Institute of Fundamental Technological Research

Hydrogels with multifunctional properties activated at specific times have gained significant attention in the biomedical field. As bacterial infections can cause severe complications that negatively impact wound repair, herein, we present the development of a stimuli-responsive, injectable, and in situ-forming hydrogel with antibacterial, self-healing, and drug-delivery properties. In this study, we prepared a Pluronic F-127 (PF127) and sodium alginate (SA)-based hydrogel that can be targeted to a specific tissue via injection. The PF127/SA hydrogel was incorporated with polymeric short-filaments (SFs) containing an anti-inflammatory drug – ketoprofen, and stimuli-responsive polydopamine (PDA) particles. The hydrogel, after injection, could be in situ gelated at the body temperature, showing great in vitro stability and self-healing ability after 4 h of incubation. The SFs and PDA improved the hydrogel injectability and compressive strength. The introduction of PDA significantly accelerated the KET release under near-infrared light exposure and extended its release validity period. The excellent composites’ photo-thermal performance led to antibacterial activity against representative Gram-positive and Gram-negative bacteria, resulting in 99.9% E. coli and S. aureus eradication after 10 min of NIR light irradiation. In vitro, fibroblast L929 cell studies confirmed the materials’ biocompatibility and paved the way toward further in vivo and clinical application of the system for chronic wound treatments.

The shortage of face masks and the lack of antipathogenic functions has been significant since the recent pandemic's inception. Moreover, the disposal of an enormous number of contaminated face masks not only carries a significant environmental impact but also escalates the risk of cross-contamination. This study proposes a strategy to upgrade available surgical masks into antibacterial masks with enhanced particle and bacterial filtration. Plasmonic nanoparticles can provide photodynamic and photothermal functionalities for surgical masks. For this purpose, gold nanorods act as on-demand agents to eliminate pathogens on the surface of the masks upon near-infrared light irradiation. Additionally, the modified masks are furnished with polymer electrospun nanofibrous layers. These electrospun layers can enhance the particle and bacterial filtration efficiency, not at the cost of the pressure drop of the mask. Consequently, fabricating these prototype masks could be a practical approach to upgrading the available masks to alleviate the environmental toll of disposable face masks.

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

Current treatments of degenerated intervertebral discs often provide only temporary relief or address specific causes, necessitating the exploration of alternative therapies. Cell-based regenerative approaches showed promise in many clinical trials, but
limitations such as cell death during injection and a harsh disk environment hinder their effectiveness. Injectable microscaffolds offer a solution by providing a supportive microenvironment for cell delivery and enhancing bioactivity. This study evaluated the
safety and feasibility of electrospun nanofibrous microscaffolds modified with chitosan (CH) and chondroitin sulfate (CS) for treating degenerated NP tissue in a large animal model. The microscaffolds facilitated cell attachment and acted as an effective delivery system, preventing cell leakage under a high disc pressure. Combining microscaffolds with bone marrow-derived mesenchymal stromal cells demonstrated no cytotoxic effects and proliferation over the entire microscaffolds. The administration of cells attached to microscaffolds into the NP positively influenced the regeneration process of the intervertebral disc. Injectable poly(L-lactide-co-glycolide) and poly(L-lactide) microscaffolds enriched with CH or CS, having a fibrous structure, showed the potential to promote intervertebral disc regeneration. These features collectively address critical challenges in the fields of tissue engineering and regenerative medicine, particularly in the context of intervertebral disc degeneration.

microscaffolds,cell carriers,injectable biomaterials,intervertebral disc,laser micromachining,electrospinning

