Instytut Podstawowych Problemów Techniki

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Recently, a growing need for sustainable materials in various industries, especially biomedical, environmental, and packaging applications, has been observed. Poly(vinyl alcohol) (PVA) is a versatile and widely used polymer, valued for its biocompatibility, water solubility, and easy processing, e.g., forming nanofibers via electrospinning. As a result of cross-linking, PVA turns into a three-dimensional structure—hydrogel with unusual sorption properties and mimicry of biological tissues. However, traditional cross-linking methods often involve toxic chemicals and harsh conditions, which can limit its eco-friendly potential and raise concerns about environmental impact. “Green” cross-linking approaches, such as the use of natural cross-linkers, freeze–thawing, enzymatic processes, irradiation, heat treatment, or immersion in alcohol, offer an environmentally friendly alternative that aligns with global trends toward sustainability. These methods not only reduce the use of harmful substances but also enhance the biodegradability and safety of the materials. By reviewing and analyzing the latest advancements in “green” PVA cross-linking approaches, this review provides a comprehensive overview of current techniques, their advantages, limitations, and potential applications. The main emphasis is placed on PVA nanostructured forms and applications of PVA-based biomaterials in areas such as wound dressings, drug delivery systems, tissue engineering, biological filters, and biosensors. Moreover, this article will contribute to the broader scientific understanding of how the materials based on PVA can be optimized both in terms of “greener” and safer production, as well as adjusting the final platform properties.

Słowa kluczowe:

cross-linking, eco-friendly approaches, nanostructured biomaterials, poly(vinyl alcohol)

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The disruption of homeostasis in the tissue microenvironment following skin injury necessitates the provision of a supportive niche for cells to facilitate the restoration of functional tissue. A meticulously engineered cell-scaffold biointerface is essential for eliciting the desired cellular responses that underpin therapeutic efficacy. To address this, we fabricated an electrospun poly-(L-lactide) (PLLA) cell scaffold enriched with graphene oxide (GO) and gold nanoparticles (AuNPs). Comprehensive characterization assessed the scaffolds’ microstructural, elemental, thermal, and mechanical properties. In vitro investigations evaluated the biocompatibility, adhesive and regenerative capabilities of the scaffolds utilizing human keratinocytes (HEKa), fibroblasts (HFFF2), and reconstructed epidermis (EpiDerm™) models. The results demonstrated that the incorporation of the GO-Au composite substantially altered the nanotopography and mechanical properties of the PLLA fibers. Cells effectively colonized the PLLA + GO-Au scaffold while preserving their structural morphology. Furthermore, PLLA + GO-Au treatment resulted in increased epidermal thickness and reduced tissue porosity. The scaffold exerted a significant influence on actin cytoskeleton architecture, facilitating cell adhesion through the upregulation of integrins, E-cadherin, and β-catenin. Keratinocytes exhibited enhanced secretion of growth factors (AREG, bFGF, EGF, EGF R), while fibroblast secretion remained stable. These findings endorse the scaffold’s potential for regulating cellular fate and preventing hypertrophic tissue formation in skin tissue engineering.

Słowa kluczowe:

Wound healing,Electrospun fibers,Graphene oxide,Gold nanoparticles,Proregenerative cell scaffold

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This study explores the development of a photo-responsive bicomponent electrospun platform and its drug delivery capabilities. This platform is composed of two polymers of poly(lactide-co-glycolide) (PLGA) and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV). Then, the platform is decorated with plasmonic gold nanostars (Au NSs) that are capable of on-demand drug release. Using Rhodamine-B (RhB) as a model drug, the drug release behavior of the bi-polymer system is compared versus homopolymer fibers. The RhB is incorporated in the PHBV part of the platform, which provides a more sustained drug release, both in the absence and presence of near-infrared (NIR) irradiation. Under NIR exposure, thermal imaging reveals a notable increase in surface temperature, facilitating enhanced drug release. Furthermore, the platform demonstrates on-demand drug release upon multiple NIR irradiation cycles. This platform offers a promising approach for stimuli-responsive drug delivery, making it a strong candidate for on-demand therapy applications.

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The mechanical mismatch between microelectrode of brain–machine interfaces (BMIs) and soft brain tissue during electrophysiological investigations leads to inflammation, glial scarring, and compromising performance. Herein, a nanostructured, stimuli-responsive, conductive, and semi-interpenetrating polymer network hydrogel-based coated BMIs probe is introduced. The system interface is composed of a cross-linkable poly(N-isopropylacrylamide)-based copolymer and regioregular poly[3-(6-methoxyhexyl)thiophene] fabricated via electrospinning and integrated into a neural probe. The coating's nanofibrous architecture offers a rapid swelling response and faster shape recovery compared to bulk hydrogels. Moreover, the smart coating becomes more conductive at physiological temperatures, which improves signal transmission efficiency and enhances its stability during chronic use. Indeed, detecting acute neuronal deep brain signals in a mouse model demonstrates that the developed probe can record high-quality signals and action potentials, favorably modulating impedance and capacitance. Evaluation of in vivo neuronal activity and biocompatibility in chronic configuration shows the successful recording of deep brain signals and a lack of substantial inflammatory response in the long-term. The development of conducting fibrous hydrogel bio-interface demonstrates its potential to overcome the limitations of current neural probes, highlighting its promising properties as a candidate for long-term, high-quality detection of neuronal activities for deep brain applications such as BMIs.

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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.

Słowa kluczowe:

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

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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.

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Bone defects resulting from congenital anomalies and trauma pose significant clinical challenges for orthopedics surgeries, where bone tissue engineering (BTE) aims to address these challenges by repairing defects that fail to heal spontaneously. Despite numerous advances, BTE still faces several challenges, i.e., difficulties in detecting and tracking implanted cells, high costs, and regulatory approval hurdles. Biomaterials promise to revolutionize bone grafting procedures, heralding a new era of regenerative medicine and advancing patient outcomes worldwide. Specifically, novel bioactive biomaterials have been developed that promote cell adhesion, proliferation, and differentiation and have osteoconductive and osteoinductive characteristics, stimulating tissue regeneration and repair, particularly in complex skeletal defects caused by trauma, degeneration, and neoplasia. A wide array of biological therapeutics for bone regeneration have emerged, drawing from the diverse spectrum of gene therapy, immune cell interactions, and RNA molecules. This review will provide insights into the current state and potential of future strategies for bone regeneration.

