Articles publicats en revistes (Institut de Bioenginyeria de Catalunya (IBEC))

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In vitro and in vivo efficacy evaluation of new self-assembling curcumin loaded nanohyaluronan-glycerosomes on wound restoring in health and diabetic rats
(Elsevier, 2025-05-26) Gómez García, Francisco José; Ramírez Andreo, Antonio; Manconi, Maria; Manca, Maria Letizia; Matricardi, Pietro; di Meo, Chiara; Fernàndez-Busquets, Xavier; Martínez Díaz, Francisco; Salmerón, Diego; López Jornet, Pía
In this study the wound healing efficacy of new self-assembling curcumin loaded nanohyaluronan-glycerosomes has been tested in healthy and diabetic rats. Curcumin was loaded in nanohyaluronan-liposomes and -glycerosomes, special vesicles obtained mixing curcumin, hyaluronan nanohydrogel and soy lecithin. Curcumin loaded liposomes and glycerosomes were also prepared, characterized and tested as references. The physico-chemical (size and size distribution, surface charge and morphology), and technological (entrapment efficiency, stability over time and skin delivery) characteristics and biological performances (safety, ability to protect in vitro cells from oxidative damage) of prepared formulations were measured. Finally, they were daily applied to skin wounds of healthy or diabetic rats. The animal skin was excided and analysed at days 3, 7 and 14. The macroscopic observation underlined the higher ability of curcumin loaded nanohyaluronan-glycerosomes to improve wound healing in diabetic rats, already on day 3 up to day 14 (p < 0.05). Histopathological analysis confirmed an accelerated re-epithelization in healthy rats, while increased angiogenesis in diabetic ones. The superior therapeutic efficacy of curcumin loaded nanohyaluronan-glycerosomes compared to other formulations can be related to their enhanced ability to deliver higher curcumin concentrations at the wound site due to a synergistic effect of glycerol, hyaluronan nanohydrogel and lecithin.
FleQ-Dependent regulation of the ribonucleotide reductase repressor NrdR in Pseudomonas aeruginosa during biofilm growth and infection
(Springer Nature, 2025-11-27) Marchan del Pino, Domingo ; Rubio Canalejas, Alba; Pedraz López, Lucas; Hernández, José María; Admella Pedrico, Joana; Blanco Cabra, Núria; Torrents Serra, Eduard
Ribonucleotide reductases (RNRs) are essential enzymes that catalyze the conversion of ribonucleotides to deoxyribonucleotides (dNTPs), a critical step in DNA synthesis and repair. While all organisms encode for at least one RNR class, Pseudomonas aeruginosa harbors three, providing a competitive advantage that allows it to adapt and colonize various environments. Despite their importance, the mechanisms coordinating the expression of different RNRs in microorganisms with multiple RNR classes remain poorly understood. The transcriptional regulator NrdR controls the expression of all three RNR classes by binding to conserved motifs (NrdR boxes) in their promoters. However, the regulation of nrdR itself remains unknown. In this study, we investigated the transcriptional regulation of nrdR using a combination of bioinformatics and experimental approaches we identified potential transcription factors (TF) involved in nrdR regulation. Our analysis identified four potential TF that could regulate nrdR, and we experimentally confirmed that specifically, FleQ is responsible for regulating nrdR expression under aerobic and anaerobic conditions. Furthermore, we explored nrdR regulation under biofilm-forming conditions and in the Galleria mellonella infection model to gain insights into how nrdR might be regulated in vivo.
