Local drug delivery systems made from nontoxic polysaccharide nanofilms have an enormous potential in wound care. A detailed understanding of the structural, surface, physicochemical, and cytotoxic ...properties of such systems is crucial to design clinically efficacious materials. Herein, we fabricated polysaccharide-based nanofilms onto either a 2D model (SiO2 and Au sensors) or on nonwoven alginate 3D substrates using an alternating assembly of N,N,N-trimethylchitosan (TMC) and alginic acid (ALG) by a spin-assisted layer-by-layer (LbL) technique. These TMC/ALG multilayered nanofilms are used for a uniform encapsulation and controlled release of pentoxifylline (PTX), a potent anti-inflammatory drug for treatment of the chronic venous ulceration. We show a tailorable film growth and mass, morphology, as well as surface properties (charge, hydrophilicity, porosity) of the assembled nanofilms through control of the coating during the spin-assisted assembly. The uniform distribution of the encapsulated PTX in the TMC/ALG nanofilms is preserved even with when the amount of the incorporated PTX increases. The PTX release mechanism from the model and real systems is studied in detail and is very comparable for both systems. Finally, different cell-based assays illustrated the potential of the TMC/ALG multilayer system in wound care (e.g., treatment chronic venous ulceration) applications, including a decrease of TNF-α secretion, a common indicator of inflammation.
Three-dimensional scaffolds (3D) with controlled shape, dual porosity and long-term mechanical and dimensional stability in biofluids are of interest as biotemplates in tissue engineering. Herein, ...self-standing and lightweight cellulose-based biogenic scaffolds with a spatially structured morphology, macropores and interconnected micropores were fabricated using a combination of direct ink writing 3D printing and freeze-drying techniques. This was achieved by developing a water-based and low-cost bicomponent ink based on commercially available nanofibrillated cellulose (NFC) and carboxymethyl cellulose (CMC). Physical cross-linking through dehydrothermal treatment significantly increased the surface hardness, indentation modulus, compression strength, as well as the dimensional stability of the scaffolds in biofluids, in comparison to untreated materials. However, no differences in the spectra of solid state nuclear magnetic resonance or infrared were observed for dehydrothermal treated samples, suggesting that the increase of mechanical properties and dimensional stability is based on the physical cross-linking of functional groups both at the interface between NFC and CMC. The supramolecular structure of the polymers was well-preserved as disclosed by X-ray diffraction measurements. The cross-linked scaffolds showed high proliferation, viability, and attachment of human bone tissue derived osteoblast cells (hFOB). The simple and straightforward avenue proposed here for the design of cellulose-based fibrous inks and dual porous scaffolds from the commercially available materials and without the need of any additional cross-linkers should pave the way for the development of implantable, degradable scaffolds and cell-laden biomaterials for bone tissue regeneration and 3D bioprinting applications.
Despite medical advances, skin-associated disorders continue to pose a unique challenge to physicians worldwide. Skin cancer is one of the most common forms of cancer, with more than one million new ...cases reported each year. Currently, surgical excision is its primary treatment; however, this can be impractical or even contradictory in certain situations. An interesting potential alternative could lie in topical treatment solutions. The goal of our study was to develop novel multilayer nanofilms consisting of a combination of polyhydroxyethyl methacrylate (PHEMA), polyhydroxypropyl methacrylate (PHPMA), sodium deoxycholate (NaDOC) with incorporated superparamagnetic iron-platinum nanoparticles (FePt NPs), and the potent anticancer drug (5-fluorouracil), for theranostic skin cancer treatment. All multilayer systems were prepared by spin-coating and characterised by atomic force microscopy, infrared spectroscopy, and contact angle measurement. The magnetic properties of the incorporated FePt NPs were evaluated using magnetisation measurement, while their size was determined using transmission electron microscopy (TEM). Drug release performance was tested in vitro, and formulation safety was evaluated on human-skin-derived fibroblasts. Finally, the efficacy for skin cancer treatment was tested on our own basal-cell carcinoma cell line.