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

Recent advances in the field of skin patches have promoted the development of wearable and implantable bioelectronics for long-term, continuous healthcare management and targeted therapy. However, the design of electronic skin (e-skin) patches with stretchable components is still challenging and requires an in-depth understanding of the skin-attachable substrate layer, functional biomaterials and advanced self-powered electronics. In this comprehensive review, we present the evolution of skin patches from functional nanostructured materials to multi-functional and stimuli-responsive patches towards flexible substrates and emerging biomaterials for e-skin patches, including the material selection, structure design and promising applications. Stretchable sensors and self-powered e-skin patches are also discussed, ranging from electrical stimulation for clinical procedures to continuous health monitoring and integrated systems for comprehensive healthcare management. Moreover, an integrated energy harvester with bioelectronics enables the fabrication of self-powered electronic skin patches, which can effectively solve the energy supply and overcome the drawbacks induced by bulky battery-driven devices. However, to realize the full potential offered by these advancements, several challenges must be addressed for next-generation e-skin patches. Finally, future opportunities and positive outlooks are presented on the future directions of bioelectronics. It is believed that innovative material design, structure engineering, and in-depth study of fundamental principles can foster the rapid evolution of electronic skin patches, and eventually enable self-powered close-looped bioelectronic systems to benefit mankind.

Cross-linking of poly(vinyl alcohol) (PVA) creates a three-dimensional network by bonding adjacent polymer chains. The cross-linked structure, upon immersion in water, turns into a hydrogel, which exhibits unique absorption properties due to the presence of hydrophilic groups within the PVA polymer chains and, simultaneously, ceases to be soluble in water. The properties of PVA can be adjusted by chemical modification or blending with other substances, such as polymers, e.g., conductive poly[3-(potassium-5-butanoate)thiophene-2,5-diyl] (P3KBT). In this work, PVA-based conductive semi-interpenetrating polymer networks (semi-IPNs) are successfully fabricated. The systems are obtained as a result of electrospinning of PVA/P3KBT precursor solutions with different polymer concentrations and then cross-linking using “green”, environmentally safe methods. One approach consists of thermal treatment (H), while the second approach combines stabilization with ethanol and heating (E). The comprehensive characterization allows to evaluate the correlation between the cross-linking methods and properties of nanofibrous hydrogels. While both methods are successful, the cross-linking density is higher in the thermally cross-linked samples, resulting in lower conductivity and swelling ratio compared to the E-treated samples. Moreover, the H-cross-linked systems have better mechanical properties─lower stiffness and greater tensile strength. All the tested systems are biocompatible, and interestingly, due to the presence of P3KBT, they show photoresponsivity to solar radiation generated by the simulator. The results indicate that both methods of PVA cross-linking are highly effective and can be applied to a specific system depending on the target, e.g., biomedical or electronic applications.

poly(vinyl alcohol),poly[3-(potassium-5-butanoate)thiophene-2.5-diyl],electrospun nanofibers,cross-linking,fibrous hydrogel,semi-IPN

Over the last few years, traditional drug delivery systems (DDSs) have been transformed into smart DDSs. Recent advancements in biomedical nanotech-nology resulted in introducing stimuli-responsiveness to drug vehicles. Nano-
platforms can enhance drug release efficacy while reducing the side effects of drugs by taking advantage of the responses to specific internal or external stim-uli. In this study, we developed an electrospun nanofibrous photo-responsive DDSs. The photo-responsivity of the platform enables on-demand elevated drug release. Furthermore, it can provide a sustained release profile and pre-vent burst release and high concentrations of drugs. A coaxial electrospinning setup paired with an electrospraying technique is used to fabricate core-shell PVA-PLGA nanofibers decorated with plasmonic nanoparticles. The fabricated
nanofibers have a hydrophilic PVA and Rhodamine-B (RhB) core, while the shell is hydrophobic PLGA decorated with gold nanorods (Au NRs). The presence of plasmonic nanoparticles enables the platform to twice the amount of drug release besides exhibiting a long-term release. Investigations into the photo-responsive release mechanism demonstrate the system's potential as a “smart” drug delivery platform.

electrospun core-shell nanofibers,NIR-light activation,on-demand drug release,plasmonic nanoparticles,stimuli-responsive nanomaterials

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.