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Bone defects and fractures present significant clinical challenges, particularly in orthopedic and maxillofacial applications. While minor bone defects may be capable of healing naturally, those of a critical size necessitate intervention through the use of implants or grafts. The utilization of traditional methodologies, encompassing autografts and allografts, is constrained by several factors. These include the potential for donor site morbidity, the restricted availability of suitable donors, and the possibility of immune rejection. This has prompted extensive research in the field of bone tissue engineering to develop advanced synthetic and bio-derived materials that can support bone regeneration. The optimal bone substitute must achieve a balance between biocompatibility, bioresorbability, osteoconductivity, and osteoinductivity while simultaneously providing mechanical support during the healing process. Recent innovations include the utilization of three-dimensional printing, nanotechnology, and bioactive coatings to create scaffolds that mimic the structure of natural bone and enhance cell proliferation and differentiation. Notwithstanding the advancements above, challenges remain in optimizing the controlled release of growth factors and adapting materials to various clinical contexts. This review provides a comprehensive overview of the current advancements in bone substitute materials, focusing on their biological mechanisms, design considerations, and clinical applications. It explores the role of emerging technologies, such as additive manufacturing and stem cell-based therapies, in advancing the field. Future research highlights the need for multidisciplinary collaboration and rigorous testing to develop advanced bone graft substitutes, improving outcomes and quality of life for patients with complex defects.

Słowa kluczowe:

bone regeneration, fractures, bone grafts, bone substitutes, bone implants

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Bacterial infections can lead to severe complications that adversely affect wound healing. Thus, the development of effective wound dressings has become a major focus in the biomedical field, as current solutions remain insufficient for treating complex, particularly chronic wounds. Designing an optimal environment for healing and tissue regeneration is essential. This study aims to optimize a multi-functional 3D printed hydrogel for infected wounds. A dexamethasone (DMX)-loaded electrospun mat, incorporated with gold nanorods (AuNRs), is structured into short filaments (SFs). The SFs are 3D printed into gelatine methacrylate (GelMA) and sodium alginate (SA) scaffold. The photo-responsive AuNRs within SFs significantly enhanced DXM release when exposed to near-infrared (NIR) light. The material exhibits excellent photothermal properties, biocompatibility, and antibacterial activity under NIR irradiation, effectively eliminating Staphylococcus aureus and Escherichia coli in vitro. In vivo, material combined with NIR light treatment facilitate infectes wound healing, killing S. aureus bacteria, reduced inflammation, and induced vascularization. The final materials’ shape can be adjusted to the skin defect, release the anti-inflammatory DXM on-demand, provide antimicrobial protection, and accelerate the healing of chronic wounds.

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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.

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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.

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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.

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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.

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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.

Słowa kluczowe:

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

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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.

Słowa kluczowe:

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

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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.

Słowa kluczowe:

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

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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.

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Nanostructuring is a process involving surface manipulation at the nanometric level, which improves the mechanical and biological properties of biomaterials. Specifically, it affects the mechanotransductive perception of the microenvironment of cells. Mechanical force conversion into an electrical or chemical signal contributes to the induction of a specific cellular response. The relationship between the cells and growth surface induces a biointerface-modifying cytophysiology and consequently a therapeutic effect. In this study, we present the fabrication of graphene oxide (GO)-based nanofilms decorated with metallic nanoparticles (NPs) as potential coatings for biomaterials. Our investigation showed the effect of decorating GO with metallic NPs for the modification of the physicochemical properties of nanostructures in the form of nanoflakes and nanofilms. A comprehensive biocompatibility screening panel revealed no disturbance in the metabolic activity of human fibroblasts (HFFF2) and bone marrow stroma cells (HS-5) cultivated on the GO nanofilms decorated with gold and copper NPs, whereas a significant cytotoxic effect of the GO nanocomplex decorated with silver NPs was demonstrated. The GO nanofilm decorated with gold NPs beneficially managed early cell adhesion as a result of the transient upregulation of α1β5 integrin expression, acceleration of cellspreading, and formation of elongated filopodia. Additionally, the cells, sensing the substrate derived from the nanocomplex enriched with gold NPs, showed reduced elasticity and altered levels of vimentin expression. In the future, GO nanocomplexes decorated with gold NPs can be incorporated in the structure of architecturally designed biomimetic biomaterials as biocompatible nanostructuring agents with proadhesive properties.

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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.

Słowa kluczowe:

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

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In recent times, the use of personal protective equipment, such as face masks or respirators, is becoming more and more critically important because of common pollution; furthermore, face masks have become a necessary element in the global fight against the COVID-19 pandemic. For this reason, the main mission of scientists has become the development of face masks with exceptional properties that will enhance their performance. The versatility of electrospun polymer nanofibers has determined their suitability as a material for constructing “smart” filter media. This paper provides an overview of the research carried out on nanofibrous filters obtained by electrospinning. The progressive development of the next generation of face masks whose unique properties can be activated in response to a specific external stimulus is highlighted. Thanks to additional components incorporated into the fiber structure, filters can, for example, acquire antibacterial or antiviral properties, self-sterilize the structure, and store the energy generated by users. Despite the discovery of several fascinating possibilities, some of them remain unexplored. Stimuli-responsive filters have the potential to become products of large-scale availability and great importance to society as a whole.

Słowa kluczowe:

nanostructured face masks, stimuli-responsive nanomaterials, electrospun nanofibers, active filtration, smart filters, COVID-19, antipathogen

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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.

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Cranial bone loss presents a major clinical challenge and new regenerative approaches to address craniofacial reconstruction are in great demand. Induced pluripotent stem cell (iPSC) differentiation is a powerful tool to generate mesenchymal stromal cells (MSCs). Prior research demonstrated the potential of bone marrow-derived MSCs (BM-MSCs) and iPSC-derived mesenchymal progenitor cells via the neural crest (NCC-MPCs) or mesodermal lineages (iMSCs) to be promising cell source for bone regeneration. Overexpression of human recombinant bone morphogenetic protein (BMP)6 efficiently stimulates bone formation. The study aimed to evaluate the potential of iPSC-derived cells via neural crest or mesoderm overexpressing BMP6 and embedded in 3D printable bio-ink to generate viable bone graft alternatives for cranial reconstruction. Cell viability, osteogenic potential of cells, and bio-ink (Ink-Bone or GelXa) combinations were investigated in vitro using bioluminescent imaging. The osteogenic potential of bio-ink-cell constructs were evaluated in osteogenic media or nucleofected with BMP6 using qRT-PCR and in vitro μCT. For in vivo testing, two 2 mm circular defects were created in the frontal and parietal bones of NOD/SCID mice and treated with Ink-Bone, Ink-Bone + BM-MSC-BMP6, Ink-Bone + iMSC-BMP6, Ink-Bone + iNCC-MPC-BMP6, or left untreated. For follow-up, µCT was performed at weeks 0, 4, and 8 weeks. At the time of sacrifice (week 8), histological and immunofluorescent analyses were performed. Both bio-inks supported cell survival and promoted osteogenic differentiation of iNCC-MPCs and BM-MSCs in vitro. At 4 weeks, cell viability of both BM-MSCs and iNCC-MPCs were increased in Ink-Bone compared to GelXA. The combination of Ink-Bone with iNCC-MPC-BMP6 resulted in an increased bone volume in the frontal bone compared to the other groups at 4 weeks post-surgery. At 8 weeks, both iNCC-MPC-BMP6 and iMSC-MSC-BMP6 resulted in an increased bone volume and partial bone bridging between the implant and host bone compared to the other groups. The results of this study show the potential of NCC-MPC-incorporated bio-ink to regenerate frontal cranial defects. Therefore, this bio-ink-cell combination should be further investigated for its therapeutic potential in large animal models with larger cranial defects, allowing for 3D printing of the cell-incorporated material.

