RESUMEN
Cell therapy and engineered tissue creation based on the use of human stem cells involves cell isolation, expansion, and cell growth and differentiation on the scaffolds. Microbial infections dramatically can affect stem cell survival and increase the risk of implant failure. To prevent these events, it is necessary to develop new materials with antibacterial properties for coating scaffold surfaces as well as medical devices, and all other surfaces at high risk of contamination. This chapter describes strategies for obtaining antibacterial blends for coating inert surfaces (polymethylmethacrylate, polycarbonate, Carbon Fiber Reinforced Polymer (CFRP)). In particular, the procedures for preparing antibacterial blends by mixing polymer resins with two types of antibacterial additives and depositing these blends on inert surfaces are described.
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Células Madre , Ingeniería de Tejidos , Humanos , Ingeniería de Tejidos/métodos , Células Madre/citología , Propiedades de Superficie , Andamios del Tejido/química , Antibacterianos/farmacología , Cemento de Policarboxilato/química , Técnicas de Cultivo de Célula/métodos , Polimetil Metacrilato/química , Fibra de Carbono/química , Carbono/química , Antiinfecciosos/farmacologíaRESUMEN
Background: The application of nanomaterials (NMs) and nano-enabled products (NEPs) across many industries has been extensive and is still expanding decades after first being identified as an emerging technology. Additive manufacturing has been greatly impacted and has seen the benefits of integrating NMs within products. With the expansion of nanotechnology, there has been a need to develop more adaptive and responsive methods to ascertain risks and ensure technology is developed safely. The Safe(r)-by-Design (SbD) concept can be used to establish safe parameters and minimise risks during the materials' lifecycle, including the early stages of the supply chain. Exposure monitoring has advanced in recent years with the creation of standardised protocols for occupational exposure assessment of nano-objects and their aggregates and agglomerates (NOAA). Methods: To aid in the development of an online SbD-supporting platform by the EU-funded project SAbyNA, we adopt a Europe Standard for monitoring release of NOAA to identify if a greater release of NOAA is associated with incorporation of NMs within NEPs compared to a polymer matrix alone. Case studies included filaments of polypropylene (PP) with nano-Ag or polycarbonate (PC) with single-walled carbon nanotubes (SWCNTs). NMs were received in masterbatch, and therefore previously modified to align with SbD interventions. Results were collected in line with European Standard recommendations: monitoring particle concentrations using direct reading instruments (DRI), sampling for offline chemical and morphological analysis, and collecting contextual information. Results and discussion: Based on the criteria described in the European standard (BS EN 17058), data from both case studies identified that inhalation exposure relating to NM was "unlikely". Despite this, during the production of the SWCNT-PC filaments, some noteworthy observations were made, including several DRI activity measurements shown to be higher than background levels, and material morphologically similar to the reference SWCNT/polymeric masterbatch observed in offline analysis. The data collected during this campaign were used to discuss choices available for data interpretation and decision-making in the European Standard for monitoring release of NOAA and also to facilitate the development of SAbyNA's user-friendly industry platform for the SbD of NMs and NEPs.
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Nanoestructuras , Exposición Profesional , Exposición Profesional/prevención & control , Humanos , Monitoreo del Ambiente , Nanotecnología , Polipropilenos , Europa (Continente) , Cemento de Policarboxilato/química , Plásticos , Nanotubos de CarbonoRESUMEN
As one of the gaseous signals in living cells, carbon monoxide (CO) not only participates in many biological activities but also serves as a therapeutic agent for the treatment of diseases. However, the limited applicability of CO in gas therapy emerges from the inconvenience of direct administration of CO. Here we reported the construction of guanidinylated CO-releasing micelles, which are composed of poly(trimethylene carbonate) (PTMC)-based CO donors. The in vitro studies demonstrated that micelles in the presence of light irradiation can induce cancer death, whereas no obvious toxicity to normal cells was observed. Moreover, the functionalization of guanidine groups imparts improved cellular uptake efficiency to micelles owing to the specific interactions with the surface of cells, which synergistically increase the anticancer capacity of the system. The guanidine-functionalized CO-releasing micelles provide a new strategy for the construction of CO-releasing nanocarriers, which are expected to find applications in gas therapeutics.
