Reactive oxygen species (ROS) are key regulators of neuronal physiology but contribute to oxidative damage when dysregulated, as in traumatic, ischemic, and inflammatory conditions. Biomaterials capable of replicating the mechanical characteristics of brain extracellular matrix while modulating oxidative stress are therefore of significant interest for neural tissue engineering and in vitro disease modeling. In this study, we functionalized dynamic hyaluronic acid (Ha) hydrogels with 3-aminomethyl phenylboronic acid (PBA) and crosslinked with poly(vinyl alcohol) (PVA) via reversible boronic ester bonds to develop ROS-responsive scaffolds. By varying the degree of PBA grafting, we observed linked feedback governed the mechano-redox properties of Ha-based dynamic hydrogels with the functionalization degree, enabling simultaneous tuning of stiffness, viscoelastic behavior, and antioxidant activity. The developed materials provide a platform for investigating cell responses to mechanically and chemically defined microenvironments and may be useful for modeling oxidative stress-related neuropathological conditions.

Innovative wound sealing and healing adhesives address a crucial medical need by facilitating faster and easier application while ensuring biocompatibility, biodegradability, and antibacterial efficacy. In this study, we developed a biologically inspired bonding hydrogel using carboxymethyl cellulose (CMC) as the gel matrix, integrated with green-synthesized silver nanoparticles (AgNPs), derived from an aqueous solution of Myrtus communis seed extract, and Aloe vera (AV), to enhance antimicrobial properties. The physical properties of this biodegradable hydrogel were characterized, and the antimicrobial response was evaluated against both Staphylococcus aureus and Escherichia coli. Additionally, the in vitro scratch assay using keratinocytes, fibroblasts, and endothelial cells, involved in the regeneration processes, demonstrated its wound healing potential. Our findings suggest that this green, natural-inspired engineered biodegradable hydrogel holds promise for advanced wound dressings.

Glioblastoma (GBM) remains highly refractory to treatment due to limited drug delivery efficiency, tumour heterogeneity, and therapeutic resistance. Here we show that direct-current electric fields (dcEF) enhance the uptake of functionalized gold nanoparticles (AuNPs) in U87-MG glioblastoma cells and reshape their intracellular responses. AuNPs carrying NFL-TBS.40–63 peptide, doxorubicin, or both displayed formulation-dependent uptake maxima at distinct field strengths, consistent with a contribution of surface charge EF-assisted cell association. Electron microscopy revealed broader intracellular distribution after field exposure, including more frequent nuclear-associated particles and reduced vacuolar sequestration. EF stimulation also amplified NP-dependent effects on cell behaviour, reducing migration velocity and shifting electrotactic directionality. In parallel, combined treatment remodelled mitochondrial architecture, lowered mitochondrial superoxide and altered mitochondrial membrane potential. These findings identify dcEF as a tunable physical cue for controlling nanoparticle uptake and intracellular state in a glioblastoma cell model.

Despite major advances in oncology, cancer remains one of the leading causes of mortality worldwide, underscoring the need for more effective and personalized therapeutic solutions. Advanced therapy medicinal products (ATMPs), including gene and cell-based therapies, have emerged as a promising frontier for immune cell engineering in oncology. However, current approaches still face several technical/safety issues, mainly associated with the delivery strategies used and their complex manufacturing processes. In this context, polymeric nanovectors (pNVs) have gained attention as a promising tool for developing efficient therapeutic delivery systems. The possibility of customizing pNVs’ composition/physicochemical properties, exploiting natural/synthetic polymers, enables more precise and controlled cargo delivery to immune cells, paving the way for the development of future ATMPs-oriented strategies for cancer immunotherapy. This review highlights the recent advancements in the application of pNVs for the editing of immune cells, focusing on innovative nanotechnology-based strategies to enhance the precision and efficacy of immunotherapy with a particular emphasis on their prospective role in next-generation ATMP development.