Słowa kluczowe:

induced pluripotnet stem cells, bone, 3d-printing

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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.

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Adhesive and stretchable nanofibrous hydrogels have attracted extensive attraction in wound dressings, especially for joint wound treatment. However, adhesive hydrogels tend to display poor stretchable behavior. It is still a significant challenge to integrate excellent adhesiveness and stretchability in a nanofibrous hydrogel. Herein, a highly adhesive, stretchable, and breathable nanofibrous hydrogel was developed via an in situ hybrid cross-linking strategy of electrospun nanofibers comprising dopamine (DA) and gelatin methacryloyl (GelMA). Benefiting from the balance of cohesion and adhesion based on photocross-linking of methacryloyl (MA) groups in GelMA and the chemical/physical reaction between GelMA and DA, the nanofibrous hydrogels exhibited tunable adhesive and mechanical properties through varying MA substitution degrees of GelMA. The optimized GelMA60-DA exhibited 2.0 times larger tensile strength (2.4 MPa) with an elongation of about 200%, 2.3 times greater adhesive strength (9.1 kPa) on porcine skin, and 3.1 times higher water vapor transmission rate (10.9 kg m–2 d–1) compared with gelatin nanofibrous hydrogels. In parallel, the GelMA60-DA nanofibrous hydrogels could facilitate cell growth and accelerate wound healing. This work presented a type of breathable nanofibrous hydrogels with excellent adhesive and stretchable capacities, showing great promise as wound dressings.

Słowa kluczowe:

nanofibrous hydrogels, hybrid cross-linking, adhesivity, stretchability, breathable capability

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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.

Słowa kluczowe:

Smart materials, Plasmonic hydrogel, Biosensing

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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.

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The spread of antimicrobial resistance requires the development of novel strategies to combat superbugs. Bacteriolytic enzymes (enzybiotics) that selectively eliminate pathogenic bacteria, including resistant strains and biofilms, are attractive alternatives to antibiotics, also as a component of a new generation of antimicrobial wound dressings. AuresinePlus is a novel, engineered enzybiotic effective against Staphylococcus aureus—one of the most common pathogenic bacteria, found in infected wounds with a very high prevalence of antibiotic resistance. We took advantage of its potent lytic activity, selectivity, and safety to prepare a set of biodegradable PLGA/chitosan fibers generated by electrospinning. Our aim was to produce antimicrobial nonwovens to deliver enzybiotics directly to the infected wound and better control its release and activity. Three different methods of enzyme immobilization were tested: physical adsorption on the previously hydrolyzed surface, and covalent bonding formation using N-hydroxysuccinimide/N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide (NHS/EDC) or glutaraldehyde (GA). The supramolecular structure and functional properties analysis revealed that the selected methods resulted in significant development of nanofibers surface topography resulting in an efficient enzybiotic attachment. Both physically adsorbed and covalently bound enzymes (by NHS/EDC method) exhibited prominent antibacterial activity. Here, we present the extensive comparison between methods for the effective attachment of the enzybiotic to the electrospun nonwovens to generate biomaterials effective against antibiotic-resistant strains. Our intention was to present a comprehensive proof-of-concept study for future antimicrobial wound dressing development.

Słowa kluczowe:

antibacterial wound dressings, enzybiotic, fibers functionalization, electrospun wound dressings, Staphylococcus aureus

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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.

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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.

Słowa kluczowe:

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

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This work describes the morphological, optical, and thermo‐optical properties of a temperature‐sensitive hydrogel poly(N‐isopropylacrylamide‐co‐N‐isopropylmethacrylamide) [P(NIPAm‐co‐NIPMAm]) film containing a specific amount of gold nanorods (GNRs). The light‐induced thermoplasmonic heating of GNRs is used to control the optical scattering of an initially transparent hydrogel film. A hydrated P(NIPAm‐co‐NIPMAm) film is optically clear at room temperature. When heated to temperatures over 37 °C via light irradiation with a resonant source (λ = 810 nm) to the GNRs, a reversible phase transition from a swollen hydrated state to a shrunken dehydrated state occurs. This phenomenon causes a drastic and reversible change in the optical transparency from a clear to an opaque state. A significant red shift (≈30 nm) of the longitudinal band can also be seen due to an increased average refractive index surrounding the GNRs. This change is in agreement with an ad hoc theoretical model which uses a modified Gans theory for ellipsoidal nanoparticles. Morphological analysis of the composite film shows the presence of well‐isolated and randomly dispersed GNRs. Thermo‐optical experiments demonstrate an all‐optically controlled light attenuator (65% contrast ratio) which can be easily integrated in several modern optical applications such as smart windows and light‐responsive optical attenuators.

Słowa kluczowe:

active plasmonics, gold nanorods, hydrogels, optical attenuators, optical transparency, plasmonic nanoparticles, polymers

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The poor intrinsic mechanical properties of chitosan hydrogels have greatly hindered their practical applications. Inspired by nature, we proposed a strategy to enhance the mechanical properties of chitosan hydrogels by construction of a nanofibrous and cellular architecture in the hydrogel without toxic chemical crosslinking. To this end, electrospun nanofibers including cellulose acetate, polyacrylonitrile, and SiO2 nanofibers were introduced into chitosan hydrogels by homogenous dispersion and lyophilization. With the addition of 30% cellulose acetate nanofibers, the cellular structure could be maintained even in water without crosslinking, and integration of 60% of the nanofibers could guarantee the free-standing structure of the chitosan hydrogel with a low solid content of 1%. Moreover, the SiO2 nanofiber-reinforced chitosan (SiO2 NF/CS) three-dimensional (3D) matrices exhibit complete shape recovery from 80% compressive strain and excellent injectability. The cellular architecture and nanofibrous structure in the SiO2 NF/CS matrices are beneficial for human mesenchymal stem cell adhesion and stretching. Furthermore, the SiO2 NF/CS matrices can also act as powerful vehicles for drug delivery. As an example, bone morphogenetic protein 2 could be immobilized on SiO2 NF/CS matrices to induce osteogenic differentiation. Together, the electrospun nanofiber-reinforced 3D chitosan matrices exhibited improved mechanical properties and enhanced biofunctionality, showing great potential in tissue engineering.

Słowa kluczowe:

chitosan hydrogel, electrospun nanofiber, mechanical property, nanofibrous matrix, tissue engineering

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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.