Rak dojk je drugi najpogostejši rak na svetu in daleč najpogostejši pri ženskah, tako v razvitem svetu kot tudi v državah v razvoju. Uvršča se na peto mesto po vzroku smrti zaradi raka. V Sloveniji ...beležimo letno približno 1310 novih primerov raka dojk. Ločimo več podtipov raka dojk, ki jih lahko delimo na podlagi histopatološke (primaren, sekundaren, invaziven, neinvaziven) ter molekularne delitve oz. intrinzičnih lastnosti. V pomoč pri raziskovanju posameznih podtipov raka dojk služijo tudi celične linije. Prva celična linija raka dojk je bila ustvarjena leta 1958 in poimenovana BT-20 (1958, Lasfargues in Ozzello). Število celičnih linij je v zadnjih letih drastično naraslo, vendar so najpogosteje uporabljene celične linije še vedno MCF7, T47D in MDAMB231. MCF7 in T47D sta vrste luminalni tip A (ER+/PR+/HER2-) in MDAMB231 je trojno negativna (ER-/PR-/HER2-). Na področju celičnih linij so vidne nedoslednosti glede poimenovanja kot tudi gojenja. Prav tako je tudi vprašljiva ponovljivost gojenja v različnih laboratorijih ali pogojih, kjer celične linije lahko razvijejo drugačne lastnosti (npr. dediferenciacija, sprememba fenotipa, mutacije). V literaturi so vidni primeri različne kategorizacije iste celične linije v edinstvene skupine na podlagi drugačnega molekularnega in morfološkega opisa. Avtorji so mnenja, da je posledično potreben pregled nad literaturo in opis trenutno znanega. V prispevku se osredotočajo na tematiko celičnih linij raka dojk, njihovo nomenklaturo, delitev, gojenje in uporabnost.
Electrospinning as method for fabrication of wound dressing materials with included medical plant extracts for wound treatment has lately gained increasing attention. However, the transfer of ...nanofiber fabrication with included plant extracts from the research to the pilot and industrial scale production, using needleless electrospinning is a vital area of research, which could enable its large-scale commercial exploitation. Carboxymethyl cellulose (CMC) is a cheap, water soluble biopolymer, and in blends with the spinning agent polyethylene oxide (PEO) it is a suitable polymer for a large-scale nanofiber production. Thus, this study addresses the needleless electrospinning of CMC/PEO/plant extract blend aqueous solutions in order to fabricate cellulose based wound dressing material, suitable for treatment of acute wounds. The influence of plant extracts on the morphology of the electrospun mats was further evaluated. The antioxidant and antibacterial properties of the as-prepared electrospun mats were determined, where special attention was devoted to the stability/degradation study of phenolic compounds in plant extracts during the electrospinning process. This research was complemented by the release study and cell viability testing with results indicating a promising potential of this product to use for wound care as a self-contained wound dressing or as a part of number of already existing novel wound dressing materials.
Graphic abstract
Limitations in wound management have prompted scientists to introduce bioprinting techniques for creating constructs that can address clinical problems. The bioprinting approach is renowned for its ...ability to spatially control the three-dimensional (3D) placement of cells, molecules, and biomaterials. These features provide new possibilities to enhance homology to native skin and improve functional outcomes. However, for the clinical value, the development of hydrogel bioink with refined printability and bioactive properties is needed. In this study, we combined the outstanding viscoelastic behavior of nanofibrillated cellulose (NFC) with the fast cross-linking ability of alginate (ALG), carboxymethyl cellulose (CMC), and encapsulated human-derived skin fibroblasts (hSF) to create a bioink for the 3D bioprinting of a dermis layer. The shear thinning behavior of hSF-laden bioink enables construction of 3D scaffolds with high cell density and homogeneous cell distribution. The obtained results demonstrated that hSF-laden bioink supports cellular activity of hSF (up to 29 days) while offering proper printability in a biologically relevant 3D environment, making it a promising tool for skin tissue engineering and drug testing applications.
