Scaffolds that combine cell adhesion and proliferation with antimicrobial properties are essential for advancing tissue engineering. This work added antimicrobial functionality by incorporating silver nanoparticles (AgNPs) into an electrospun nanofiber membrane composed of polycaprolactone, chitosan, and gelatin for skin tissue engineering. AgNPs were synthesized via chemical reduction within the electrospinning solution. These novel composite nanofiber membranes were evaluated for their physical, chemical and biological properties: morphology, porosity, mechanical properties, crystallinity, thermal properties, swelling, degradation, silver release, antibacterial activity, and cell viability were assessed. All membranes exhibited high porosity (≈75–80%), confirming that AgNP incorporation did not compromise the fibrous architecture. The mechanical properties were dependent on AgNP content, with the optimized formulation (M-1:150) reaching a Young’s modulus of 7.8 ± 0.5 MPa, within the range of soft tissues relevant for skin applications. Silver ion release after 7 days ranged between 0.44 and 0.70 μg/mL, remaining below reported cytotoxic thresholds while ensuring antimicrobial activity. In vitro biocompatibility tests showed no cytotoxicity for any formulation, but only low AgNP loadings supported fibroblast proliferation, with proliferation ratios of approximately 2.7 after 7 days. AgNP-loaded nanofibers showed effective antibacterial activity against representative bacterial species, Escherichia coli and Staphylococcus aureus. Overall, AgNP-loaded nanofibers combined antibacterial activity with suitable mechanical properties and cytocompatibility, supporting their potential application as wound dressings and scaffolds for skin tissue engineering.

The rising problem of chronic wounds demands the investigation of therapeutic solutions that are easy to use, target microbial infection and excessive reactive oxygen species (ROS) at the wound site, and account for skin reinnervation. The aim of this research was to develop electrospun membranes from natural polymers - chitosan (CS) and fish gelatin (FG) - crosslinked with citric acid, incorporating quercetin as an active pharmaceutical ingredient (API) to enhance its therapeutic potential. The produced membranes exhibited a uniform morphology and a cross-shaped network, providing porosity and the ability to sustain hydrolytic degradation. Drug delivery assays revealed a higher release percentage at pH 7.4 and pH 8, which correspond to wound site conditions. However, quercetin degradation at this pH suggests the need for encapsulation. Antioxidant activity analysis confirmed quercetin's great antioxidant capabilities, reaching up to 93.71 ± 0.92 % for pure quercetin, and 53.77 ± 3.09 % for quercetin-containing fibers. Neuronal differentiation assays demonstrated quercetin's ability to promote neuronal differentiation. Antibacterial activity was tested for the membranes against Escherichia coli (E. coli) and Methycillin-resistant staphylococcus aureus (MRSA). The results showed a beneficial effect from incorporating quercetin into the membranes in reducing MRSA growth but no noticeable effects on E. coli. These findings highlight the potential of quercetin-loaded fibers for wound healing applications, with antioxidant, antibacterial, and neurogenic properties.

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.

Wound dressings have long been used to promote the healing of skin injuries. In the work reported here, fibrous membranes were produced by electrospinning poly(N-vinylpyrrolidone) (PVP) solutions containing silver nitrate at varying mass ratios (1:200, 1:100 and 1:50 AgNO3:PVP). PVP solutions without AgNO3 were used as a control. The electrospun membranes were irradiated using 254 nm UV light to simultaneously photo-crosslink PVP and promote the formation of silver nanoparticles (AgNPs). The formation of AgNPs was confirmed by scanning electron microscopy and transmission electron microscopy, as well as by detecting the surface plasmon resonance peak at 420 nm in the UV-Vis spectrum during release studies. The swelling rate of fibrous membranes was lower for those containing AgNPs compared to PVP-only membranes. The Kirby-Bauer diffusion test performed against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus epidermidis and Candida albicans showed that all AgNPs-containing membranes exhibited an inhibitory effect on all microorganisms tested. The in vitro cytotoxicity assay showed that membranes with lower silver concentration were less cytotoxic. This study presents a simple route to producing a wound dressing with antimicrobial action that has a swelling behavior capable of absorbing exudates, provides controlled release of silver and has low cytotoxicity.