Słowa kluczowe:

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

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Nanofibrous materials find a wide range of applications, such as vascular grafts, tissue-engineered scaffolds, or drug delivery systems. This phenomenon can be attributed to almost arbitrary biomaterial modification opportunities created by a multitude of polymers used to form nanofibers, as well as by surface functionalization methods. Among these applications, the hemostatic activity of nanofibrous materials is gaining more and more interest in biomedical research. It is therefore crucial to find both materials and nanofiber structural properties that affect organism responses. The present review critically analyzes the response of blood elements to natural and synthetic polymers, and their blends and composites. Also assessed in this review is the incorporation of pro-coagulative substances or drugs that can decrease bleeding time. The review also discusses the main animal models that were used to assess hemostatic agent safety and effectiveness.

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blood-biomaterial interactions, coagulation, electrospinning, nanofibers, platelets, hemorrhage

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Materials for the treatment of cancer have been studied comprehensively over the past few decades. Among the various kinds of biomaterials, polymer-based nanomaterials represent one of the most interesting research directions in nanomedicine because their controlled synthesis and tailored designs make it possible to obtain nanostructures with biomimetic features and outstanding biocompatibility. Understanding the chemical and physical mechanisms behind the cascading stimuli-responsiveness of smart polymers is fundamental for the design of multifunctional nanomaterials to be used as photothermal agents for targeted polytherapy. In this review, we offer an in-depth overview of the recent advances in polymer nanomaterials for photothermal therapy, describing the features of three different types of polymer-based nanomaterials. In each case, we systematically show the relevant benefits, highlighting the strategies for developing light-controlled multifunctional nanoplatforms that are responsive in a cascade manner and addressing the open issues by means of an inclusive state-of-the-art review. Moreover, we face further challenges and provide new perspectives for future strategies for developing novel polymeric nanomaterials for photothermally assisted therapies.

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Highly efficient single-material organic solar cells (SMOCs) based on fullerene-grafted polythiophenes were fabricated by incorporating electrospun one-dimensional (1D) nanostructures obtained from polymer chain stretching. Poly(3-alkylthiophene) chains were chemically tailored in order to reduce the side effects of charge recombination which severely affected SMOC photovoltaic performance. This enabled us to synthesize a donor–acceptor conjugated copolymer with high solubility, molecular weight, regioregularity, and fullerene content. We investigated the correlations among the active layer hierarchical structure given by the inclusion of electrospun nanofibers and the solar cell photovoltaic properties. The results indicated that SMOC efficiency can be strongly increased by optimizing the supramolecular and nanoscale structure of the active layer, while achieving the highest reported efficiency value (PCE = 5.58%). The enhanced performance may be attributed to well-packed and properly oriented polymer chains. Overall, our work demonstrates that the active material structure optimization obtained by including electrospun nanofibers plays a pivotal role in the development of efficient SMOCs and suggests an interesting perspective for the improvement of copolymer-based photovoltaic device performance using an alternative pathway.

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The recent progress in bioengineering has created great interest in the dynamics and manipulation of long, deformable macromolecules interacting with fluid flow. We report experimental data on the cross-flow migration, bending, and buckling of extremely deformable hydrogel nanofilaments conveyed by an oscillatory flow into a microchannel. The changes in migration velocity and filament orientation are related to the flow velocity and the filament's initial position, deformation, and length. The observed migration dynamics of hydrogel filaments qualitatively confirms the validity of the previously developed worm-like bead-chain hydrodynamic model. The experimental data collected may help to verify the role of hydrodynamic interactions in molecular simulations of long molecular chains dynamics.

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Composite nanofibers made of a polyaniline-based polymer blend and different thiol-capped metal nanoparticles were prepared using ex situ synthesis and electrospinning technique. The effects of the nanoparticle composition and chemical structure on the electrical properties of the nanocomposites were investigated. This study confirmed that Brust's procedure is an effective method for the synthesis of sub-10 nm silver, gold, and silver-gold alloy nanoparticles protected with different types of thiols. Electron microscopy results demonstrated that electrospinning is a valuable technique for the production of composite nanofibers with similar morphology and revealed that nanofillers are well-dispersed into the polymer matrix. X-ray diffraction tests proved the lack of a significant influence of the nanoparticle chemical structure on the polyaniline chain arrangement. However, the introduction of conductive nanofillers in the polymer matrix influences the charge transport noticeably improving electrical conductivity. The enhancement of electrical properties is mediated by the nanoparticle capping layer structure. The metal nanoparticle core composition is a key parameter, which exerted a significant influence on the conductivity of the nanocomposites. These results prove that the proposed method can be used to tune the electrical properties of nanocomposites.

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In this article, we report on the production by electrospinning of P3HT/PEO, P3HT/PEO/GO, and P3HT/PEO/rGO nanofibers in which the filler is homogeneously dispersed and parallel oriented along the fibers axis. The effect of nanofillers' presence inside nanofibers and GO reduction was studied, in order to reveal the influence of the new hierarchical structure on the electrical conductivity and mechanical properties. An in-depth characterization of the purity and regioregularity of the starting P3HT as well as the morphology and chemical structure of GO and rGO was carried out. The morphology of the electrospun nanofibers was examined by both scanning and transmission electron microscopy. The fibrous nanocomposites are also characterized by differential scanning calorimetry to investigate their chemical structure and polymer chains arrangements. Finally, the electrical conductivity of the electrospun fibers and the elastic modulus of the single fibers are evaluated using a four-point probe method and atomic force microscopy nanoindentation, respectively. The electrospun materials crystallinity as well as the elastic modulus increase with the addition of the nanofillers while the electrical conductivity is positively influenced by the GO reduction.

Słowa kluczowe:

electrospun composite nanofibers, poly(3-hexylthiophene), graphene oxide, electrical conductivity, mechanical properties

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The role of mechanical properties is essential to understand molecular, biological materials, and nanostructures dynamics and interaction processes. Atomic force microscopy (AFM) is the most commonly used method of direct force evaluation, but due to its technical limitations this single probe technique is unable to detect forces with femtonewton resolution. In this paper we present the development of a combined atomic force microscopy and optical tweezers (AFM/OT) instrument. The focused laser beam, on which optical tweezers are based, provides us with the ability to manipulate small dielectric objects and to use it as a high spatial and temporal resolution displacement and force sensor in the same AFM scanning zone. We demonstrate the possibility to develop a combined instrument with high potential in nanomechanics, molecules manipulation and biological studies. AFM/OT equipment is described and characterized by studying the ability to trap dielectric objects and quantifying the detectable and applicable forces. Finally, optical tweezers calibration methods and instrument applications are given.

