Institute of Fundamental Technological Research

Detection of lysozyme levels in ocular fluids is considered crucial for diagnosing and monitoring various health and eye conditions, including dry-eye syndrome. Hydrogel-based nanocomposites have been demonstrated to be one of the most promising platforms for fast and accurate sensing of different biomolecules. In this work, hydrogel, electrospun nanofibers, and plasmonic nanoparticles are combined to fabricate a sensitive and easy-to-use biosensor for lysozyme. Poly(L-lactide-co-caprolactone) (PLCL) nanofibers were covered with silver nanoplates (AgNPls), providing a stable plasmonic platform, where a poly(N-isopropylacrylamide)-based (PNIPAAm) hydrogel layer allows mobility and good integration of the biomolecules. By integrating these components, the platform can also exhibit a colorimetric response to the concentration of lysozyme, allowing for easy and non-invasive monitoring. Quantitative biosensing operates on the principle of localized surface plasmon resonance (LSPR) induced by plasmonic nanoparticles. Chemical, structural, thermal, and optical characterizations were performed on each platform layer, and the platform's ability to detect lysozyme at concentrations relevant to those found in tears of patients with dry-eye syndrome and other related diseases was investigated by colorimetry and UV-Vis spectroscopy. This biosensor's sensitivity and rapid response time, alongside the easy detection by the naked eye, make it a promising tool for early diagnosis and treatment monitoring of eye diseases.

electrical properties, energy, hydrogel, hydrogen, oxygen evolution reaction, polymer composites

Development and step-by-step characterizations of a novel cationic thiophene based copolymer (P1buP), including ionic phosphonium salt and dye-tetraphenylporphyrin (TPP) moiety in side chains, with an iconic property of solubility in a wide range of polar solvents is reported. Synthesized by using simple, low-cost, and straightforward procedures, the material is used to fabricate completely halogen-free (i.e., from ethanol) ternary organic solar cells (OSCs), in the presence of an alcohol-soluble ionic 3,4-dialkoxythiophene based homopolymer (P2buP) and a serinol-fullerene derivative (C60-Ser). Indeed, thanks to co-sensitization techniques, where multiple dyes harvest different parts of the solar spectrum, the power conversion efficiency of the best final device dramatically increases up to nearly 5.0%, as the light absorption is usually optimized. Additionally, since the use of a cathode interlayer in OSCs also plays a pivotal role in electron extraction and device stability, a possible application of the ionic TPP material as the interfacial layer is also investigated. Furthermore, to improve and optimize the best performing device, a successful post-metalation with Zn of the porphyrin core is carried out, and a ternary OSC (P1buP:P2buP:C60-Ser = 0.33:0.67:1 w/w) is fabricated, resulting in a photoconversion efficiency (PCE) of ∼6.0%.

Ionic dye-tetraphenylporphyrin, Co-sensitization, Ternary OSCs, Cathode interlayers, Halogen-free deposition

Polycaprolactone (PCL), a recognized biopolymer, has emerged as a prominent choice for diverse biomedical endeavors due to its good mechanical properties, exceptional biocompatibility, and tunable properties. These attributes render PCL a suitable alternative biomaterial to use in biofabrication, especially the electrospinning technique, facilitating the production of nanofibers with varied dimensions and functionalities. However, the inherent hydrophobicity of PCL nanofibers can pose limitations. Conversely, acrylamide-based hydrogels, characterized by their interconnected porosity, significant water retention, and responsive behavior, present an ideal matrix for numerous biomedical applications. By merging these two materials, one can harness their collective strengths while potentially mitigating individual limitations. A robust interface and effective anchorage during the composite fabrication are pivotal for the optimal performance of the nanoplatforms. Nanoplatforms are subject to varying degrees of tension and physical alterations depending on their specific applications. This is particularly pertinent in the case of layered nanostructures, which require careful consideration to maintain structural stability and functional integrity in their intended applications. In this study, we delve into the influence of the fiber dimensions, orientation and surface modifications of the nanofibrous layer and the hydrogel layer's crosslinking density on their intralayer interface to determine the optimal approach. Comprehensive mechanical pull-out tests offer insights into the interfacial adhesion and anchorage between the layers. Notably, plasma treatment of the hydrophobic nanofibers and the stiffness of the hydrogel layer significantly enhance the mechanical effort required for fiber extraction from the hydrogels, indicating improved anchorage. Furthermore, biocompatibility assessments confirm the potential biomedical applications of the proposed nanoplatforms.