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Monóxido de Carbono , Micelas , Cemento de Policarboxilato , Monóxido de Carbono/química , Humanos , Cemento de Policarboxilato/química , Guanidina/química , Portadores de Fármacos/química , Portadores de Fármacos/síntesis química , Polímeros/química , Dioxanos/químicaRESUMEN
A backbone-substituted N-heterocyclic carbene (NHC) zinc complex, in combination with alcohol initiators, has been shown to be an effective catalyst for the ring-opening polymerization (ROP) of trimethylene carbonate (TMC) to poly(trimethylene carbonate) (PTMC) devoid of oxetane linkages. The ROP of TMC proceeded in solution to give PTMC, possessing controlled molecular mass (2500 < Mn < 10000) and low dispersity (D â¼ 1.2). Changing the alcohol initiators, PTMCs with different end-groups were obtained, included a telechelic polymer. The results of MALDI-ToF and NMR analysis confirmed the controlled/living nature of the present ROP catalytic system, where side reactions, such as inter- and intramolecular transesterifications, were minimized during the polymerization. Solution studies in different solvents demonstrated the polymerization reaction to proceed via a mechanism first order in monomer and in catalyst. The zinc complex was also able to convert substituted cyclic carbonates, which were purposely synthesized from renewable feedstocks such as CO2 and 1,3-diols. For the asymmetric 2-Me TMC monomer, good regioselectivity was observed (Xreg up to 0.92). The excellent control of the polymerization process was finally brought to light through the preparation of polycarbonate/polyether triblock copolymers by using polyethylene glycol (PEG) as a macroinitiator and of well-defined di- and triblock polycarbonate/polylactide copolymers by sequential ROP of TMC and L-LA.
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Cemento de Policarboxilato , Polimerizacion , Zinc , Cemento de Policarboxilato/química , Zinc/química , Catálisis , Dióxido de Carbono/química , Metano/química , Metano/análogos & derivados , Polímeros/química , Carbonatos/química , Complejos de Coordinación/química , Compuestos Heterocíclicos/química , Dioxanos/química , Poliésteres/química , Poliésteres/síntesis químicaRESUMEN
Polymers are the most commonly used packaging materials for nutrition and consumer products. The ever-growing concern over pollution and potential environmental contamination generated from single-use packaging materials has raised safety questions. Polymers used in these materials often contain impurities, including unreacted monomers and small oligomers. The characterization of transport properties, including diffusion and leaching of these molecules, is largely hampered by the long timescales involved in shelf life experiments. In this work, we employ atomistic molecular simulation techniques to explore the main mechanisms involved in the bulk and interfacial transport of monomer molecules from three polymers commonly employed as packaging materials: polyamide-6, polycarbonate, and poly(methyl methacrylate). Our simulations showed that both hopping and continuous diffusion play important roles in inbound monomer diffusion and that solvent-polymer compatibility significantly affects monomer leaching. These results provide rationalization for monomer leaching in model food formulations as well as bulky industry-relevant molecules. Through this molecular-scale characterization, we offer insights to aid in the design of polymer/consumer product interfaces with reduced risk of contamination and longer shelf life.
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Embalaje de Alimentos , Difusión , Plásticos/química , Simulación de Dinámica Molecular , Polimetil Metacrilato/química , Cemento de Policarboxilato/química , Polímeros/química , Contaminación de Alimentos/análisisRESUMEN
BACKGROUND: Low mechanical properties are the main limitation of glass ionomer cements (GICs). The incorporation of elastomeric micelles is expected to enhance the strength of GICs without detrimentally affecting their physical properties and biocompatibility. This study compared the chemical and mechanical properties, as well as the cytotoxicity, of elastomeric micelles-containing glass ionomer cement (DeltaFil, DT) with commonly used materials, including EQUIA Forte Fil (EF), Fuji IX GP Extra (F9), and Ketac Molar (KT). METHOD: Powder particles of GICs were examined with SEM-EDX. Setting kinetics were assessed using ATR-FTIR. Biaxial flexural strength/modulus and Vickers surface microhardness were measured after immersion in water for 24 h and 4 weeks. The release of F, Al, Sr, and P in water over 8 weeks was analyzed using a fluoride-specific electrode and ICP-OES. The toxicity of the material extract on mouse fibroblasts was also evaluated. RESULTS: High fluoride levels in the powder were detected with EF and F9. DT demonstrated an initial delay followed by a faster acid reaction compared to other cements, suggesting an improved snap set. DT also exhibited superior flexural strength than other materials at both 24 h and 4 weeks but lower surface microhardness (p < 0.05). EF and F9 showed higher release of F, Al, and P than DT and KT. There was no statistically significant difference in fibroblast viability among the tested materials (p > 0.05). CONCLUSIONS: Elastomeric micelles-containing glass ionomer cement (DT) exhibited satisfactory mechanical properties and cytocompatibility compared with other materials. DT could, therefore, potentially be considered an alternative high-strength GIC for load-bearing restorations.