Extreme loss of skeletal muscle overwhelms the natural regenerative capability of the body, results in permanent disability and substantial economic burden. Current surgical techniques result in poor healing, secondary injury to the autograft donor site, and incomplete recuperation of muscle function. Most current tissue engineering and regenerative strategies fail to create an adequate mechanical and biological environment that enables cell infiltration, proliferation, and myogenic differentiation. In this study, we present a nanoengineered skeletal muscle scaffold based on functionalized gelatin methacrylate (GelMA) hydrogel, optimized for muscle progenitors’ proliferation and differentiation. The scaffold was capable of controlling the release of insulin-like growth factor 1 (IGF-1), an important myogenic growth factor, by utilizing the electrostatic interactions with LAPONITE® nanoclays (NCs). Physiologically relevant levels of IGF-1 were maintained during a controlled release over two weeks. The NC was able to retain 50% of the released IGF-1 within the hydrogel niche, significantly improving cellular proliferation and differentiation compared to control hydrogels. IGF-1 supplemented medium controls required 44% more IGF-1 than the comparable NC hydrogel composites. The nanofunctionalized scaffold is a viable option for the treatment of extreme muscle injuries and offers scalable benefits for translational interventions and the growing field of clean meat production.

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.

The recent burst of research on smart materials is a clear evidence of the growing interest of the scientific community, industry, and society in the field. The exploitation of the great potential of stimuli-responsive materials for sensing, actuation, logic, and control applications is favored and supported by new manufacturing technologies, such as electrospinning, that allows to endow smart materials with micro- and nanostructuration, thus opening up additional and unprecedented prospects. In this wide and lively scenario, this article systematically reviews the current advances in the development of thermoactive electrospun fibers and textiles, sorting them, according to their response to the thermal stimulus. Hence, several platforms including thermoresponsive systems, shape memory polymers, thermo-optically responsive systems, phase change materials, thermoelectric materials, and pyroelectric materials, are described and critically discussed. The difference in active species and outputs of the aforementioned categories is highlighted, evidencing the transversal nature of temperature stimulus. Moreover, the potential of novel thermoactive materials are pointed out, revealing how their development could take to utmost interesting achievements.

electrospinning, phase change materials, pyroelectric materials, shape memory polymers, thermoelectric materials, thermo-optically responsive materials, thermoresponsive materials

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

Intrinsically conducting polymers (ICPs) are widely used to fabricate biomaterials; their application in neural tissue engineering, however, is severely limited because of their hydrophobicity and insufficient mechanical properties. For these reasons, soft conductive polymer hydrogels (CPHs) are recently developed, resulting in a water-based system with tissue-like mechanical, biological, and electrical properties. The strategy of incorporating ICPs as a conductive component into CPHs is recently explored by synthesizing the hydrogel around ICP chains, thus forming a semi-interpenetrating polymer network (semi-IPN). In this work, a novel conductive semi-IPN hydrogel is designed and synthesized. The hybrid hydrogel is based on a poly(N-isopropylacrylamide-co-N-isopropylmethacrylamide) hydrogel where polythiophene is introduced as an ICP to provide the system with good electrical properties. The fabrication of the hybrid hydrogel in an aqueous medium is made possible by modifying and synthesizing the monomers of polythiophene to ensure water solubility. The morphological, chemical, thermal, electrical, electrochemical, and mechanical properties of semi-IPNs were fully investigated. Additionally, the biological response of neural progenitor cells and mesenchymal stem cells in contact with the conductive semi-IPN was evaluated in terms of neural differentiation and proliferation. Lastly, the potential of the hydrogel solution as a 3D printing ink was evaluated through the 3D laser printing method. The presented results revealed that the proposed 3D printable conductive semi-IPN system is a good candidate as a scaffold for neural tissue applications.

In recent years, the main quest of science has been the pioneering of the groundbreaking biomedical strategies needed for achieving a personalized medicine. Ribonucleic acids (RNAs) are outstanding bioactive macromolecules identified as pivotal actors in regulating a wide range of biochemical pathways. The ability to intimately control the cell fate and tissue activities makes RNA-based drugs the most fascinating family of bioactive agents. However, achieving a widespread application of RNA therapeutics in humans is still a challenging feat, due to both the instability of naked RNA and the presence of biological barriers aimed at hindering the entrance of RNA into cells. Recently, material scientists’ enormous efforts have led to the development of various classes of nanostructured carriers customized to overcome these limitations. This work systematically reviews the current advances in developing the next generation of drugs based on nanotechnology-assisted RNA delivery. The features of the most used RNA molecules are presented, together with the development strategies and properties of nanostructured vehicles. Also provided is an in-depth overview of various therapeutic applications of the presented systems, including coronavirus disease vaccines and the newest trends in the field. Lastly, emerging challenges and future perspectives for nanotechnology-mediated RNA therapies are discussed.