Diet-induced obesity disrupts sexually dimorphic gene expression in mice
(2025-10-04) Ribas, Vicent; Morón-Ros, Samantha; Mari, Helena; Gracia-Batllori, Albert; Brugnara, Laura; Herrero Gómez, Alba; Eyre, Elena; Claret, Marc; Marco Rius, Irene; Novials, Anna; Servitja, Joan-Marc
Biological sex significantly influences the prevalence, incidence, and severity of numerous human diseases, yet it remains an underappreciated variable in biomedical research. Although sexually dimorphic genes contribute to sex-specific traits and disease manifestations, their regulation under metabolic stress is poorly understood. To explore sex-specific metabolic adaptations, we analyzed responses to high-fat diet (HFD)-induced obesity in male and female mice, focusing on the regulation of sex-biased genes. Despite similar adiposity, HFD-fed males displayed more severe metabolic impairments than females, highlighting divergent metabolic outcomes. To investigate the basis for these sex-specific differences, we performed whole transcriptomic profiling of liver and white adipose tissue (WAT) at early (2 wk) and late (12 wk) stages of HFD exposure. Our analysis revealed marked sex-specific gene expression changes across multiple categories, particularly pronounced in male WAT after prolonged HFD feeding. Strikingly, genes exhibiting sexual dimorphism under normal conditions were preferentially modulated in both sexes, comprising up to 46% of all HFD-regulated genes. This led to a substantial loss of sex-biased gene expression in both liver and WAT after HFD exposure, correlating with metabolic dysfunction. Male-biased genes associated with cilia function and estrogen response were among the most affected, showing significant downregulation in male WAT under HFD. Our findings provide a novel perspective on how obesity disrupts sex-specific gene expression in key metabolic tissues, particularly targeting sex-biased genes. By revealing that a considerable proportion of sex-biased genes exhibit HFD-regulated modulation, our study highlights the critical role of these genes in maintaining metabolic health. NEW & NOTEWORTHY Biological sex shapes metabolic tissue physiology, largely through sex-biased gene regulation. Our comprehensive transcriptomic analysis reveals that sex-biased genes in liver and white adipose tissue undergo the most significant regulation during obesity-driven metabolic dysfunction, resulting in a loss of their bias. This disruption highlights a previously unrecognized role of sex-biased genes in maintaining metabolic health in both males and females.
Pegylated-liposomes increase the efficacy of Idelalisib in lymphoma B-cells
(Elsevier, 2024-05-25) Maroni, Giorgia; Tomassi, Elena; Valenti, Donatella; Fernàndez-Busquets, Xavier; Pucci, Laura; Levantini, Elena; Caddeo, Carla
New drugs and technologies are continuously developed to improve the efficacy and minimize the critical side effects of cancer treatments. The present investigation focuses on the development of a liposomal formulation for Idelalisib, a small-molecule kinase inhibitor approved for the treatment of lymphoid malignancies. Idelalisib is a potent and selective antitumor agent, but it is not indicated nor recommended for first-line treatment due to fatal and serious toxicities. Herein, liposomes are proposed as a delivery tool to improve the therapeutic profile of Idelalisib. Specifically, PEGylated liposomes were prepared, and their physicochemical and technological features were investigated. Light-scattering spectroscopy and cryo-transmission electron microscopy revealed nanosized unilamellar vesicles, which were proved to be stable in storage and in simulated biological fluids. The cytotoxicity of the liposome formulation was investigated in a human non-Hodgkin's lymphoma B cell line. Idelalisib was able to induce death of tumor cells if delivered by the nanocarrier system at increased efficacy. These findings suggest that combining Idelalisib and nanotechnologies may be a powerful strategy to increase the antitumor efficacy of the drug.
