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Nanogels represent an innovative platform for tunable drug release and targeted therapy in several biomedical applications, ranging from cancer to neurological disorders. The design of these nanocarriers is a pivotal topic investigated by the researchers over the years, with the aim to optimize the procedures and provide advanced nanomaterials. Chemical reactions, physical interactions and the developments of engineered devices are the three main areas explored to overcome the shortcomings of the traditional nanofabrication approaches. This review proposes a focus on the current techniques used in nanogel design, highlighting the upgrades in physico-chemical methodologies, microfluidics and 3D printing. Polymers and biomolecules can be combined to produce ad hoc nanonetworks according to the final curative aims, preserving the criteria of biocompatibility and biodegradability. Controlled polymerization, interfacial reactions, sol-gel transition, manipulation of the fluids at the nanoscale, lab-on-a-chip technology and 3D printing are the leading strategies to lean on in the next future and offer new solutions to the critical healthcare scenarios.

Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease worldwide, ranging from simple steatosis to nonalcoholic steatohepatitis, which may progress to cirrhosis, eventually leading to hepatocellular carcinoma (HCC). HCC ranks as the third highest cause of cancer-related death globally, requiring an early diagnosis of NAFLD as a potential risk factor. However, the molecular mechanisms underlying NAFLD are still under investigation. So far, many in vitro studies on NAFLD have been hampered by the limitations of 2D culture systems, in which cells rapidly lose tissue-specific functions. The present liver-on-a-chip approach aims at filling the gap between conventional in vitro models, often scarcely predictive of in vivo conditions, and animal models, potentially biased by their xenogeneic nature. HepG2 cells were cultured into a microfluidically perfused device under free fatty acid (FFA) supplementation, namely palmitic and oleic acid, for 24h and 48h. The device mimicked the endothelial-parenchymal interface of a liver sinusoid, allowing the diffusion of nutrients and removal of waste products similar to the hepatic microvasculature. Assessment of intracellular lipid accumulation, cell viability/cytotoxicity and oxidative stress due to the FFA overload, was performed by high-content analysis methodologies using fluorescence-based functional probes. The chip enables gradual and lower intracellular lipid accumulation, higher hepatic cell viability and minimal oxidative stress in microfluidic dynamic vs. 2D static cultures, thus mimicking the chronic condition of steatosis observed in vivo more closely. Overall, the liver-on-a-chip system provides a suitable culture microenvironment, representing a more reliable model compared to 2D cultures for investigating NAFLD pathogenesis. Hence, our system is amongst the first in vitro models of human NAFLD developed within a microfluidic device in a sinusoid-like fashion, endowing a more permissive tissue-like microenvironment for long-term culture of hepatic cells than conventional 2D static cultures.

The possibility of detecting and classifying living cells in a label-free and non-invasive manner holds significant theranostic potential. In this work, Hyperspectral Imaging (HSI) has been successfully applied to the analysis of macrophagic polarization, given its central role in several pathological settings, including the regulation of tumour microenvironment. Human monocyte derived macrophages have been investigated using hyperspectral reflectance confocal microscopy, and hyperspectral datasets have been analysed in terms of M1 vs. M2 polarization by Principal Components Analysis (PCA). Following PCA, Linear Discriminant Analysis has been implemented for semi-automatic classification of macrophagic polarization from HSI data. Our results confirm the possibility to perform single-cell-level in vitro classification of M1 vs. M2 macrophages in a non-invasive and label-free manner with a high accuracy (above 98% for cells deriving from the same donor), supporting the idea of applying the technique to the study of complex interacting cellular systems, such in the case of tumour-immunity in vitro models.

Alzheimer’s disease (AD) represents the major cause of dementia worldwide, involving different etiopathogenetic mechanisms, but with no definitive cure. The efficacy of new AD drugs is limited by the multifactorial disease nature that involves several targets, but also by the difficult penetration across the blood–brain barrier (BBB) for reaching the target area at therapeutic doses. Thus, the inability of many compounds to efficiently bypass the BBB makes it arduous to treat the disease. Furthermore, the lack of more representative BBB in vitro models than conventional 2D cultures, and xenogeneic animal models that recapitulate AD pathogenesis, makes it even more difficult to develop definitive cures. In this context, microfluidics has emerged as a promising tool, offering advanced strategies for simulating the BBB, investigating its crossing mechanisms, and developing nanocarriers that successfully pass the BBB for brain-targeting, with particular interest in pathological states. The advantages of microfluidic platforms for studying the BBB role in pathophysiological conditions might herald more tailored and effective approaches based on functionalized nanosystems for treating AD. Here, we provide an overview of the latest advances in microfluidic-based technologies both for the synthesis of nanodrug delivery systems, and for developing advanced models of the BBB-on-a-chip to simulate this biological barrier, facing open challenges in AD, and improving our understanding of the disease.

