using Finite Element Analysis software.

La thérapie génique de myopathies telles que la dystrophie musculaire de Duchenne nécessite une approche systémique afin de traiter l'ensemble de la musculature. Le vecteur AAV est actuellement le plus efficace pour transduire le muscle. Nous montrons que la biodistribution du vecteur AAV administré par voie veineuse peut être modifiée en utilisant diverses stratégies adjuvantes chez la souris saine. La pré-injection de polymères permet ainsi d'améliorer la transduction des muscles par le vecteur AAV, ou encore de baisser la réponse immune neutralisante induite par l'injection intraveineuse du vecteur. Nous abordons également l'impact de facteurs modulateurs exogènes ou endogènes – tels que la procédure d'administration ou certains facteurs sanguins – sur la transduction systémique de l'AAV. Dans une seconde approche, nous avons évalué le transfert de gènes dans le muscle dystrophique afin de sécréter dans la circulation sanguine une protéine transgénique fusionnant le récepteur soluble I du TNF-α avec le fragment constant d'une immunoglobuline (TNFR-Is/mIgG1). La comparaison des cinétiques de sécrétion obtenu après le transfert de gène dans le muscle de souris saines ou de souris dystrophiques mdx indique que le contexte inflammatoire du muscle dystrophique favorise une réponse immune contre le transgène. Nous montrons que l'expression et la sécrétion d'un variant murin peu immunogène du TNFR-Is/mIgG1 améliore la fonction musculaire de la souris mdx sans toutefois conférer un avantage sélectif aux fibres musculaires dystrophiques qui continuent leur cycle de nécrose et de régénération.

In the recent years, development of various organic and inorganic nano-sized systems has gained great interests especially for cancer diagnosis and treatment and intense researches are carried out in this area. Regarding to the recent trends for drug delivery system design, the novel approaches for drug carriers are mainly based on development of smart and nano-size drug carriers which are targeted to cancer cells. Hence, for an effective tumor-targeted delivery device, besides its chemical structure further criteria such as detection of tumor site and sensitivity to the higher temperature and lower pH of the tumor compare to rest of the body gains importance. The aim of this study is to design and prepare polysebacic anhydride (PSA) based nanocapsules (NCs) loaded with Doxorubicin (DOX) which is an anti cancer drug. In order to obtain an intelligent delivery system, drug-loaded nanocapsules were coated with pH sensitive poly (L-histidine). PSA nano-carriers were firstly loaded with DOX and then in order to introduce pH sensitivity, they were coated with poly (L-histidine). PLH-coated NCs were modified with polyethylene glycol (PEG) to prevent their macrophage uptake. Drug release profile from this system was examined in two different buffer solutions prepared as acidic (pH 4) and physiological (pH 7.4) media. The physical and chemical properties of the nano particles were characterized by Fourier transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), ultraviolet and visible absorption spectroscopy (UV-VIS), and scanning electron microscopy (SEM). In vitro studies of the prepared nanocapsules were performed on MDA-MB-231 breast cancer cells by using WST Kit 8 cell viability test. In order to obtained results, pH sensitive nanocapsules with size 230 nm exhibited cellular uptake and promising intracellular release of drug.