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Elastómeros , Fibroblastos , Resistencia Flexional , Cementos de Ionómero Vítreo , Dureza , Ensayo de Materiales , Micelas , Cementos de Ionómero Vítreo/toxicidad , Cementos de Ionómero Vítreo/química , Animales , Ratones , Fibroblastos/efectos de los fármacos , Elastómeros/química , Elastómeros/toxicidad , Aluminio/química , Fluoruros/química , Estroncio/química , Cemento de Policarboxilato/química , Cemento de Policarboxilato/toxicidad , Supervivencia Celular/efectos de los fármacos , Microscopía Electrónica de Rastreo , Propiedades de Superficie , Docilidad , Cinética , Espectroscopía Infrarroja por Transformada de Fourier , Estrés Mecánico , Factores de Tiempo , Materiales Biocompatibles/químicaRESUMEN
Zinc polycarboxylate cement is one of the few dental materials that demonstrate true adhesion to tooth structure. It is suitable for use in living organisms without causing harm. Its strong adhesion to teeth and low level of irritancy are two important parameters for the dental applications. In this study, the dosimetry properties of zinc polycarboxylate cement using thermoluminescence (TL) method were investigated and determined the effectiveness of its use as a good dosimeter. According to the results of this study, the sample shows a good TL properties with three main peaks found around 140°C, 220°C and 330°C. It has a wide linear dose response between 72 Gy and 2.3 kGy and good reusability of the TL peak found at 330°C. Unfortunately, the TL peak intensity values are rapidly faded within a short waiting time interval. Zinc polycarboxylate cement, which is frequently used in dental crowns, can be used as a retrospective dosimeter for measuring the amount of radiation in space studies and nuclear accidents due to its wide linear dose-response curve in the high dose region.
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Cemento de Policarboxilato , Dosimetría Termoluminiscente , Zinc , Zinc/química , Cemento de Policarboxilato/química , Cementos Dentales/química , Estudios RetrospectivosRESUMEN
A "one-step" strategy has been demonstrated for the tunable synthesis of multifunctional aliphatic polycarbonates (APCs) with ethylene oxide (EO), ethylene carbonate (EC), and cyclohexene oxide (CHO) side groups by the copolymerization of 4-vinyl-1-cyclohexene diepoxide with carbon dioxide under an aminotriphenolate iron/PPNBz (PPN = bis(triphenylphosphine)-iminium, Bz = benzoate) binary catalyst. By adjusting the PPNBz-to-iron complex ratio and incorporating auxiliary solvents, the content of functional side groups can be tuned within the ranges of 53-75% for EO, 18-47% for EC, and <1-7% for CHO. The yield and molecular weight distribution of the resulting multifunctional APCs are affected by the viscosity of the polymerization system. The use of tetrahydrofuran as an auxiliary solvent enables the preparation of narrow-distribution polycarbonates at high conversion. This work presents a novel perspective for the preparation of tailorable multifunctional APCs.
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Dióxido de Carbono , Cemento de Policarboxilato , Polimerizacion , Dióxido de Carbono/química , Cemento de Policarboxilato/química , Compuestos Epoxi/química , Óxido de Etileno/química , Ciclohexenos/química , Catálisis , Viscosidad , DioxolanosRESUMEN
This study aimed to investigate the bisphenol A (BPA) release from four CAD/CAM splint materials: three polycarbonate-based (DD BioSplint C, Splint Plus Biostar, Temp Premium Flexible) and one polymethylmethacrylate-based (Temp Basic) material. From each material, ten cylindrical samples (n = 40) were immersed in high-performance liquid chromatography (HPLC) grade water following ISO 10993-12 and incubated for 24 h in an incubation shaker at 37°C and 112 rpm. Following BPA derivatization, analysis was performed by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). After 24 h of incubation, all investigated materials released significant amounts of BPA compared to water blanks. The material-dependent elution increased in the following order: DD BioSplint C < Splint Plus Biostar < Temp Basic < Temp Premium Flexible. Subtracting extraneous BPA, the concentrations ranged between 2.27 ng/mL and 12.65 ng/mL. After extrapolating the concentrations in relation to the average surface area of occlusal splints, the amount of BPA per mL exceeded the Tolerable Daily Intake (TDI) set by the European Union for a person weighing 70 kg by 1.32-6.16 times. Contrary to the release from previously investigated materials, BPA elution from CAD/CAM splint materials was highly elevated. Considering the increasing adaptation of CAD/CAM techniques, elution from them may represent a relevant BPA source in daily dental practice.
