Bioactive Hydroxyapatite Aerogels with Piezoelectric Particles.

Open-cell foams based on hydroxyapatite (HAp) can mimic the extracellular matrix (ECM) to better replace damaged hard tissues and assist in their regeneration processes. Aerogels of HAp nanowires (NW) with barium titanate (BT) particles were produced and characterized regarding their physical and chemical properties, bioactivity, and in vitro cytotoxicity. Considering the role of piezoelectricity (mainly due to collagen) and surface charges in bone remodeling, all BT particles, of size 280 nm and 2 and 3 µm, contained BaTiO3 in their piezoelectric tetragonal phase. The synthesized nanowires were verified to be AB-type carbonated hydroxyapatite. The aerogels showed high porosity and relatively homogeneous distribution of the BT particles. Barium titanate proved to be non-cytotoxic while all the aerogels produced were cytotoxic for an extract concentration of 1 mg/mL but became non-cytotoxic at concentrations of 0.5 mg/mL and below. It is possible that these results were affected by the higher surface area and quicker dissolution rate of the aerogels. In the bioactivity assays, SEM/EDS, it was not easy to differentiate between the apatite deposition and the surface of the HAp wires. However, a quantitative EDS analysis shows a possible CaP deposition/dissolution cycle taking place.

Electrospun Polycaprolactone Membranes Expanded with Chitosan Granules for Cell Infiltration.

The small pore size of electrospun membranes prevents their use as three-dimensional scaffolds. In this work, we produced polycaprolactone (PCL) electrospun fibrous membranes with expanded pores by incorporating chitosan (CS) granules into the PCL solution. Scanning electron microscopy images confirmed the presence of the CS granules embedded in the PCL fibers, creating an open structure. Tensile testing results showed that the addition of CS decreased both Young's modulus and the yield stress, but co-electrospun membranes (PCL fibers blended with CS-containing PCL fibers) exhibited higher values compared to single electrospun membranes (CS-containing PCL fibers). Human fibroblasts adhered to and proliferated on all scaffolds. Nuclear staining revealed that cells populated the entire scaffold when CS granules were present, while in PCL membranes, cells were mostly limited to the surface due to the small pore size. Overall, our findings demonstrate that electrospun membranes containing CS granules have sufficiently large pores to facilitate fibroblast infiltration without compromising the mechanical stability of the structure.

Biocomposite Macrospheres Based on Strontium-Bioactive Glass for Application as Bone Fillers.

Traditional bioactive glass powders are typically composed of irregular particles that can be packed into dense configurations presenting low interconnectivity, which can limit bone ingrowth. The use of novel biocomposite sphere formulations comprising bioactive factors as bone fillers are most advantageous, as it simultaneously allows for packing the particles in a 3-dimensional manner to achieve an adequate interconnected porosity, enhanced biological performance, and ultimately a superior new bone formation. In this work, we develop and characterize novel biocomposite macrospheres of Sr-bioactive glass using sodium alginate, polylactic acid (PLA), and chitosan (CH) as encapsulating materials for finding applications as bone fillers. The biocomposite macrospheres that were obtained using PLA have a larger size distribution and higher porosity and an interconnectivity of 99.7%. Loose apatite particles were observed on the surface of macrospheres prepared with alginate and CH by means of soaking into a simulated body fluid (SBF) for 7 days. A dense apatite layer was formed on the biocomposite macrospheres' surface produced with PLA, which served to protect PLA from degradation. In vitro investigations demonstrated that biocomposite macrospheres had minimal cytotoxic effects on a human osteosarcoma cell line (SaOS-2 cells). However, the accelerated degradation of PLA due to the degradation of bioactive glass may account for the observed decrease in SaOS-2 cells viability. Among the biocomposite macrospheres, those composed of PLA exhibited the most promising characteristics for their potential use as fillers in bone tissue repair applications.

Cobalt Ferrite Synthesized Using a Biogenic Sol-Gel Method for Biomedical Applications.

