RESUMEN
In orthopedic surgery, metals are preferred to support or treat damaged bones due to their high mechanical strength. However, the necessity for a second surgery for implant removal after healing creates problems. Therefore, biodegradable metals, especially magnesium (Mg), gained importance, although their extreme susceptibility to galvanic corrosion limits their applications. The focus of this study was to control the corrosion of Mg and enhance its biocompatibility. For this purpose, surfaces of magnesium-calcium (MgCa1) alloys were modified with calcium phosphate (CaP) or CaP doped with zinc (Zn) or gallium (Ga) via microarc oxidation. The effects of surface modifications on physical, chemical, and mechanical properties and corrosion resistance of the alloys were studied using surface profilometry, goniometry, scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), nanoindentation, and electrochemical impedance spectroscopy (EIS). The coating thickness was about 5-8 µm, with grain sizes of 43.1 nm for CaP coating and 28.2 and 58.1 nm for Zn- and Ga-doped coatings, respectively. According to EIS measurements, the capacitive response (Yc) decreased from 11.29 to 8.72 and 0.15 Ω-1 cm-2 sn upon doping with Zn and Ga, respectively. The Ecorr value, which was -1933 mV for CaP-coated samples, was found significantly electropositive at -275 mV for Ga-doped ones. All samples were cytocompatible according to indirect tests. In vitro culture with Saos-2 cells led to changes in the surface compositions of the alloys. The numbers of cells attached to the Zn-doped (2.6 × 104 cells/cm2) and Ga-doped (6.3 × 104 cells/cm2) coatings were higher than that on the surface of the undoped coating (1.0 × 103 cells/cm2). Decreased corrosivity and enhanced cell affinity of the modified MgCa alloys (CaP coated and Zn and Ga doped, with Ga-doped ones having the greatest positive effect) make them novel and promising candidates as biodegradable metallic implant materials for the treatment of bone damages and other orthopedic applications.
Asunto(s)
Aleaciones/química , Fosfatos de Calcio/química , Materiales Biocompatibles Revestidos/química , Implantes Absorbibles , Aleaciones/toxicidad , Animales , Calcio/química , Calcio/toxicidad , Fosfatos de Calcio/toxicidad , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Materiales Biocompatibles Revestidos/toxicidad , Corrosión , Módulo de Elasticidad , Galio/química , Galio/toxicidad , Humanos , Magnesio/química , Magnesio/toxicidad , Ensayo de Materiales , Ratones , Humectabilidad , Zinc/química , Zinc/toxicidadRESUMEN
The titanium implant was treated with plasma electrolytic oxidation and subsequent ionic exchange and thermal treatment in order to obtain bioactive layer consisting of titanium oxide, calcium and sodium titanates and hydroxyapatite, as confirmed by X-ray diffraction (XRD). Scanning electron microscopy (SEM) revealed that the given method, besides corresponding phase composition, enables suitable nanotopology for cell attachment and proliferation. Cytotoxicity investigations by MTT, LDH and propidium iodide assays and light microscopy showed that these coatings were not toxic to L929 cells.
Asunto(s)
Materiales Biocompatibles Revestidos , Titanio , Materiales Biocompatibles Revestidos/toxicidad , Durapatita , Microscopía Electrónica de Rastreo , Oxidación-Reducción , Propiedades de Superficie , Difracción de Rayos XRESUMEN
Thrombus, bacterial infections, and severe inflammation are still serious problems that have to be faced with blood-contacting materials. However, it is a great challenge to simultaneously meet the above functional requirements in a simple, economical and efficient method. As such, we put forward a robust and versatile coating strategy by covalently modifying the multi-pharmacological drug honokiol (HK) with an amine-rich polydopamine/polyethyleneimine coating, through which anticoagulant, antibacterial and anti-inflammatory properties were obtained (DPHc) simultaneously. The amine content in the DPHc coating was lower than the detection limit, while it contained abundant phenolic hydroxyl groups (49 µmol cm-2). Meanwhile, the 30 day drug release test confirmed that the drug was firmly modified on the surface of the coating without release. A systematic in vitro and ex vivo evaluation confirmed that the coating had significant anti-thrombotic properties. The antibacterial rates of the DPHc coating against Staphylococcus aureus and Escherichia coli reached 99.98% and 99.99%, respectively. In addition, subcutaneous implantation indicated that the DPHc coating also has excellent histocompatibility. To the best of our knowledge, this is the first study using HK as a coating material that can not only combat thrombosis and infection but also significantly inhibit inflammation associated with the use of blood-contacting materials, thus expanding the application of HK in the field of biomaterials.