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optical trap, nanomanipulation, nanomechanics, femtonewton forces

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An excessive glutamate level can result in excitotoxic damage and death of central nervous system (CNS) cells, and is involved in the pathogenesis of many CNS diseases. It may also be related to a failure of the blood-spinal cord barrier (BSCB). This study was aimed at examining the effects of extended administration of monosodium glutamate on the BSCB and spinal cord cells in adult male Wistar rats. The glutamate was delivered by subarachnoidal application of glutamate-carrying electrospun nanofiber mat dressing at the lumbar enlargement level. Half of the rats with the glutamate-loaded mat application were treated systemically with the histone deacetylase inhibitor valproic acid. A group of intact rats and a rat group with subarachnoidal application of an ‘empty’ (i.e., carrying no glutamate) nanofiber mat dressing served as controls. All the rats were euthanized three weeks later and lumbar fragments of their spinal cords were harvested for histological, immunohistochemical and ultrastructural studies. The samples from controls revealed normal parenchyma and BSCB morphology, whereas those from rats with the glutamate-loaded nanofiber mat dressing showed many intraparenchymal microhemorrhages of variable sizes. The capillaries in the vicinity of the glutamate-carrying dressing (in the meninges and white matter alike) were edematous and leaky, and their endothelial cells showed degenerative changes: extensive swelling, enhanced vacuo­lization and the presence of vascular intraluminal projections. However, endothelial tight junctions were generally well preserved. Some endothelial cells were dying by necrosis or apoptosis. The adjacent parenchyma showed astrogliosis with astrocytic hypertrophy and swelling of perivascular astrocytic feet. Neurons in the parenchyma revealed multiple symptoms of degeneration, including, inter alia, perikaryal, dendritic and axonal swelling, and destruction of organelles. All the damage symptoms were slightly less severe in the rats given valproic acid treatment, and were absent from both the intact rats and the rats with ‘empty’ nanofiber mat dressing. These results demonstrate that glutamate-loaded nanofiber mat dressing can locally create glutamate levels capable of damaging BSCB and that the resulting damage can be mitigated with concurrent systemic valproate treatment.

Słowa kluczowe:

astrocyte, blood-spinal cord barrier, CNS damage, degeneration, endothelium, excitotoxicity, glutamate, neuron, valproate, vessels

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Recent biomedical hydrogels applications require the development of nanostructures with controlled diameter and adjustable mechanical properties. Here we present a technique for the production of flexible nanofilaments to be used as drug carriers or in microfluidics, with deformability and elasticity resembling those of long DNA chains. The fabrication method is based on the core-shell electrospinning technique with core solution polymerisation post electrospinning. Produced from the nanofibers highly deformable hydrogel nanofilaments are characterised by their Brownian motion and bending dynamics. The evaluated mechanical properties are compared with AFM nanoindentation tests.

Correction: Hydrogel Nanofilaments via Core-Shell Electrospinning, Nakielski P., Pawłowska S., Pierini F., Liwińska W., Hejduk P., Zembrzycki K., Zabost E., Kowalewski T.A., PLOS ONE, ISSN: 1932-6203, DOI: 10.1371/journal.pone.0133458, Vol.10, No.7, pp.e0133458-1-2, 2015

Słowa kluczowe:

Gels, Nanomaterials, Atomic force microscopy, Polymerization, Bending, Mass diffusivity, Mechanical properties, Hydrodynamics

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Drug delivery systems based on nanofibrous mats appear to be a promising healing practice for preventing brain neurodegeneration after surgery. One of the problems encountered during planning and constructing optimal delivery system based on nanofibrous mats is the estimation of parameters crucial for predicting drug release dynamics. This study describes our experimental setup allowing for spatial and temporary evaluation of drug release from nanofibrous polymers to obtain data necessary to validate appropriate numerical models. We applied laser light sheet method to illuminate released fluorescent drug analog and CCD camera for imaging selected cross-section of the investigated volume. Transparent hydrogel was used as a brain tissue phantom. The proposed setup allows for continuous observation of drug analog (fluorescent dye) diffusion for time span of several weeks. Images captured at selected time intervals were processed to determine concentration profiles and drug release kinetics. We used presented method to evaluate drug release from several polymers to validate numerical model used for optimizing nanofiber system for neuroprotective dressing.

Słowa kluczowe:

neural therapy, brain phantom, drug delivery, laser light sheet, computational modeling, nanofibers

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The purpose of this study was to compare: a new five-layered poly (L–lactide–co–caprolactone) (PLC) membrane and small intestinal submucosa (SIS) as a control in rat urinary bladder wall regeneration. The five-layered poly (L–lactide–co–caprolactone) membrane was prepared by an electrospinning process. Adipose tissue was harvested from five 8-week old male Wistar rats. Adipose derived stem cells (ADSCs) were seeded in a density of 3×106 cells/cm2 onto PLC membrane and SIS scaffolds, and cultured for 5-7 days in the stem cell culture medium. Twenty male Wistar rats were randomly divided into five equal groups. Augmentation cystoplasty was performed in a previously created dome defect. Groups: (I) PLC+ 3×106ADSCs; (II) SIS+ 3×106ADSCs; (III) PLC; (IV) SIS; (V) control. Cystography was performed after three months. The reconstructed urinary bladders were evaluated in H&E and Masson's trichrome staining. Regeneration of all components of the normal urinary bladder wall was observed in bladders augmented with cell-seeded SIS matrices. The urinary bladders augmented with SIS matrices without cells showed fibrosis and graft contraction. Bladder augmentation with the PLC membrane led to numerous undesirable events including: bladder wall perforation, fistula or diverticula formation, and incorporation of the reconstructed wall into the bladder lumen. The new five-layered poly (L–lactide–co–caprolactone) membrane possesses poorer potential for regenerating the urinary bladder wall compared with SIS scaffold.

Słowa kluczowe:

urinary bladder regeneration, electrospinning

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Traumatic/surgical brain injury can initiate a cascade of pathological changes that result, in the long run, in severe damage of brain parenchyma and encephalopathy. Excessive scarring can also interfere with brain function and the glial scar formed may hamper the restoration of damaged brain neural pathways. In this preliminary study we aimed to investigate the effect of dressing with an L-lactide-caprolactone copolymer nanofiber net on brain wound healing and the fate of the formed glial scar. Our rat model of surgical brain injury (SBI) of the fronto-temporal region of the sensorimotor cortex imitates well the respective human neurosurgery situation. Brains derived from SBI rats with net-undressed wound showed massive neurodegeneration, entry of systemic inflammatory cells into the brain parenchyma and the astrogliosis due to massive glial scar formation. Dressing of the wound with the nanofiber net delayed and reduced the destructive phenomena. We observed also a reduction in the scar thickness. The observed modification of local inflammation and cicatrization suggest that nanofiber nets could be useful in human neurosurgery.