Cancer is one of the leading causes of death worldwide. Conventional treatments such as surgery, chemotherapy, and radiotherapy have limitations and severe side effects. Magnetic hyperthermia (MH) is an alternative method that can be used alone or in conjunction with chemotherapy or radiotherapy to treat cancer. Cobalt ferrite particles were synthesized using an innovative biogenic sol-gel method with powder of coconut water (PCW). The obtained powders were subjected to heat treatments between 500 °C and 1100 °C. Subsequently, they were characterized by thermal, structural, magnetic, and cytotoxic analyses to assess their suitability for MH applications. Through X-ray diffraction and Raman spectroscopy, it was possible to confirm the presence of the pure phase of CoFe2O4 in the sample treated at 1100 °C, exhibiting a saturation magnetization of 84 emu/g at 300 K and an average grain size of 542 nm. Furthermore, the sample treated at 1100 °C showed a specific absorption rate (SAR) of 3.91 W/g, and at concentrations equal to or below 5 mg/mL, is non-cytotoxic, being the most suitable for biomedical applications.

Injectable Thermoresponsive Microparticle/Hydrogel System with Superparamagnetic Nanoparticles for Drug Release and Magnetic Hyperthermia Applications.

Cancer is a disease that continues to greatly impact our society. Developing new and more personalized treatment options is crucial to decreasing the cancer burden. In this study, we combined magnetic polysaccharide microparticles with a Pluronic thermoresponsive hydrogel to develop a multifunctional, injectable drug delivery system (DDS) for magnetic hyperthermia applications. Gellan gum and alginate microparticles were loaded with superparamagnetic iron oxide nanoparticles (SPIONs) with and without coating. The magnetic microparticles' registered temperature increases up to 4 °C upon the application of an alternating magnetic field. These magnetic microparticles were mixed with drug-loaded microparticles, and, subsequently, this mixture was embedded within a Pluronic thermoresponsive hydrogel that is capable of being in the gel state at 37 °C. The proposed DDS was capable of slowly releasing methylene blue, used as a model drug, for up to 9 days. The developed hydrogel/microparticle system had a smaller rate of drug release compared with microparticles alone. This system proved to be a potential thermoresponsive DDS suitable for magnetic hyperthermia applications, thus enabling a synergistic treatment for cancer.

Potassium Ferrite for Biomedical Applications.

Ferrites have been widely studied for their use in the biomedical area, mostly due to their magnetic properties, which gives them the potential to be used in diagnostics, drug delivery, and in treatment with magnetic hyperthermia, for example. In this work, KFeO2 particles were synthesized with a proteic sol-gel method using powdered coconut water as a precursor; this method is based on the principles of green chemistry. To improve its properties, the base powder obtained was subjected to multiple heat treatments at temperatures between 350 and 1300 °C. The samples obtained underwent structural, morphological, biocompatibility, and magnetic characterization. The results show that upon raising the heat treatment temperature, not only is the wanted phase detected, but also the secondary phases. To overcome these secondary phases, several different heat treatments were carried out. Using scanning electron microscopy, grains in the micrometric range were observed. Saturation magnetizations between 15.5 and 24.1 emu/g were observed for the samples containing KFeO2 with an applied field of 50 kOe at 300 K. From cellular compatibility (cytotoxicity) assays, for concentrations up to 5 mg/mL, only the samples treated at 350 °C were cytotoxic. However, the samples containing KFeO2, while being biocompatible, had low specific absorption rates (1.55-5.76 W/g).

Phototoxic Potential of Different DNA Intercalators for Skin Cancer Therapy: In Vitro Screening.

Photodynamic therapy is a minimally invasive procedure used in the treatment of several diseases, including some types of cancer. It is based on photosensitizer molecules, which, in the presence of oxygen and light, lead to the formation of reactive oxygen species (ROS) and consequent cell death. The selection of the photosensitizer molecule is important for the therapy efficiency; therefore, many molecules such as dyes, natural products and metallic complexes have been investigated regarding their photosensitizing potential. In this work, the phototoxic potential of the DNA-intercalating molecules-the dyes methylene blue (MB), acridine orange (AO) and gentian violet (GV); the natural products curcumin (CUR), quercetin (QT) and epigallocatechin gallate (EGCG); and the chelating compounds neocuproine (NEO), 1,10-phenanthroline (PHE) and 2,2'-bipyridyl (BIPY)-were analyzed. The cytotoxicity of these chemicals was tested in vitro in non-cancer keratinocytes (HaCaT) and squamous cell carcinoma (MET1) cell lines. A phototoxicity assay and the detection of intracellular ROS were performed in MET1 cells. Results revealed that the IC50 values of the dyes and curcumin in MET1 cells were lower than 30 µM, while the values for the natural products QT and EGCG and the chelating agents BIPY and PHE were higher than 100 µM. The IC50 of MB and AO was greatly affected by irradiation when submitted to 640 nm and 457 nm light sources, respectively. ROS detection was more evident for cells treated with AO at low concentrations. In studies with the melanoma cell line WM983b, cells were more resistant to MB and AO and presented slightly higher IC50 values, in line with the results of the phototoxicity assays. This study reveals that many molecules can act as photosensitizers, but the effect depends on the cell line and the concentration of the chemical. Finally, significant photosensitizing activity of acridine orange at low concentrations and moderate light doses was demonstrated.