In neuroscience, the acquisition of neural signals from the brain cortex is crucial to analyze brain processes, detect neurological disorders, and offer therapeutic brain–computer interfaces. The design of neural interfaces conformable to the brain tissue is one of today’s major challenges since the insufficient biocompatibility of those systems provokes a fibrotic encapsulation response, leading to an inaccurate signal recording and tissue damage precluding long-term/permanent implants. The design and production of a novel soft neural biointerface made of polyacrylamide hydrogels loaded with plasmonic silver nanocubes are reported herein. Hydrogels are surrounded by a silicon-based template as a supporting element for guaranteeing an intimate neural-hydrogel contact while making possible stable recordings from specific sites in the brain cortex. The nanostructured hydrogels show superior electroconductivity while mimicking the mechanical characteristics of the brain tissue. Furthermore, in vitro biological tests performed by culturing neural progenitor cells demonstrate the biocompatibility of hydrogels along with neuronal differentiation. In vivo chronic neuroinflammation tests on a mouse model show no adverse immune response toward the nanostructured hydrogel-based neural interface. Additionally, electrocorticography acquisitions indicate that the proposed platform permits long-term efficient recordings of neural signals, revealing the suitability of the system as a chronic neural biointerface.

brain−machine interface,conductive hydrogels,nanostructured biomaterials,in vitro and in vivo biocompatibility,long-term neural recording

As scientists discovered that raw neurological signals could translate into bioelectric information, brain–machine interfaces (BMI) for experimental and clinical studies have experienced massive growth. Developing suitable materials for bioelectronic devices to be used for real-time recording and data digitalizing has three important necessitates which should be covered. Biocompatibility, electrical conductivity, and having mechanical properties similar to soft brain tissue to decrease mechanical mismatch should be adopted for all materials. In this review, inorganic nanoparticles and intrinsically conducting polymers are discussed to impart electrical conductivity to systems, where soft materials such as hydrogels can offer reliable mechanical properties and a biocompatible substrate. Interpenetrating hydrogel networks offer more mechanical stability and provide a path for incorporating polymers with desired properties into one strong network. Promising fabrication methods, like electrospinning and additive manufacturing, allow scientists to customize designs for each application and reach the maximum potential for the system. In the near future, it is desired to fabricate biohybrid conducting polymer-based interfaces loaded with cells, giving the opportunity for simultaneous stimulation and regeneration. Developing multi-modal BMIs, Using artificial intelligence and machine learning to design advanced materials are among the future goals for this field.

3D printing,brain–machine interface,conductive hydrogels,electrospinning,neural recording

Utilization of CoO@Co3O4-x-Ag (x denotes 1, 3, and 5 wt% of Ag) nanocomposites as supercapacitor electrodes is the main aim of this study. A new low-temperature wet chemical approach is proposed to modify the commercial cobalt oxide material with silver nanoparticle (NP) balls of size 1–5 nm. The structure and morphology of the as-prepared nanocomposites were investigated by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and N2 adsorption–desorption measurements. Hydrogels known to be soft but stable structures were used here as perfect carriers for conductive nanoparticles such as carbons. Furthermore, hydrogels with a large amount of water in their network can give more flexibility to the system. Fabrication of an electrochemical cell can be achieved by combining these materials with a layer-by-layer structure. The performance characteristics of the cells were examined by electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV), and galvanostatic charge discharge (GCD). Cobalt oxide modified with 5 wt% Ag gave the best supercapacitor results, and the cell offers a specific capacitance of ∼38 mF cm−2 in two-electrode configurations.

The use of injectable biomaterials for cell delivery is a rapidly expanding field which may revolutionize the medical treatments by making them less invasive. However, creating desirable cell carriers poses significant challenges to the clinical implementation of cell-based therapeutics. At the same time, no method has been developed to produce injectable microscaffolds (MSs) from electrospun materials. Here the fabrication of injectable electrospun nanofibers is reported on, which retain their fibrous structure to mimic the extracellular matrix. The laser-assisted micro-scaffold fabrication has produced tens of thousands of MSs in a short time. An efficient attachment of cells to the surface and their proliferation is observed, creating cell-populated MSs. The cytocompatibility assays proved their biocompatibility, safety, and potential as cell carriers. Ex vivo results with the use of bone and cartilage tissues proved that NaOH hydrolyzed and chitosan functionalized MSs are compatible with living tissues and readily populated with cells. Injectability studies of MSs showed a high injectability rate, while at the same time, the force needed to eject the load is no higher than 25 N. In the future, the produced MSs may be studied more in-depth as cell carriers in minimally invasive cell therapies and 3D bioprinting applications.