In this study we fabricated free standing multilayer films of polyelectrolyte complexes for potential use in tissue engineering of corneal stroma by using the layer-by-layer (LbL) approach. In the formation of these LbL films negatively charged, photocrosslinkable (methacrylated) hyaluronic acid (MA-HA) was used along with polycations polyethyleneimine (PEI) and poly(L-lysine) (PLL). Type I collagen (Col) was blended in with PLL for improving the water absorption and cell attachment properties of the films. It was shown that the LbL films could be easily peeled off from glass substrates due to the photocrosslinking of one of the LbL components, the hyaluronic acid. Film growth and composition were monitored with FTIR-ATR. Heights of peaks at 3383 cm-1, and 2958 cm-1increased along with the bilayer number confirming the polymer build-up. Film integrity and thickness were investigated by scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). Films thicker than 5 bilayers (BLs) were found to be uniform in appearance and 10 BL (PEI/MeHA) films were calculated to be ca. 6 &mu / m thick. Atomic force microscopy (AFM) revealed that as the number of BLs increased, surface roughness decreased. Activity of methacrylated hyaluronic acid was shown by the increased resistance of photocrosslinked multilayer films against hydrolysis by hyaluronidase. Patterns could be created on the films by photocrosslinking further proving that the crosslinking step is successful. Since the ultimate goal was to construct a corneal stroma PEI/MA-HA films were tested with corneal stroma cells, keratocytes. Cell proliferation on PEI/MA-HA films was quite poor in comparison to TCPS. In order to improve the cell adhesion the tests were repeated with PLL/MA-HA. Collagen was added to decrease the hydrophilicity and introduce cell adhesion sequences (Arg-Gly-Asp, RGD) to improve cell proliferation on the films and thus PLL+Col/MA-HA films were also tested. Introduction of collagen to the PLL/MA-HA films was found to decrease water retention of the multilayer films and improve cell viability and proliferation. Col+PLL/MA-HA LbL thus appear to be a promising platform for tissue engineering, especially of corneal stroma.

Meniscus is a fibrocartilaginous tissue which plays an important role in joint stability, lubrication, and load bearing and transmission. Meniscal tears are commonly encountered in sports activities, or caused by degeneration of the cartilage with ageing. They lead to pain, loss of work, disturbed biomechanics of the knee and inability to walk or even move the legs. As the meniscal tissue is avascular in the inner portion, injury to this part does not heal by itself, and therefore treatments are needed. In some cases when complex tears occur, the tissue cannot be successfully treated with the conventional methods. Tissue engineering appears to be a promising alternative to treat such complex tears. It includes the application of cells on scaffolds (or cell carriers), and provision of bioactive agents to the site of injury in order to regenerate the damaged tissue. The cells and the bioactive agents are involved in the synthesis of the new tissue, while the scaffold acts as a support to guide the cells until the new tissue is formed, and it is slowly absorbed by the body leaving the new tissue behind. Thus, a natural tissue is generated at the end. Few studies have been reported on the tissue engineering of meniscus, but neither of them was able to completely mimic the meniscus structure, nor could they succeed in constructing scaffolds with sufficiently high tensile properties. In the current in vitro study, a novel 3D construct was proposed, in which the natural tissue is perfectly mimicked. The 3D construct consisted of aligned collagen fibers embedded within a foam network which stabilizes the structure. The foam was prepared by freezing a polymer solution with a certain concentration, and lyophilizing it. Aligned fibers were aimed to improve the tensile properties. The construct was impregnated in alginate gel, which was then crosslinked, to improve the compressive properties. The foam was prepared from (poly(L-lactic acid)/poly(lactic-co-glycolic acid) (PLLA/PLGA) solutions of various concentrations (2%, 2.5%, 3%, and 4% w/v) and at different freezing temperatures (-20oC or -80oC) to select the best preparation condition. After analysis of the microstructure and mechanical properties, foams prepared from 3% polymer solution frozen at -20oC were found to be the most appropriate for use as scaffold for the 3D construct, since they had large pores, high and interconnected porosity, as well as high mechanical strength. The 3D constructs were seeded with human meniscus cells and incubated for 21 days. Cell behavior on the constructs was examined. Cell attachment and proliferation was found to be better with the constructs not coated with alginate. However, the constructs coated with alginate demonstrated higher compressive strength. It was also found that incorporation of collagen fibers significantly improved the tensile properties. All the constructs were shown to lead to the production of extracellular components specific for fibrocartilages, and thus it was concluded that they were promising for use in meniscal replacement.