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Compuestos de Bencidrilo , Diseño Asistido por Computadora , Fenoles , Compuestos de Bencidrilo/análisis , Compuestos de Bencidrilo/química , Fenoles/análisis , Cromatografía Líquida de Alta Presión , Cemento de Policarboxilato/química , Polimetil Metacrilato/química , Espectrometría de Masas en Tándem , Ensayo de Materiales , Férulas (Fijadores) , Materiales Dentales/química , HumanosRESUMEN
Hydrophilic antifouling polymers provide excellent antifouling effects under usual short-term use conditions, but the long-term accumulation of contaminants causes them to lose their antifouling properties. To overcome this drawback, surface-initiated ring-opening graft polymerization (SI-ROP) was performed on the surface of the material by applying the cyclic carbide monomer 4'-(fluorosulfonyl)benzyl-5-methyl-2-oxo-1,3-dioxane-5-carboxylate (FMC), which contains a sulfonylfluoride group on the side chain, followed by a "sulfur(IV)-fluorine exchange" (SuFEx) post click modification reaction to link the hydrophilic polyethylene glycol (PEG) to the polyFMC (PFMC) brush, and a novel antifouling strategy for self-polishing dynamic antifouling surfaces was developed. The experimental results showed that the antifouling surface could effectively prevent the adsorption of proteins such as bovine serum albumin (BSA, â¼96.4%), fibrinogen (Fg, â¼87.8%) and lysozyme (Lyz â¼69.4%) as well as the adhesion of microorganisms such as the bacteria Staphylococcus aureus (S. aureus) (â¼87.5%) and HeLa cells (â¼67.2%). Moreover, the enzymatically self-polished surface still has excellent antifouling properties. Therefore, this modification method has potential applications in the field of biosensors and novel antifouling materials.
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Adhesión Bacteriana , Incrustaciones Biológicas , Cemento de Policarboxilato , Polietilenglicoles , Albúmina Sérica Bovina , Staphylococcus aureus , Propiedades de Superficie , Staphylococcus aureus/efectos de los fármacos , Cemento de Policarboxilato/química , Polietilenglicoles/química , Incrustaciones Biológicas/prevención & control , Adhesión Bacteriana/efectos de los fármacos , Humanos , Albúmina Sérica Bovina/química , Adsorción , Polimerizacion , Bovinos , Animales , Fibrinógeno/química , Fibrinógeno/metabolismo , Interacciones Hidrofóbicas e Hidrofílicas , Muramidasa/química , Muramidasa/metabolismo , Muramidasa/farmacologíaRESUMEN
Osteoarthritis (OA) poses significant therapeutic challenges, particularly OA that affects the hand. Currently available treatment strategies are often limited in terms of their efficacy in managing pain, regulating invasiveness, and restoring joint function. The APRICOTâ implant system developed by Aurora Medical Ltd (Chichester, UK) introduces a minimally invasive, bone-conserving approach for treating hand OA (https://apricot-project.eu/). By utilizing polycarbonate urethane (PCU), this implant incorporates a caterpillar track-inspired design to promote the restoration of natural movement to the joint. Surface modifications of PCU have been proposed for the biological fixation of the implant. This study investigated the biocompatibility of PCU alone or in combination with two surface modifications, namely dopamine-carboxymethylcellulose (dCMC) and calcium-phosphate (CaP) coatings. In a rat soft tissue model, native and CaP-coated PCU foils did not increase cellular migration or cytotoxicity at the implant-soft tissue interface after 3 d, showing gene expression of proinflammatory cytokines similar to that in non-implanted sham sites. However, dCMC induced an amplified initial inflammatory response that was characterized by increased chemotaxis and cytotoxicity, as well as pronounced gene activation of proinflammatory macrophages and neoangiogenesis. By 21 d, inflammation subsided in all the groups, allowing for implant encapsulation. In a rat bone model, 6 d and 28 d after release of the periosteum, all implant types were adapted to the bone surface with a surrounding fibrous capsule and no protracted inflammatory response was observed. These findings demonstrated the biocompatibility of native and CaP-coated PCU foils as components of APRICOTâ implants. STATEMENT OF SIGNIFICANCE: Hand osteoarthritis treatments require materials that minimize irritation of the delicate finger joints. Differing from existing treatments, the APRICOTâ implant leverages polycarbonate urethane (PCU) for minimally invasive joint replacement. This interdisciplinary, preclinical study investigated the biocompatibility of thin polycarbonate urethane (PCU) foils and their surface modifications with calcium-phosphate (CaP) or dopamine-carboxymethylcellulose (dCMC). Cellular and morphological analyses revealed that both native and Ca-P coated PCU elicit transient inflammation, similar to sham sites, and a thin fibrous encapsulation in soft tissues and on bone surfaces. However, dCMC surface modification amplified initial chemotaxis and cytotoxicity, with pronounced activation of proinflammatory and neoangiogenesis genes. Therefore, native and CaP-coated PCU possess sought-for biocompatible properties, crucial for patient safety and performance of APRICOTâ implant.
