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PURPOSE: This study is an approach to a dressing platform based on support functionalized with oxygenating factors within an alginate layer, constituting a safe and even contact surface for interface with a wound. METHODS: An alginate layer with incorporated oxygenating elements deposited on the support patch was assessed. As an oxygenating factor, perfluorooctyl was applied, and the layer coatings in two options, cross-linked and not, were evaluated. The function of human dermal fibroblast cells cultured in the presence of these constructs was analyzed, as well as their morphology using flow cytometry, fluorescence microscopy, and scanning electron microscopy. In addition, the membrane coating material was assessed using FTIR, AFM, and SEM-EDX characterization. RESULTS: The applied membrane coatings adsorbed on the patch ensured the viability of the human fibroblasts cultured on the membranes during 10 days of culture. However, on the sixth day of culture, the percentage of live cells grown in the presence of cross-linked alginate with oxygenating factor ((ALG-PFC)net) was significantly higher than that of the cells cultured in the presence of the alginate coatings alone. SEM-EDX analysis of the (ALG-PFC)net confirmed the presence of oxygenating and cross-linking factors. In addition, the regular granular branched structure of the layer coating material involving the oxygenating and cross-linking factors was observed using the AFM technique. CONCLUSION: The topography of the layer coating material involving the oxygenating and cross-linking factors ensures an even contact surface for interface with the wound. Considering 5-day intervals between dressing replacements, the platform with an oxygenating configuration ensuring the growth and morphology of the human fibroblasts can be recommended at this time as an element of a dressing system.
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Wound management is the burning problem of modern medicine, significantly burdening developed countries' healthcare systems. In recent years, it has become clear that the achievements of nanotechnology have introduced a new quality in wound healing. The application of nanomaterials in wound dressing significantly improves their properties and promotes the healing of injuries. Therefore, this review paper presents the subjectively selected nanomaterials used in wound dressings, including the metallic nanoparticles (NPs), and refers to the aspects of their application as antimicrobial factors. The literature review was supplemented with the results of our team's research on the elements of multifunctional new-generation dressings containing nanoparticles. The wound healing multiple molecular pathways, mediating cell types, and affecting agents are discussed herein. Moreover, the categorization of wound dressings is presented. Additionally, some materials and membrane constructs applied in wound dressings are described. Finally, bacterial participation in wound healing and the mechanism of the antibacterial function of nanoparticles are considered. Membranes involving NPs as the bacteriostatic factors for improving wound healing of skin and bones, including our experimental findings, are discussed in the paper. In addition, some studies of our team concerning the selected bacterial strains' interaction with material involving different metallic NPs, such as AuNPs, AgNPs, Fe3O4NPs, and CuNPs, are presented. Furthermore, nanoparticles' influence on selected eukaryotic cells is mentioned. The ideal, universal wound dressing still has not been obtained; thus, a new generation of products have been developed, represented by the nanocomposite materials with antibacterial, anti-inflammatory properties that can influence the wound-healing process.
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Cardiovascular diseases (CVD), with myocardial infarction (MI) being one of the crucial components, wreak havoc in developed countries. Advanced imaging technologies are required to obtain quick and widely available diagnostic data. This paper describes a multimodal approach to in vivo perfusion imaging using the novel SYN1 tracer based on the fluorine-18 isotope. The NOD-SCID mice were injected intravenously with SYN1 or [18F] fluorodeoxyglucose ([18F]-FDG) radiotracers after induction of the MI. In all studies, the positron emission tomography-computed tomography (PET/CT) technique was used. To obtain hemodynamic data, mice were subjected to magnetic resonance imaging (MRI). Finally, the biodistribution of the SYN1 compound was performed using Wistar rat model. SYN1 showed normal accumulation in mouse and rat hearts, and MI hearts correctly indicated impaired cardiac segments when compared to [18F]-FDG uptake. In vivo PET/CT and MRI studies showed statistical convergence in terms of the size of the necrotic zone and cardiac function. This was further supported with RNAseq molecular analyses to correlate the candidate function genes' expression, with Serpinb1c, Tnc and Nupr1, with Trem2 and Aldolase B functional correlations showing statistical significance in both SYN1 and [18F]-FDG. Our manuscript presents a new fluorine-18-based perfusion radiotracer for PET/CT imaging that may have importance in clinical applications. Future research should focus on confirmation of the data elucidated here to prepare SYN1 for first-in-human trials.
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Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Corazón/diagnóstico por imagen , Infarto del Miocardio/genética , Proteínas de Neoplasias/genética , Serpinas/genética , Tenascina/genética , Animales , Medios de Contraste/farmacología , Fluorodesoxiglucosa F18/farmacología , Fructosa-Bifosfato Aldolasa/genética , Regulación de la Expresión Génica/efectos de los fármacos , Corazón/efectos de los fármacos , Humanos , Imagen por Resonancia Magnética , Masculino , Glicoproteínas de Membrana/genética , Ratones , Infarto del Miocardio/patología , Tomografía Computarizada por Tomografía de Emisión de Positrones , Ratas , Receptores Inmunológicos/genética , Distribución Tisular/efectos de los fármacosRESUMEN
Preclinical and clinical studies have shown that stem cells can promote the regeneration of damaged tissues, but therapeutic protocols need better quality control to confirm the location and number of transplanted cells. This study describes in vivo imaging while assessing reporter gene expression by its binding to a radiolabelled molecule to the respective receptor expressed in target cells. Five mice underwent human skeletal muscle-derived stem/progenitor cell (huSkMDS/PC EF1-HSV-TK) intracardial transplantation after induction of myocardial infarction (MI). The metabolic parameters of control and post-infarction stem progenitor cell-implanted mice were monitored using 2-deoxy-18F-fluorodeoxyglucose ([18F]-FDG) before and after double promotor/reporter probe imaging with 9-(4-18F-fluoro-3-[hydroxymethyl]butyl)guanine ([18F]-FHBG) using positron emission tomography (PET) combined with computed tomography (CT). Standardized uptake values (SUVs) were then calculated based on set regions of interest (ROIs). Experimental animals were euthanized after magnetic resonance imaging (MRI). Molecular [18F]-FHBG imaging of myogenic stem/progenitor cells in control and post-infarction mice confirmed the survival and proliferation of transplanted cells, as shown by an increased or stable signal from the PET apparatus throughout the 5 weeks of monitoring. huSkMDS/PC EF1-HSV-TK transplantation improved cardiac metabolic ([18F]-FDG with PET) and haemodynamic (MRI) parameters. In vivo PET/CT and MRI revealed that the precise use of a promotor/reporter probe incorporated into stem/progenitor cells may improve non-invasive monitoring of targeted cellular therapy in the cardiovascular system.