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

Engineering tissue-like scaffolds that can mimic the microstructure, architecture, topology, and mechanical properties of native tissues while offering an excellent environment for cellular growth has remained an unmet need. To address these challenges, multi-compartment composite fibers are fabricated. These fibers can be assembled through textile processes to tailor tissue-level mechanical and electrical properties independent of cellular level components. Textile technologies also allow controlling the distribution of different cell types and microstructure of fabricated constructs and directing cellular growth within 3D microenvironment. Here, we engineered composite fibers from biocompatible cores and biologically relevant hydrogel sheaths. The fibers are mechanically robust to be assembled using textile processes and could support adhesion, proliferation and maturation of cell populations important for engineering of skeletal muscles. We also demonstrated that the changes in the electrical conductivity of the multi-compartment fibers could significantly enhance myogenesis in vitro.

reinforced fibers, biotextiles, tissue engineering, organ weaving, interpenetrating network hydrogels, skeletal muscles

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

Liquid-crystal-based biomaterials provide promising platforms for the development of dynamic and responsive interfaces for tissue engineering. Cholesteryl ester liquid crystals (CLCs) are particularly well suited for these applications, due to their roles in cellular homeostasis and their intrinsic ability to organize into supramolecular helicoidal structures on the mesoscale. Here, we developed a nonwoven CLC electrospun scaffold by dispersing three cholesteryl ester-based mesogens within polycaprolactone (PCL). We tuned the ratio of our mesogens so that the CLC would be in the mesophase at the cell culture incubator temperature of 37°C. In these scaffolds, the PCL polymer provided an elastic bulk matrix while the homogeneously dispersed CLC established a viscoelastic fluidlike interface. Atomic force microscopy revealed that the 50% (w/v) cholesteryl ester liquid crystal scaffold (CLC-S) exhibited a mesophase with topographic striations typical of liquid crystals. Additionally, the CLC-S favorable wettability and ultrasoft fiber mechanics enhanced cellular attachment and proliferation. Increasing the CLC concentration within the composites enhanced myoblast adhesion strength promoted myofibril formationin vitrowith mouse myoblast cell lines.

Fiber-based approaches hold great promise for tendon tissue engineering enabling the possibility of manufacturing aligned hydrogel filaments that can guide collagen fiber orientation, thereby providing a biomimetic micro-environment for cell attachment, orientation, migration, and proliferation. In this study, a 3D system composed of cell-laden, highly aligned hydrogel yarns is designed and obtained via wet spinning in order to reproduce the morphology and structure of tendon fascicles. A bioink composed of alginate and gelatin methacryloyl (GelMA) is optimized for spinning and loaded with human bone morrow mesenchymal stem cells (hBM-MSCs). The produced scaffolds are subjected to mechanical stretching to recapitulate the strains occurring in native tendon tissue. Stem cell differentiation is promoted by addition of bone morphogenetic protein 12 (BMP-12) in the culture medium. The aligned orientation of the fibers combined with mechanical stimulation results in highly preferential longitudinal cell orientation and demonstrates enhanced collagen type I and III expression. Additionally, the combination of biochemical and mechanical stimulations promotes the expression of specific tenogenic markers, signatures of efficient cell differentiation towards tendon. The obtained results suggest that the proposed 3D cell-laden aligned system can be used for engineering of scaffolds for tendon regeneration.

hydrogel fibers, static mechanical stretching, stem cell alignment, tenogenic differentiation, wet spinning