One of the most fascinating areas in the field of smart biopolymers is biomolecule sensing. Accordingly, multifunctional biomimetic, biocompatible, and stimuli-responsive materials based on hydrogels have attracted much interest. Within this framework, the design of nanostructured materials that do not require any external energy source is beneficial for developing a platform for sensing glucose in body fluids. In this article, we report the realization and application of an innovative platform consisting of two outer layers of a nanocomposite plasmonic hydrogel plus one inner layer of electrospun mat fabricated by electrospinning, where the outer layers exploit photoinitiated free radical polymerization, obtaining a compact and stable device. Inspired by the exceptional features of chameleon skin, plasmonic silver nanocubes are embedded into a poly(N-isopropylacrylamide)-based hydrogel network to obtain enhanced thermoresponsive and antibacterial properties. The introduction of an electrospun mat creates a compatible environment for the homogeneous hydrogel coating while imparting excellent mechanical and structural properties to the final system. Chemical, morphological, and optical characterizations were performed to investigate the structure of the layers and the multifunctional platform. The synergetic effect of the nanostructured system’s photothermal responsivity and antibacterial properties was evaluated. The sensing features associated with the optical properties of silver nanocubes revealed that the proposed multifunctional system is a promising candidate for glucose-sensing applications.

Four new conjugated polymers alternating benzothiadiazole units and thiophene moieties functionalized with ionic phosphonium or sulfonic acid salts in the side chains were synthesized by a postfunctionalization approach of polymeric precursors. The introduction of ionic groups makes the conjugated polymers soluble in water and/or polar solvents, allowing for the fabrication of bulk heterojunction (BHJ) solar cells using environmentally friendly conditions. All polymers were fully characterized by spectroscopic, thermal, electrochemical, X-ray diffraction, scanning electron, and atomic force techniques. BHJ solar cells were obtained from halogen-free solvents (i.e., ethanol and/or anisole) by blending the synthesized ionic push–pull polymers with a serinol-fullerene derivative or an ionic homopolymer acting as electron-acceptor (EA) or electron-donor (ED) counterparts, respectively. The device with the highest optical density and the smoothest surface of the active layer was the best-performing, showing a 4.76% photoconversion efficiency.

donor–acceptor systems, bifunctional materials, phosphonium salts, eco-friendly BHJ solar cells, anisole

The importance of having a fast, accurate, and reusable track for detection has led to an increase investigation in the field of biosensing. Optical biosensing using plasmonic nanoparticles, such as gold and silver, introduces localized surface plasmon resonance (LSPR) sensors. LSPR biosensors are progressive in their sensing precision and detection limit. Also, the possibility to tune the sensing range by varying the size and shape of the particles has made them extremely useful. Hydrogels being hydrophilic 3D networks can be beneficial when used as matrices, because of a more efficient biorecognition. Stimuli-responsive hydrogels can be great candidates, as their response to a stimulus can increase recognition and detection. This article highlights recent advances in combining hydrogels as a matrix and plasmonic nanoparticles as sensing elements. The end capability and diversity of these novel biosensors in different applications in the near future are discussed.

Smart materials, Plasmonic hydrogel, Biosensing

A new side-chain C60-fullerene functionalized thiophene copolymer bearing tributylphosphine-substituted hexylic lateral groups was successfully synthesized by means of a fast and effective post-polymerization reaction on a regioregular ω-alkylbrominated polymeric precursor. The growth of the polymeric intermediate was followed by NMR spectrometry in order to determine the most convenient reaction time. The obtained copolymer was soluble in water and polar solvents and was used as a photoactive layer in single-material organic photovoltaic (OPV) solar cells. The copolymer photovoltaic efficiency was compared with that of an OPV cell containing a water-soluble polythiophenic homopolymer, functionalized with the same tributylphosphine-substituted hexylic side chains, in a blend with a water-soluble C60-fullerene derivative. The use of a water-soluble double-cable copolymer made it possible to enhance the control on the nanomorphology of the active blend, thus reducing phase-segregation phenomena, as well as the macroscale separation between the electron acceptor and donor components. Indeed, the power conversion efficiency of OPV cells based on a single material was higher than that obtained with the classical architecture, involving the presence of two distinct ED and EA materials (PCE: 3.11% vs. 2.29%, respectively). Moreover, the synthetic procedure adopted to obtain single material-based cells is more straightforward and easier than that used for the preparation of the homopolymer-based BHJ solar cell, thus making it possible to completely avoid the long synthetic pathway which is required to prepare water-soluble fullerene derivatives.

water-soluble polymers, double-cable copolymers, polythiophenes, GRIM polymerization, tributylphosphine, water-soluble fullerenes, OPVs

