The development of physiologically relevant in vitro models of the blood-brain barrier (BBB) is critical for reliable assessment of drug permeability and neurotherapeutic transport. Current platforms often fail to reproduce the three-dimensional geometry and mechanical compliance of cerebral microvessels, limiting their translational relevance. Here, we report the fabrication of soft, flexible and self-supporting tubular membranes via polyelectrolyte complexation of alginate and ε-poly-L-lysine, yielding cylindrical constructs that closely mimic the architecture and flexibility of small brain vessels. The resulting biomaterials support robust endothelial cell adhesion and the formation of a functional barrier, exhibiting controlled permeability consistent with selective molecular transport. Importantly, the compliant tubular constructs enable the application of external mechanical compression, allowing controlled modulation of vessel deformation and barrier integrity in a manner relevant to pathological conditions such as tumor-induced vascular compression. By integrating physiologically relevant cylindrical geometry with a mechanically compliant and deformable microenvironment, this platform provides a tunable and reproducible basis for endothelial barrier formation and mechanical perturbation, enabling the development of a more biomimetic in vitro BBB model.

This review surveys recent advances in active nanomaterials for neuromodulation, with a focus on remotely controlled nanotransducers for precise manipulation of brain functions. We discuss how stimuli-responsive nanomaterials enable spatiotemporally precise brain interfacing through remotely controlled actuation; furthermore, we examine energy transduction mechanisms underlying nanoparticle-assisted neuromodulation, and highlight nanosensors that monitor bioelectrical and neurochemical activity with high spatial and temporal resolution. Beyond neurons, we consider strategies targeting glial function, as well as emerging approaches to cross or bypass the blood-brain barrier. Finally, we outline key challenges for clinical translation, including long-term safety, biointegration, and regulatory considerations. Together, these developments position smart nanotechnologies as a foundation for next-generation precision brain interfacing, with the potential to design patient-tailored therapeutic solutions across neurological and psychiatric disorders.

The spaceflight environment exposes biological systems to microgravity and cosmic radiation, which are factors known to induce oxidative stress and neurodegenerative processes. As the central nervous system is highly susceptible to disruptions in redox homeostasis, the development of effective strategies to safeguard astronaut health and cognitive function during extended space missions has become imperative. In this study, we investigate cerium oxide nanoparticles (nanoceria, NC) as an antioxidant agent for human neuron-like cells aboard the International Space Station. Nanoceria demonstrated excellent biocompatibility, strong antioxidant properties, and the ability to stimulate neurite extension under both Earth gravity and simulated microgravity. Following the return of the samples to Earth, transcriptomic analyses revealed that nanoceria effectively counteracted the detrimental transcriptional alterations triggered by spaceflight stressors, thereby maintaining neuronal homeostasis. Importantly, the expression of genes involved in antioxidant defense, mitochondrial activity, and dopamine metabolism remained stable in nanoceria-treated neurons, in contrast to the dysregulation observed in untreated controls. These findings position cerium oxide nanoparticles as promising antioxidant neuroprotectants for long-duration space missions and related neurodegenerative conditions.

Magnetoelectric (ME) nanostructures, responsive to low-intensity magnetic fields, have emerged as promising multifunctional platforms for diverse biomedical applications, including targeted drug delivery, neural stimulation, cancer therapy, bioimaging, and nanocatalysis. Their magnetic sensitivity enables precise spatial and temporal control over biomolecule delivery, offering advantages over traditional chemical, biological, or physical interventions. ME coupling further supports non-invasive electrical stimulation, enabling on-demand drug release, catalytic activity, and regulation of cellular behaviors such as stem cell differentiation, neural activation, and apoptosis. While prior reviews have focused on ME nanomaterials in 2D and 3D biomedical contexts, a comprehensive examination of their design, structure, composition, characterization, and modeling remains lacking. This review fills that gap by presenting a detailed overview of recent advances in ME nanostructures – highlighting fabrication techniques, physical properties, and performance modeling across diverse morphologies, anisotropies, and compositions. Current challenges and future directions for ME nanomaterials in nanomedicine are also discussed. The review underscores the high potential of ME-based nanostructures to integrate electrical stimulation with bioimaging, biosensing, and therapeutic functions, thereby paving the way for the next-generation of multifunctional tools in nanomedicine.

