The acceptance of blood contacting implants creating favorable conditions in vivo is decisively determined by their interaction with proteins that mediate inter cellular interactions with synthetic substrates. Adsorbed proteins can activate blood cascade systems like coagulation and complement that may result in serious blood clots, and/or immunological reactions. Poly (ethylene glycol) (PEG), heparin, and phosphoryl choline (PC) functional poly (methacrylates) are previously used polymers with known non-adhesive properties in blood contacting events. This thesis contributes to this extensive research by introducing a novel type of biomaterial that equips biodegradable polymers with biomimetic functionalities. The phospholipid mimetic material is synthesized by combining biodegradable polymers with various functional polar end-groups consisting of zwitterionic phosphoryl choline (PC), anionic succinates, and cationic quaternary ammonium. The polymer backbone provides mechanical stability and biodegradability whilst the various head groups provide a variety of functions. The careful evaluation of the synthesis has allowed reaction conditions to be optimized leading to complete conversion at each step and subsequently high yields. Initially, poly (e-caprolactone) (PCL) was used since it provided a suitable synthetic starting point. However, the synthesis has also included poly (trimethylene carbonate) (PTMC) to provide a material that allows spontaneous surface enrichment of the polar PC group. This was achieved with an added hydrophilic environment. Through the synthesis of multi PC functional PTMC, additional bulk organisation by the formation of zwitterionomers (PC ionomer) was achieved. Low modulus elasticity and water uptake were some of the properties of the formed material. As a result it was shown that the PC ionomer could be used for protein/drug loading and subsequent release. Furthermore, the material possessed non-adhesive properties in different biological environments. Importantly, the result suggests that a versatile synthetic platform has been established that may provide a smorgasbord of different functional polymers, or combinations of such. This is indeed important since it was shown that the polymer in many ways dictates how the material may take advantage of an added functionality. Such materials should be interesting for a variety of biomedical applications including the production of soft hemocompatible tissue.

Chitosan, Whey Protein Isolate (WPI) and vital wheat gluten (WG) are three biomaterials that have quite promising properties for packaging purposes. They have good film forming properties and good gas barrier properties in dry conditions. Moreover, because they are produced from industrial waste of food processing, they offer an ecological advantage over polymers made from petroleum. However, their physicochemical characteristics still must be improved for them to be of commercial interest for the food packaging industry. The purpose of this work was to study different strategies aiming to improve the water resistance and aging properties of these polymers, which are some of the key disadvantages of these materials. The produced solution cast chitosan and WPI films were characterised with scanning electron microscopy (SEM), density measurements and thermogravimetry. The water vapour transmission rate was determined at a relative humidity of 11%. In the first part, mechanical properties of solid films and seals were assessed by tensile testing. WG film’s tensile properties and oxygen and water vapour permeabilities were measured as a function of aging time. The changes in the protein structure were determined by infrared spectroscopy and size-exclusion high-performance liquid chromatography and the film structure was revealed by optical and scanning electron microscopy. Gluten-clay nanocomposites were characterised by tensile testing, X-ray diffraction and transmission electron microscopy. The incorporation of a hydrophobic biodegradable polymer, poly ( ε-caprolactone), PCL, in both chitosan and whey protein, yielded a significant decrease in water vapour transmission rate. It was observed that a certain amount of the PCL particles were ellipsoidal in chitosan and fibrous in WPI. The obtained data also indicated that the particle shape had an important influence in the water vapour transmission rate. In the second part, the aging properties of WG films, plasticized with glycerol and cast from water/ethanol solutions with pH=4 or pH=11 were investigated. WG films made from alkaline solutions were mechanically more time-stable than the acidic ones, the latter being initially very ductile but turning brittle towards the end of the aging period. The protein solubility measurements indicated that the protein structure of the acidic films was initially significantly less aggregated than the in basic films. During aging the acidic films lost more mass than the basic films through slow evaporation of volatiles (water/ethanol) and through migration of glycerol to the paper support. The oxygen permeability was also lower for the basic films. In the last part, the properties of new and aged glycerol-plasticized WG films at acidic and basic conditions containing ≤4.5 wt% natural or quaternary-ammonium-salt-modified montmorillonite were studied. Films of WG with montmorillonite were possible to produce by solution casting. The aging rate of acidic and basic films was unaffected by the incorporation of clay. However, the large reduction in water vapour permeability for most systems suggested that the clay sheets were evenly distributed within the films. The film prepared from basic solution and containing natural clay was almost completely exfoliated as revealed by transmission electron microscopy and X-ray diffraction. The best water vapour barrier properties were obtained by using modified clay. / QC 20101013