Thesis (Ph. D.)--Auburn University, 2008. / Abstract. Vita. The following patent resulted from the dissertation research: Davis, V., Simonian, A.L., Nepal, D., Balasubramanian, S, "Preparation of Precisely Controlled Thin Film Nanocomposites of Carbon Nanotubes and Biomaterials", U.S. Provisional Patent Application No. 61/000,938, filed on 30 October 2007. The following peer-reviewed publications resulted from the dissertation research: Dhriti Nepal, Shankar Balasubramanian, Aleksandr Simonian, and Virginia Davis, "Mechanically Strong Antibacterial Thin Film Based on Single-Walled Carbon Nanotubes Armored with Biopolymers", Nano Letters ASAP article, May 2008 (# equal contribution) -- Shankar Balasubramanian, Iryna B. Sorokulova, Vitaly J. Vodyanoy, and Aleksandr L. Simonian, "Lytic Phage as a Specific and Selective Probe For Detection of Staphylococcus Aureus: A Surface Plasmon Resonance Spectroscopic Study", Biosensors and Bioelectronics, 2007, 22, 948-955 -- Shankar Balasubramanian, Alexander Revzin, Aleksandr Simonian, "Electrochemical Desorption of Proteins from Gold Electrode Surface", Electroanalysis, 2006, 18, 1885-1892 (Invited article) -- Vishwaprakash Nanduri, Shankar Balasubramanian, Srinivas Sista, Vitaly J. Vodyanoy, and Aleksandr L. Simonian, "Highly Sensitive Phage-based Biosensor for the Detection of ß-galactosidase", Analytica Chimica Acta, 2007, 589, 166- 172 -- H. Luckarift, Shankar Balasubramanian, S. Paliwal, G. Johnson and A. Simonian, "Enzyme-Encapsulated Silica Monolayers For Rapid Functionalization of a Gold Surface", Colloids and Surfaces B: Biointerfaces, 2007, 58, 28-33 (Invited article) -- Dong Wei, Omar Oyarzabal, Tung-Shi Huang, Shankar Balasubramanian, Srinivas Sista, Aleksandr Simonian, "Development of Surface Plasmon Resonance Biosensor For The Identification of Campylobacter jejuni", Journal of Microbiological Methods, 2007, 69, 78-85. The following conferences presentations resulted from the dissertation research: Covalent Immobilization of Organophosphorus Hydrolase on Carbon Nanotubes for Biosensor Applications, accepted for oral presentation at 12th International Meeting on Chemical Sensors, Jul. 13-16, 2008, Columbus, OH -- Electrochemical characteristics of SWNT-biopolymer nanocomposites, accepted for 213th meeting of The Electrochemical Society, May 18-23, 2008, Phoenix, AR -- Mechanically Robust Antibacterial Thin Films Composed of Single-Walled Carbon Nanotubes and Biopolymers, 2008 AIChE Spring National Meeting, Apr. 6-10, New Orleans, LA -- Production and characterization of protein and DNA based single wall carbon nanocomposites by layer-by-layer assembly, MRS Fall Meeting, Nov. 26-30, 2007, Boston, MA -- Gold surface modified with enzyme-encapsulated silica monolayers for biosensor application, The 58th Southeast Regional Meeting of the American Chemical Society, Nov. 1-4, 2006, Augusta, GA -- Electrochemical modulation of biological interfaces, 209th meeting of The Electrochemical Society, May 7-12, 2006, Denver, CO -- SPR based biosensor using lytic phage as a specific and selective probe for staphylococcus aureus detection, 57th Pittsburgh Conference on Analytical Chemistry and Applied Spectroscopy, Mar. 12-17, 2006, Orlando, FL -- Specific & selective detection of staphylococcus aureus by lytic phage using SPR biosensor, 57th Southeast / 61st Southwest Joint Regional Meeting of the American Chemical Society, Nov. 1-4, 2005, Memphis, TN -- Prevention of non-specific binding as a way to increase sensitivity of SPR-based sensors, 206th meeting of The Electrochemical Society, October 3-8, 2004, Honolulu, HI. Includes bibliographical references.