Multicomponent nasal spray delivered via penetration-enhancer containing vesicles (PEVs) for antioxidant and antibacterial protection
(Elsevier, 2025-11-01) Rached, Rita Abi; Shakya, Ashok K.; Manca, Maria Letizia; Aroffu, Matteo; García-Villén, Fátima; Touma, Joe A.; Fernàndez-Busquets, Xavier; Ivanov, Marija; Pedraz, José Luis; Louka, Nicolas; Maroun, Richard G.; Manconi, Maria
In this study, a nasal spray was formulated and tested co-loading grape seed extract, thymol, and camphor in penetration enhancer containing vesicles (PEVs) tailored to synergistically protect the nasal mucosa against oxidative stress and bacterial colonization. Based on their previously demonstrated effects, PEVs were prepared with propylene glycol (PG) and further enriched with carrageenan to promote muco-adhesion. The mean diameter of PG-PEVs was similar to 177 nm, and that of carrageenan PG-PEVs was similar to 194 nm. The polydispersity index ranged from 0.25 to 0.27, confirming the homogeneity of the dispersions. The zeta potential was significantly negative (similar to- 63 mV) and the entrapment efficiency was similar to 88 %, irrespective of vesicle composition. Sprayability studies disclosed that both PG-PEVs and carrageenan-PG-PEVs generated droplets larger than 10 mu m, thus appropriate for the deposition in the nasal cavity. Regional nasal deposition studies, carried out with a realistic nasal replica, highlighted that formulation droplets were deposited in the vestibule and turbinate areas of the nose. The ability of formulations to inhibit protein denaturation confirmed their anti-inflammatory effects. In vitro study with A549 and CuFi-1 cells, underlined that PG-PEVs and especially carrageenan PG-PEVs were nontoxic (viability similar to 140 %) and effectively counteracted cell apoptosis caused by hydrogen peroxide, restoring healthy conditions. The in vivo study in mice demonstrated that grape seed extract, thymol, and camphor-loaded carrageenan PG-PEVs were highly effective in counteracting the proliferation of Staphylococcus aureus.
Disclosure of cinnamic acid/4,9-diaminoacridine conjugates as multi-stage antiplasmodial hits
(Elsevier, 2024-04-15) Fonte, Mélanie ; Rôla, Catarina; Santana, Sofia; Avalos Padilla, Yunuen; Fernàndez-Busquets, Xavier; Prudêncio, Miguel ; Gomes, Paula A. C ; Teixeira, Catia Marlene
4,9-diaminoacridines with reported antiplasmodial activity were coupled to different trans-cinnamic acids, delivering a new series of conjugates inspired by the covalent bitherapy concept. The new compounds were more potent than primaquine against hepatic stages of Plasmodium berghei, although this was accompanied by cytotoxic effects on Huh-7 hepatocytes. Relevantly, the conjugates displayed nanomolar activities against blood stage P. falciparum parasites, with no evidence of hemolytic effects below 100 mu M. Moreover, the new compounds were at least 25-fold more potent than primaquine against P. falciparum gametocytes. Thus, the new antiplasmodial hits disclosed herein emerge as valuable templates for the development of multi-stage antiplasmodial drug candidates.
Liposomal sprays for nasal vaccination: a comparative study of cationic and anionic formulations involving stability upon nebulization, sprayability, and in vitro immune activation
(Elsevier, 2025-09-07) Aroffu, Matteo; Fulgheri, Federica; Rached, Rita Abi; Castangia, Ines; Corteggio, Annunziata; Italiani, Paola; D'Apice, Luciana; Sainz-Ramos, Myriam; García-Villén, Fátima; Fernàndez-Busquets, Xavier; Manconi, Maria; Pedraz, José Luis; Manca, Maria Letizia; Fadda, Anna Maria
Nasal immunization is a promising non-invasive route, enabling needle-free self-administration and activating immune cells in the mucosal tissue of the upper airways. This vaccination method is particularly appealing when paired with biocompatible and biodegradable nanocarriers like liposomes, which serve as an effective tool for the nasal delivery of antigenic molecules. In the present study, the model antigen ovalbumin was encapsulated in liposomes using an eco-friendly method. Negative and positive liposomes were formulated with Phospholipon®90 G alone (anionic liposomes) or combined with 1,2-dioleoyl-3-trimethylammonium-propane (cationic DOTAPliposomes). These liposomes were smaller than 130 nm and remained stable for up to 3 months. Their sprayability was assessed based on criteria established by the European Medicines Agency and the Food and Drug Administration for nasal products. Both formulations were easily sprayable, generating droplets larger than 5 μm, which are expected to deposit in the nose while avoiding the lungs. Furthermore, after nebulization, they retained their dimensions, structures, and high encapsulation efficiencies (>70 %). In a co-culture system of dendritic cells and B3Z OT-I hybridoma cells, it was shown that they enhanced antigen elivery and presentation,producing approximately 6–9 times more interleukin-2 compared to the ovalbumin solution. Lastly, when tested on macrophages, they did not induce any proinflammatory effect. However, due to their higher mucoadhesiveness (~88 % vs ~8 %) and better deposition in the posterior nasal cavity (~52 % vs ~43 %) compared to anionic liposomes, cationic DOTAP-liposomes appeared more suitable for nasal administration.