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Fosfatos de Calcio , Animales , Masculino , Ratas , Fosfatos de Calcio/química , Fosfatos de Calcio/farmacología , Dopamina/metabolismo , Dopamina/farmacología , Materiales Biocompatibles Revestidos/química , Materiales Biocompatibles Revestidos/farmacología , Cemento de Policarboxilato/química , Prótesis Articulares , Carboximetilcelulosa de Sodio/química , Carboximetilcelulosa de Sodio/farmacología , Uretano/químicaRESUMEN
The synthesis of three-dimensional silver nanopopcorns (Ag NPCs) onto a flexible polycarbonate membrane (PCM) for the detection of nitrofurazone (NFZ) on the fish surface by surface-enhanced Raman spectroscopy (SERS) is presented. The proposed flexible Ag-NPCs/PCM SERS substrate exhibits significant Raman signal intensity enhancement with the measured enhancement factor of 2.36 × 106. This is primarily attributed to the hotspots created on Ag NPCs, including numerous nanoscale protrusions and internal crevices distributed across the surface of Ag NPCs. The detection of NFZ by this flexible SERS substrate demonstrates a low limit of detection (LOD) of 3.7 × 10-9 M and uniform and reproducible Raman signal intensities with a relative standard deviation below 8.34%. It also exhibits excellent stability, retaining 70% of its efficacy even after 10 days of storage. Notably, the practical detection of NFZ in tap water, honey water, and fish surfaces achieves LOD values of 1.35 × 10-8 M, 5.76 × 10-7 M, and 3.61 × 10-8 M, respectively, which highlights its effectiveness across different sample types. The developed Ag-NPCs/PCM SERS substrate presents promising potential for sensitive SERS detection of toxic substances in real-world samples.
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Límite de Detección , Nanopartículas del Metal , Nitrofurazona , Plata , Espectrometría Raman , Espectrometría Raman/métodos , Plata/química , Nitrofurazona/análisis , Nitrofurazona/química , Nanopartículas del Metal/química , Animales , Peces , Miel/análisis , Agua Potable/análisis , Cemento de Policarboxilato/química , Membranas Artificiales , Contaminantes Químicos del Agua/análisis , Propiedades de Superficie , Contaminación de Alimentos/análisisRESUMEN
Three-dimensional (3D) printing with polycarbonate (PC) plastic occurs in manufacturing settings, homes, and schools. Emissions generated during printing with PC stock and bisphenol-A (BPA), an endocrine disrupter in PC, may induce adverse health effects. Inhalation of 3D printer emissions, and changes in endocrine function may lead to cardiovascular dysfunction. The goal of this study was to determine whether there were any changes in markers of peripheral or cardiovascular dysfunction in animals exposed to PC-emissions. Male Sprague Dawley rats were exposed to PC-emissions generated by 3D printing for 1, 4, 8, 15 or 30 d. Exposure induced a reduction in the expression of the antioxidant catalase (Cat) and endothelial nitric oxide synthase (eNos). Endothelin and hypoxia-induced factor 1α transcripts increased after 30 d. Alterations in transcription were associated with elevations in immunostaining for estrogen and androgen receptors, nitrotyrosine, and vascular endothelial growth factor in cardiac arteries of PC-emission exposed animals. There was also a reduction eNOS immunostaining in cardiac arteries from rats exposed to PC-emissions. Histological analyses of heart sections revealed that exposure to PC-emissions resulted in vasoconstriction of cardiac arteries and thickening of the vascular smooth muscle wall, suggesting there was a prolonged vasoconstriction. These findings are consistent with studies showing that inhalation 3D-printer emissions affect cardiovascular function. Although BPA levels in animals were relatively low, exposure-induced changes in immunostaining for estrogen and androgen receptors in cardiac arteries suggest that changes in the action of steroid hormones may have contributed to the alterations in morphology and markers of cardiac function.