Słowa kluczowe:

brain injury, L-lactide-caprolactone copolymer nanofiber net, glial scar, neurodegeneration

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(Sub)chronic local drug application is clearly superior to systemic administration, but may be associated with substantial obstacles, particularly regarding the applications to highly sensitive central nervous system (CNS) structures that are shielded from the outer environment by the blood-brain barrier. Violation of the integrity of the barrier and CNS tissues by a permanently implanted probe or cannula meant for prolonged administration of drugs into specific CNS structures can be a severe confounding factor because of the resulting inflammatory reactions. In this study, we tested the utility of a novel way for (sub)chronic local delivery of highly active (i.e., used in very low amounts) drugs to the rat spinal cord employing a non-woven nanofiber mat dressing. To this end, we compared the morphology and motoneuron ( + ) counts in spinal cord cervical and lumbar segments between rats with glutamate-loaded nanofiber mats applied to the lumbar enlargement and rats with analogical implants carrying no glutamate. Half of the rats with glutamate-loaded implants were given daily valproate treatment to test its potential for counteracting the detrimental effects of glutamate excess. The mats were prepared in-house by electrospinning of an emulsion made of a solution of the biocompatible and biodegradable poly(L-lactide-co-caprolactone) polymer in a mixture of organic solvents, an aqueous phase with or without monosodium glutamate, and sodium dodecyl sulfate as an emulsifier; the final glutamate content was 1.4 µg/mg of the mat. Three weeks after mat implantation there was no inflammation or considerable damage of the spinal cord motoneuron population in the rats with the subarachnoid dressing of a glutamate-free mat, whereas the spinal cords of the rats with glutamate-loaded nanofiber mats showed clear symptoms of excitotoxic damage and a substantial increase in dying/damaged motoneuron numbers in both segments studied. The rats given systemic valproate treatment showed significantly lower percentages of damaged/dying motoneurons in their lumbar enlargements. These results demonstrate the capacity of nanofiber mats for generation of neurotoxic glutamate in the rat CNS. However, the tested nanofiber mats need further improvements aimed at extending the period of effective drug release and rendering the release more steady.

Słowa kluczowe:

CNS injury, electrospinning, excitotoxicity, glutamate, motoneuron, nanofibers, neurodegeneration, spinal cord, valproate

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W pracy przedstawiono symulacje metodą elementów skończonych procesu desorpcji leku z powierzchni nanowłókien oraz dyfuzji wewnątrz porowatego materiału w zależności od wzajemnej konfiguracji włókien. Zbadano uwalnianie leku w różnych typach ułożenia włókien w materiale od idealnie ukierunkowanych po włókna ułożone nieregularnie. Dodatkowo przeanalizowano wpływ lokalnego zagęszczenia włókien i porowatości materiału na proces dyfuzji w macie. Przedstawiony model porównano z wynikiem eksperymentalnym uwalniania Rodaminy B z elektroprzędzonych nanowłókien oraz rozwiązaniem analitycznym dyfuzji z płaskiej płyty z homogenicznie rozmieszczonym lekiem. Celem przeprowadzonych obliczeń jest znalezienie kluczowych parametrów materiału, stosowanego jako system uwalniania leków w zapobieganiu neurodegeneracji po operacjach neurochirurgicznych.

Słowa kluczowe:

desorpcja, dyfuzja, FRAP, nanowłókna, uwalnianie leków

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This work presents our attempts to characterize release of two model drugs from electrospun polymer nanofibers. Such drug delivery system offers great potential for applications in medicine especially as neurosurgery protective membranes. Proper delivery of drugs requires precise control of the drug diffusion process during the release for days or even weeks. Lipophilic model drug Rhodamine B and hydrophilic Bovine Serum Albumin conjugated with Fluoresceine (BSA - FITC) were embedded in electrospun poly(L -lactide-co -ε-caprolactone) (PLC) nanofibers. Release of Rhodamine B showed saturation in cumulative release profile at 60% and 86% for 1.5% and 3% wt. initial drug content, respectively. Nanofibers electrospun from emulsion released almost entire drug encapsulated in water vesicles inside the nanofibers. Possible location of vesicles close to the surface of the nanofibers exposed them for surrounding fluid and caused leaching of the drug. In this case encapsulation of drug in emulsion prevented the initial burst release.Dependence of a drug release and composition of nanofiber is essential for production of drug delivery systems. Mathematical model constructed with this data allows to avoid tedious experimental work. This research was supported by Ministry of Science and Higher Education, National Centre for Research and Development Project grant no. R13008110. The first author has been supported with a scholarship from the European Social Fund, Human Capital Operational Programme.

Słowa kluczowe:

nanofibres, drug delivery, vesicles

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The current task of contemporary fluid mechanics evidently moves from modeling large scale turbulence to lower, molecular scale limit, where assumption of a continuous and deterministic description becomes questionable again. Once the scaling length of flow becomes comparable with structure dimensions, transport phenomena are strongly modulated by molecular interactions and its proper interpretation needs involvement of deeper physics. New experimental tools largely help in understanding transport phenomena at nanoscales. In the following review we give few examples of problems appealing for new theoretical and numerical models embracing continuous flow modeling with molecular scale phenomena.

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Comprehensive studies of drug transport in nanofibres based mats have been performed to predict drug release kinetics. The paper presents our approach to analyze the impact of fibers arrangement, one of the parameters varied in our parallel experimental studies. Drug encapsulation in submicron fibers and subsequent controlled release of drugs is a tedious task due to the large number of process and material parameters involved. In the numerical study we constructed a 3D finite element geometry representing nanofibrous cubic element. COMSOL Multiphysics has been used to assess the impact of the various purposed arrangements of fibers within the mat. Drug release from nanofibers was modeled by adsorption -desorption and diffusion equation, where drug diffusion coefficient in the fluid between the fibers was altered depending on porosity of the material. Our study shows that for the same material porosity drug release from the matrix of regularly oriented fibers is slower than from randomly oriented, isotropic nanofibrous material. Also by decreasing distance between the fibers drug transport rate is reduced.

Słowa kluczowe:

Nanofibres, finite elements, drug release modelling

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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.

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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.

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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.

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electrospinning, PVA, Green crosslinking

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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.

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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.

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Pulsatile drug delivery systems are gaining a lot of interest because of their numerous advantages, especially when compared to conventional pharmaceutical dosage forms [1]. These materials are time- and site-specific drug delivery systems which can minimize deleterious side effects of conventional drug administration systems. Nevertheless, the delivery systems that are of particular interest are the ones with reversible on-off switching capability, because they allow the delivery of therapeutic agents at the proper time after a predetermined lag time. Among the polymers used for biomedical applications, hydrogels are a class of materials of particular significance, because they can provide spatial and temporal control over the release of various types of drugs. Stimuli-responsive hydrogels can release drugs on-demand with a fast release rate through different mechanisms. The effectiveness of this process can be maximized using nanostructured materials with a large surface-area-to-volume ratio such as electrospun nanofibers. Current challenges in the development of hydrogel electrospun fibrous nanomaterials lie in the lack of spinnability of pure hydrogel precursor solutions. Addressing this issue, we firstly designed a new core-shell nanofibrous material in which the poly(N-isopropylacrylamide)-derivative hydrogel is confined within a shell of a spinnable polymer (Figure 1a). Alternatively, we developed a scaffold material in which electrospun nanofibers loaded with different bioactive molecules where surrounded by a stimuli-responsive hydrogel (Figure 1b). Morphological and chemical characterization as well as drug release studies were carried out to confirm the material’s ability to supply different doses of drugs on demand and to study the release mechanism.