Engineering dual-stimuli responsive poly(vinyl alcohol) nanofibrous membranes for cancer treatment by magnetic hyperthermia.

The development of new cancer treatment options, such as multifunctional devices, allows for a more personalized treatment, avoiding the known severe side effects of conventional options. In this context, on-demand drug delivery systems can actively control the rate of drug release offering a precise control of treatment. Magnetically and thermally controlled drug delivery systems have been explored as on-demand devices to treat chronic diseases and cancer tumors. In the present work, dual-stimuli responsive systems were developed by incorporating Fe3O4 magnetic nanoparticles (NPs) and poly(N-isopropylacrylamide) (PNIPAAm) microgels into electrospun polymeric fibers for application in cancer treatment. First, Fe3O4 NPs with an average diameter of 8 nm were synthesized by chemical precipitation technique and stabilized with dimercaptosuccinic acid (DMSA) or oleic acid (OA). PNIPAAm microgels were synthesized by surfactant-free emulsion polymerization (SFEP). Poly(vinyl alcohol) (PVA) was used as a fiber template originating fibers with an average diameter of 179 ± 14 nm. Stress tests of the membranes showed that incorporating both microgels and Fe3O4 NPs in electrospun fibers increases their Young's modulus. Swelling assays indicate that PVA membranes have a swelling ratio of around 3.4 (g/g) and that the presence of microgels does not affect its swelling ability. However, with the incorporation of Fe3O4 NPs, the swelling ratio of the membranes decreases. Magnetic hyperthermia assays show that a higher concentration of NPs leads to a higher heating ability. The composite membrane with the most promising results is the one incorporated with DMSA-coated NPs, since it shows the highest temperature variation, 5.1 °C. To assess the membranes biocompatibility and ability to promote cell proliferation, indirect and direct contact cell viability assays were performed, as well as cell adhesion assays. Following an extract method viability assay, all membrane designs did not reveal cytotoxic effects on dermal fibroblasts and melanoma cancer cells, after 48 h exposure and support long-term viability. The present work demonstrates the potential of dual-stimuli composite membranes for magnetic hyperthermia and may in the future be used as an alternative cancer treatment particularly in anatomically reachable solid tumors.

Liposomes encapsulating methylene blue and acridine orange: An approach for phototherapy of skin cancer.

Photodynamic therapy uses photosensitizer molecules for the photo-mediated treatment of several diseases such as cancer and skin disorders. However, most of the photosensitizer molecules present problems such as aggregation and low solubility in physiological environments which hinders the treatment efficacy. To overcome these problems, the development of stable liposomes loading photosensitizing molecules as delivery systems can be explored as promising alternatives to enhance cellular uptake and the therapy's efficacy. In this work, liposomes composed by different lipids with or without surfactants were characterized for the encapsulation of photosensitizer molecules such as Methylene Blue (MB) and Acridine Orange (AO). Liposomes were produced by the thin-film hydration method followed by extrusion to reduce particle size and were characterized by Dynamic Light Scattering and Atomic Force Microscopy. Encapsulation efficiency was evaluated as well as the release profile of these molecules from the liposome systems. Cytotoxicity and phototoxicity studies were performed on keratinocytes with and without carcinoma. Results showed that liposome's stability depends on the composition of lipids regardless of the presence of surfactants. Most stable liposomes were those with cholesterol plus the surfactants Span® 80 or sodium cholate that were able to provide higher stability for the liposomes considering the MB and AO encapsulation. Encapsulation efficiency (EE) studies revealed that AO had greater affinity for the vesicles presenting high EE (>98%) while for MB the encapsulation was, in general, moderate (between 63% and 86%). Greater phototoxicity was observed for MET1 squamous cell carcinoma (SCC) cells treated with AO liposomes, achieving similar half-maximal inhibition concentration (IC50) as for the free drug. Finally, two different possible approaches were found, namely, MB-liposomes with potential as a cytotoxic agent for cancer cells; and AO liposomes with a great phototoxicity potential at very low concentrations.

Study on the Incorporation of Chitosan Flakes in Electrospun Polycaprolactone Scaffolds.