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Estrés Oxidativo , Cemento de Policarboxilato , Impresión Tridimensional , Ratas Sprague-Dawley , Animales , Masculino , Ratas , Estrés Oxidativo/efectos de los fármacos , Biomarcadores/metabolismo , Compuestos de Bencidrilo/toxicidad , Fenoles/toxicidad , Miocardio/metabolismo , Contaminantes Atmosféricos/toxicidad , Corazón/efectos de los fármacos , Óxido Nítrico Sintasa de Tipo III/metabolismoRESUMEN
Single-use laboratory plastics exacerbate the pollution crisis and contribute to consumable costs. In extracellular vesicle (EV) isolation, polycarbonate ultracentrifuge (UC) tubes are used to endure the associated high centrifugal forces. EV proteomics is an advancing field and validated re-use protocols for these tubes are lacking. Re-using consumables for low-yield protein isolation protocols and downstream proteomics requires reagent compatibility with mass spectroscopy acquisitions, such as the absence of centrifuge tube-derived synthetic polymer contamination, and sufficient removal of residual proteins. This protocol describes and validates a method for cleaning polycarbonate UC tubes for re-use in EV proteomics experiments. The cleaning process involves immediate submersion of UC tubes in H2O to prevent protein drying, washing in 0.1% sodium dodecyl sulfate (SDS) detergent, rinsing in hot tap water, demineralized water, and 70% ethanol. To validate the UC tube re-use protocol for downstream EV proteomics, used tubes were obtained following an experiment isolating EVs from cardiovascular tissue using differential UC and density gradient separation. Tubes were cleaned and the experimental process was repeated without EV samples comparing blank never-used UC tubes to cleaned UC tubes. The pseudo-EV pellets obtained from the isolation procedures were lysed and prepared for liquid chromatography-tandem mass spectrometry using a commercial protein sample preparation kit with modifications for low-abundance protein samples. Following cleaning, the number of identified proteins was reduced by 98% in the pseudo-pellet versus the previous EV isolation sample from the same tube. Comparing a cleaned tube against a blank tube, both samples contained a very small number of proteins (≤20) with 86% similarity. The absence of polymer peaks in the chromatograms of the cleaned tubes was confirmed. Ultimately, the validation of a UC tube cleaning protocol suitable for the enrichment of EVs will reduce the waste produced by EV laboratories and lower the experimental costs.
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Vesículas Extracelulares , Cemento de Policarboxilato , Proteómica , Proteómica/métodos , Vesículas Extracelulares/metabolismo , Proteínas/metabolismo , Polímeros/análisis , Agua/metabolismoRESUMEN
Currently available focal knee resurfacing implants (FKRIs) are fully or partially composed of metals, which show a large disparity in elastic modulus relative to bone and cartilage tissue. Although titanium is known for its excellent osseointegration, the application in FKRIs can lead to potential stress-shielding and metal implants can cause degeneration of the opposing articulating cartilage due to the high resulting contact stresses. Furthermore, metal implants do not allow for follow-up using magnetic resonance imaging (MRI).To overcome the drawbacks of using metal based FKRIs, a biomimetic and MRI compatible bi-layered non-resorbable thermoplastic polycarbonate-urethane (PCU)-based FKRI was developed. The objective of this preclinical study was to evaluate the mechanical properties, biocompatibility and osteoconduction of a novel Bionate® 75D - zirconium oxide (B75D-ZrO2) composite material in vitro and the osseointegration of a B75D-ZrO2 composite stem PCU implant in a caprine animal model. The tensile strength and elastic modulus of the B75D-ZrO2 composite were characterized through in vitro mechanical tests under ambient and physiological conditions. In vitro biocompatibility and osteoconductivity were evaluated by exposing human mesenchymal stem cells to the B75D-ZrO2 composite and culturing the cells under osteogenic conditions. Cell activity and mineralization were assessed and compared to Bionate® 75D (B75D) and titanium disks. The in vivo osseointegration of implants containing a B75D-ZrO2 stem was compared to implants with a B75D stem and titanium stem in a caprine large animal model. After a follow-up of 6 months, bone histomorphometry was performed to assess the bone-to-implant contact area (BIC). Mechanical testing showed that the B75D-ZrO2 composite material possesses an elastic modulus in the range of the elastic modulus reported for trabecular bone. The B75D-ZrO2 composite material facilitated cell mediated mineralization to a comparable extent as titanium. A significantly higher bone-to-implant contact (BIC) score was observed in the B75D-ZrO2 implants compared to the B75D implants. The BIC of B75D-ZrO2 implants was not significantly different compared to titanium implants. A biocompatible B75D-ZrO2 composite approximating the elastic modulus of trabecular bone was developed by compounding B75D with zirconium oxide. In vivo evaluation showed an significant increase of osseointegration for B75D-ZrO2 composite stem implants compared to B75D polymer stem PCU implants. The osseointegration of B75D-ZrO2 composite stem PCU implants was not significantly different in comparison to analogous titanium stem metal implants.