The search for alternatives to the fossil-based products has dramatically surged during past few decades primarily due to the problems associated with the scarcity of these sources and global environmental concerns. Among those many alternatives, exploitation of cellulose, as a raw material to develop novel products has been a constant attempt since it has never lost its both economic and industrial impact. Cellulose is known for its significant contribution as a raw material and as a fascinating sustainable macromolecule, which exhibits wide availability and versatile chemical reactivity to discover novel derivatives for broad range of applications. Conversion of cellulose C2/C3 secondary hydroxyl groups to dialdehyde groups in the presence of periodate is an extremely useful method for regioselective oxidation of cellulose and to activate the polymer for further derivatization. This thesis is primarily focused on synthesis and characterization of wide range of cellulose derivatives exploiting facile periodate oxidation methodology. The first study investigated the use of periodate oxidation as a potential method to synthesize a novel water soluble derivative of cellulose from bleached hardwood Kraft pulp. The work focused on the effect of periodate oxidation and sulfonation reaction on water solubility, morphology and structure of cellulose fibers. The results showed a significant increase in water solubility (2.85 -28.5 g/L) and complete change in surface morphology of the fibers due to the introduction of sulfonic acid groups. In the second study, the same reaction scheme was employed on bead cellulose to prepare anionic 2,3-disulfonated beads. Due to the presence of negatively charged sulfonic acid groups, the beads were found to be agglomerated in presence of cationic starch, exhibiting their future application in chromatographic separation. In the third study, model primary amine compounds such as methyl and butyl amines were grafted to nanowhisker surfaces following periodate oxidation and reductive amination. Then, based on the grafting procedure, in the following study, gamma aminobutyric acid (spacer) and syringyl alcohol (linker) was attached to periodate oxidized nanowhiskers to synthesize a novel drug delivery system. The final study investigated the application of periodate oxidized nanowhiskers as chemical cross-linkers to stabilize gelatin gels. It was concluded that the chemical cross-linking has a significant effect on relative increase in percentage of rigid protons, reduced water uptake ability and reduced pore size of the gels. Not only did the chemical cross-linking improve the storage modulus of the gels (150%) and but it also increased the thermal resistance until 50 oC.

In the present work, a study of the preparation of new formulations of acrylic bone cements (ABC) has been carried, to obtain materials with capacity for controlled drug delivery of medicaments useful in the therapeutic treatment of osteoporosis. The main research line has been focused on the partial modification of the solid phase of the conventional formulation of ABC, by substituting part of the PMMA beads with different microparticles of synthetic as well as natural biodegradable polymers. The incorporation of these polymers to the conventional formulation, with a structure based on PMMA, has been focused on two well defined points of view: as a structural component, and as a model component to study its delivery from the material to the external medium, to determine the capacity of the formulation for drug delivery. The work was finished with the evaluation of the capacity of controlled release of proteins and the determination of biocompatibility. / En este trabajo se ha llevado a cabo el estudio de nuevas formulaciones de cementos óseos acrílicos (COA) para su posterior evaluación como sistema de liberación controlada de medicamentos útiles en el tratamiento terapéutico de la osteoporosis. El trabajo se ha fundamentado en la modificación parcial de la fase sólida de los COA, mediante la substitución parcial de las microesferas de PMMA, por diferentes micropartículas de polímeros biodegradables, tanto de naturaleza sintética como natural. La incorporación de estos polímeros a la formulación del COA convencional, cuya estructura polimérica básica es el PMMA, ha sido enfocada desde dos puntos de vista bien diferenciados: como un componente estructural, que aporta resistencia mecánica al material, o como un componente que nos permita determinar la capacidad de liberación de un fármaco como el Ibandronato o de una proteína modelo como el colágeno hidrolizado. Finalmente se ha evaluado la biocompatibilidad de los COA modificados.