Tendon injuries are frequent and occur in the elderly, young, and athletic populations. The inadequate number of donors combined with many challenges associated with autografts, allografts, xenografts, and prosthetic devices have added to the value of engineering biological substitutes, which can be implanted to repair the damaged tendons. Electrospun scaffolds have the potential to mimic the native tissue structure along with desired mechanical properties and, thus, have attracted noticeable attention. In order to improve the biological responses of these fibrous structures, we designed and fabricated 3D multilayered composite scaffolds, where an electrospun nanofibrous substrate was coated with a thin layer of cell-laden hydrogel. The whole construct composition was optimized to achieve adequate mechanical and physical properties as well as cell viability and proliferation. Mesenchymal stem cells (MSCs) were differentiated by the addition of bone morphogenetic protein 12 (BMP-12). To mimic the natural function of tendons, the cell-laden scaffolds were mechanically stimulated using a custom-built bioreactor. The synergistic effect of mechanical and biochemical stimulation was observed in terms of enhanced cell viability, proliferation, alignment, and tenogenic differentiation. The results suggested that the proposed constructs can be used for engineering functional tendons.

tendon tissue engineering, composite scaffolds, nanofibrous materials, mechanical stimulation, stem cell differentiation

Biological gradients profoundly influence many cellular activities, such as adhesion, migration, and differentiation, which are the key to biological processes, such as inflammation, remodeling, and tissue regeneration. Thus, engineered structures containing bioinspired gradients can not only support a better understanding of these phenomena, but also guide and improve the current limits of regenerative medicine. In this review, we outline the challenges behind the engineering of devices containing chemical-physical and biomolecular gradients, classifying them according to gradient-making methods and the finalities of the systems. Different manufacturing processes can generate gradients in either in-vitro systems or scaffolds, which are suitable tools for the study of cellular behavior and for regenerative medicine; within these, rapid prototyping techniques may have a huge impact on the controlled production of gradients. The parallel need to develop characterization techniques is addressed, underlining advantages and weaknesses in the analysis of both chemical and physical gradients.

graded scaffolds, rapid prototyping, bioinspired, microfluidic, gradient characterization, cartilage, bone

Chronic, non-healing wounds place a significant burden on patients and healthcare systems, resulting in impaired mobility, limb amputation, or even death. Chronic wounds result from a disruption in the highly orchestrated cascade of events involved in wound closure. Significant advances in our understanding of the pathophysiology of chronic wounds have resulted in the development of drugs designed to target different aspects of the impaired processes. However, the hostility of the wound environment rich in degradative enzymes and its elevated pH, combined with differences in the time scales of different physiological processes involved in tissue regeneration require the use of effective drug delivery systems. In this review, we will first discuss the pathophysiology of chronic wounds and then the materials used for engineering drug delivery systems. Different passive and active drug delivery systems used in wound care will be reviewed. In addition, the architecture of the delivery platform and its ability to modulate drug delivery are discussed. Emerging technologies and the opportunities for engineering more effective wound care devices are also highlighted.

Wound healing, Drug delivery, Transdermal delivery, Microtechnologies, Nanotechnologies

Electrospun nanofibrous scaffolds are willingly used in tissue engineering applications due to their tunable mechanical, chemical and physical properties. Additionally, their complex openworked architecture is similar to the native extracellular matrix of living tissue. After implantation such scaffolds should provide sufficient mechanical support for cells. Moreover, it is of crucial importance to ensure sterility and hydrophilicity of the scaffold. For this purpose, a low temperature surface plasma treatment can be applied. In this paper, we report physico-mechanical evaluation of stiffness and adhesive properties of electrospun mats after their exposition to low temperature plasma. Complex morphological and mechanical studies performed with an atomic force microscope were followed by scanning electron microscope imaging and a wettability assessment. The results suggest that plasma treatment can be a useful method for the modification of the surface of polymeric scaffolds in a desirable manner. Plasma treatment improves wettability of the polymeric mats without changing their morphology.