Preliminary evaluation of the in vitro and in vivo efficacy of a novel nanovesicle-doped nanoemulsion co-loading artemisinin and quercetin as a promising strategy to improve the oral malaria therapy
(Elsevier, 2025-05-01) Fulgheri, Federica; Ramírez Moreno, Miriam; Román Álamo, Lucía ; Gasco, Paolo; Manconi, Maria; Aroffu, Matteo; Rached, Rita Abi; Baroli, Biancamaria; Fernàndez-Busquets, Xavier; Manca, Maria Letizia
The minimal chemotactic cell
(American Association for the Advancement of Science, 2025-07-25) Battaglia, Giuseppe; Borges Fernandes, Barbara; Apriceno, Azzurra; Arango-Restrepo, Andrés; Almadhi, Safa; Ghosh, Subhadip; Forth, Joe; López-Alonso, Jorge Pedro; Ubarretxena-Belandia, Iban; Rubi, José Miguel; Ruiz-Perez, Lorena; Williams, Ian
The movement of cells and microorganisms in response to chemical gradients (chemotaxis) has played an essential role in the evolution of many biological processes. Cellular navigation works via the holistic assembly of numerous components into machineries that transform chemical energy into locomotion. Herein we present and discuss the minimal elements required for cell-like vesicles to be chemotactic. We show that lipid vesicles can propel themselves in response to chemical gradients when only a transmembrane protein and an encapsulated enzyme are incorporated into the vesicle structure. The herein proposed model serves as a proof of concept to show that even the simplest cell-like structure can experience chemotactic navigation.
Rapid amyloid-β clearance and cognitive recovery through multivalent modulation of blood–brain barrier transport
(Springer Nature, 2025-12-01) Gong, Qiyong; Tian, Xiaohe; Battaglia, Giuseppe; Chen, Junyang; Xiang, Pan; Duro-Castano, Aroa; Cai, Huawei; Guo, Bin; Liu, Xiqin; Yu, Yifan; Lui, Su; Luo, Kui; Ke, Bowen; Ruiz-Perez, Lorena
The blood‒brain barrier (BBB) is a highly selective permeability barrier that safeguards the central nervous system (CNS) from potentially harmful substances while regulating the transport of essential molecules. Its dysfunction is increasingly recognized as a pivotal factor in the pathogenesis of Alzheimer’s disease (AD), contributing to the accumulation of amyloid-β (Aβ) plaques. We present a novel therapeutic strategy that targets low-density lipoprotein receptor-related protein 1 (LRP1) on the BBB. Our design leverages the multivalent nature and precise size of LRP1-targeted polymersomes to modulate receptor-mediated transport, biasing LRP1 traf cking toward transcytosis and thereby upregulating its expression to promote ef cient Aβ removal. In AD model mice, this intervention signi cantly reduced brain Aβ levels by nearly 45% and increased plasma Aβ levels by 8-fold within 2 h, as measured by ELISA. Multiple imaging techniques con rmed the reduction in brain Aβ signals after treatment. Cognitive assessments revealed that treated AD mice exhibited signi cant improvements in spatial learning and memory, with performance levels comparable to those of wild-type mice. These cognitive bene ts persisted for up to 6 months post-treatment. This work pioneers a new paradigm in drug design, where function arises from the supramolecular nature of the nanomedicine, harnessing multivalency to elicit biological action at the membrane traf cking level. Our ndings also reaf rm the critical role of the BBB in AD pathogenesis and demonstrate that targeting the BBB can make therapeutic interventions signi cantly more effective. We establish a compelling case for BBB modulation and LRP1-mediated Aβ clearance as a transformative foundation for future AD therapies.