Background/Objectives: The unique properties of iron oxide nanoparticles have attracted significant interest within the biomedical community, particularly for magnetic hyperthermia applications. Various synthesis methods have been developed to optimize these nanoparticles. Methods: In this study, we employed a powdered coconut water (PCW)-assisted sol–gel method to produce magnetite nanoparticles for the first time. A comprehensive analysis of the thermal (differential thermal analysis and thermogravimetry), structural (X-ray diffraction), morphological (scanning electron microscopy with energy dispersive spectroscopy), magnetic (vibrating sample magnetometer and hyperthermia), and biological (cytotoxicity essays) properties was conducted to assess their potential for magnetic hyperthermia. Results: Samples heat-treated at 700 °C and 400 °C (washed powder) for 4 h under argon presented only magnetite in their composition. The micrometer-sized particles exhibited ferrimagnetic behavior, with saturation magnetization values of 37, 76, and 10 emu/g and specific absorption rates (SAR) of 27.1, 19.9, and 14.1 W/g, respectively, for treatments at 350 °C (48 h), 700 °C (4 h), and 400 °C (washed powder, 4 h) under an argon atmosphere. Biological tests showed no cytotoxicity below 10 mg/mL. Conclusions: The findings highlight the potential of PCW-assisted synthesis as a sustainable and efficient strategy for producing pure magnetite, with powder washing preceding the heat treatment enabling the attainment of this phase at lower temperatures. Nevertheless, the micrometer-scale dimensions is observed in the morphological analysis limit their suitability for biomedical applications.

A renal infarction occurs when kidney's arterial blood supply is compromised, causing parenchymal necrosis and loss of function. It is a relatively uncommon complication and its treatment is time -dependent. We present a case where a female patient with a history of bilateral aortic -iliac stenting over 10 years before presented with chest pain, palpitations, and dyspnea associated with hypertension. The patient progressed with an acute worsening of renal function and anuria, with an urgent need for renal replacement therapy. The abdominal CT angiography confirmed a complete chronic stent thrombosis and a recent occlusion of the right renal artery causing an acute renal infarction; however, this exam was performed more than 72 hours after admission. There was no longer indication for reperfusion therapy, taking into account the time course. This case reinforces the importance of a thorough clinical history and awareness of risk factors to raise the suspicion of renal infarction that should lead to an early contrast -enhanced CT scan so that adequate therapy can be performed.

Previously, a new biodegradable poly(ester urethane urea) was synthesized based on polycaprolactone-diol and fish gelatin (PU-Gel). In this work, the potential of this new material for neural tissue engineering is evaluated. Membranes with randomly oriented fibers and with aligned fibers are produced using electrospinning and characterized regarding their mechanical behavior under both dry and wet conditions. Wet samples exhibit a lower Young's modulus than dry ones and aligned membranes are stiffer and more brittle than those randomly oriented. Cyclic tensile tests are conducted and high values for recovery ratio and resilience are obtained. Both membranes exhibited a hydrophobic surface, measured by the water contact angle (WCA). Human mesenchymal stem cells from umbilical cord tissue (UC-MSCs) and human neural stem cells (NSCs) are seeded on both types of membranes, which support their adhesion and proliferation. Cells stained for the cytoskeleton and nucleus in membranes with aligned fibers display an elongated morphology following the alignment direction. As the culture time increased, higher cell viability is obtained on randomfibers for UC-MSCs while no differences are observed for NSCs. The membranes support neuronal differentiation of NSCs, as evidenced by markers for a neuronal filament protein (NF70) and for a microtubule-associated protein (MAP2).