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Intervertebral disc diseases are a significant medical problem affecting many people around the world. In Poland, the statistics of the Social Insurance Institution (Medical Abuse in 2016) indicate that low back pains and other intervertebral disc diseases constitute 17% of the total number of days of sick leave. In connection with the above, current work describes design of a composite scaffold as a carrier in cell therapy, which will contribute to the regeneration of the intervertebral disc, including the increase of its height. Our composite scaffold include nanofibers that were prepared with the use of the electrospinning method. This method is a simple but powerful technique for fabricating desirable nano- and microfibers by using a high potential electric field. Human Mesenchymal stem cells (MSCs) were cultured on the scaffold from poly(L-lactide). Proliferation kits and fluorescence microscopy were used to asses cells’ viability and adherence to the nanofibers’ surface. hMSCs were efficiently cultured on the nanofibrous scaffold. Cells could be readily detected in porous structure of the scaffold after 7 and 14 days of culture. Viability and proliferation kits proved that the material is not toxic. Drug release from nanofibrous material of model growth factor was conducted with pharmacopeia protocols. Drug release of the 14 kDa growth factor was achieved for 14 days without burst release. Nanofibrous biomaterials prove their advances in many tissue engineering applications. Adjustable porosity of the scaffold and the biocompability of biomaterial make it perfect candidate for cells’ scaffold in many medical procedures and also as a drug release carrier. With the use of single nanofibers, such biomaterials can also be readily used in minimally invasive procedures to regenerate IVD.

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nanofibers, IVD, MSC

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Stimuli-responsive drug delivery systems are gaining a lot of interest due to their numerous advantages, especially when compared to conventional pharmaceutical dosage forms. One of the examples is photo stimulation that together with nanometer size agents, having high absorption in the near-infrared region, generate heat due to the interaction with light. Stimuli-responsive hydrogels with gold nanorods (AuNRs), that are used as photothermal converters, can aid in releasing drugs on-demand with a fast release rate through different mechanisms. Here we report an easy method for preparing AuNRs encapsulated in a poly(N-isopropylacrylamide) (PNIPAm) hydrogel that release water-soluble drugs due to photo stimulation. PNIPAm-AuNRs demonstrated remote, pulsatile drug release and ex vivo action after irradiation using a NIR laser. Morphological and chemical characterization as well as drug release studies were carried out to confirm the material’s ability to supply different doses of drugs on demand and to study the release mechanism. By combining the photothermal property of AuNRs and thermal-responsive effect of PNIPAm, the hydrogel shows fast thermal/photoresponse, high heating rate, high structural integrity and increased drug release due to phase change mechanism.

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drug delivery systems, nanofibers

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Single-material organic solar cells (SMOCs) based on fullerene-grafted polythiophenes are considered promising devices for organic solar cells (OSCs). The main efforts in this field focus on the chemical tailoring of polymer molecules to reduce the side effects of charge recombination. These advances have made it possible to obtain a power conversion efficiency (PCE) close to conventional bulk heterojunction (BHJ) cells. So far, however, SMOCs still show inadequate efficiencies due to ineffective charge transport. Here we show how SMOC efficiency can be strongly increased by optimizing the supramolecular and nanoscale structure of the active layer, while achieving the highest reported efficiency value (PCE = 5.58%) [1]. The enhanced performance may be attributed to well-packed and properly oriented polymer chains. The hierarchical structure is given by the incorporation of electrospun one-dimensional nanostructures obtained from polymer chain stretching. Our results suggest that the active material optimization obtained by the use of electrospun nanofibers plays a key role in the development of efficient SMOCs.

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Atomic force microscopy (AFM) is an evolution of scanning tunnelling microscopy that immediately gained popularity thanks to its ability to analyse nanomaterials. Initially, AFM was developed for nanomaterials imaging purposes, however the development of new features made it the most commonly used tool for studying the biophysical properties of biological samples. On the other hand, atomic force microscopy has limited use for examining sub-piconewton forces. Few techniques have been developed to measure forces below the AFM limit of detection. Among them, optical tweezers (OT) stand out for their high resolution, flexibility, and because they make it possible to accurately manipulate biological samples and carry out biophysics experiments without side effects thanks to their non-invasive properties. The combination of AFM with other techniques in the last decades has significantly extended its capability. The improvement of the AFM force resolution by developing a hybrid double probe instrument based on the combination of AFM and OT has great potential in cell or molecular biology. [1] We outline principles of atomic force microscopy combined with optical tweezers (AFM/OT) developed by our team underlying the techniques applied during the design, building and instrument use stages. We describe the experimental procedure for calibration of the system and we prove the achievement of a higher resolution (force: 10 fN – spatial: 0.1 nm – temporal: 10 ns) than the stand alone AFM. We show the use of the hybrid equipment in a number of different biophysics experiments performed employing both AFM and OT probes. The presented studies include the demonstration of simultaneous high-precision nanomanipulation and imaging, the evaluation of single biomolecule mechanical properties and the single cell membrane activation and probing. Finally, we show the further potential applications of our AFM/OT.

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AFM, Optical Tweezers

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Electrospun nanofibers are increasingly studied thanks to their potential applications in biomedical devices that include drug delivery systems and tissue engineering scaffolds [1]. Numerous synthetic and natural polymers were used to develop nanofibrous materials. Nanostructured materials high porosity, surface-to- volume ratio together with the ease in surface functionalization and drug incorporation, make them perfect candidates for the development of hemostats. Immediate hemorrhage management becomes crucial to preventing death and serious injury in emergency situations. Severe injuries caused by e.g. traffic accidents are the third leading cause of death worldwide [2]. Research on medical incidents of soldiers stationed in Iraq in 2003-2004 showed that the main cause of death was massive hemorrhage that led to death in about 51% of the rescued soldiers [3]. There is no universal dressing and despite the development of new hemostats, they fail in many preclinical studies. Therefore, there is a need to define most important nanofibrous material characteristics that are responsible for rapid and effective bleeding arrest. There is little research on nanostructured hemostats, regarding the impact of nanofibrous surface on blood and its components. Nonetheless, because of the wide use of nanofibres in wound dressings, artificial blood vessels as well as heart valves, there is knowledge helpful in determining material surface chemistry, wettability and other, which can affect blood coagulation. The very first findings appeared in the research where it was found that even polymers having excellent antiplatelet adhesion abilities, triggered increased platelet adhesion and activation when they were in the form of nanofibers. In several other studies, scaffold morphology, was found to have larger impact on platelet adhesion and activation than differences in the chemistry of the polymers used [4]. More specifically, it was found that materials with fiber diameter higher than 1 µm triggered higher platelet adhesion and aggregation than smaller fibers. In other research, nanofiber stiffness was assessed as more dominating than biological moieties and surface roughness of the nanofiber [5]. In spite of all, analyzed literature presents many contradictory results or findings that had low or no impact on blood clotting in research results of other groups. Hence, additional research and novel experimental methods are needed to find nano features that impact hemostat efficiency.