Polydopamine nanotubes (PDA-NTs) represent a recently developed and scarcely explored class of nanostructures with exceptional multifunctionality. Synthesized through a ZnO-templated Stöber-like process followed by template removal, PDA-NTs exhibit a combination of piezoelectric, photothermal, and antioxidant properties, a collection of features never observed together in a single organic nanoparticle. This work provides the demonstration of electromechanical conversion in polydopamine structures, with PDA-NTs showing a robust piezoelectric coefficient (d33 = 15.0 ± 0.7 pC/N), a property completely absent in spherical PDA nanoparticles. PDA-NTs are efficiently internalized by cells and display excellent biocompatibility; upon remote stimulation, they can modulate intracellular calcium levels via ultrasound-driven activation or near-infrared (NIR) photothermal heating. In addition, their strong antioxidant capacity mitigates oxidative stress, while controlled dopamine release (both passive and ultrasound-triggered) induces functional effects in human neural stem cells. This unique combination of mechanical and NIR responsiveness, antioxidant activity, and neuromodulatory drug release within a single organic nanostructure marks a significant breakthrough, allowing PDA-NTs to emerge as a unique class of "smart" multifunctional nanomaterials, enabling remote cellular control and offering exciting opportunities for regenerative medicine, neurostimulation, and advanced bioelectronics.

Laser-induced graphene (LIG) derived from renewable precursors has attracted significant attention in functional devices applications. It combines a facile preparation through transformative laser processing, a tunable morphology, a good electrical conductivity, and high surface area with potential degradability and environmental sustainability compared to LIG from synthetic precursors. In this work, we investigate a variety of biowastes as precursors of conductive LIG, including almond shells, almond skins, hazelnut shells, mandarin peels, coffee grounds, lignin, to fabricate LIG through UV-laser scribing. These abundant agricultural and food-industry biowastes are first ground into a powder. Then, powders are used in the shape of pellets and as fillers in chitosan-based composites to investigate the LIG formation, by optimizing UV laser scribing parameters. Laser scribing of raw biowaste materials rich in lignin and phenolic compounds results in efficient graphitization and low sheet resistance (<60 Ω sq−1) of the resulting LIG. Scanning electron microscopy (SEM) and Raman spectroscopy confirm the formation of LIG networks with a porous three-dimensional structure. Microscopic morphology, Raman spectroscopy, and sheet resistance of the resulting LIG are analyzed in detail and correlated with the lignin content of each bio-waste. The results highlight the influence of precursor chemical composition and structure on the LIG quality. These findings open new possibilities for the development of sustainable materials for eco-friendly electronics in a circular economy approach, where low-value waste is upcycled, and an overall mitigation of environmental impact is expected. Various biowaste serve as a sustainable and accessible carbon source. Laser processing of biomass produces porous graphene LIG structures with high electrical conductivity and large surface area. The circular nature of the process, which transforms waste into high value-added materials, might help in reducing the environmental footprint, minimize waste, and develop sustainable technologies for various sensor applications.

The obtainment of innovative models recalling complex tumour architectures and activitiesin vitrois a challenging drive in the understanding of pathology molecular bases, yet it is a crucial path to the identification of targets for advanced oncotherapy. Cell environment recapitulation by 3D scaffolding and gravitational unloading of cell cultures represent powerful means in tumour biomimicry processes, but their simultaneous adoption has consistently been explored only in the latest decade. Here, an unprecedented bioengineering approach capitalizing on spaceflight biology practice is proposed for modelling of glioblastoma multiforme, a highly aggressive neoplasm that affects the central nervous system and has poorly effective pharmacological and radiological countermeasures. Tumour modelling was pursued by the original implementation of two-photon polymerization in fast prototyping of 3D scaffolds on flexible substrates for U87-MG glioma cell culture, and by the exposure of cell-laden scaffolds to simulated microgravity (s-μg). Realistic spaceflight conditions were applied to collect preliminary information suitable for testing of U87-MG cell-laden scaffold in low Earth orbit. Responses of glioma cells anchored to 3D scaffolds were investigated by microscopy, quantitative reverse transcription-polymerase chain reaction and proteomic analyses, revealing synergic regulatory effects of cell scaffolding and s-μg on markers of tumour cell growth, metabolism and invasiveness.

