In vivo imaging of glycol chitosan-based nanogel biodistribution

The preclinical development of nanomedicines raises several challenges and requires a comprehensive characterization. Among them is the evaluation of the biodistribution following systemic administration. In previous work, the biocompatibility and in vitro targeting ability of a glycol chitosan (GC) based nanogel have been validated. In the present study, its biodistribution in the mice is assessed, using near-infrared (NIR) fluorescence imaging as a tool to track the nanogel over time, after intravenous administration. Rapid whole body biodistribution of both Cy5.5 labeled GC nanogel and free polymer is found at early times. It remains widespreadly distributed in the body at least up to 6 h postinjection and its concentration then decreases drastically after 24 h. Nanogel blood circulation half-life lies around 2 h with the free linear GC polymer presenting lower blood clearance rate. After 24 h, the blood NIR fluorescence intensity associated with both samples decreases to insignificant values. NIR imaging of the organs shows that the nanogel had a body clearance time of 48 h, because at this time point a weak signal of NIR fluorescence is observed only in the kidneys. Hereupon it can be concluded that the engineered GC nanogel has a fairly long blood circulation time, suitable for biomedical applications, namely, drug delivery, simultaneously allowing efficient and quick body clearance.

DOTA-based Ga(III) and Gd(III) chelates for medical imaging (PET, SPECT and MRI)

PhD Thesis in Sciences Specialization in Chemistry

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.

Gd2O3: Eu3+/PPO/POPOP/PS composites for digital imaging radiation detectors

Polymer based scintillator composites have been produced by combining polystyrene (PS) and Gd2O3:Eu3+ scintillator nanoparticles. Polystyrene has been used since it is a flexible and stable binder matrix, resistant to thermal and light deterioration and with suitable optical properties. Gd2O3:Eu3+ has been selected as scintillator material due to its wide band gap, high density and visible light yield. The optical, thermal and electrical characteristics of the composites were studied as a function of filler content, together with their performance as scintillator material. Additionally 1wt.% of 2,5 dipheniloxazol (PPO) and 0.01wt.% of (1,4-bis(2-(5-phenioxazolil))-benzol (POPOP) were introduced in the polymer matrix in order to strongly improve light yield, i.e. the measured intensity of the output visible radiation, under X-ray irradiation. Whereas increasing scintillator filler concentration (from 0.25wt.% to 7.5wt.%) increases scintillator light yield, decreases the optical transparency of the composite. The addition of PPO and POPOP, strongly increased the overall 2 transduction performance of the composite due to specific absorption and re-emission processes. It is thus shown that Gd2O3:Eu3+/PPO/POPOP/PS composites in 0.25 wt.% of scintillator content with fluorescence molecules is suitable for the development of innovate large area X-ray radiation detectors with huge demand from the industries.

Volumetric alterations in the nucleus accumbens and caudate nucleus in bulimia nervosa: a structural magnetic resonance imaging study

Bulimia nervosa (BN) is an eating disorder characterized by recurrent episodes of binge eating and inappropriate compensatory behaviors (such as purging, fasting, or excessive exercise) to prevent weight gain. BN has been associated with deficits in inhibitory control processes. The basal ganglia specifically, the nucleus accumbens (NAc) and the caudate nucleus (CN) are part of the frontostriatal circuits involved in inhibitory control. The main goal of this study was to investigate the presence of morphological alterations in the NAc and the CN in a sample of patients diagnosed with BN.

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)

Nanocellulose in biomedical area: brief review

Due to remarkable physical properties, special surface chemistry and excellent biological properties, as low toxicity, biocompatibility and biodegradability, nanocellulose has gained much attention for its use as biomedical material, applied in medical implants, tissue engineering, drug delivery, wound-healing, cardiovascular applications, among others. This paper presents a review on nanocellulose applied in biomedical area.

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.

Multifunctional Ti–Me (Me=Al, Cu) thin film systems for biomedical sensing devices

Ti-Me binary intermetallic thin films based on a titanium matrix doped with increasing amounts of Me (Me = Al, Cu) were prepared by magnetron sputtering (under similar conditions), aiming their application in biomedical sensing devices. The differences observed on the composition and on the micro(structural) features of the films, attributed to changes in the discharge characteristics, were correlated with the electrical properties of the intermetallic systems (Ti-Al and Ti-Cu). For the same Me exposed areas placed on the Ti target (ranging from 0.25 cm2 to 20 cm2) the Cu content increased from 3.5 at.% to 71.7 at.% in the Ti-Cu system and the Al content, in Ti-Al films, ranged from 11 to 45 at.%. The structural characterization evidenced the formation of metastable Ti-Me intermetallic phases for Al/Ti atomic ratios above 0.20 and for Cu/Ti ratios above 0.25. For lower Me concentrations, the effect of the α-Ti(Me) structure domains the overall structure. With the increase amount of the Me into Ti structure a clear trend for amorphization was observed. For both systems it was observed a significant decrease of the electrical resistivity with increasing Me/Ti atomic ratios (higher than 0.5 for Al/Ti atomic ratio and higher than 1.3 for Cu/Ti atomic ratio). Although similar trends were observed in the resistivity evolution for both systems, the Ti-Cu films presented lower resistivity values in comparison to Ti-Al system.

Development of procedures for the design, optimization and manufacturing of customized orthopaedic and trauma implants: Geometrical/anatomical modelling from 3D medical imaging

Tese de Doutoramento (Programa Doutoral em Engenharia Biomédica)

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

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

Micro/nano-structured superhydrophobic surfaces in the biomedical field: part I: basic concepts and biomimetic approaches.

Inspired by natural structures, great attention has been devoted to the study and development of surfaces with extreme wettable properties. The meticulous study of natural systems revealed that the micro/nano-topography of the surface is critical to obtaining unique wettability features, including superhydrophobicity. However, the surface chemistry also has an important role in such surface characteristics. As the interaction of biomaterials with the biological milieu occurs at the surface of the materials, it is expected that synthetic substrates with extreme and controllable wettability ranging from superhydrophilic to superhydrophobic regimes could bring about the possibility of new investigations of cellâ material interactions on nonconventional surfaces and the development of alternative devices with biomedical utility. This first part of the review will describe in detail how proteins and cells interact with micro/nano-structured surfaces exhibiting extreme wettabilities.

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. (...)