Institute of Fundamental Technological Research

Atopic dermatitis (AD) is a chronic inflammatory skin disease with a complex etiology that lacks effective treatment. The therapeutic goals include alleviating symptoms, such as moisturizing and applying antibacterial and anti-inflammatory medications. Hence, there is an urgent need to develop a patch that effectively alleviates most of the AD symptoms. In this study, we employed a “green” cross-linking approach of poly(vinyl alcohol) (PVA) using glycerol, and we combined it with polyacrylonitrile (PAN) to fabricate core–shell (CS) nanofibers through electrospinning. Our designed structure offers multiple benefits as the core ensures controlled drug release and increases the strength of the patch, while the shell provides skin moisturization and exudate absorption. The efficient PVA cross-linking method facilitates the inclusion of sensitive molecules such as fermented oils. In vitro studies demonstrate the patches’ exceptional biocompatibility and efficacy in minimizing cell ingrowth into the CS structure containing argan oil, a property highly desirable for easy removal of the patch. Histological examinations conducted on an ex vivo model showed the nonirritant properties of developed patches. Furthermore, the eradication of Staphylococcus aureus bacteria confirms the potential use of CS nanofibers loaded with argan oil or norfloxacin, separately, as an antibacterial patch for infected AD wounds. In vivo patch application studies on patients, including one with AD, demonstrated ideal patches’ moisturizing effect. This innovative approach shows significant promise in enhancing life quality for AD sufferers by improving skin hydration and avoiding infections.

atopic dermatitis, core−shell electrospun nanofibers, antibacterial, mucoadhesive, moisturizing patch

Intervertebral disc (IVD) degeneration is a leading cause of lower back pain (LBP). Current treatments primarily address symptoms without halting the degenerative process. Cell transplantation offers a promising approach for early-stage IVD degeneration, but challenges such as cell viability, retention, and harsh host environments limit its efficacy. This study aimed to compare the injectability and biocompatibility of human nucleus pulposus cells (hNPC) attached to two types of microscaffolds designed for minimally invasive delivery to IVD. Microscaffolds are developed from poly(lactic-co-glycolic acid) (PLGA) using electrospinning and femtosecond laser structuration. These microscaffolds are tested for their physical properties, injectability, and biocompatibility. This study evaluates cell adhesion, proliferation, and survival in vitro and ex vivo within a hydrogel-based nucleus pulposus model. The microscaffolds demonstrate enhanced surface architecture, facilitating cell adhesion and proliferation. Laser structuration improved porosity, supporting cell attachment and extracellular matrix deposition. Injectability tests show that microscaffolds can be delivered through small-gauge needles with minimal force, maintaining high cell viability. The findings suggest that laser-structured PLGA microscaffolds are viable for minimally invasive cell delivery. These microscaffolds enhance cell viability and retention, offering potential improvements in the therapeutic efficiency of cell-based treatments for discogenic LBP.

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.

Hierarchical nanostructures fabricate by electrospinning in combination with light-responsive agents offer promising scenarios for developing novel activable antibacterial interfaces. This study introduces an innovative antibacterial face mask developed from poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) nanofibers integrated with indocyanine green (ICG), targeting the urgent need for effective antimicrobial protection for community health workers. The research focuses on fabricating and characterizing this nanofibrous material, evaluating the mask's mechanical and chemical properties, investigating its particle filtration, and assessing antibacterial efficacy under photothermal conditions for reactive oxygen species (ROS) generation. The PHBV/ICG nanofibers are produced using an electrospinning process, and the nanofibrous construct's morphology, structure, and photothermal response are investigated. The antibacterial efficacy of the nanofibers is tested, and substantial bacterial inactivation under both near-infrared (NIR) and solar irradiation is demonstrated due to the photothermal response of the nanofibers. The material's photothermal response is further analyzed under cyclic irradiation to simulate real-world conditions, confirming its durability and consistency. This study highlights the synergistic impact of PHBV and ICG in enhancing antibacterial activity, presenting a biocompatible and environmentally friendly solution. These findings offer a promising path for developing innovative face masks that contribute significantly to the field of antibacterial materials and solve critical public health challenges.

Functional antibacterial textiles fabricated from a hybrid of organic waste-derived and bio-inspired materials offer sustainable solutions for preventing microbial infections. In this work, we developed a novel antibacterial textile created through the valorization of spent coffee grounds (SCG). Electrospinning and electrospraying techniques were employed to integrate the biowaste within a polymeric nanofiber matrix, ensuring uniform particle distribution and providing structural support for enhanced applicability. Modification with polydopamine (PDA) significantly enhanced the textile's photothermal performance. Specific attention was paid to understanding the relation between temperature change and key variables, including the surrounding liquid volume, textile layer stacking, and applied laser power. Developed platforms demonstrated excellent photothermal stability. While the SCG-based textile demonstrated exceptional biocompatibility, the PDA-modified textile effectively eradicated Staphylococcus aureus (S. aureus) under near-infrared (NIR) irradiation. The developed textiles in our work demonstrate a dynamic balance between biocompatibility and on-demand antibacterial functionality, offering adaptable solutions in accordance with the desired application.

Organic waste valorization, Spent coffee grounds, Micro-nanostructured textiles, Bio-inspired photothermal agents, Polydopamine, Antibacterial textiles

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

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.

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.

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