Free-standing multilayered membranes based on graphene and natural polymers for biomedical applications

Dissertação de mestrado integrado em Engenharia Biomédica (área de especialização em Biomateriais, Reabilitação e Biomecânica)

Evolution of the functional properties of titanium–silver thin films for biomedical applications: Influence of in-vacuum annealing

In this work, the thermal stability of TiAgx thin films, deposited by magnetron sputtering, was evaluated, envisaging their application in biomedical devices, namely as electrodes for biosignal acquisition. Based on the composition and microstructural characterization, a set of four representative TiAgx thin films was selected in order to infer whether they are thermally stable in terms of functional properties. In order to achieve this purpose, the structural and morphological evolution of the films with annealing temperature was correlated with their electrical, mechanical and thermal properties. Two distinct zones were identified and two samples from each zone were extensively analysed. In the first zone (zone I), Ti was the main component (Ti-rich zone) while in the second, zone II, the Ag content was more significant. The selected samples were annealed in vacuum at four different temperatures up to 500 oC. For the samples produced within zone I, small microstructural changes were observed due to the recrystallization of the Ti structure and grain size increment. Also, no significant changes were observed with annealing temperature regarding the f l ’ functional properties, being thermally stable up to 500 oC. For higher Ag contents (zone II) the energy supplied by thermal treatments was sufficient to activate the crystallization of Ti-Ag intermetallic phases. A strong increase of the grain size of these phases was also reported. The structural and morphological organization proved to be determinant for the physical responses of the TiAgx system. The hardness and Y g’s modulus were significantly improved with the formation of the intermetallic phases. The silver addition and annealing treatments also played an important role in the electrical conductivity of the films, which was once again improved by the formation of Ti-Ag phases. The thermal diffusivity of the films was practically unchanged with the heat-treatment. This set of results shows that this intermetallic-like thin film system has good thermal stability up to high temperatures (as high as 500 oC), which in case of the highest Ag content zone is particularly evident for electrical and mechanical properties, showing an important improvement. Hardness increases about three times, while resistivity values become half of those from the lowest Ag contents zone. These set of characteristics are consistent with the targeted applications, namely in terms of biomedical sensing devices.

Synthesis of new peptide derivatives that self-assemble into nanostructured hydrogels for biomedical applications

Tese de Doutoramento em Ciências (área de especialização em Química)

Development of multifunctional coatings deposited on polymers based sensors for biomedical applications

Tese de Doutoramento (Programa Doutoral em Engenharia de Materiais)

Biomedical applications of human cathelicidin

[Excerpt] Antimicrobial peptides (AMPs) are good candidates to treat burn wounds, a major cause of morbidity, impaired life quality and resources consumption in developed countries. Tuberculosis (TB), a disease caused by the human pathogen Mycobacterium tuberculosis, represents the second world’s deadliest infectious disease, affecting around 9 million people worldwide in 2013. Of those, about 1.1 million died from the disease. The potential of cathelicin, a human AMP, in the treatment of mycobacteriosis and wound regeneration was assessed in pre-clinical trials. (...)

Ag-TiNx electrodes deposited on piezoelectric poly(vinylidene fluoride) for biomedical sensor applications

Electroactive polymers are one of the most interesting class of polymers used as smart materials in various applications, such as the development of sensors and actuators for biomedical applications in areas such as smart prosthesis, implantable biosensors and biomechanical signal monitoring, among others. For acquiring or applying the electrical signal from/to the piezoelectric material, suitable electrodes can be produced from Ti based coatings with tailored multifunctional properties, conductivity and antibacterial characteristics, through Ag inclusions. This work reports on Ag-TiNx electrodes, deposited by d. c. and pulsed magnetron sputtering at room temperature on poly(vinylidene fluoride), PVDF, the all-round best piezoelectric polymer.. Composition of the electrodes was assessed by microanalysis X-ray system (EDS - energy dispersive spectrometer). The XRD results revealed that the deposition conditions preserve the polymer structure and suggested the presence of crystalline fcc-TiN phase and fcc-Ag phase in samples with N2 flow above 3 sccm. According to the results obtained from SEM analysis, the coatings are homogeneous and Ag clusters were found for samples with nitrogen flow above 3 sccm. With increasing nitrogen flow, the sheet resistivity tend to be lower than the samples without nitrogen, leading also to a decrease of the piezoelectric response. It is concluded that the deposition conditions do significantly affect the piezoelectric polymer, which maintain its characteristics for sensor/actuator applications.

Compact saloplastic membranes of natural polysaccharides for soft tissue engineering

The regeneration of soft biological tissues requires new substitutes that exhibit mechanical properties similar to the native tissue. Herein, thin saloplastic membranes with tunable physical properties are prepared by complexation of chitosan and alginate solutions containing different concentrations of sodium chloride. Polyelectrolyte complexes (PECs) are transferred to flat Petri dishes for compaction into membrane shapes by sedimentation and solvent evaporation. All membranes are resistant to degradation by lysozyme and are stable in solutions with pH values between 1 and 13. Immersing the different membranes in new doping solutions of increasing salt concentrations triggers the typical saloplastic behavior, with a high water absorption and decrease of the rigidity and ultimate tensile strength. The range of such variations is tuned by the sodium chloride amount used in the synthesis: high salt concentrations increase water uptake and tensile moduli, while decreasing the ultimate strength. Cellular assays demonstrate high proliferation rates and viability of L929 fibroblasts seeded onto the most rigid membranes. The results validate the use of saloplastic membranes as soft tissue substitutes for future biomedical applications.