The interactions between polymers and components of biological systems are an important area of interest within the fields of tissue engineering, polymer chemistry, medicine and biomaterials. In order to create such a biomimetic material, it must show the inherent ability to reproduce or elicit a biological function. How do we design synthetic materials in order to direct their interactions with biological systems? This thesis contributes to this research with aspects of how polymers interact with biological materials with the help of ionic interactions. Polyesters, biodegradable or not, may after a hydrolytic cleavage interact ionically with protonated amines by the liberated carboxylate functions. Amines are found in proteins and this fact will help us to anchor proteins to polyester surfaces. Another type of interaction is to culture cells in polymeric materials, i.e. scaffolds. We have been working on compliant substrates, knitted structures, to allow cell culture in three dimensions. A problem that arises here is how to get a high cell seeding efficiency? By working on the interactions between polymers, proteins and finally cells, it is possible to create a polarized protein membrane that allows for very efficient cell seeding, and subsequent three dimensional cell cultures. Finally a synthetic route to taylor interaction was developed. Here a group of polymers known as ionomers were synthesized. In our case ionic end groups have been placed onto biodegradable polycarbonates, we have created amphiphilic telechelic ionomers. Functionalization, anionic or cationic, changes the properties of the material in many ways due to aggregation and surface enrichment of ionic groups. It is possible to add functional groups for a variety of different interactions, for example introducing ionic groups that interact and bind to the complementary charge of proteins or on the other hand one can chose groups to prevent protein interactions, like the phosphorylcholine zwitterionomers. Such interactions can be utilized to modulate the release of proteins from these materials when used in protein delivery applications. The swelling properties, Tg, degradation rate and mechanical properties are among other things that will easily be altered with the choice of functional groups or backbone polymer.

Tissue engineering is a promising alternative strategy to produce artificial bone substitutes / however, the control of the cell organization and cell behavior to create fully functional 3-D constructs has not yet been achieved. To overcome these, activities have been concentrated on the development of multi-functional tissue engineering scaffolds capable of delivering the required bioactive agents to initiate and control cellular activities. The aim of this study was to prepare tissue engineered constructs composed of polymeric scaffolds seeded with mesenchymal stem cells (MSCs) carrying a nanoparticulate growth factor delivery system that would sequentially deliver the growth factors in order to mimic the natural bone healing process. To achieve this, BMP-2 and BMP-7, the osteogenic growth factors, were encapsulated in different polymeric nanocapsules (poly(lactic acid-co-glycolic acid) (PLGA) and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV)) with different properties (degradation rates, crystallinity) and, therefore, different release rates to achieve the early release of BMP-2 followed by the release of BMP-7, as it is in nature. Initially, these nanoparticulate delivery systems were characterized and then the effect of single, simultaneous and sequential delivery of BMP-2 and BMP-7 from these delivery systems was studied in vitro using rat bone marrow MSCs. The effect of using these two growth factors in a sequential manner by mimicking their natural bioavailability timing was shown with maximized osteogenic activity results. BMP-2 loaded PLGA nanocapsules were subcutaneously implanted into Wistar rats and according to initial results, their biocompatibility as well as the positive effect of BMP-2 release on the formation of osteoclast-like cells was shown. To complete the construction of the bioactive scaffold, this nanoparticulate sequential delivery system was incorporated into two different types of polymeric systems / natural (chitosan) and synthetic (poly(&amp / #949 / -caprolactone) (PCL)). 3-D fibrous scaffolds were produced using these materials by wet spinning and 3-D plotting. Incorporation of nanocapsules into 3-D chitosan scaffolds was studied by two different methods: incorporation within and onto chitosan fibers. Incorporation into 3-D PCL scaffolds was achieved by coating the nanocapsules onto the fibers of the scaffolds in an alginate layer. With both scaffold systems, incorporation of nanocapsule populations capable of delivering BMP-2 and BMP-7 in single, simultaneous and sequential fashion was achieved. As with free nanocapsules, the positive effect of sequential delivery on the osteogenic differentiation of MSCs was shown with both scaffold systems, creating multi-functional scaffolds capable of inducing bone healing.

Cotton stalk lignin extractions were performed via alkaline methods at different conditions. Crude and post treated cotton stalk lignins, olive mill wastewater and garlic stalk juice were examined in terms of antimicrobial activity. Antimicrobial lignin was isolated depending on alkaline extraction conditions. Lignin extracted at 60&deg / C exhibited significant antimicrobial effect towards both Escherichia coli and Bacillus pumilus. However different post treatments such as ultrasonication and TiO2-assisted photocatalytic oxidation did not result in antimicrobial compounds. Olive mill wastewater and garlic stalk juice exerted substantial antimicrobial effects towards tested microorganisms. Xylan-based biodegradable films containing lignin, garlic stalk juice, tannic acid and olive mill wastewater were characterized against both B. pumilus and E. coli by means of their antimicrobial activities. E. coli exhibited lesser sensitivity to all tested antimicrobial xylan films except tannic acid-integrated xylan film than B. pumilus. Antimicrobial lignin integrated-xylan film exhibited stronger effect towards tested microorganisms than tannic acid-integrated film. In the case of both antimicrobial lignin and tannic acid integrated xylan films, 4% was found to be the maximum antimicrobial compound percentage in film forming solutions to observe continuous film formation. Lignin samples with/without antimicrobial activity were characterized by means of their chemical structure via FTIR and LC-MS. FTIR results revealed that cotton stalk lignins were significantly broken down via alkaline treatment and this breakdown resulted in the formation of new fractions and also ester &amp / ether bonds between antimicrobial hydroxycinnamic acids and lignin were cleaved during the alkaline treatments of cotton stalk lignins. By FTIR results, C=C bonds were found to be characteristic for antimicrobial lignin sample and it was suggested that these bonds might be the reason of the antimicrobial activity. By LC-MS qualitative mass analysis, antibacterial lignin fractions were found to be quite different from non-antibacterial lignin fractions. LC-MS results indicated that the antimicrobial lignin fractions might be lignin-derived oligomers and/or might be flavonoids. Cotton stalk lignin fractions demonstrated different antimicrobial activities depending on the method of isolation and chemical treatment.