Piezoelectric nanomaterials are highly promising for remote cell stimulation due to their ability to convert mechanical energy, such as ultrasound (US), into electrical cues that modulate cellular behavior. In the context of cancer treatment, piezoelectric stimulation has recently shown antiproliferative, chemosensitizing, antiangiogenic, and immunomodulatory effects. Despite growing interest in organic alternatives, no biodegradable or bioabsorbable nanoparticles with clinically approved components have yet been developed with piezoelectric properties for cell stimulation, limiting the translational potential of this approach. Here, chitosan nanoparticles (ChNPs) have been engineered to exhibit intrinsic piezoelectric properties, enabling US‐mediated activation. Their structural, mechanical, and piezoelectric characteristics have been investigated using advanced physicochemical and electromechanical techniques. Biological evaluation of US‐driven ChNPs‐assisted piezostimulation has been tested on patient‐derived glioblastoma cells. When stimulated with US, ChNPs demonstrate not only excellent antiproliferative activity, but also proapoptotic efficacy, even in the absence of any chemotherapeutic agent. This drug‐free anticancer stimulation approach is attributed to reactive oxygen species generation triggered by the ChNP piezocatalytic properties. The antitumor activity is further validated in more complex ex ovo models. The combination of piezoelectric responsiveness, biodegradability, and preclinical feasibility highlights the potential of ChNPs as a safe, noninvasive therapeutic platform for next‐generation cancer treatments.

The term protein corona (PC) indicates proteins adsorbed onto the surface of nanostructures exposed to biological media such as blood or serum. The analysis of the composition, evolution, and effect of the PC complexed with nanomaterials gained attention in recent years due to the importance of these parameters in determining the biological fate of nanostructures. In particular, the PC represents the first component of a nanomaterial interfacing with biological structures, dictating parameters such as nanoparticle internalization, immune response, bioavailability, and even toxicity. Polydopamine nanoparticles (PDNPs), obtained through the polymerization of dopamine, are "smart" materials characterized by high biocompatibility, high antioxidant capacities, high tunability and surface reactivity, biodegradability, and the ability to act as photothermal conversion agents when irradiated with a near-infrared (NIR) light source. Despite many interesting applications of PDNPs are currently described in the scientific literature, there is still no comprehensive analysis of the phenomenon of PC formation consequent to the exposure of these nanomaterials to biological media. Moreover, to date, the investigation of the effects of light irradiation of photothermally active nanomaterials on the composition and evolution of the associated PC has been extremely limited. With this work, we aim to provide for the first time an analysis of the phenomenon of PC formation associated with PDNPs, before and after NIR light stimulation. We characterized the PC formed following exposure to human plasma and analyzed the effects of several parameters on the overall PC composition and quantity, such as the PDNP size, presence of a surface functionalization, exposure time, and irradiation with an NIR laser, demonstrating that these parameters play a pivotal role in the resulting PC composition. Eventually, we showed that PDNPs exposed to human plasma have significantly different properties with respect to bare PDNPs, showing higher internalization rates in human glioblastoma cells, a higher light absorption value, and enhanced photothermal conversion abilities.