Asunto(s)
Antibacterianos/farmacología , Antiinflamatorios/farmacología , Compuestos de Bifenilo/farmacología , Materiales Biocompatibles Revestidos/farmacología , Fibrinolíticos/farmacología , Lignanos/farmacología , Animales , Antibacterianos/química , Antibacterianos/toxicidad , Antiinflamatorios/química , Antiinflamatorios/toxicidad , Compuestos de Bifenilo/química , Compuestos de Bifenilo/toxicidad , Línea Celular , Materiales Biocompatibles Revestidos/química , Materiales Biocompatibles Revestidos/toxicidad , Escherichia coli/efectos de los fármacos , Fibrinolíticos/química , Fibrinolíticos/toxicidad , Lignanos/química , Lignanos/toxicidad , Masculino , Ratones , Pruebas de Sensibilidad Microbiana , Conejos , Ratas Sprague-Dawley , Staphylococcus aureus/efectos de los fármacos , Trombosis/prevención & controlRESUMEN
Biofilms formed from the pathogenic bacteria that attach to the surfaces of biomedical devices and implantable materials result in various persistent and chronic bacterial infections, posing serious threats to human health. Compared to the elimination of matured biofilms, prevention of the formation of biofilms is expected to be a more effective way for the treatment of biofilm-associated infections. Herein, we develop a facile method for endowing diverse substrates with long-term antibiofilm property by deposition of a hybrid film composed of tannic acid/Cu ion (TA/Cu) complex and poly(ethylene glycol) (PEG). In this system, the TA/Cu complex acts as a multifunctional building block with three different roles: (i) as a versatile "glue" with universal adherent property for substrate modification, (ii) as a photothermal biocidal agent for bacterial elimination under irradiation of near-infrared (NIR) laser, and (iii) as a potent linker for immobilization of PEG with inherent antifouling property to inhibit adhesion and accumulation of bacteria. The resulted hybrid film shows negligible cytotoxicity and good histocompatibility and could prevent biofilm formation for at least 15 days in vitro and suppress bacterial infection in vivo, showing great potential for practical applications to solve the biofilm-associated problems of biomedical materials and devices.
Asunto(s)
Antibacterianos/uso terapéutico , Biopelículas/efectos de los fármacos , Incrustaciones Biológicas/prevención & control , Materiales Biocompatibles Revestidos/uso terapéutico , Cobre/uso terapéutico , Taninos/uso terapéutico , Animales , Antibacterianos/química , Antibacterianos/efectos de la radiación , Antibacterianos/toxicidad , Adhesión Bacteriana/efectos de los fármacos , Línea Celular , Materiales Biocompatibles Revestidos/química , Materiales Biocompatibles Revestidos/efectos de la radiación , Materiales Biocompatibles Revestidos/toxicidad , Cobre/química , Cobre/efectos de la radiación , Cobre/toxicidad , Escherichia coli/efectos de los fármacos , Rayos Infrarrojos , Masculino , Ratones , Pruebas de Sensibilidad Microbiana , Terapia Fototérmica , Polietilenglicoles/química , Polietilenglicoles/toxicidad , Ratas Sprague-Dawley , Piel/patología , Infecciones Cutáneas Estafilocócicas/tratamiento farmacológico , Infecciones Cutáneas Estafilocócicas/patología , Staphylococcus aureus/efectos de los fármacos , Taninos/química , Taninos/efectos de la radiación , Taninos/toxicidadRESUMEN
Titanium is widely utilized for manufacturing medical implants due to its inherent mechanical strength and biocompatibility. Recent studies have focused on developing coatings to impart unique properties to Ti implants, such as antimicrobial behavior, enhanced cell adhesion, and osteointegration. Ca- and Si-based ceramic (CS) coatings can enhance bone integration through the release of Ca and Si ions. However, high degradation rates of CS ceramics create a basic environment that reduces cell viability. Polymeric or protein-based coatings may be employed to modulate CS degradation. However, it is challenging to ensure coating stability over extended periods of time without compromising biocompatibility. In this study, we employed a fluorous-cured collagen shell as a drug-loadable scaffold around CS nanorod coatings on Ti implants. Fluorous-cured collagen coatings have enhanced mechanical and enzymatic stability and are able to regulate the release of Ca and Si ions. Furthermore, the collagen scaffold was loaded with antimicrobial peptides to impart antimicrobial activity while promoting cell adhesion. These multifunctional collagen coatings simultaneously regulate the degradation of CS ceramics and enhance antimicrobial activity, while maintaining biocompatibility.