The tumour microenvironment of glioblastoma (GBM) as defined by mechanical heterogeneity, hypoxia, and hyaluronic acid (HA)-rich extracellular matrix (ECM), is a highly dynamic milieu which influences tumour progression and therapeutic resistance. Yet, how these cues converge to regulate mechanosensitive pathways in 3D remains poorly understood. Here, we engineered agar-based porous hydrogels functionalized with HA to independently tune stiffness and ECM composition, creating biomimetic 3D niches for GBM cells. The presence of HA coating showed to increase hydrogel stiffness, promote YAP/TAZ nuclear localisation, and elevate total LATS1/2 expression, consistent with Hippo pathway feedback regulation. Over time, however, hypoxic niches emerged that destabilised this feedback, enabling sustained YAP nuclear activity. HA also modulated OCT4 and Sox2 localisation and attenuated HIF-1α nuclear accumulation, indicating that HA also modulates the spatial distribution and nuclear accumulation of HIF-1α. Also, a cooperative regulation through the HA-CD44-CXCR4 axis, showed integrated biochemical and mechanical signals to reinforce YAP/HIF crosstalk. Together, these results reveal a dynamic interplay between ECM stiffness, HA signalling, and hypoxia in shaping YAP/HIF crosstalk and stem-like phenotypes in GBM and establish our hydrogel platform as a powerful tool to dissect and therapeutically exploit these interactions.

Cells respond dynamically to multiple cues in complex microenvironments, which influence their behaviour, function, and molecular pathways. Despite recent advances, understanding cell interactions in such environments remains challenging. While biophysical cues are recognized for interacting with mechano-transduction proteins like YAP/TAZ, their role under glioblastoma electrotaxis is unclear. Our study investigates the functional role of mechano-transduction proteins under a physiological electric field (EF) with different rigidities. EF exposure highlights rigidity-dependent responses involving focal adhesion, cytoskeletal remodelling and YAP/TAZ coactivators relocation, showing to induce a shuttling in a rigidity-dependent manner. Further inhibition of PI3K/Akt and pharmacologically disrupting YAP/TAZ-TEAD interaction was shown to induce marked cytoskeletal remodelling under EFs. Our work characterises the therapeutic opportunities and limitations of EFs and uncovers the intricate interplay of physical cues and molecular signalling pathways in glioblastoma, offering potential insights for the development of therapeutic interventions in the future.

Conventional treatments for glioblastoma (GBM) are hindered by systemic toxicity, limited blood-brain barrier penetration, and therapeutic resistance. To address these challenges, we developed dual-functionalized gold nanoparticles (AuNPs) conjugated with a biotinylated NFL-TBS.40-63 peptide and the chemotherapeutic agent doxorubicin. This platform integrates targeted delivery and therapeutic action to enhance efficacy while minimising off-target effects. Our findings reveal superior cellular uptake, dose- and time-dependent cytotoxicity, and apoptosis induction in GBM cells compared to mono-functionalized counterparts. Furthermore, pH-sensitive drug release profiles underscore the system's potential to exploit the tumour microenvironment's acidic conditions for precise drug delivery. Comprehensive characterisation confirmed the stability, biocompatibility, and functional efficacy of the dual-functionalized AuNPs. This study highlights the promise of these nanoconjugates as a multimodal approach to GBM therapy, paving the way for further translational research in nanomedicine.

Transparent wood composites are gaining interest for their superior properties over natural wood (PW), including superior transparency, thermal insulation, and stability. These composites are manufactured via infiltration of bio-based polymers into porous bleached wood (BW), offering a sustainable alternative to glass and plastic in applications such as energy-efficient windows and smartphone displays. In this study, the highest level of transparency in transparent wood (TW) substrates is achieved using biobased resins and an environmentally friendly bleaching process. Pristine balsa wood is bleached using non-toxic chemicals and subsequently infiltrated with two bio-based commercial resins, both sustainable and biocompatible. The performance of these bio-based composites is compared to conventional epoxy resin. Resin viscosity is shown to influence the physical, optical, thermal, and mechanical characteristics of the final composite due to its ability to penetrate and interact with the wood's porous structure. Notably, the plant-based soya resin-infiltrated TW achieves exceptional properties, as 91% transparency at 550 nm, alongside remarkable UV stability and hydrophobicity. Additionally, this bio-based composite shows a approximate to 50% reduction in thermal conductivity compared to standard glass (approximate to 1 W mK-1), highlighting its potential as a thermally insulative, energy-efficient material for building-integrated applications.