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Ensayo de Materiales , Oseointegración , Cemento de Policarboxilato , Uretano , Circonio , Circonio/química , Circonio/farmacología , Animales , Oseointegración/efectos de los fármacos , Uretano/química , Cemento de Policarboxilato/química , Prótesis de la Rodilla , Humanos , Cabras , Materiales Biocompatibles/química , Células Madre Mesenquimatosas/citologíaRESUMEN
Glutathione (GSH) depletion-induced ferroptosis has emerged as a promising treatment for malignant cancer. It works by inactivating glutathione peroxidase 4 (GPX4) and facilitating lipid peroxidation. However, effectively delivering inducers and depleting intracellular GSH remains challenging due to the short half-lives and high hydrophobicity of small-molecule ferroptosis inducers. These inducers often require additional carriers. Herein, diselenide-containing polymers can consume GSH to induce ferroptosis for pancreatic cancer therapy. The diselenide bonds are controllably built into the backbone of the polycarbonate with a targeting peptide CRGD (Cys-Arg-Gly-Asp), which allows for self-assembly into stable nanoparticles (denoted CRNSe) for self-delivery. Significantly, at a concentration of 12 µg mL-1, CRNSe binds to the active site cysteine of GSH resulting in a thorough depletion of GSH. In contrast, the disulfide-containing analog only causes a slight decrease in GSH level. Moreover, the depletion of GSH inactivates GPX4, ultimately inducing ferroptosis due to the accumulation of lipid peroxide in BxPC-3 cells. Both in vitro and in vivo studies have demonstrated that CRNSe exhibits potent tumor suppressive ability with few side effects on normal tissue. This study validates the anti-tumor mechanism of diselenide-containing polymers in addition to apoptosis and also provides a new strategy for inherently inducing ferroptosis in cancer therapy.
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Ferroptosis , Glutatión , Ferroptosis/efectos de los fármacos , Humanos , Glutatión/metabolismo , Animales , Línea Celular Tumoral , Ratones , Fosfolípido Hidroperóxido Glutatión Peroxidasa/metabolismo , Nanopartículas/química , Antineoplásicos/farmacología , Antineoplásicos/química , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patología , Polímeros/química , Polímeros/farmacología , Ratones Desnudos , Cemento de Policarboxilato/química , Oligopéptidos/química , Oligopéptidos/farmacología , Ratones Endogámicos BALB CRESUMEN
During fused filament fabrication (FFF) 3D printing with polycarbonate (PC) filament, a release of ultrafine particles (UFPs) and volatile organic compounds (VOCs) occurs. This study aimed to determine PC filament printing emission-induced toxicity in rats via whole-body inhalation exposure. Male Sprague Dawley rats were exposed to a single concentration (0.529 mg/m3, 40 nm mean diameter) of the 3D PC filament emissions in a time-course via whole body inhalation for 1, 4, 8, 15, and 30 days (4 hr/day, 4 days/week), and sacrificed 24 hr after the last exposure. Following exposures, rats were assessed for pulmonary and systemic responses. To determine pulmonary injury, total protein and lactate dehydrogenase (LDH) activity, surfactant proteins A and D, total as well as lavage fluid differential cells in bronchoalveolar lavage fluid (BALF) were examined, as well as histopathological analysis of lung and nasal passages was performed. To determine systemic injury, hematological differentials, and blood biomarkers of muscle, metabolic, renal, and hepatic functions were also measured. Results showed that inhalation exposure induced no marked pulmonary or systemic toxicity in rats. In conclusion, inhalation exposure of rats to a low concentration of PC filament emissions produced no significant pulmonary or systemic toxicity.