Thermoplasmonic Polymersome Membranes by In Situ Synthesis
(American Chemical Society, 2025-04-18) Barbieri, Valentino; González Colsa, Javier; Matias, Diana; Duro-Castano, Aroa; Thapa, Anshu; Ruiz-Perez, Lorena; Albella, Pablo; Volpe, Giorgio; Battaglia, Giuseppe
Thermoplasmonic nanoparticles, known for releasing heat upon illumination, find diverse applications in catalysis, optics, and biomedicine. Incorporating plasmonic metals within organic vesicle membranes can lead to the formation of nanoreactors capable of regulating temperature-sensitive microscopic processes. Yet, the controlled formation of stable hybrid vesicles displaying significant thermoplasmonic properties remains challenging. This work presents the in situ synthesis of highly efficient thermoplasmonic polymer vesicles, or hybrid polymersomes, by nucleating ∼2 nm gold nanoparticles within preformed polymersome membranes. This process preserves the vesicles’ morphology, stability, and overall functionality. Despite the small size of the embedded plasmonic nanoparticles, these hybrid polymersomes can efficiently convert laser light into a notable temperature increase on a larger scale through collective heating. We develop a theoretical framework that rationalizes the structure–property relations of hybrid polymersomes and accurately predicts their collective thermoplasmonic response. Finally, we demonstrate the biomedical potential of our polymersomes by employing their photothermal properties to induce the hyperthermal death of cancer cells in vitro, an effect amplified by their superior cellular uptake. We envision that these hybrid polymersomes will evolve into a versatile platform for precise control over nanoscale chemical and biological processes through plasmonic heating, unlocking numerous opportunities across various scientific and medical contexts.
Portable ion mobility spectrometry and partial least squared discriminant analysis for odour source discrimination in wastewater treatment plants
(Elsevier B.V., 2025-11-15) Villa, Veronica; Fernández Romero, Luis; Lotesoriere, Beatrice Julia; Alonso Valdesueiro, Javier; Gutiérrez Gálvez, Agustín; Capelli, Laura; Marco Colás, Santiago
Odour emissions from Wastewater Treatment Plants are a relevant issue concerning environmental and social impact, regulatory compliance, and plant management. Instrumental Odour Monitoring Systems are widely used for real-time odour emissions monitoring, but seasonal and plant variability limit their long-term reliability. Therefore, new sensing technologies and approaches are being studied to improve their reliability and the transferability of predictions between different plants and seasons. In this context, this work investigates the suitability of portable Ion Mobility Spectrometers to discriminate the main odour sources in Wastewater Treatment Plants. Two measurement campaigns were carried out in different seasons, considering different odour sources in two independent plants. Through a proper data analysis approach, based on the importance of ionic information, portable Ion Mobility Spectrometry proved effective in discriminating odour sources from the two main process lines: water and sludge treatment. In the first phase, conducted in the same plant and season, a balanced classification rate of 94 % (95 %CI: 82 %–100 %) was achieved. Subsequently, including seasonal and plant variability, a model trained on one plant was applied to the second. The direct transfer of the calibration achieved a balanced classification accuracy of 96 % (95 %CI: 86 %–100 %), confirming the relevance of the selected ions for odour assessment across different plants. These results suggest that portable Ion Mobility Spectrometry is a technology that deserves further attention for instrumental odour monitoring. The consistent classification rates obtained both within a single plant and when transferring the model demonstrate that Ion Mobility Spectrometry, combined with feature selection, can reliably identify ions specifically relevant for odour emission assessment.