Inorganic nanoparticles (INPs) offer unique physicochemical properties that can be exploited as tools in biomedicine. We examine top-down and bottom-up fabrication methods, highlighting the impact of each route on NP size, shape, and biocompatibility. Green synthesis strategies are obtaining more attention due to their sustainability and low toxicity. We explain how synthesis conditions affect colloidal stability, crystallinity, and surface reactivity. Surface functionalization is vital for using INPs in gene delivery. It helps with targeted uptake and controlled release. This review describes how the choice of synthesis methods and surface functionalization influences the physicochemical properties of INPs by affecting their biodistribution, cellular uptake, and biological response. Although the potential is promising, challenges remain in scaling up production and assessing long-term safety. Future integration of responsive design strategies with clinical applications will be crucial for unlocking the full therapeutic potential of INPs.

High-precision biosensors for single or few molecules detection play a central role in numerous key fields, such as environmental monitoring and healthcare for early-stage disease diagnosis. In the last decade, laser biosensors have been investigated as proofs of concept, and several technologies have been proposed. Here we propose a demonstration of polymeric whispering gallery microlasers as biosensors for detecting proteins at low concentrations. Free space microlasers have the great advantage of working without any need for waveguiding for input excitation or output signal detection. The photonic microsensors can be easily patterned on microscope slides and operate in air and solution. We could detect down to 400 pg of protein without specific binding, and few tens of pg/mL with specific binding.

The resistance of glioblastomas (GBM) to standard therapies poses a clinical challenge with limited survival despite interventions. The tumor microenvironment (TME) orchestrates GBM progression, comprising stromal and immune cells and is characterized by extensive hypoxic regions. Hypoxia activates the hypoxia-inducible factor 1 alpha (HIF-1α) pathway, interacting with the Hippo pathway (YAP/TAZ) in crucial cellular processes. We discuss here the related signaling crosstalk between YAP/TAZ and regions of hypoxia in the TME with particular attention on the MST1/2 and LATS1/2-regulated YAP/TAZ activation, impacting cell proliferation, invasion, and stemness. Moreover, the hypoxia-YAP/TAZ axis influence on angiogenesis, stem cells, and metabolic regulators is defined. By reviewing extracellular matrix alterations activation of YAP/TAZ, modulation of signaling pathways we also discuss the significance of spatial constraints and epigenetic modifications contribution to GBM progression, with potential therapeutic targets in YAP/TAZ-mediated gene regulation. Comprehensive understanding of the hypoxia-Hippo pathway-TME interplay offers insights for novel therapeutic strategies, aiming to provide new directions for treatment.

TAR DNA-binding protein 43 (TDP-43) is a ubiquitously expressed DNA/RNA binding protein critical for regulating gene expression, including transcription, splicing, mRNA stability, and protein translation. Aggregation of pathological TDP-43 proteins in the cytoplasm of neurons and glial cells appears to be a common feature of amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases such as frontotemporal dementia (FTD), contributing to motor neuron degeneration and clinical symptoms. Downregulation of TDP-43 expression to prevent or reduce the formation of pathological aggregates is a potential therapeutic approach for treating TDP-43-related diseases. However, therapeutic strategies to reduce TDP-43 aggregation face significant challenges, as the downregulation of TDP-43 must balance the need to maintain its normal functions, which are essential for RNA metabolism and cellular homeostasis. In this study, we developed novel polymeric nanovectors for the delivery of TDP-43 siRNAs in neuronal cells. These nanovectors were designed to provide adequate TDP-43 silencing to achieve the desired functional reduction of TDP-43 levels, thereby optimizing its impact on cellular functions. Our results demonstrate that the polymeric nanovector formulations effectively reduced TDP-43 mRNA and protein levels to an extent comparable to those observed with traditional lipid-based systems. Concurrently, the polymeric nanovectors exhibited an enhanced capacity to reduce stress granules (SG) formation and facilitate TDP-43-containing SG disassembly, while preserving its essential cellular functions. This study provides the first evidence that polymeric nanovectors may be a valuable tool for developing therapeutic strategies to treat TDP-43 protein diseases, such as ALS and FTD, by directly silencing TDP-43 to reduce its aggregation.