Hybrid scaffolds obtained by combining two or more biopolymers are studied in the context of tissue regeneration due to the possibility of achieving new functional properties or structural features. The aim of this work was to produce a new type of hybrid polycaprolactone (PCL)/chitosan (CS) electrospun mat through the controlled deposition of CS flakes interspaced between the PCL fibers. A poly(ethylene oxide) (PEO) solution was used to transport CS flakes with controlled size. This, and the PCL solution, were simultaneously electrospun onto a rotatory mandrel in a perpendicular setup. Different PCL/CS mass ratios were also studied. The morphology of the resulting fibers, evaluated by SEM, confirmed the presence of the CS flakes between the PCL fibers. The addition of PEO/CS fibers resulted in hydrophilic mats with lower Young's modulus relatively to PCL mats. In vitro cell culture results indicated that the addition of CS lowers both the adhesion and the proliferation of human dermal fibroblasts. The present work demonstrates the feasibility of achieving a controlled deposition of a polymeric component in granular form onto a collector where electrospun nanofibers are being deposited, thereby producing a hybrid scaffold.

Impact of obesity and ovariectomy on respiratory function in female mice.

Obesity and the corresponding variations in female sex hormones are associated with severe lung disease. We determined the potential effects of obesity and sex hormones in female mice by investigating changes in lung structure and respiratory function in an obesity model induced by postnatal overnutrition. Obese female mice exhibited pronounced weight gain, abdominal fat accumulation and collagen type I deposition in the airways. However, neither elastic tissue nor estrogen receptors-α/-ß were affected in obese female mice after ovariectomy or sham-operated mice. Bronchoconstriction in response to methacholine challenge in obese sham-operated mice was higher than in the obese group after ovariectomy. Our results suggest that the coexistence of obesity and ovariectomy impacted on respiratory system and airway resistance (attenuates bronchoconstriction after methacholine), on collagen I deposition and on airway estrogen ß-receptors of mice.

Nanostructured LiFe5O8 by a Biogenic Method for Applications from Electronics to Medicine.

The physical properties of the cubic and ferrimagnetic spinel ferrite LiFe5O8 has made it an attractive material for electronic and medical applications. In this work, LiFe5O8 nanosized crystallites were synthesized by a novel and eco-friendly sol-gel process, by using powder coconut water as a mediated reaction medium. The dried powders were heat-treated (HT) at temperatures between 400 and 1000 °C, and their structure, morphology, electrical and magnetic characteristics, cytotoxicity, and magnetic hyperthermia assays were performed. The heat treatment of the LiFe5O8 powder tunes the crystallite sizes between 50 nm and 200 nm. When increasing the temperature of the HT, secondary phases start to form. The dielectric analysis revealed, at 300 K and 10 kHz, an increase of ε' (≈10 up to ≈14) with a tanδ almost constant (≈0.3) with the increase of the HT temperature. The cytotoxicity results reveal, for concentrations below 2.5 mg/mL, that all samples have a non-cytotoxicity property. The sample heat-treated at 1000 °C, which revealed hysteresis and magnetic saturation of 73 emu g-1 at 300 K, showed a heating profile adequate for magnetic hyperthermia applications, showing the potential for biomedical applications.

A New Long-Term Composite Drug Delivery System Based on Thermo-Responsive Hydrogel and Nanoclay.

Several problems and limitations faced in the treatment of many diseases can be overcome by using controlled drug delivery systems (DDS), where the active compound is transported to the target site, minimizing undesirable side effects. In situ-forming hydrogels that can be injected as viscous liquids and jellify under physiological conditions and biocompatible clay nanoparticles have been used in DDS development. In this work, polymer-clay composites based on Pluronics (F127 and F68) and nanoclays were developed, aiming at a biocompatible and injectable system for long-term controlled delivery of methylene blue (MB) as a model drug. MB release from the systems produced was carried out at 37 °C in a pH 7.4 medium. The Pluronic formulation selected (F127/F68 18/2 wt.%) displayed a sol/gel transition at approx. 30 °C, needing a 2.5 N force to be injected at 25 °C. The addition of 2 wt.% of Na116 clay decreased the sol/gel transition to 28 °C and significantly enhanced its viscoelastic modulus. The most suitable DDS for long-term application was the Na116-MB hybrid from which, after 15 days, only 3% of the encapsulated MB was released. The system developed in this work proved to be injectable, with a long-term drug delivery profile up to 45 days.