Bacterial cellulose as a novel substrate for retinal pigment epithelium cells transplantation in age-related macular degeneration

Tese de Doutoramento em Engenharia Química e Biológica.

Nonsolvent induced phase separation preparation of poly(vinylidene fluoride-co-chlorotrifluoroethylene) membranes with tailored morphology, piezoelectric phase content and mechanical properties

Poly(vinylidene fluoride-co-chlorotrifluoroethylene) – P(VDF-CTFE) membranes are increasingly interesting for a wide range of applications, including battery separators, filtration membranes and biomedical applications. This work reports on the morphology, hydrophobicity, thermal and mechanical properties variation of P(VDF-CTFE) membranes processed by nonsolvent induced phase separation technique (NIPS) as a function of the main processing parameters. All membranes show a porous structure composed of large spherulites, (interconnected) micropores and/or microvoids depending on the processing conditions used that in turn affect their hydrophobicity and mechanical properties. The degree of crystallinity of the membranes remains approximately constant with a value of about 15 %, except for the membranes immediately immersed in ethanol, which is of about 23 %. In turn, the crystalline phases present in the copolymer is mainly affected by the temperature and nonsolvent characteristics of the coagulation bath, the β-phase content ranging from 33 to 100 %, depending on those processing parameters. It was show that the temperature of water-based coagulation bath plays an important role in order to produce structurally uniform and homogeneous porous membranes, which is particularly important from the point of view of technological applications.

Hydrophobic/hydrophilic P(VDF-TrFE)/PHEA polymer blend membranes

Polymer blend membranes have been obtained consisting of a hydrophilic and a hydrophobic polymers distributed in co-continuous phases. In order to obtain stable membranes in aqueous environments, the hydrophilic phase is formed by a poly(hydrohyethyl acrylate), PHEA, network while the hydrophobic phase is formed by poly(vinylidene fluoride-co-trifluoroethylene) P(VDF-TrFE). To obtain the composites, in a first stage, P(VDF-TrFE) is blended with poly(ethylene oxyde) (PEO), the latter used as sacrificial porogen. P(VDF-TrFE)/PEO blend membranes were prepared by solvent casting at 70° followed by cooling to room temperature. Then PEO is removed from the membrane by immersion in water obtaining a P(VDF-TrFE) porous membrane. After removing of the PEO polymer, a P(VDF-TrFE) membrane results in which pores are collapsed. Nevertheless the pores reopen when a mixture of hydroxethyl acrylate (HEA) monomer, ethyleneglycol dimethacrylate (as crosslinker) and ethanol (as diluent) is absorbed in the membrane and subsequent polymerization yields hybrid hydrophilic/hydrophobic membranes with controlled porosity. The membranes are thus suitable for lithium-ion battery separator membranes and/or biostable supports for cell culture in biomedical applications.

Estudo das propriedades físicas fundamentais de filmes finos intermetálicos do tipo Ti-Me (Me = Al, Au) na funcionalização de elétrodos - sensores para dispositivos biomédicos

Dissertação de mestrado integrado em Engenharia de Materiais

Clivagem e caracterização de frutalina recombinante produzida em Escherichia coli

Dissertação de mestrado integrado em Engenharia Biomédica (área de especialização em Engenharia Clínica)

Otimização do perfil farmacocinético e farmacodinâmico de fármacos anticancerígenos através da sua veiculação em nanossistemas lipídicos

Dissertação de mestrado em Biofísica e Bionanossistemas

Dissolution enhancement of active pharmaceutical ingredients by therapeutic deep eutectic systems

A therapeutic deep eutectic system (THEDES) is here defined as a deep eutectic solvent (DES) having an active pharmaceutical ingredient (API) as one of the components. In this work, THEDESs are proposed as enhanced transporters and delivery vehicles for bioactive molecules. THEDESs based on choline chloride (ChCl) or menthol conjugated with three different APIs, namely acetylsalicylic acid (AA), benzoic acid (BA) and phenylacetic acid (PA), were synthesized and characterized for thermal behaviour, structural features, dissolution rate and antibacterial activity. Differential scanning calorimetry and polarized optical microscopy showed that ChCl:PA (1:1), ChCl:AA (1:1), menthol:AA (3:1), menthol:BA (3:1), menthol:PA (2:1) and menthol:PA (3:1) were liquid at room temperature. Dissolution studies in PBS led to increased dissolution rates for the APIs when in the form of THEDES, compared to the API alone. The increase in dissolution rate was particularly noticeable for menthol-based THEDES. Antibacterial activity was assessed using both Gram-positive and Gram-negative model organisms. The results show that all the THEDESs retain the antibacterial activity of the API. Overall, our results highlight the great potential of THEDES as dissolution enhancers in the development of novel and more effective drug delivery systems.

Light responsive multilayer surfaces with controlled spatial extinction capability

Multilayer systems obtained using the Layer-by-Layer (LbL) technology have been proposed for a variety of biomedical applications in tissue engineering and regenerative medicine. LbL assembly is a simple and highly versatile method to modify surfaces and fabricate robust and highly-ordered nanostructured coatings over almost any type of substrates and with a wide range of substances. The incorporation of polyoxometalate (POM) inorganic salts as constituents of the layers presents a possibility of promoting light-stimuli responses in LbL substrates. We propose the design of a biocompatible photo-responsive multilayer system based on a Preyssler-type POM ([NaP5W30O110]14â ) and a natural origin polymer, chitosan, using the LbL methodology. The photo-reduction properties of the POM allow the spatially controlled disruption of the assembled layers due to the weakening of the electrostatic interactions between the layers. This system has found applicability in detaching devices, such as the cell sheet technology, which may solve the drawbacks actually found in other cell treatment proposals.