Polymeric hydrogels are soft materials with a three-dimensional (3D) hydrophilic network capable of retaining and absorbing large amounts of water or biological fluids. Due to their customizable properties, these materials are extensively studied for developing matrices for 3D cell culture scaffolds, drug delivery systems, and tissue engineering. However, conventional hydrogels still exhibit many drawbacks; thus, significant efforts have been directed towards developing dynamic hydrogels that draw inspiration from organisms’ natural self-repair abilities after injury. The self-healing properties of these hydrogels are closely associated with their ability to form, break, and heal dynamic bonds in response to various stimuli. The primary objective of this review is to provide a comprehensive overview of dynamic hydrogels by examining the types of chemical bonds associated with them and the biopolymers utilized, and to elucidate the chemical nature of dynamic bonds that enable the modulation of hydrogels’ properties. While dynamic bonds ensure the self-healing behavior of hydrogels, they do not inherently confer adhesive properties. Therefore, we also highlight emerging approaches that enable dynamic hydrogels to acquire adhesive properties.

It is widely acknowledged that microglia actively regulate synaptic function in the brain. Remarkably, much of our understanding regarding the role of microglia in synaptic regulation is derived from studies in acute brain slices. However, it is still uncertain to what extent the preparation and maintenance of acute slices can influence microglial function and whether microglial changes may affect synaptic transmission. In this study, we examined the impact of acute slice resting time on hippocampal CA1 microglia, by assessing morphological and functional parameters at two distinct time intervals. We report that after 4 h from slicing microglia undergo morphological, functional, and transcriptional changes, including a decrease in the number of branches and in their movement speed. Furthermore, microglia acquire a reactive phenotype, characterized by increased amplitude of outward rectifying K+ currents, increased expression of the pro-inflammatory cytokine Tnfα and altered expression of the microglial receptors Cx3cr1 and P2y12r. We also examined time-dependent changes of excitatory synaptic transmission in CA1 pyramidal neurons from acute hippocampal slices, reporting time-dependent decrease in both amplitude and frequency of postsynaptic currents (sEPSCs), along with a decrease in spine density. Noticeably, sEPSCs amplitude decrease was absent in slices prepared from PLX5622 microglia-depleted mice, suggesting that this time-dependent effect on synaptic transmission is microglia-dependent. Our findings highlight possible causal relation between microglia phenotypic changes in the hours following slice preparation and concomitant synaptic changes, pointing to the mechanisms of acute synaptic modulation, whose understanding is crucial for unraveling microglia-neurons interplay in nature. Furthermore, they emphasize the potential issues associated with experimental time windows in ex vivo samples.

In recent years, Electrospinning (ES) has been revealed to be a straightforward and innovative approach to manufacture functionalized nanofiber-based membranes with high filtering performance against fine Particulate Matter (PM) and proper bioactive properties. These qualities are useful for tackling current issues from bacterial contamination on Personal Protective Equipment (PPE) surfaces to the reusability of both disposable single-use face masks and respirator filters. Despite the fact that the conventional ES process can be upscaled to promote a high-rate nanofiber production, the number of research works on the design of hybrid materials embedded in electrospun membranes for face mask application is still low and has mainly been carried out at the laboratory scale. In this work, a multi-needle ES was employed in a continuous processing for the manufacturing of both pristine Poly (Vinylidene Fluoride-co-Hexafluoropropylene) (PVDF-HFP) nanofibers and functionalized membrane ones embedded with TiO2 Nanoparticles (NPs) (PVDF-HFP@TiO2). The nanofibers were collected on Polyethylene Terephthalate (PET) nonwoven spunbond fabric and characterized by using Scanning Electron Microscopy and Energy Dispersive X-ray (SEM-EDX), Raman spectroscopy, and Atomic Force Microscopy (AFM) analysis. The photocatalytic study performed on the electrospun membranes proved that the PVDF-HFP@TiO2 nanofibers provide a significant antibacterial activity for both Staphylococcus aureus (~94%) and Pseudomonas aeruginosa (~85%), after only 5 min of exposure to a UV-A light source. In addition, the PVDF-HFP@TiO2 nanofibers exhibit high filtration efficiency against submicron particles (~99%) and a low pressure drop (~3 mbar), in accordance with the standard required for Filtering Face Piece masks (FFPs). Therefore, these results aim to provide a real perspective on producing electrospun polymer-based nanotextiles with self-sterilizing properties for the implementation of advanced face masks on a large scale.