The precise control of cell activity is crucial for understanding and potentially treating many disorders. Focusing on neurons and myotubes, recent advancements in nanotechnology have introduced photoresponsive nanoparticles as an alternative tool for modulating cell function with high spatial and temporal resolution. This approach offers a noninvasive alternative to traditional stimulation techniques, reducing potential tissue damage and improving the specificity of cell activation. Here, we introduce an approach envisioning fully organic polydopamine nanoparticles (PDNPs) to remotely modulate the activity of differentiated SH-SY5Y cells and differentiated C2C12 cells, via near-infrared (NIR) laser stimulation. Confocal microscopy imaging revealed the possibility of thermally activating individual neuron-like cells, eliciting a significant cellular response characterized by the generation of calcium transients and the subsequent release of the neurotransmitter acetylcholine. Similarly, we demonstrated the possibility of precisely triggering the muscle contraction of single myotubes. Additionally, we investigated the antioxidant properties of PDNPs, demonstrating their capacity to prevent an increase in oxidative stress levels related to an increase in intracellular temperature. Moreover, proteomic analysis revealed that a PDNP treatment could positively affect neuronal plasticity and nervous system maturation, besides promoting muscle growth and preserving its functional integrity, underscoring its potential to support both neural and musculoskeletal development. Eventually, the effect of the NIR laser irradiation in the presence of PDNPs in neuron-like cells was successfully evaluated ex vivo on brains of Drosophila melanogaster, genetically modified to express the fluorescent calcium indicator jGCaMP7c.

Laser‐induced graphene (LIG) is a 3D conductive carbon material typically produced from petroleum‐based polymers via a one‐step laser‐induced pyrolysis in air, without chemicals. Recently, the focus has shifted toward bioderived and biodegradable precursors as potentially sustainable alternatives. Here, this approach is advanced by repurposing almond shells–an abundant raw agricultural by‐product–blended with chitosan to form almond shell composites (ASC). ASC exhibits over 60% weight loss after 90 days under soil burial. It serves both as a bioderived substrate for electronics and as a precursor for LIG. ASC is converted into LIG through UV and IR laser scribing, and its structure is thoroughly investigated. ASC‐LIG achieves sheet resistance values as low as 114.3 ± 0.9 Ω sq −1 (UV), and an electrochemical impedance modulus |Z| ≈ 1 kΩ at 10⁶ Hz (1 cm 2 electrodes). It is implemented in proof‐of‐concept electronic devices, including circuits with resistive and capacitive elements, and humidity sensors, which show sensitivities of 2.25 ± 0.13 pf%RH −1 (30%–55% RH) and 19.8 ± 2.69 pf%RH −1 (55%–80% RH). These results highlight the potential of upcycling agricultural by‐products into functional materials, demonstrating the suitability of ASC‐LIG for transient electronic applications such as environmental sensors.

The growing global demand for sustainability is driving the scientific community to explore alternative manufacturing approaches, particularly in the electronics field, where resource scarcity and e-waste pose significant environmental challenges. One promising solution is the direct patterning of laser-induced graphene (LIG) conductive tracks onto bioderived substrates. In this study, several wood panels are successfully fabricated with different resin formulations from Jatropha curcas L. seeds to reduce the urea-formaldehyde content, and the feasibility of LIG-based electronics on these panels is assessed. The panels' physical and mechanical properties are evaluated, including thickness swelling and internal bond strength, and conductive LIG is successfully scribed on all samples. Proofs of concept include a four-LED circuit and humidity sensors, with the best sensor achieving approximate to 0.2031 pF %RH-1 sensitivity and approximate to 5% hysteresis error. These results demonstrate the feasibility of embedding functional circuits into bioderived substrates and pave the way for sustainable smart furniture by integrating bioderived materials with advanced manufacturing techniques.