Many groups have already investigated the use of NiCu magnetic nanoparticles (MNPs) as mediators for magnetic fluid hyperthermia, but we were the first to report the potential of NiCu MNPs as bimodal ...therapeutic systems, capable of simultaneous magnetic hyperthermia (MH) and targeted drug delivery. The superparamagnetic nanoparticles have a magnetic core, which enables their manipulation through an external magnetic field, a biocompatible layer, providing a surface for attachment of suitable receptors for targeting specific tissues, and a therapeutic load either incorporated inside the coating pores or hosted within internal cavities of the particles. In this study, we incorporated three model drugs with different pharmacological activity into superparamagnetic Ni
x
Cu
1−
x
nanoparticles. The superparamagnetic Ni
x
Cu
1−
x
nanoparticles were prepared using a sol–gel method, and exhibited a Curie temperature (
T
C
) in the therapeutic range for use in MH. The nanoparticles were prepared in a silica matrix to avoid their agglomeration during thermal treatment and to provide suitable compartments for incorporation inside the pores. The release of the incorporated drugs paracetamol, bupivacaine hydrochloride, and pentoxifylline was studied using an in vitro release system, where UV–visible spectrophotometry (UV/Vis) was used for quantification of the released drug. The Ni
x
Cu
1−
x
nanoparticles were characterized using X-ray diffraction analysis, thermogravimetric analysis (TGA/SDTA), Fourier transform infrared spectroscopy, scanning electron microscopy, and magnetic measurements. Surface area and pore size were determined by using BET analysis. Finally, the biocompatibility of the samples was tested on human skin-derived fibroblasts.
Highlights
NiCu MNPs are often functionalized to improve their potential for biomedicine.
NiCu magnetic nanoparticles are very promising for multimodal cancer therapies through combination of magnetic hyperthermia and controlled drug delivery.
Controlled drug delivery systems have several advantages compared with traditional pharmaceutical formulations.
Despite the extensive utilization of polysaccharide hydrogels in regenerative medicine, current fabrication methods fail to produce mechanically stable scaffolds using only hydrogels. The recently ...developed hybrid extrusion-based bioprinting process promises to resolve these current issues by facilitating the simultaneous printing of stiff thermoplastic polymers and softer hydrogels at different temperatures. Using layer-by-layer deposition, mechanically advantageous scaffolds can be produced by integrating the softer hydrogel matrix into a stiffer synthetic framework. This work demonstrates the fabrication of hybrid hydrogel-thermoplastic polymer scaffolds with tunable structural and chemical properties for applications in tissue engineering and regenerative medicine. Through an alternating deposition of polycaprolactone and alginate/carboxymethylcellulose gel strands, scaffolds with the desired architecture (e.g., filament thickness, pore size, macro-/microporosity), and rheological characteristics (e.g., swelling capacity, degradation rate, and wettability) were prepared. The hybrid fabrication approach allows the fine-tuning of wettability (approx. 50-75°), swelling (approx. 0-20× increased mass), degradability (approx. 2-30+ days), and mechanical strength (approx. 0.2-11 MPa) in the range between pure hydrogels and pure thermoplastic polymers, while providing a gradient of surface properties and good biocompatibility. The controlled degradability and permeability of the hydrogel component may also enable controlled drug delivery. Our work shows that the novel hybrid hydrogel-thermoplastic scaffolds with adjustable characteristics have immense potential for tissue engineering and can serve as templates for developing novel wound dressings.
The blood-brain barrier (BBB) functions as a highly selective border of endothelial cells, protecting the central nervous system from potentially harmful substances by selectively controlling the ...entry of cells and molecules, including components of the immune system. To study the BBB properties, find suitable therapies, and identify new drug targets, there is a need to develop representative in vitro BBB models. In this article, we describe the astrocyte roles in the BBB functioning and human in vitro BBB models.
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•Novel carboxymethyl cellulose/diclofenac coatings on AISI 316LVM steel were prepared.•Interdisciplinary analytical methods were employed to characterize the coatings.•Biocompatible ...coatings enable controlled drug release and high corrosion resistance.•Higher osteointegration rate and increased BMP2 and OMD gene expression achieved.
This work reports on the preparation and systematic testing of a novel multi-layered coating, comprised of the non-steroid anti-inflammatory drug diclofenac and biopolymer carboxymethyl cellulose. Drug release testing was performed on an Automated Transdermal Diffusion Cells Sampling System in combination with UV-VIS spectroscopy as the released drug concentration determination method. The results showed that most of the drug is released in the first six hours, whereas the overall released amount could be tailored through changes in the multi-layered coating composition. Biocompatibility tests performed on human osteoblast cells, showed cell viability improvement between 7% and 17% compared to the control sample. The expression of proteins playing important roles in extracellular matrix production and functioning was performed in order to obtain additional proof of the prepared materials’ osteointegration boosting capacity. Finally, electrochemical measurements confirmed that the coatings do not influence the corrosion susceptibility of AISI 316LVM stainless steel.
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