The long 5′ UTR of nrdAB modulates mRNA levels, stability, and virulence in Pseudomonas aeruginosa PAO1
(Nature Publishing Group, 2025-12-01) Martínez Mateos, Ángela; Rubio Canalejas, Alba; Pedraz López, Lucas; Torrents Serra, Eduard
The class Ia ribonucleotide reductase (RNR), encoded by the nrdAB operon in Pseudomonas aeruginosa, has a long 5’ untranslated region (5’ UTR) whose regulatory role remains poorly understood. In this study, we investigated the functional significance of the nrdAB 5’ UTR using a comprehensive set of bioinformatic and experimental approaches, including gene expression profiling, relative protein levels, and in vivo infection assays in the Galleria mellonella animal model. Our results demonstrate that the 5’ UTR negatively regulates nrdA expression by reducing transcript levels, decreasing mRNA stability and limiting protein abundance. Truncation of this region led to increased expression, particularly during the stationary phase, suggesting that this region may contribute to modulating RNR activity during the stationary phase, when dNTP demand is reduced. In vivo, the Δ5’ UTR mutant exhibited reduced virulence compared to the wild-type strain, accompanied by elevated nrdA mRNA levels and a modest decrease in nrdJ expression. Although these changes may contribute to altered RNR regulation during infection, they are unlikely to fully explain the observed phenotype, indicating that additional factors may be involved. Although no specific regulatory elements within or acting upon the 5’ UTR were probed under the tested conditions, the possibility of such mechanisms cannot be excluded, and further studies will be needed to elucidate the underlying molecular mechanisms. Overall, our findings demonstrate that the 5’ UTR plays a regulatory role in modulating nrdAB operon expression and contributes to maintaining RNR system homeostasis in P. aeruginosa.
Myo-MOVES: a custom electrical stimulation system for functional studies of 3D bioengineered muscle
(The Royal Society of Chemistry, 2025-10-01) Ruiz Gutiérrez, Martín; Tejedera Villafranca, Ainoa; Pujol Pinto, Sergi; Ramón Azcón, Javier; Fernandez Costa, Juan M.
Electrical pulse stimulation (EPS) is used to replicate motor neuron activation in muscle tissues, enabling in vitro studies of muscle contraction. However, both custom-built and commercial existing EPS systems often suffer from significant limitations, including limited scalability, high cost, and lack of flexibility for experimental adaptation. This work presents the Myo-MOVES platform, a practical solution for stimulating 3D skeletal muscle tissues. The device has been designed as an intuitive EPS system consisting of two main components: a selector and a stimulator that adapts to commercial 24-well culture plates. The Myo-MOVES selector enables targeted stimulation of single or multiple wells, while the stimulator delivers electrical signals via graphite electrodes to the plate containing 3D skeletal muscle samples. The Myo-MOVES platform was technically validated and employed as a proof of concept to investigate sarcolemmal damage induced by muscle contraction in Duchenne muscular dystrophy (DMD) 3D skeletal muscle tissues. Taking advantage of the versatility of the device, we validated Myo-MOVES through the assessment of force generation in DMD engineered muscle tissues and the detection of contraction-induced sarcolemmal damage via Evans blue dye uptake and the release of creatine kinase (CK), the gold standard marker of muscle damage. These findings demonstrate the feasibility of using Myo-MOVES to induce and study functionally relevant disease phenotypes in DMD 3D skeletal muscle tissues. These results highlight the system's potential as a valuable tool for future applications in the field of 3D skeletal muscle tissue engineering, including drug screening and the study of DMD therapies and other muscular diseases.