Microglia, the main immune cells in the central nervous system (CNS), maintain physiological homeostasis and react to pathological changes. Besides their neuroprotective function, they play a crucial role in brain tumor microenvironments such as glioblastoma (GBM), by composing up 40% of the tumor mass. Glioma-associated microglia exhibit a dynamic activation state characterized mainly by an immunosuppressive (M2-like) response, with a lesser contribution of pro-inflammatory (M1-like) response. Modulating microglial into M1-like phenotype offers antitumor response and a promising immunotherapy strategy against GBM. Nanoparticles can induce microglial polarization, also modulating pro-inflammatory responses for tumor suppression. Magnetically responsive nanoparticles are promising nanotransducers due to their remote-control capabilities via external magnetic fields, enabling precise therapeutic interventions. This study proposes a novel strategy that exploits lipid-based magnetic nanovectors (LMNVs) composed of a lipid matrix doped with iron oxide nanoparticles to induce M1-like microglial response through magneto-thermal conversion. Results demonstrated that LMNVs exhibit excellent biocompatibility and efficient internalization within human microglia (HMC3 cells). Upon alternating magnetic field (AMF) stimulation, LMNVs triggered a sustained increase in intracellular Ca2+ levels, leading to the polarization of microglia toward a pro-inflammatory M1-like phenotype. This activation was confirmed by the upregulation of key inflammatory markers (CD40, CD86) and cytokine release (IL-6, IL-8, and TNF-α), mirroring the effects of IFN-γ stimulation. These findings were further corroborated by comparative transcriptomic analysis. Notably, conditioned medium from LMNVs + AMF-stimulated microglia significantly impaired the viability and proliferation of both immortalized and patient-derived GBM cells, demonstrating a potent antitumor response. The tumor cell death was associated with immunogenic cell death (ICD), as indicated by the translocation of the damage-associated molecular patterns, in particular high mobility group box 1 (HMGB1) and calreticulin (CRT). Overall, these results highlight the potential of LMNVs as a remotely activatable nanoplatform capable of reprogramming microglia and to promote antitumor immunity in GBM.

Exposure to microgravity and cosmic radiation during spaceflight is responsible for oxidative stress onset, contributing to neuronal dysfunction and degeneration. The central nervous system is particularly vulnerable to redox imbalance and requires effective countermeasures to ensure astronaut health and performance on long-duration missions. In this study, the neuroprotective properties of polydopamine nanoparticles (PDNPs), known for their antioxidant activity, are investigated on neuron-like cells exposed to different gravitational and radiation regimes. Culture conditions included administration of PDNPs and permanence aboard the International Space Station (ISS) or on a random positioning machine. Transcriptomic analyses are conducted to assess gene expression alterations associated with oxidative stress, nuclear and mitochondrial integrity, and dopamine metabolism. In-flight, PDNP treatment mitigates the transcriptional changes induced by space stressors, preserving neuronal homeostasis. Notably, expression of key antioxidant defense genes, mitochondrial function markers and dopamine metabolism genes is stabilized in PDNP-treated neurons. This study provides preliminary evidence on the efficacy of PDNPs in protecting neuronal cells from the combined stressors associated with spaceflight: these findings suggest PDNPs as a promising countermeasure for space-induced neurodegeneration and support their potential translational application in the treatment of oxidative stress-related neurodegenerative pathologies on Earth.

Mitochondrial disorders are hereditary diseases caused by mutations in nuclear or mitochondrial DNA that impair organelle function. Key features include excessive production of reactive oxygen species (ROS), mitochondrial abnormalities, and metabolic dysfunctions. Systemically, these defects can lead to severe conditions affecting the central nervous system, muscles, heart, and gastrointestinal tract. Organic antioxidants such as idebenone and resveratrol have been explored as potential treatments; in the framework of nanotechnological antioxidants, polydopamine nanoparticles (PDNPs), derived from the oxidative self-polymerization of dopamine, are highly biocompatible, biodegradable, easy to functionalize, and possess potent ROS-scavenging and photothermal properties. In this study, we investigated PDNPs as a nonpharmaceutical therapy for mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) and progressive external ophthalmoplegia (PEO). PDNPs were evaluated in fibroblasts from healthy donors and patients with MELAS and PEO. Molecular characterization was performed via proteomic analysis, followed by assessment of PDNP biocompatibility, internalization, intracellular localization, and antioxidant effects. Their protective activity was also confirmed in vivo, exploiting zebrafish embryos. Our findings demonstrate that PDNPs effectively protect cells from ROS-induced damage, oxidative stress, apoptosis, and mitochondrial dysfunction. Additionally, PDNPs were able to preserve zebrafish embryos against pro-oxidative stimuli. Overall, this work highlights the potential of polydopamine nanostructures as promising therapeutic tools for mitigating the molecular hallmarks of mitochondrial disorders and supporting future clinical applications.

