Staff

Abstract:
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.

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

Abstract:
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.

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

Abstract:
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.

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

Abstract:
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.

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

Abstract:
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.

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

Abstract:
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.

Abstract:
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.

Abstract:
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.

Abstract:
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.

Abstract:
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.

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

Abstract:
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.

Keywords:
optical trap, nanomanipulation, nanomechanics, femtonewton forces

Abstract:
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.

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

Abstract:
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

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

Abstract:
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.

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

Abstract:
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.

Keywords:
urinary bladder regeneration, electrospinning

Abstract:
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.

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

Abstract:
(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.

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

Abstract:
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.

Keywords:
desorpcja, dyfuzja, FRAP, nanowłókna, uwalnianie leków

Abstract:
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.

Keywords:
nanofibres, drug delivery, vesicles

Abstract:
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.

Abstract:
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.

Keywords:
Nanofibres, finite elements, drug release modelling

Abstract:
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.

Abstract:
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.

Keywords:
nanofibers, IVD, MSC

Abstract:
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.

Keywords:
drug delivery systems, nanofibers

Abstract:
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.

Abstract:
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.

Keywords:
AFM, Optical Tweezers

Abstract:
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.

Keywords:
blood-biomaterial interactions, nanofibers, clotting

Keywords:
thermal fluctuations, lateral migration, flexible filaments

Abstract:
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.

Abstract:
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.

Keywords:
persistence length, macromolecules, electrospinning, DNA, Brownian motion

Abstract:
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.

Keywords:
optical trap, nanomanipulation, femtonewtons

Keywords:
Hydrogel Nanofilaments, Bending Dynamics, Poiseuille Flow, Electrospinning

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

Keywords:
nanofilaments, hydrogel, long molecules flexibility

Abstract:
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).

Keywords:
Biocompatible nanoobjects, highly deformable nanofilaments, regeneration of tissue

Keywords:
Nanofilaments, hydrogel filaments, nanofibres, long nanoobjects deformability

Abstract:
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.

Keywords:
Nanofilaments, electrospinning, core-shell method, hydrogel

Abstract:
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?

Keywords:
microfluidics, nanofluids, Brownian motion, nanofilaments

Keywords:
nanomaty, modelowanie uwalniania leku

Keywords:
drug delivery, electrospinning, mathematical modeling, nanofibres

Keywords:
elektroprzędzenie, nanowłókna, uwalnianie leków, TBI

Keywords:
electrospinning, flexible nanorods, Brownian motion

Keywords:
brain, drug delivery, nanofibres, mathematical modelling

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

Keywords:
Nanoparticles, Brownian motion, hydrodynamic diameter

Abstract:
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.

Keywords:
Nanofibers, Electrospinning, Drug Delivery Systems

Abstract:
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.

Keywords:
drug delivery, electrospinning, nanofibers

Abstract:
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.

Keywords:
Electrospinnig, Nanofibers, Drug Delivery Systems