Multifunctional nanomaterials with the ability torespond to near-infrared (NIR) light stimulation are vital for thedevelopment of highly efficient biomedical nanoplatforms with apolytherapeutic approach. Inspired by the mesoglea structure ofjellyfish bells, a biomimetic multifunctional nanostructured pillowwith fast photothermal responsiveness for NIR light-controlled on-demand drug delivery is developed. We fabricate a nanoplatformwith several hierarchical levels designed to generate a series ofcontrolled, rapid, and reversible cascade-like structural changesupon NIR light irradiation. The mechanical contraction of thenanostructured platform, resulting from the increase of temper-ature to 42°C due to plasmonic hydrogel−light interaction, causesa rapid expulsion of water from the inner structure, passing through an electrospun membrane anchored onto the hydrogel core. Themutual effects of the rise in temperature and waterflow stimulate the release of molecules from the nanofibers. To expand thepotential applications of the biomimetic platform, the photothermal responsiveness to reach the typical temperature level forperforming photothermal therapy (PTT) is designed. The on-demand drug model penetration into pig tissue demonstrates theefficiency of the nanostructured platform in the rapid and controlled release of molecules, while the high biocompatibility confirmsthe pillow potential for biomedical applications based on the NIR light-driven multitherapy strategy.

bioinspired materials, NIR-light responsive nanomaterials, multifunctional platforms, electrospun nanofibers, plasmonic hydrogel, photothermal-based polytherapy, on-demand drug delivery

Body tissues and organs have complex functions which undergo intrinsic changes during medical treatments. For the development of ideal drug delivery systems, understanding the biological tissue activities is necessary to be able to design materials capable of changing their properties over time, on the basis of the patient's tissue needs. In this study, a nanofibrous thermal‐responsive drug delivery system is developed. The thermo‐responsivity of the system makes it possible to self‐regulate the release of bioactive molecules, while reducing the drug delivery at early stages, thus avoiding high concentrations of drugs which may be toxic for healthy cells. A co‐axial electrospinning technique is used to fabricate core–shell cross‐linked copolymer poly(N‐isopropylacrylamide‐co‐N‐isopropylmethacrylamide) (P(NIPAAm‐co‐NIPMAAm)) hydrogel‐based nanofibers. The obtained nanofibers are made of a core of thermo‐responsive hydrogel containing a drug model, while the outer shell is made of poly‐l‐lactide‐co‐caprolactone (PLCL). The custom‐made electrospinning apparatus enables the in situ cross‐linking of P(NIPAAm‐co‐NIPMAAm) hydrogel into a nanoscale confined space, which improves the electrospun nanofiber drug dosing process, by reducing its provision and allowing a self‐regulated release control. The mechanism of the temperature‐induced release control is studied in depth, and it is shown that the system is a promising candidate as a "smart" drug delivery platform.

biomimetic nanomaterials, electrospun core–shell nanofibers, hierarchical nanostructures, smart drug delivery, thermo‐responsive hydrogels

Lysozyme, an enzyme found in various bodily fluids, holds immense importance as a biomolecule with numerous diagnostic implications. In the realm of ophthalmology, lysozyme detection in tears emerges as a precious tool for identifying and addressing dry and inflamed eyes. To enhance the precision and efficiency of lysozyme detection, Smart materials, such as hydrogels and electrospun nanofibers, have been confirmed to be promising candidates for sensing platforms. Plasmonic nanoparticles, on the other hand, offer enhanced optical properties that allow for localized surface plasmon resonance (LSPR), which has been used alongside these substrates. By integrating these smart materials into biosensing platforms, researchers can achieve rapid, reliable, and non-invasive lysozyme detection from tears.
To achieve this goal, a layered platform consisting of a hydrogel layer, electrospun nanofibers, and plasmonic nanoparticles was designed and fabricated. Electrospun mat of poly (L-lactide-co-caprolactone) (PLCL) was used as the support, providing suitable mechanical properties to the platform. Silver nanoplates were immobilized on top of the electrospun nanofibers, where a layer of poly(N-isopropylacrylamide)-based hydrogel was added. With its porous 3D structure and high water content, the hydrogel network allows enhancement in photothermal responsivity. Moreover, due to its fluid nature, the maneuvering of the biomolecules is much easier, making the biosensing procedure more accurate. The structure of each layer, their cross-section, and the whole platform were investigated chemically, morphologically, and optically. The fast photothermal responsitivity of the platform and sensing features were studied, revealing the applicability of the system as a biosensor for detecting lysozyme.

Due to their importance in various fields of bio-nanotechnology, the synthesis of thermoresponsive smart polymers has been the focus of recent research. Poly(N-isopropylacrylamide) (PNIPAAm) is a well-known thermal-stimulus responsive polymer that has attracted much attention. For PNIPAAm hydrogels to acquire fast thermo-responsive properties, water molecules must have quick access to the entire material. However, isotropic PNIPAAm-based hydrogels have a slow stimulus-responsivity. Hydrophilic cross-linkable nanostructures are gaining interest as a viable alternative to traditional hydrogels to address this issue. System miniaturization via electrospinning exhibits nanostructures with significantly larger porosity and specific surface area. If the constituting hydrophilic polymer of the electrospun fibrous material were cross-linkable, the resulting would display a rapid hydration/dehydration response. As a result, developing a new class of cross-linkable PNIPAAm copolymers is highly desired.