Invasive intraneural electrodes can control advanced neural-interfaced prostheses in human amputees. Nevertheless, in chronic implants, the progressive formation of a fibrotic capsule can gradually isolate the electrode surface from the surrounding tissue leading to loss of functionality. This is due to a nonspecific inflammatory response called foreign-body reaction (FBR). The commonly used poly(ethylene glycol) (PEG)-based low-fouling coatings of implantable devices can be easily encapsulated and are susceptible to oxidative damage in long-term in vivo applications. Recently, sulfobetaine-based zwitterionic hydrogels have emerged as an important class of robust ultra-low fouling biomaterials, holding great potential to mitigate FBR. The aim of this proof-of-principle in vitro work was to assess whether the organic zwitterionic—poly(sulfobetaine methacrylate) [poly(SBMA)]—hydrogel could be a suitable coating for Polyimide (PI)-based intraneural electrodes to reduce FBR. We first synthesized and analyzed the hydrogel through a mechanical characterization (i.e., Young’s modulus). Then, we demonstrated reduced adhesion and activation of fibrogenic and pro-inflammatory cells (i.e., human myofibroblasts and macrophages) on the hydrogel compared with PEG-coated and polystyrene surfaces using cell viability assays, confocal fluorescence microscopy and high-content analysis of oxidative stress production. Interestingly, we successfully coated PI surfaces with a thin film of the hydrogel through covalent bond and demonstrated its high hydrophilicity via water contact angle measurement. Importantly, we showed the long-term release of an anti-fibrotic drug (i.e., Everolimus) from the hydrogel. Because of the low stiffness, biocompatibility, high hydration and ultra-low fouling characteristics, our zwitterionic hydrogel could be envisioned as long-term diffusion-based delivery system for slow and controlled anti-inflammatory and anti-fibrotic drug release in vivo.

Active life monitoring via chemosensitive sensors could hold promise for enhancing athlete monitoring, training optimization, and performance in athletes. The present work investigates a resistive flex sensor (RFS) in the guise of a chemical sensor. Its carbon ‘texture’ has shown to be sensitive to CO2, O2, and RH changes; moreover, different bending conditions can modulate its sensitivity and selectivity for these gases and vapors. A three-step feasibility study is presented including: design and fabrication of the electronic read-out and control; calibration of the sensors to CO2, O2 and RH; and a morphological study of the material when interacting with the gas and vapor molecules. The 0.1 mm−1 curvature performs best among the tested configurations. It shows a linear response curve for each gas, the ranges of concentrations are adequate, and the sensitivity is good for all gases. The curvature can be modulated during data acquisition to tailor the sensitivity and selectivity for a specific gas. In particular, good results have been obtained with a curvature of 0.1 mm−1. For O2 in the range of 20–70%, the sensor has a sensitivity of 0.7 mV/%. For CO2 in the range of 4–80%, the sensitivity is 3.7 mV/%, and for RH the sensitivity is 33 mV/%. Additionally, a working principle, based on observation via scanning electron microscopy, has been proposed to explain the chemical sensing potential of this sensor. Bending seems to enlarge the cracks present in the RFS coverage; this change accounts for the altered selectivity depending on the sensor’s curvature. Further studies are needed to confirm result’s reliability and the correctness of the interpretation.