Electrospun biodegradable chitosan based-poly(urethane urea) scaffolds for soft tissue engineering.

The composition and architecture of a scaffold determine its supportive role in tissue regeneration. In this work, we demonstrate the feasibility of obtaining a porous electrospun fibrous structure from biodegradable polyurethanes (Pus) synthesized using polycaprolactone-diol as soft segment and, as chain extenders, chitosan (CS) and/or dimethylol propionic acid. Fourier transform infrared spectroscopy and proton nuclear magnetic resonance confirmed the syntheses. Fibre mats' properties were analysed and compared with those of solvent cast films. Scanning electron microscopy images of the electrospun scaffolds revealed fibres with diameters around 1 µm. From tensile tests, we found that Young's modulus increases with CS content and is higher for films (2.5 MPa to 6.5 MPa) than for the corresponding fibre mats (0.8 MPa to 3.2 MPa). The use of CS as the only chain extender improves recovery ratio and resilience. From X-ray diffraction, a higher crystalline degree was identified in fibre mats than in the corresponding films. Films' wettability was enhanced by the presence of CS as shown by the decrease of water contact angle. X-ray photoelectron spectroscopy revealed that while ester groups are predominant at the films' surface, ester and urethanes are present in similar concentrations at fibres' surface, favouring the interaction with water molecules. Both films and fibres undergo hydrolytic degradation. In vitro evaluation was performed with human dermal fibroblasts. No PU sample revealed cytotoxicity. Cells adhered to fibre mats better than to films and proliferation was observed only for samples of CS-containing PUs. Results suggest that electrospun fibres of CS-based polyurethanes are good candidate scaffolds for soft tissue engineering.

Effect of testosterone cypionate and stanozolol on the heart of young trained mice: A morphometric study.

Testosterone cypionate and Stanozolol are Anabolic-Androgenic Steroids (AAS) which are synthetic substances that possess functions similar to testosterone. The use of these substances has increased considerably among youngsters and sports practitioners aiming better performance of with aesthetic purposes. The major concern is the effects caused by the inappropriate use of the substances, such as hypertension, myocardial ischemia, and left ventricle hypertrophy. The objective of the present research was to measure the diameter of the left ventricle lumen and the thickness of the left ventricle myocardium in mice submitted to supraphysiological doses of AAS. A total of 30 female Swiss mice were used in the experiments. The animals received supraphysiological doses of the AAS for 30 days, and during the treatment period, they were put to swim in intercalated days. After treatment animals were euthanized and slides were made from the hearts for measurements. Results demonstrated that both AAS changed significantly the heart morphology: Testosterone cypionate led to an increase in the ventricular lumen and stanozolol increased left ventricle myocardium thickness. In conclusion, the use of AAS in supraphysiological doses can change the heart morphology and can lead to serious health consequences.

A atuação do profissional assistêncial e administrativo da área da saúde e a integralidade do cumprimento da Política Nacional de Humanização

O Hospital Nossa Senhora da Conceição (HNSC), um dos hospitais que fazem parte do Grupo Hospitalar Conceição (GHC), é referência no atendimento do Sistema Único de Saúde (SUS) e está vinculado ao Ministério da Saúde (MS). Tem como missão “oferecer atenção integral à saúde, com acesso, qualidade e eficácia organizacional, e desenvolver ações de ensino e pesquisa, fortalecendo o SUS”.(BRASIL. Ministério da Saúde. GHC, 2016). Observações visuais foram realizadas, durante a disciplina de Prática Profissional Simulada II do curso Técnico em Registro e Informações em Saúde no setor de emergência e na unidade de medicina interna deste hospital durante o período de uma semana por mês, durante quatro meses. Nesse período foram vivenciados quatro momentos que aqui são relatados e que reafirmam o compromisso dessa instituição junto á comunidade local, região metropolitana, trabalhadores e gestores. A análise qualitativa conclui que a área física de um hospital fundado como unidade privada em 26 de julho de 1960 não responde favoravelmente ao compromisso com a ambiência, melhoria das condições de trabalho e de atendimento que entendemos como um dos itens de humanização, mas a estrutura gestora desta instituição que tem entre seus princípios a valorização do trabalho e do trabalhador demonstra estabelecimento de vínculos solidários e de participação coletiva no processo de gestão permitindo assim viabilizar a Politica Nacional de Humanização (PNH) através da preocupação dos profissionais envolvidos em prestar ou receber atendimento de boa qualidade