Optimized alveolar epithelial cell model for chronic Pseudomonas aeruginosa and Staphylococcus aureus coinfections
(Elsevier, 2025-11-21) Admella, Joana; Alcàcer Almansa, Júlia; Julian, Esther; Torrents Serra, Eduard
Pseudomonas aeruginosa is a relevant pathogen in chronic respiratory infections, which are usually associated with biofilm formation, complicating in vitro modeling and effective treatment strategies. While P. aeruginosa can coexist with several microorganisms, its association with Staphylococcus aureus is widespread in cystic fibrosis (CF) patients and other bronchiectasis. Finding a reliable and straightforward in vitro model to study long-term P. aeruginosa infections is extremely hard due to the secretion of highly virulent toxins that compromise the model within less than 10 h. Several optimizations, including the use of bovine serum albumin (BSA) and extracellular matrix proteins, led to enhanced A549 cell viability up to 30 h post-infection. Within this time frame, we developed P. aeruginosa biofilms, explored host-pathogen interactions, and delved deeper into the relationship between P. aeruginosa and S. aureus. Additionally, ciprofloxacin treatment was evaluated, revealing changes and differences in antibiotic susceptibility and underlying significant differences between bacterial strains
CSRR chemical sensing in uncontrolled environments by PLS regression
(Institute of Electrical and Electronics Engineers (IEEE), 2025-09-18) Alonso Valdesueiro, Javier; Fernández Romero, Luis; Gutiérrez Gálvez, Agustín; Marco Colás, Santiago
Complementary Split Ring Resonators (CSRRs) have been widely researched as planar sensors, but their use in routine chemical analysis is limited due to dependence on high-end equipment, controlled conditions, and susceptibility to environmental and handling variations. This work introduces a novel approach combining a CSRR sensor with machine learning (ML) to enable reliable quantification of compounds. A low-cost benchtop CSRR system was tested for ethanol concentration prediction in water (10–96%), using 450 randomized measurements. PCA was applied for data exploration, and a PLS regression model with Leave-One-Group-Out cross-validation achieved a 3.7% RMSEP, six times better than univariate calibration (23.4%). The results show that ML can mitigate measurement uncertainties, making CSRR sensors viable for robust, low-cost concentration analysis under realistic laboratory conditions.
Ferrofluid-based bioink for 3d printed skeletal muscle tissues with enhanced force and magnetic response
(John Wiley & Sons, 2025-06-25) Fuentes Llanos, Judith; Guix Noguera, Maria; Cenev, Zoran M.; Bakenecker, Anna; Ruiz González, Noelia; Beaune, Grégory; Timonen, Jaakko V. I.; Sánchez Ordóñez, Samuel; Magdanz, Veronika
3D printing has emerged as a transformative technology in several manufacturing processes, being of particular interest in biomedical research for allowing the creation of 3D structures that mimic native tissues. The process of tissue 3D printing entails the construction of functional, 3D tissue structures. In this article, the integration of ferrofluid consisting of iron oxide nanoparticles into muscle cell-laden bioink is presented to obtain a 3D printed magnetically responsive muscle tissue, i.e., the ferromuscle. Using extrusion-based methods, the seamless integration of biocompatible ferrofluids are achieved to cell-laden hydrogels. The resulting ferromuscle tissue exhibits improved tissue differentiation demonstrated by the increased force output upon electrical stimulation compared to muscle tissue prepared without ferrofluid. Moreover, the magnetic component originating from the iron oxide nanoparticles allows magnetic guidance, as well as good cytocompatibility and biodegradability in cell culture. These findings offer a new versatile fabrication approach to integrate magnetic components into living constructs, with potential applications as bioactuators and for future integration in smart, functional muscle implants.