Asunto(s)
Antibacterianos/farmacología , Nanotubos/química , Proteínas Citotóxicas Formadoras de Poros/farmacología , Silicatos/química , Titanio/química , Cicatrización de Heridas/efectos de los fármacos , Antibacterianos/química , Antibacterianos/toxicidad , Materiales Biocompatibles Revestidos/química , Materiales Biocompatibles Revestidos/toxicidad , Colágeno/química , Colágeno/toxicidad , Humanos , Pruebas de Sensibilidad Microbiana , Nanotubos/toxicidad , Osteoblastos/efectos de los fármacos , Proteínas Citotóxicas Formadoras de Poros/química , Proteínas Citotóxicas Formadoras de Poros/toxicidad , Silicatos/toxicidad , Staphylococcus aureus/efectos de los fármacos , Titanio/toxicidad , HumectabilidadRESUMEN
Biomaterials constructed exclusively of sintered microspheres have great potential in tissue engineering scaffold applications, offering the ability to create shape-specific scaffolds with precise controlled release yet to be matched by traditional additive manufacturing methods. The problem is that these microsphere-based scaffolds are limited in their stiffness for applications such as bone regeneration. Our vision to solve this problem was borne from a hierarchical structure perspective, focusing on the individual unit of the structure: the microsphere itself. In a core-shell approach, we envisioned a stiff core to create a stiff microsphere unit, with a polymeric shell that would enable sintering to the other microsphere units. Therefore, the current study provided a comparison of macroscopic biomaterials built on either polymer microspheres or polymer-coated hard glass microspheres. Identical polycaprolactone (PCL) polymer solutions were used to fabricate microspheres and as a thin coating on soda lime glass microspheres (hard phase). The materials were characterized as loose particles and as scaffolds via scanning electron microscopy, thermogravimetry, differential scanning calorimetry, Raman spectroscopy, mechanical testing, and a live/dead analysis with human umbilical cord-derived Wharton's jelly cells. The elastic modulus of the scaffolds with the thinly coated hard phase was about five times higher with glass microspheres (up to about 25 MPa) than pure polymer microspheres, while retaining the structure, cell adhesion, and chemical properties of the PCL polymer. This proof-of-concept study demonstrated the ability to achieve at least a five-fold increase in macroscopic stiffness via altering the core microsphere units with a core-shell approach.
Asunto(s)
Materiales Biocompatibles Revestidos/química , Poliésteres/química , Ingeniería de Tejidos/métodos , Andamios del Tejido/química , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Materiales Biocompatibles Revestidos/toxicidad , Módulo de Elasticidad , Humanos , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/efectos de los fármacos , Microesferas , Sistema Musculoesquelético/citologíaRESUMEN
Due to their simple crystal structures, one-dimensional hydroxyapatite (HA) nanostructures are easily to be applied to understand the fundamental concepts about the influences of HA dimensionality on physical, chemical, and biological properties. So, in this work, three typical HA one-dimensional nanostructures, HA nanotubes, HA nanowires, and HA nanospheres, were prepared, whose theoretical structures were built also. in vitro cytocompatibility test proved that, contrasting with TCPS, HA one-dimensional nanostructures had certain degree of cytotoxicity because HA nanostructures increase the generation of intracellular reactive oxygen species (ROS) and intracellular calcium. Theoretical simulation indicated that HA nanosphere has higher intracellular ROS generation and lower ROS storage amount than HA nanowire and HA nanotube, which were the possible reasons for its stronger cytotoxicity. Among these typical one-dimensional nanostructures, owing to higher drug storage amount and sustained delivery ability, HA nanotube was more potential application in orthopedics. The tubular structure of HA nanotubes could be used as reservoirs for small molecule drugs or growth factors. The cytocompatibility of HA nanostructures can be improved obviously when they were produced into two-dimensional structures. The prepared multilayer structure can simulate lamellar structures of Harvard system and enhance the cytocompatibility of Ti substrate. Therefore, the method used in this work is a prospective method to improve the inherently bio-inert of Ti when used in hard tissue repairing.