Acute liver failure is a major cause of death in the world, and effective treatments are greatly needed. Liver macrophages (Kupffer cells) play a major role in the pathology of acute liver failure, and drug delivery vehicles that can target therapeutics to Kupffer cells have great therapeutic potential for treating acute liver failure. Microparticles, formulated from biodegradable polymers, are advantageous for treating acute liver failure because they can passively target therapeutics to Kupffer cells. However, existing biomaterials are not suitable for the treatment of acute liver failure because of their slow hydrolysis and acidic degradation products. In this dissertation, I present the development of a new class of biodegradable materials, termed aliphatic polyketals, which have considerable potential as drug delivery vehicles for the treatment of acute liver failure because of their neutral degradation products and tunable hydrolysis kinetics. The anti-inflammatory enzyme, superoxide dismutase (SOD), was delivered using polyketal microparticles to the liver for treating acute liver Failure. Our results demonstrated that polyketal microparticles significantly improved the efficacy of SOD in treating LPS-induced acute liver damage in vivo, as evidenced by decreased levels of serum alanine transaminase, which corresponds to the extent of damage in the liver, and serum level of tumor necrosis factor-alpha, which corresponds to the secretion of pro-inflammatory cytokines. The completion of this thesis research demonstrates the ability of polyketal-based drug delivery systems for treating acute inflammatory diseases and creates a potential therapy for enhancing the treatment of acute liver failure.

We studied PLA-microcrystalline cellulose composites, focusing on the effects of processing, particle size and surface modification. The thermal and mechanical properties of these PLA based composites were studied and the effect of cellulose addition on PLA degradation was analyzed. For our system, the degradation rate was found to depend on initial sample crystallinity, pH of the degradation media and cellulose content of the composite. Composites were prepared using solution processing and melt mixing methods. The processing methods influenced the polymer's ability to crystallize affecting the mechanical properties. Isothermal crystallization studies carried out to study the kinetics of crystallization showed melt processed samples to have lower half time for crystallization and higher value for the Avrami exponent. The crystallization rate of PLA was also found to depend on surface chemical composition of cellulose particles and the particle size. Influence of filler surface modification on the composite properties was studied via grafting of lactic acid and polylactic acid to cellulose particles and the effect of filler size was studied using hydrolyzed microcrystalline cellulose particles. A simple esterification reaction that required no external catalyst was used for surface modification of cellulose particles. Surface modification of cellulose particles enhanced the static and dynamic mechanical properties of the composite samples due to improvement in the PLA-cellulose compatibility that resulted in better interfacial interactions. The utility of cellulose, available from a renewable resource, as an effective reinforcement for PLA is demonstrated.

This research is directed toward understanding the effect of nanoparticle attributes and polymer morphology on the properties of the nanocomposites with analogous nanoparticle chemistry. In order to develop this understanding, polymer nanocomposites containing calcium phosphate nanoparticles of different specific surface areas and shapes were fabricated and characterized through thermal and thermomechanical techniques. Nanoparticles were synthesized using reverse microemulsion technique. For nanocomposites with different surface area particles, the mobility of amorphous polymer chains was restricted significantly by the presence of particles with an interphase network morphology at higher loadings. Composites fabricated with different crystallinity matrices showed that the dispersion characteristics and reinforcement behavior of nanoparticles were governed by the amount of amorphous polymer fraction available. The study conducted on the effect of nanoparticle shape with near-spherical and nanofiber nanoparticles illustrated that the crystallization kinetics and the final microstructure of the composites was a function of shape of the nanoparticles. The results of this research indicate that nanoparticle geometry and matrix morphology are important parameters to be considered in designing and characterizing the structure-property relationship in polymer nanocomposites.