Antifouling surface-attached hydrogel nanocoatings redefined: green solvent-based, degradable, and high-performance protection against foulants
(John Wiley & Sons, 2025-05-28) Englert, Jenny; Palà Sánchez, Marc; Quandt, Jonas; Sieben, Hannah; Grottke, Oliver; Marx, Bernd; Lligadas, Gerard; Rodríguez Emmenegger, César
Antifouling coatings are vital to enhance the performance of medical devices, aiming to mitigate bodily reactions by shielding their surface. Despite significant advancements in antifouling coatings, like those based on zwitterionic monomers and hydroxyl-functionalized (meth)acrylamides, limitations like decreased antifouling properties after functionalization and complement system activation hinder their application in blood. Here, a novel class of ultrathin surface-attached hydrogels is presented, consisting of hydrophilic non-charged green solvent-based monomers and preventing protein adsorption while offering on-demand degradability. Unlike the best antifouling brushes, the coatings are easily applicable, unaffected by charges, and free of complement system-activating groups. The hydrogels are formed using copolymers of N,N-dimethyl lactamide acrylate (DMLA) and benzophenone acrylate (BPA). Moreover, 5,6-benzo-2-methylene-1,3-dioxepane (BMDO) is incorporated to introduce hydrolyzable ester. The coating of state-of-the-art devices is demonstrated with X-ray photoelectron spectroscopy (XPS), analyze surface energy components, and confirm their antifouling properties with surface plasmon resonance (SPR). The coatings are non-cytotoxic toward MRC-5 fibroblasts, exhibit repellency against methicillin-resistant Staphylococcus aureus (MRSA), and effectively prevent thrombus formation on devices in blood. This work establishes a versatile platform for next-generation coatings in medical and industrial applications, matching the antifouling efficiency of the most advanced solutions and offering regeneration of substrates by erasing the coating.
Advanced antibacterial strategies for combatting biomaterial-associated infections: a comprehensive review
(John Wiley & Sons, 2024-12-09) Kasapgil, Esra; Garay Sarmiento, Manuela; Rodríguez Emmenegger, César
Biomaterial-associated infections (BAIs) pose significant challenges in modern medical technologies, being a major postoperative complication and leading cause of implant failure. These infections significantly risk patient health, resulting in prolonged hospitalization, increased morbidity and mortality rates, and elevated treatment expenses. This comprehensive review examines the mechanisms driving bacterial adhesion and biofilm formation on biomaterial surfaces, offering an in-depth analysis of current antimicrobial strategies for preventing BAIs. We explore antimicrobial-eluting biomaterials, contact-killing surfaces, and antifouling coatings, emphasizing the application of antifouling polymer brushes on medical devices. Recent advancements in multifunctional antimicrobial biomaterials, which integrate multiple mechanisms for superior protection against BAIs, are also discussed. By evaluating the advantages and limitations of these strategies, this review aims to guide the design and development of highly efficient and biocompatible antimicrobial biomaterials. We highlight potential design routes that facilitate the transition from laboratory research to clinical applications. Additionally, we provide insights into the potential of synthetic biology as a novel approach to combat antimicrobial resistance. This review aspires to inspire future research and innovation, ultimately improving patient outcomes and advancing medical device technology.
Extubating of a patient undergoing mechanical ventilation: What is the right time? A retrospective study assisted by artificial intelligence techniques
(International University of Sarajevo, 2024-12-25) Arismendi Pererira, Carlos Julio; Sandoval Rodríguez, Camilo Leonardo; Giraldo Giraldo, Beatriz F. (Beatriz Fabiola); Solano, E. H.
In the presence of acute respiratory failure, mechanical ventilation emerges as a temporary alternative to maintain adequate gas exchange in the body such as that which occurs in natural respiration. This technique is widely used in intensive care units. Our objective was to carry out an analysis and interpretation of cardiorespiratory signals in patients assisted by mechanical ventilation, using non-linear analysis techniques of dynamic systems, data mining and machine learning techniques to establish indices that allow determining the appropriate moment of disconnection. in patients during the weaning process. We use three categories: Failure, success and reintubated. We introduced a new variant of Moving Window with Variance Analysis, with which good results are obtained. We have found that by using all the time series available in the database, we have obtained an accuracy of 96% when using simple symbolic dynamics to differentiate between successful weaning and reintubated cases. and 86% when comparing success and failure, which contrasts with the results observed in the state of the art.

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