Atomic force microscopy, Surface modification, Electrospun fibers, RF plasma treatment, Tissue engineering, Nanomaterial

Tissue engineering holds great potential in the production of functional substitutes to restore, maintain or improve the functionality in defective or lost tissues. So far, a great variety of techniques and approaches for fabrication of scaffolds have been developed and evaluated, allowing researchers to tailor precisely the morphological, chemical and mechanical features of the final constructs. Electrospinning of biocompatible and biodegradable polymers is a popular method for producing homogeneous nanofibrous structures, which might reproduce the nanosized organization of the tendons. Moreover, composite scaffolds obtained by incorporating nanoparticles within electrospun fibers have been lately explored in order to enhance the properties and the functionalities of the pristine polymeric constructs. The present study is focused on the design and fabrication of biocompatible electrospun nanocomposite fibrous scaffolds for tendon regeneration. A mixture of poly(amide 6) and poly(caprolactone) is electrospun to generate constructs with mechanical properties comparable to that of native tendons. To improve the biological activity of the constructs and modify their topography, wettability, stiffness and degradation rate, we incorporated silica particles into the electrospun substrates. The use of nanosize silica particles enables us to form bead-on-fiber topography, allowing the better exposure of ceramic particles to better profit their beneficial characteristics. In vitro biocompatibility studies using L929 fibroblasts demonstrated that the presence of 20 wt% of silica nanoparticles in the engineered scaffolds enhanced cell spreading and proliferation as well as extracellular matrix deposition. The results reveal that the electrospun nanocomposite scaffold represents an interesting candidate for tendon tissue engineering.

Periodontitis is a prevalent chronic, destructive inflammatory disease affecting tooth‐supporting tissues in humans. Guided tissue regeneration strategies are widely utilized for periodontal tissue regeneration generally by using a periodontal membrane. The main role of these membranes is to establish a mechanical barrier that prevents the apical migration of the gingival epithelium and hence allowing the growth of periodontal ligament and bone tissue to selectively repopulate the root surface. Currently available membranes have limited bioactivity and regeneration potential. To address such challenges, an osteoconductive, antibacterial, and flexible poly(caprolactone) (PCL) composite membrane containing zinc oxide (ZnO) nanoparticles is developed. The membranes are fabricated through electrospinning of PCL and ZnO particles. The physical properties, mechanical characteristics, and in vitro degradation of the engineered membrane are studied in detail. Also, the osteoconductivity and antibacterial properties of the developed membrane are analyzed in vitro. Moreover, the functionality of the membrane is evaluated with a rat periodontal defect model. The results confirmed that the engineered membrane exerts both osteoconductive and antibacterial properties, demonstrating its great potential for periodontal tissue engineering.

electrospinning, guided tissue regeneration, osteoconductive, periodontal regeneration, zinc oxide

Tissue engineering (TE) aims to mimic the complex environment where organogenesis takes place using advanced materials to recapitulate the tissue niche. Cells, three-dimensional scaffolds and signaling factors are the three main and essential components of TE. Over the years, materials and processes have become more and more sophisticated, allowing researchers to precisely tailor the final chemical, mechanical, structural and biological features of the designed scaffolds. In this review, we will pose the attention on two specific classes of naturally derived polymers: fibrous proteins and glycosaminoglycans (GAGs). These materials hold great promise for advances in the field of regenerative medicine as i) they generally undergo a fast remodeling in vivo favoring neovascularization and functional cells organization and ii) they elicit a negligible immune reaction preventing severe inflammatory response, both representing critical requirements for a successful integration of engineered scaffolds with the host tissue. We will discuss the recent achievements attained in the field of regenerative medicine by using proteins and GAGs, their merits and disadvantages and the ongoing challenges to move the current concepts to practical clinical application.

Natural polymers, Hydrogel scaffolds, Glycosaminoglycans (GAGs), Fibrous proteins, Regenerative medicine