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Fluorodesoxiglucosa F18 , Imagen Molecular , Mioblastos Cardíacos/metabolismo , Infarto del Miocardio/metabolismo , Infarto del Miocardio/patología , Tomografía Computarizada por Tomografía de Emisión de Positrones , Células Madre Adultas/metabolismo , Animales , Modelos Animales de Enfermedad , Ecocardiografía , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Ratones , Ratones SCID , Imagen Molecular/métodos , Infarto del Miocardio/diagnóstico por imagen , Infarto del Miocardio/etiología , PoliésteresRESUMEN
Current treatment protocols for myocardial infarction improve the outcome of disease to some extent but do not provide the clue for full regeneration of the heart tissues. An increasing body of evidence has shown that transplantation of cells may lead to some organ recovery. However, the optimal stem cell population has not been yet identified. We would like to propose a novel pro-regenerative treatment for post-infarction heart based on the combination of human skeletal myoblasts (huSkM) and mesenchymal stem cells (MSCs). huSkM native or overexpressing gene coding for Cx43 (huSKMCx43) alone or combined with MSCs were delivered in four cellular therapeutic variants into the healthy and post-infarction heart of mice while using molecular reporter probes. Single-Photon Emission Computed Tomography/Computed Tomography (SPECT/CT) performed right after cell delivery and 24 h later revealed a trend towards an increase in the isotopic uptake in the post-infarction group of animals treated by a combination of huSkMCx43 with MSC. Bioluminescent imaging (BLI) showed the highest increase in firefly luciferase (fluc) signal intensity in post-infarction heart treated with combination of huSkM and MSCs vs. huSkM alone (p < 0.0001). In healthy myocardium, however, nanoluciferase signal (nanoluc) intensity varied markedly between animals treated with stem cell populations either alone or in combinations with the tendency to be simply decreased. Therefore, our observations seem to show that MSCs supported viability, engraftment, and even proliferation of huSkM in the post-infarction heart.
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Células Madre Mesenquimatosas/citología , Imagen Molecular/métodos , Mioblastos Esqueléticos/citología , Infarto del Miocardio/patología , Miocardio/patología , Animales , Modelos Animales de Enfermedad , Genes Reporteros , Humanos , Células Madre Mesenquimatosas/metabolismo , Ratones , Ratones Endogámicos NOD , Ratones SCID , Mioblastos Esqueléticos/metabolismo , Infarto del Miocardio/metabolismo , Miocardio/metabolismoRESUMEN
Background: Wound dressing plays a vital role in post-operative aftercare. There is the necessity to develop dressings for application on the border of soft and hard tissue. This study aimed to develop multifunctional polyelectrolyte layers enhanced by hydroxyapatite nanoparticles, gold nanoparticles (AuNPs), and/or fullerenol nanocomposites to achieve a wound dressing that could be applied on the bone-skin interface. Methods: Constructed shells were examined using TEM, STEM, and EDX techniques. The human osteoblasts or fibroblasts were immobilized within the shells. The systems morphology was assessed using SEM. The functioning of cells was determined by flow cytomery. Moreover, the internalization of AuNPs was assessed. Results: Involvement of fullerenol and/or hydroxyapatite nanoparticles influenced the immobilized cell systems morphology. Membranes with fullerenol and hydroxyapatite nanoparticles were observed to block the internalization of AuNPs by immobilized hFOB cells. Conclusions: The designed bilayer membranes incorporating fullerenol, and bacteriostatic elements, prevented the internalization of AuNPs by hFOB cells and ensured the proper counts and morphology of eukaryotic cells. The developed material can be recommended for dressings at the bone-skin interface.
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Nanocomposite multilayered membrane coatings have been widely used experimentally to enhance biomedical materials surfaces. By the selection of reliable components, such systems are functionalized to be adjusted to specific purposes. As metal nanoparticles can reduce bacterial cell adhesion, the idea of using gold and silver nanoparticles of unique antimicrobial properties within membrane structure is outstandingly interesting considering dressings facilitating wound healing. The study was aimed to explore the interface between eukaryotic cells and wound dressing materials containing various nanoelements. The proposed systems are based on polyethyleneimine and hydroxyapatite thin layers incorporating metallic nanoparticles (silver or gold). To examine the structure of designed materials scanning electron and transmission electron microscopies were applied. Moreover, Fourier-transform infrared and energy-dispersive X-ray spectroscopies were used. Additionally, water contact angles of the designed membranes and their transport properties were estimated. The functioning of human fibroblasts was examined via flow cytometry to assess the biocompatibility of developed shells in the aspect of their cytotoxicity. The results indicated that designed nanocomposite membrane scaffolds support eukaryotic cells' functioning, confirming that the elaborated systems might be recommended as wound healing materials.