Asunto(s)
Exposición por Inhalación , Pulmón , Cemento de Policarboxilato , Ratas , Masculino , Animales , Ratas Sprague-Dawley , Pulmón/metabolismo , Líquido del Lavado BronquioalveolarRESUMEN
The emerging antibiotic resistance has been named by the World Health Organization (WHO) as one of the top 10 threats to public health. Notably, methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecalis (VREF) are designated as serious threats, whereas Clostridioides difficile (C. difficile) is recognized as one of the most urgent threats to human health and unmet medical need. Herein, they report the design and application of novel biodegradable polymers - the lipidated antimicrobial guanidinylate polycarbonates. These polymers showed potent antimicrobial activity against a panel of bacteria with fast-killing kinetics and low resistance development tendency, mainly due to their bacterial membrane disruption mechanism. More importantly, the optimal polymer showed excellent antibacterial activity against C. difficile infection (CDI) in vivo via oral administration. In addition, compared with vancomycin, the polymer demonstrated a much-prolonged therapeutic effect and virtually diminished recurrence rate of CDI. The convenient synthesis, easy scale-up, low cost, as well as biodegradability of this class of polycarbonates, together with their in vitro broad-spectrum antimicrobial activity and orally in vivo efficacy against CDI, suggest the great potential of lipidated guandinylate polycarbonates as a new class of antibacterial biomaterials to treat CDI and combat emerging antibiotic resistance.
Asunto(s)
Clostridioides difficile , Cemento de Policarboxilato , Clostridioides difficile/efectos de los fármacos , Animales , Cemento de Policarboxilato/química , Cemento de Policarboxilato/farmacología , Ratones , Administración Oral , Antibacterianos/farmacología , Antibacterianos/química , Pruebas de Sensibilidad Microbiana , Guanidinas/química , Guanidinas/farmacología , Infecciones por Clostridium/tratamiento farmacológico , Antiinfecciosos/farmacología , Antiinfecciosos/químicaRESUMEN
In this work, hyperbranched polycarbonate-poly(ethylene oxide) (PEO)-based solid polymer electrolytes (HBPC-SEs) are successfully synthesized via a straightforward organo-catalyzed "A1"+"B2"-ring-opening polymerization approach. The temperature-dependent ionic conductivity of HBPC-SEs, composed of different polycarbonate linkages and various LiTFSI concentrations, is investigated. The results demonstrate that HBPC-SE with an ether-carbonate alternating structure exhibits superior ionic conductivity, attributed to the solubility of Li salts in the polymer matrix and the mobility of the polymer segments. The HBPC1-SE with 30 wt% LiTFSI presents the highest ionic conductivities of 2.15 × 10-5, 1.78 × 10-4, and 6.07 × 10-4 Scm-1 at 30, 60, and 80 °C, respectively. Compared to traditional PEO-based electrolytes, the incorporation of polycarbonate segments significantly enhances the electrochemical stability window (5 V) and Li+ transference number (0.53) of HBPC-SEs. Furthermore, the LiFePO4/HBPC1-SE-3/Li cell exhibits exceptional rate capability and long-cycling performance, maintaining a discharge capacity of 130 mAh g-1 at 0.5C with a capacity retention of 95% after 300 cycles.
Asunto(s)
Litio , Cemento de Policarboxilato , Polímeros , Electrólitos , Metales , CarbonatosRESUMEN
The convergence of organoid and organ-on-a-chip (OoC) technologies is urgently needed to overcome limitations of current 3D in vitro models. However, integrating organoids in standard OoCs faces several technical challenges, as it is typically laborious, lacks flexibility, and often results in even more complex and less-efficient cell culture protocols. Therefore, specifically adapted and more flexible microfluidic platforms need to be developed to facilitate the incorporation of complex 3D in vitro models. Here, a modular, tubeless fluidic circuit board (FCB) coupled with reversibly sealed cell culture bricks for dynamic culture of embryonic stem cell-derived thyroid follicles is developed. The FCB is fabricated by milling channels in a polycarbonate (PC) plate followed by thermal bonding against another PC plate. LEGO-like fluidic interconnectors allow plug-and-play connection between a variety of cell culture bricks and the FCB. Lock-and-play clamps are integrated in the organoid brick to enable easy (un)loading of organoids. A multiplexed perfusion experiment is conducted with six FCBs, where thyroid organoids are transferred on-chip within minutes and cultured up to 10 d without losing their structure and functionality, thus validating this system as a flexible, easy-to-use platform, capable of synergistically combining organoids with advanced microfluidic platforms.