The development of an effective therapy against glioblastoma (GBM) remains a significant and unmet clinical need. To address this challenge, creating predictive, physiologically relevant screening models is essential for accelerating the identification of promising drug candidates. In this paper, we present a novel impedance-based device where two-photon polymerization-fabricated scaffolds embedding electrodes are colonized by GBM cells, effectively replicating the three-dimensional environment of the microscopic tumor foci that persist following tumor resection and cause recurrence. The results demonstrated that the proposed GBM-on-chip model enables high-throughput, multiplexed, and real-time monitoring of the development of tumor spheroids and their responses to therapeutic agents. Validation studies demonstrated the platform ability to detect subtle cytotoxic effects undetectable by traditional immunofluorescence methods, with optical transparency enabling complementary imaging analysis. This system represents a versatile framework for assessing drug efficacy in complex, physiologically relevant 3D tumor models, paving the way for innovations in cancer pharmacology.

Glioblastoma multiforme (GBM) is the most aggressive brain cancer, characterized by a rapid and drug-resistant progression. GBM "builds" around its primary core a genetically heterogeneous tumor-microenvironment (TME), recruiting surrounding healthy brain cells by releasing various intercellular signals. Glioma-associated microglia (GAM) represent the largest population of collaborating cells, which, in the TME, usually exhibit the anti-inflammatory M2 phenotype, thus promoting an immunosuppressing environment that helps tumor growth. Conversely, "classically activated" M1 microglia could provide proinflammatory and antitumorigenic activity, expected to exert a beneficial effect in defeating glioblastoma. In this work, an immunotherapy approach based on proinflammatory modulation of the GAM phenotype is proposed, through a controlled and localized electrical stimulation. The developed strategy relies on the wireless ultrasonic excitation of polymeric piezoelectric nanoparticles coated with GBM cell membrane extracts, to exploit homotypic targeting in antiglioma applications. Such camouflaged nanotransducers locally generate electrical cues on GAM membranes, activating their M1 phenotype and ultimately triggering a promising anticancer activity. Collected findings open new perspectives in the modulation of immune cell activities through "smart" nanomaterials and, more specifically, provide an innovative auspicious tool in glioma immunotherapy.

Nano-sized piezoelectric materials allow for precise interaction with living systems to local deliver electrical cues. Recent innovations enhance their potential in tissue engineering and regenerative medicine.

The regenerative capacity of the central nervous system (CNS) is limited. Understanding and enhancing the mechanisms that induce neural differentiation of neural stem cells (NSCs) is crucial for advancing regenerative medicine; one significant challenge in this effort is the remote delivery of pro-differentiation cues. In this framework, a nanotechnology-based solution able to remotely trigger the differentiation of human NSCs (hNSCs) into neurons is proposed. The approach involves organic piezoelectric nanotransducers, which can be remotely activated by low-intensity ultrasound (US) for local and noninvasive electrical stimulation. Highly biocompatible piezoelectric polymeric nanoparticles, when activated by US, demonstrate the ability to induce calcium influx, exit from the cell cycle, and neuronal differentiation in hNSCs, as evidenced by calcium imaging experiments and the expression analysis of the NeuN post-mitotic neural marker; additionally, an increased outgrowth of the developing axons is observed. Gene expression analysis moreover suggests that the neural differentiation mechanism induced by piezoelectric stimulation acts by upregulating the calcium signaling-sensitive NeuroD1 neural inducer and the Lamb1 marker, independently of the c-Jun/c-Fos pathway. Considering the high biocompatibility and the good piezoelectricity of the polymeric nanotransducers used in this work, it is believed that this "wireless" stimulation approach holds high potential in CNS regenerative medicine.