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blood-biomaterial interactions, nanofibers, clotting

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thermal fluctuations, lateral migration, flexible filaments

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Nanofibers have received considerable attention in the past years, mainly due to their vast application in medicine [1]. One of the fastest growing areas of application are wound dressings and hemostats. Among the major causes of death from trauma, massive bleeding is responsible for 30 – 40% of mortality. In the hospital, massive bleeding are the second most common cause of death (22%) just after cardiac factors (33%) [2]. Despite a large number of experiments done in the topic of blood-biomaterial interactions, coagulation mechanisms are still not fully understood. Therefore, the main objective of our work is the analysis of protein adsorption, platelet adhesion and aggregation, and blood plasma coagulation in the contact with polymer nanofibers. Various synthetic polymers, their blends with natural polymers of confirmed hemostatic effect e.g. collagen and gelatine, and additionally nanofibers made of chitosan are investigated for their potential to stop bleeding. In the final, controlled release of drugs affecting coagulation cascade will be an important step providing accelerated blood clot formation.

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Mobility of hydrogel nanofilaments suspended in liquid is investigated to gain basic knowledge on hydrodynamic interactions biased by Brownian fluctuations. Typical for long macromolecules effects like spontaneous conformational changes and cross-flow migration are observed and evaluated. The collected experimental data can be used to validate assumptions present in numerical models describing intercellular transport of long biomolecules.

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persistence length, macromolecules, electrospinning, DNA, Brownian motion

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Atomic force microscopy (AFM) is the most commonly used method of direct force evaluation, but due to its technical limitations this single probe technique is unable to detect forces with femtonewton resolution. We present the development of a combined atomic force microscopy and optical tweezers (AFM/OT) instrument. The optical tweezers system provides us the ability to manipulate small dielectric objects and to use it as a high spatial and temporal resolution displacement and force sensor in the same AFM scanning zone. We demonstrate the possibility to develop a combined instrument with high potential in nanomechanics, molecules manipulation and biologic al studies. The presented study is aimed to quantify the interaction forces between two single polystyrene particles in the femtonewton scale by using the developed AFM/OT equipment.

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optical trap, nanomanipulation, femtonewtons

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Hydrogel Nanofilaments, Bending Dynamics, Poiseuille Flow, Electrospinning

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Atomic force microscopy/optical tweezers, Nanomanipulation, Single particles analysis, Interaction force measurement, DLVO theory

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nanofilaments, hydrogel, long molecules flexibility

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We propose a microscale experimental model in form of highly deformable nanofilaments, which permits for precise optical measurements and to evaluate hydrodynamic interactions (mobility). The conducted research includes determination of the mechanical properties of elastic hydrogel nanofilaments obtained by electrospinning that can serve as experimental benchmark to validate theoretical and numerical models describing dynamics of long biological molecules (e.g. proteins, DNA). Nanofilaments mechanical properties are determined by studying their dynamic bending. in shear flow and deformations due to the thermal fluctuations (Brownian motion). These results are compared with AFM nanoindentation measurements. Data obtained from this research project will be a base to crea te biocompatible nanoobjects that can become tools for the regeneration of tissue (e.g. neural tissue).

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Biocompatible nanoobjects, highly deformable nanofilaments, regeneration of tissue

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Nanofilaments, hydrogel filaments, nanofibres, long nanoobjects deformability

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Controlled drug delivery systems are used to improve the conventional administration of drugs. One of the main challenges is to synthesize materials able to find a defined target and to release drugs in a controlled manner [1]. Several research tasks have been focused on developing ideal drug delivery systems made by hydrogel due to their unique properties [2]. The present study is based on the idea that soft and flexible nanomaterials can easily travel in crowed environments of body fluids and biological tissues. Modification of their mechanical properties obtained by changing of the cross-linker amount may give us the possibility to tune the material rigidity according to desired application. Here, we describe a novel method based on coaxial electrospinning for obtaining highly flexible hydrogel nanofilaments able to transport and release dedicated molecules. Two different types of hydrogels (poly(N,Nisopropyl acrylamide) and polyacrylamide) with three polymer/cross-linker ratios were produced and deeply studied. The nanofilaments morphology was characterized and the release of bovine serum albumin as a function of time was quantified. Mechanical properties of highly deformable hydrogel nanofilaments were evaluated by bending dynamics and Brownian motion observation techniques. The calculated mechanical properties were compared with data obtained by nanoindention. The results highlight the crucial role of morphology and stiffness on mobility of nanofilaments colloid systems. The information gained are fundamental to design nanoobjects with well-defined chemical and physical behaviour.

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Nanofilaments, electrospinning, core-shell method, hydrogel

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In this talk we would like to tackle general question of contemporary fluid dynamics, how far its assumption of a continuous, smooth medium remains useful when size and time scales start to approach molecular ones. The question is not trivial and seems to depend on several additional factors usually minored. For example, when full Navier-Stokes equations are replaced by their linear approximation we are loosing basic characteristics of convective motion, and still we use such approach. Once our fluid becomes granular matter with its own internal properties, proper interpretation of flow interactions with other molecular structures probably needs deeper physics. But still we try to convert such problem to the classical macro/micro scale description. Hence a general question arises, how small does a fluid have to be before it is not a fluid anymore?

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microfluidics, nanofluids, Brownian motion, nanofilaments

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nanomaty, modelowanie uwalniania leku

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drug delivery, electrospinning, mathematical modeling, nanofibres

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elektroprzędzenie, nanowłókna, uwalnianie leków, TBI

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electrospinning, flexible nanorods, Brownian motion

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brain, drug delivery, nanofibres, mathematical modelling

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Nanoparticles, polystyrene beads, surface properties, atomic force microscopy, hydrodynamic properties

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Nanoparticles, Brownian motion, hydrodynamic diameter

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The paper contains our attempts to estimate diffusion parameters of nanofibers actually applied as protective mats for neurosurgery. Measurements of concentration profiles of fluorophore released from stained nanofibres are performed. The two release systems are investigated: solid nanofibres and core-shell nanofibres with targeted drug simulator encapsulated inside nanofibres. The gathered information allows us to estimate parameters necessary for controlling drug release profiles.

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Nanofibers, Electrospinning, Drug Delivery Systems

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Nanofibers produced by electrospinning of biologically active substances became attractive material for encapsulating living cells, bacteria, and drugs for targeted therapy. Here, we aim to use nanofiber matrices as neurosurgery protective membranes and drug carriers. Proper administration of drugs requires precise control of the diffusion process during the time of release of days or even weeks. Construction of such system is a tedious experimental task. To avoid hundreds of tests it is aimed to build a numerical model including essential information about composition, process conditions, and fibers geometry necessary to construct suitable polymer matrices for dedicated drug delivery systems.

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drug delivery, electrospinning, nanofibers

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This paper describes the results of our preliminary studies on Drug Delivery Systems. Two distinct types of drugs are being investigated: lipophylic (soluble in organic solvents) and hydrophylic (soluble in water). Direct measurements of drugs and dye release from nanofibers were done for application in an animat model - rat.

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Electrospinnig, Nanofibers, Drug Delivery Systems

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