Bioengineered hydrogels represent physiologically relevant platforms for cell behaviour studies in the tissue engineering and regenerative medicine fields, as well as in in vitro disease models. Hyaluronic acid (HA) is an ideal platform since it is a natural biocompatible polymer that is widely used to study cellular crosstalk, cell adhesion and cell proliferation, and is one of the major components of the extracellular matrix (ECM). We synthesised chemically modified HA with photo-crosslinkable methacrylated groups (HA-MA) in aqueous solutions and in strictly monitored pH and temperature conditions to obtain hydrogels with controlled bulk properties. The physical and chemical properties of the different HA-MA hydrogels were investigated via rheological studies, mechanical testing and scanning electron microscopy (SEM) imaging, which allowed us to determine the optimal biomechanical properties and develop a biocompatible scaffold. The morphological evolution processes and proliferation rates of glioblastoma cells (U251-MG) cultured on HA-MA surfaces were evaluated by comparing 2D structures with 3D structures, showing that the change in dimensionality impacted cell functions and interactions. The cell viability assays and evaluation of mitochondrial metabolism showed that the hydrogels did not interfere with cell survival. In addition, morphological studies provided evidence of cell–matrix interactions that promoted cell budding from the spheroids and the invasiveness in the surrounding environment.

Pediatric brain tumors represent the most common types of childhood cancer and novel diagnostic and therapeutic solutions are urgently needed. The gold standard treatment option for brain cancers in children, as in adults, is tumor resection followed by radio- and chemotherapy, but with discouraging therapeutic results. In particular, the last two treatments are often associated to significant neurotoxicity in the developing brain of a child, with resulting disabilities such as cognitive problems, neuroendocrine, and neurosensory dysfunctions/deficits. Nanoparticles have been increasingly and thoroughly investigated as they show great promises as diagnostic tools and vectors for gene/drug therapy for pediatric brain cancer due to their ability to cross the blood–brain barrier. In this review we will discuss the developments of nanoparticle-based strategies as novel precision nanomedicine tools for diagnosis and therapy in pediatric brain cancers, with a particular focus on targeting strategies to overcome the main physiological obstacles that are represented by blood–brain barrier.

Optical diffraction tomography (ODT) is a label-free technique for three dimensional imaging of micron-sized objects. Coherence and limited sampling of 3D Fourier space are often responsible for the appearance of artifacts. Here we present an ODT microscope that uses low temporal coherence light and spatial light modulators to retrieve reliable 3D maps of the refractive index. A common-path interferometer, based on a spatial light modulator, measures the complex fields transmitted by a sample. Measured fields, acquired while scanning the illumination direction using a digital micro-mirror device, are fed into a Rytov reconstruction algorithm to obtain refractive index maps whose accuracy is directly evaluated on microfabricated 3D test objects. Even for challenging shapes such as pyramids, bridges, and dumbbells, we obtain volumetric reconstructions that compare very well with electron microscopy images.

Cancer biology research is increasingly moving toward innovative in vitro 3D culture models, as conventional and current 2D cell cultures fail to resemble in vivo cancer biology. In the current study, porous 3D scaffolds, designed with two different porosities along with 2D tissue culture polystyrene (TCP) plates were used with a model breast cancer human cell line. The 3D engineered system was evaluated for the optimal seeding method (dynamic versus static), adhesion, and proliferation rate of MDA-MB-231 breast cancer cells. The expression profiles of proliferation-, stemness-, and dormancy-associated cancer markers, namely, ki67, lamin A/C, SOX2, Oct3/4, stanniocalcin 1 (STC1), and stanniocalcin 2 (STC2), were evaluated in the 3D cultured cells and compared to the respective profiles of the cells cultured in the conventional 2D TCP. Our data suggested that static seeding was the optimal seeding method with porosity-dependent efficiency. Moreover, cells cultured in 3D scaffolds displayed a more dormant phenotype in comparison to 2D, which was manifested by the lower proliferation rate, reduced ki67 expression, increased lamin A/C expression, and overexpression of STCs. The possible relationship between the cell affinity to different extracellular matrix (ECM) proteins and the RANK expression levels was also addressed after deriving collagen type I (COL-I) and fibronectin (FN) MDA-MB-231 filial cell lines with enhanced capacity to attach to the respective ECM proteins. The new derivatives exhibited a more mesenchymal like phenotype and higher RANK levels in relation to the parental cells, suggesting a relationship between ECM cell affinity and RANK expression. Therefore, the present 3D cell culture model shows that cancer cells on printed scaffolds can work as better representatives in cancer biology and drug screening related studies.