Electrospun membranes are compact structures with small pore sizes that hinder cell infiltration, resulting in membranes with cells attached only to the external surface rather than throughout the entire volume. Thus, there is a need to increase the pore size of electrospun membranes maintaining their structural similarity to the extracellular matrix. In this work, we used glucose crystals embedded in polyethylene oxide (PEO) fibers to create large pores in poly(lactic acid) (PLA) electrospun membranes to allow for cellular infiltration. The PEO fibers containing glucose crystals of different sizes (>50, 50-100 and 100-150 mu m) and in varying concentrations (10, 15 and 20 %) were co-electrospun with PLA fibers and subsequently leached out using distilled water. PLA fibrous membranes without glucose crystals were also produced as controls. The membranes were examined for their morphology, mechanical properties, and potential to support the proliferation of fibroblasts. In addition, the immune response to the membranes was evaluated using monocyte-derived macrophages. The glucose crystals were uniformly distributed in the PLA membranes and their removal created open pores without collapsing the structure. Although a reduced Young's modulus was observed for membranes produced using higher glucose crystal concentrations and larger crystal sizes, the structural integrity remained intact, and the values are still suitable for tissue engineering. In vitro results showed that the scaffolds supported the adhesion and proliferation of fibroblasts and the pores created in the PLAmembranes were large enough for fibroblasts infiltration and colonization of the entire scaffold without inducing an inflammatory response.

Flexible and transparent microelectrodes can provide large-scale neural recordings with temporal and spatial resolution when used alongside functional calcium imaging. Patterned metal grids defined by direct laser writing (DWL) are a promising approach for these electrodes, as they resort to standard microfabrication processes and materials, allowing the possibility of mass production. For these reasons, a study exploring transparent grid-based electrodes using DWL for measuring electrocorticography signal was performed. Patterned metal grids with 1 μm of linewidth and 22 μm of spacing between lines showed a sheet resistance of 6 Ω/sq and a transmittance of 81% at 550 nm. The grids were transferred to a 5 μm Parylene-C membrane using an optimized procedure that involves an oxygen plasma pre-treatment. This procedure ensures mechanical robustness and stability of the grids. Finally, a flexible and transparent prototype was fabricated with a microelectrode array composed by 16 electrodes with 500 μm of diameter. These microelectrodes shown an impedance of 10 kΩ at 1 kHz in saline solution and they are highly conformal facilitating in vivo implantation and the recording of neural activity in the mouse cerebellum surface. To conclude, patterned metal grids based-electrodes exhibit a promising performance compared to transparent conductive oxides or graphene. Moreover, the introduction of DLW enables easy and fast manipulation of grid shape and dimensions without the need of physical masks, while keeping large scale compatibility, which is important for tools used in neuroscience community.

Metamizole is a drug with analgesic and antipyretic properties widely available in Portugal. Its use is highly controversial because of the risk of agranulocytosis, a rare but serious adverse event. A 70-year-old female patient with a recent history of treatment with metamizole for post-surgery fever and pain presented to the ED with sustained fever, diarrhea, and painful mouth ulcers. Laboratory tests revealed agranulocytosis. The patient was placed under protective isolation and started treatment with granulocyte-colony stimulating factor (G-CSF) and empiric antibiotic therapy with piperacillin/tazobactam and vancomycin for neutropenic fever. After an extensive workup, no source of infection was identified. During hospitalization, infectious and neoplastic causes of agranulocytosis were investigated, but the results were negative. Metamizole-induced agranulocytosis was suspected. The patient completed a total of three days of G-CSF and eight days of empiric antibiotic therapy with sustained clinical improvement. She was discharged completely asymptomatic and remained clinically stable during follow-up without a resurgence of agranulocytosis. This case report is intended to increase awareness of metamizole-induced agranulocytosis. While this is a well-known side effect, it is also often overlooked. It is paramount that both physicians and patients know how to correctly manage metamizole to prevent and promptly treat agranulocytosis.