Developing an efficient wound dressing has gained significant attention in the biomedical field, as infected wounds can cause severe complications that negatively impact human health. Creating an optimal environment for wound healing and tissue remodeling is crucial. Hydrogel dressings have become increasingly popular for skin repair due to their oxygen permeability, ability to absorb wound exudate, and moisture retention properties1. Additionally, electrospun materials offer unique properties such as biodegradability and the ability to control drug release, which makes them potential candidates for treating infected wounds2. Electrospinning is a simple method for producing ultrafine fibers that range from nano- to micrometers in diameter. Fibers can be used as drug delivery systems, allowing for controlled and on-demand drug release with the addition of stimuli-responsive particles. The main aim of this study was to develop a multi-functional 3D-printed hydrogel composite for infected wound healing. Ketoprofen-loaded poly(lactic-co-glycolic acid) (PLGA) mat incorporated with gold nanorods (AuNRs) was structured to the short filaments (SFs) using the aminolysis method (Fig. 1A). SFs were loaded into 3d printing ink composed of gelatine-methacrylate (GelMA) and alginate sodium (AS) (Fig. 1B). Introducing photo-responsive AuNRs in SFs significantly accelerated the ketoprofen release under near-infrared (NIR) light exposure. The ketoprofen release of the activated platform by NIR light, compared to the non-irradiated system, exhibited a significant elevation of the drug release resulting from the response to the stimuli (Fig. 1C). The composite dressing also showed excellent photo-thermal performance and good mechanical properties. The stability of the print before and after NIR irradiation was also investigated. Moreover, 3D-printed hydrogel demonstrated antibacterial activity under the NIR laser due to the photo-thermal activity, leading to E. coli eradication after multiple times of exposure. Evaluated tests and achieved results paved the way toward further composite’s ex vivo and in vivo application in the field of infected wounds.

In recent years, novel strategies and approaches to develop antimicrobial biomaterials have attracted increasing attention, targeting multi-functional systems to eliminate bacteria from membranes, surfaces, medical devices, infected sites, contact lenses, etc. More specifically, eradicating bacteria (both resident and exogenous) at the wound site is crucial to guarantee fast and effective wound healing without complications, while sterilization of personal protective equipment (e.g., face masks) makes it possible the safe re-use.[1,2] In this frame, photothermal therapy holds great potential since it can kill pathogenic bacteria with minimal invasiveness.[3]

In this study, plasmonic nanoparticles have been combined with biopolymers to provide the system with bactericide functions. More in detail, plasmonic gold nanorods (AuNRs) are encapsulated into electrospun matrices made of poly(lactic-co-glycolic acid) or polyacrylonitrile by loading into the polymeric solution prior to electrospinning or spraying on the already spun material to obtain the final composites (Figure 1A). The photo-thermal properties of the incorporated AuNRs are exploited to activate the near infrared (NIR)-mediated temperature response upon exposure to NIR light. By reaching a temperature > 55°C, the eradication of 99.5% of bacteria is achieved (Figure 1B), while the stability of the composite materials is maintained. Additionally, in vitro biocompatibility tests performed by culturing fibroblast cells onto the proposed systems show suitable biological properties with no toxic or inflammatory reactions. Taking into account the results, the biocompatible photothermal-responsive nanocomposites reveal their potential in photothermal therapy as a wound dressing and face mask coating.

Hard-to-heal wounds represent a significant public health problem that often carries a considerable risk of health complications with a negative impact on the quality of a patient's life [1]. The lack of effective treatments for skin damage can be attributed in part to the complexity of a physiological process occurring during the healing and microbial invasion from both resident and exogenous bacteria [2,3]. This research aimed to meet these challenges by developing a multifunctional core-shell nanofiber scaffold releasing the drugs and consisted antimicrobial peptides that hinder bacterial colonization while accelerating the healing process. Core-shell electrospun naofiber systems can control the biomolecule release profile providing sustainable drugs for wound healing. Implemented antimicrobial peptides effectively destroy a large spectrum of pathogens by contact with the cell membrane, decreasing the rate of antibiotic resistance in our healthcare system. The combination of the coaxial system with electrospinning allowed to obtain well-defined fibers. In this study, highly hydrophilic polyvinyl alcohol was confined into water-stable electrospun fibers using optimized polymer blends and cross-linking methods. All employed structures showed ideal morphology, construct's stability over time, and appropriate drug release profile as well as high-cell viability and antimicrobial properties. The developed multifunctional platforms represent a robust and valid candidate for fabricating skin dressings, accelerating the healing of patients' wounds while protecting against bacterial infection.

electrospinning, PVA, Green crosslinking

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.