Purpose The present study evaluated the presence of stem cells in hamstring tendons from adult subjects of different ages. The aim was to isolate, characterize and expand these cells in vitro, and to evaluate whether cell activities are influenced by age. Methods Tendon stem cells (TSCs) were isolated through magnetic sorting from the hamstring tendons of six patients. TSC percentage, morphology and clonogenic potential were evaluated, as well as the expression of specific surface markers. TSC multi-potency was also investigated as a function of age, and quantitative polimerase chain reaction was used to evaluate gene expression of TSCs cultured in suitable differentiating media. Results The presence of easily harvestable stem cell population within adult human hamstring tendons was demonstrated. These cells exhibit features such as clonogenicity, multi-potency and mesenchymal stem cells markers expression. The age-related variations in human TSCs affect the number of isolated cells and their self-renewal potential, while multi-potency assays are not influenced by tendon ageing, even though cells from younger individuals expressed higher levels of osteogenic and adipogenic genes, while chondrogenic genes were highly expressed in cells from older individuals. Conclusions These results may open new opportunities to study TSCs to better understand tendon physiology, healing and pathological processes such as tendinopathy and degenerative age-related changes opening new frontiers in the management of tendinopathy and tendon ruptures.

Scaffolds populated with human cardiac progenitor cells (CPCs) represent a therapeutic opportunity for heart regeneration after myocardial infarction. In this work, square-grid scaffolds are prepared by melt-extrusion additive manufacturing from a polyurethane (PU), further subjected to plasma treatment for acrylic acid surface grafting/polymerization and finally grafted with laminin-1 (PU-LN1) or gelatin (PU-G) by carbodiimide chemistry. LN1 is a cardiac niche extracellular matrix component and plays a key role in heart formation during embryogenesis, while G is a low-cost cell-adhesion protein, here used as a control functionalizing molecule. X-ray photoelectron spectroscopy analysis shows nitrogen percentage increase after functionalization. O1s and C1s core-level spectra and static contact angle measurements show changes associated with successful functionalization. ELISA assay confirms LN1 surface grafting. PU-G and PU-LN1 scaffolds both improve CPC adhesion, but LN1 functionalization is superior in promoting proliferation, protection from apoptosis and expression of differentiation markers for cardiomyocytes, endothelial and smooth muscle cells. PU-LN1 and PU scaffolds are biodegraded into non-cytotoxic residues. Scaffolds subcutaneously implanted in mice evoke weak inflammation and integrate with the host tissue, evidencing a significant blood vessel density around the scaffolds. PU-LN1 scaffolds show their superiority in driving CPC behavior, evidencing their promising role in myocardial regenerative medicine.

Wearable sensors that combine high precision with conformability and skin adhesion are crucial for reliable and highly unobtrusive physiological monitoring. In this context, increasing efforts are directed toward next‐generation miniaturized self‐adhesive sensors employing different sensing technologies. Herein, for the first time a self‐adhesive sensor is developed for real‐time detection of physiological and biomechanical strain signals, by embedding a fiber Bragg grating (FBG) sensor into a soft, biomimetic, flexible matrix. This hydrogel‐based matrix, composed of gelatin methacrylate, xanthan gum, and glycerol, is engineered to balance fiber–matrix mechanical coupling and skin adhesion. The encapsulated FBG sensor exhibits stable optical response, reduced signal attenuation, and retains good sensitivity to both strain (0.07 nm mε−1) and temperature (0.01 nm °C−1). Preliminary on‐skin tests on a healthy volunteer demonstrate the ability to capture subtle physiological signals such as breathing and heartbeats, as well as limb motion. Notably, the self‐adhesive properties of the matrix enable firm skin contact without additional tapes, enhancing signal reliability, and reducing motion artifacts. This approach offers a robust, biocompatible, and scalable solution for wearable sensing, opening new opportunities in health monitoring, rehabilitation, and human–machine interfaces. A novel self‐adhesive hydrogel matrix is engineered to embed a fiber Bragg grating sensor for real‐time monitoring of physiological strain signals. The developed system conforms to the skin without external supports and, thanks to the fiber–matrix mechanical coupling, captures both subtle and large‐scale deformations. This platform offers a promising solution for unobtrusive, tape‐free wearable sensing in biomedical applications.

Electrospinning is a versatile, simple, and low cost process for the controlled production of fibers. In recent years, its application to the development of multifunctional materials has encountered increasing success. In this paper, we briefly overview the general aspects of electrospinning and then we focus on the implementation of inorganic nanoantimicrobials, e.g., nanosized antimicrobial agents in electrospun fibers. The most relevant characteristics sought in nanoantimicrobials supported on (or dispersed into) polymeric materials are concisely discussed as well. The interesting literature issued in the last decade in the field of antimicrobial electrospun nanomaterials is critically described. A classification of the most relevant studies as a function of the different approaches chosen for incorporating nanoantimicrobials in the final material is also provided.