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.

Introduction Recurrent hospitalizations for worsening heart failure (WHF) represent a major global public health concern, resulting in significant individual morbimortality and socioeconomic costs. This real-life study aimed to determine the rate and predictors of readmission for WHF in a cohort of outpatients with chronic heart failure (CHF) followed in a heart failure clinic (HFC) at a university hospital. Methods We conducted a longitudinal, observational, and retrospective study of all consecutive CHF patients seen at the HFC of the São Francisco Xavier Hospital, Lisbon, by a multidisciplinary team in 2019. The patients were followed for one year and were on optimized therapy. The inclusion criteria for the study were patients who had been hospitalized and subsequently discharged at least three months prior to their enrollment. Patient demographics, heart failure (HF) characterization, comorbidities, pharmacological treatment, treatments of decompensated HF in the day hospital (DH), hospitalizations for WHF, and death were recorded. We applied logistic regression analysis to assess predictors of hospital readmission for HF. Results A total of 351 patients were included: 90 patients (26%) had WHF requiring treatment with intravenous diuretics in the DH; 45 patients (mean age: 79.1 ± 9.0 years) were readmitted for decompensated HF within one year (12.8%) with no gender difference, while 87.2% of the patients (mean age: 74.9 ± 12.1 years) were never readmitted. Readmitted patients were significantly older than those who were not (p=0.031). Additionally, they had a higher New York Heart Association (NYHA) functional classification (p<.001), were on a higher daily dose of furosemide (p=0.008) at the time of the inclusion visit, were more frequently affected by the chronic obstructive pulmonary disease (COPD) (p=0.004); had been treated more often in the DH for WHF (p<.001) and had a higher mortality rate (p<.001) at one year. Conclusions This study aimed to determine WHF patient readmission rates and predictors. According to our results, a higher NYHA class, the need for treatment in the DH for WHF, a daily dose of furosemide equal to or greater than 80 mg, and COPD were predictors of readmission for WHF. CHF patients continue to experience WHF and recurrent hospitalizations despite therapeutic advances and close follow-up in the HFC with the multidisciplinary team. Besides COPD, the HF readmission risk factors found were mainly related to advanced disease. Furthermore, the structured and multidisciplinary approach of our disease management program likely contributed to our relatively low rate of readmissions.

Therapeutic solutions for injuries in the peripheral nervous system are limited and not existing in the case of the central nervous system. The electrical stimulation of cells through a cell-supporting conductive scaffold may contribute to new therapeutic solutions for nerve regeneration. In this work, biocompatible Polylactic acid (PLA) fibrous scaffolds incorporating Fe(III)Tosylate (FeTos) were produced by electrospinning a mixture of PLA/FeTos solutions towards a rotating cylinder, inducing fiber alignment. Fibers were coated with the conductive polymer Poly(3,4 ethylenedioxythiophene) (PEDOT) formed by vapor-phase polymerization of EDOT at 70 °C for 2 h. Different solvents (ETH, DMF and THF) were used as FeTos solvents to investigate the impact on the scaffold’s conductivity. Scaffold conductivity was estimated to be as high as 1.50 × 10−1 S/cm when FeTos was dissolved in DMF. In vitro tests were performed to evaluate possible scaffold cytotoxicity, following ISO 10993-5, revealing no cytotoxic effects. Differentiation and growth of cells from the neural cell line SH-SY5Y seeded on the scaffolds were also assessed, with neuritic extensions observed in cells differentiated in neurons with retinoic acid. These extensions tended to follow the preferential alignment of the scaffold fibers.

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.

Whether because of sudden trauma or neurodegenerative diseases, nerve injuries impact millions of people worldwide, as in many cases there is no nerve recovery after damage, leaving patients with life-long repercussions [...]

Therapeutic solutions for nerve injuries are limited to small gaps in peripheral nerves (PNs) [...]

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.