Asunto(s)
Materiales Biocompatibles Revestidos/farmacología , Durapatita/química , Nanoestructuras/química , Animales , Animales Recién Nacidos , Calcio/metabolismo , Materiales Biocompatibles Revestidos/toxicidad , Sistemas de Liberación de Medicamentos , Liberación de Fármacos , Durapatita/farmacología , Durapatita/toxicidad , Ensayo de Materiales , Nanotubos/química , Nanocables/química , Osteoblastos/efectos de los fármacos , Osteoblastos/metabolismo , Ratas , Especies Reactivas de Oxígeno/metabolismo , Cráneo/citología , Espectroscopía Infrarroja por Transformada de Fourier , Vancomicina/administración & dosificaciónRESUMEN
Surface modification techniques are often used to enhance the properties of Ti-based materials as hard-tissue replacements. While the microstructure of the coating and the quality of the interface between the substrate and coating are essential to evaluate the reliability and applicability of the surface modification. In this study, both a hydroxyapatite (HA) coating and a collagen-hydroxyapatite (Col-HA) composite coating were deposited onto a Ti-6Al-4V substrate using a biomimetic coating process. Importantly, a gradient cross-sectional structure with a porous coating toward the surface, while a dense layer adjacent to the interface between the coating and substrate was observed in three-dimensional (3D) from both the HA and Col-HA coatings via a dual-beam focused ion beam-scanning electron microscope (FIB-SEM). Moreover, the pore distributions within the entire coatings were reconstructed in 3D using Avizo, and the pores size distributions along the coating depth were calculated using RStudio. By evaluating the mechanical property and biocompatibility of these materials and closely observing the cross-sectional cell-coating-substrate interfaces using FIB-SEM, it was revealed that the porous surface created by both coatings well supports osteoblast cell adhesion while the dense inner layer facilitates a good bonding between the coating and the substrate. Although the mechanical property of the coating decreased with the addition of collagen, it is still strong enough for implant handling and the biocompatibility was promoted.
Asunto(s)
Materiales Biomiméticos/química , Biomimética/métodos , Materiales Biocompatibles Revestidos/química , Células 3T3 , Adhesivos , Aleaciones , Animales , Materiales Biomiméticos/toxicidad , Materiales Biocompatibles Revestidos/toxicidad , Colágeno Tipo I , Durapatita , Procesamiento de Imagen Asistido por Computador , Imagenología Tridimensional , Ensayo de Materiales , Ratones , Microscopía Electrónica de Rastreo , Porosidad , Resistencia a la Tracción , TitanioRESUMEN
The excellent biocompatibility of calcium phosphate (CaP) coatings makes them widely used in magnesium (Mg) alloy orthopedic implant materials. However, the porous morphology of CaP coatings limits their corrosion resistance. A cupric oxide (CuO) doped titania (TiO2) sol-gel coating is prepared on a porous hydroxyapatite (HA) coating. According to electrochemical test results, the HA/CuO-TiO2 coating obtains a current density of 6 × 10-4 mA/cm2, lower than that of the Mg alloy (2.6 × 10-2 mA/cm2). The hydrogen evaluation of the HA/CuO-TiO2 coating is only 1/12 that of the Mg alloy after immersion for 7 days. In addition, the HA/CuO-TiO2 coating has an antibacterial rate of 99.5 ± 0.4% against Staphylococcus aureus, significantly higher than that of the HA coating (19.8 ± 0.3%) and HTC0 coating (38.4 ± 0.5%). The CuO doped composite coating has no adverse effect or cytotoxicity on cell proliferation (cell viability ≥79.6%). Hence, the HA/CuO-TiO2 composite coating is useful for enhancing the corrosion resistance and antibacterial properties of Mg alloys while ensuring cytocompatibility. The HA/CuO-TiO2 coated AZ60 Mg alloy can meet the requirements of clinical application.
Asunto(s)
Aleaciones , Magnesio , Aleaciones/toxicidad , Antibacterianos/toxicidad , Materiales Biocompatibles Revestidos/toxicidad , Cobre , Corrosión , Durapatita , Propiedades de Superficie , TitanioRESUMEN
The high surface elastic modulus of the titanium (Ti) implant is one of the critical factors causing poor osteointegration between the implant surface and surrounding bone tissue. To address this challenge, spherical silica nanoparticles (SSNs) and spherical titania nanoparticles (STNs) with different sizes were synthesized and embedded into Ti surfaces via a micro-arc oxidation (MAO) technique. There were no significant changes in the surface roughness and protein adsorption behaviors before and after the embedding of spherical silica nanoparticles and titania nanoparticles into the Ti implant. However, the surface elastic modulus of Ti-SSNs decreased from 93 GPa to 6.7 GPa, while there was still no change in surface elastic modulus between Ti and Ti-STN groups. In vitro experiments showed that Ti-SSNs, especially Ti-SSN3, significantly stimulated the expression level and nuclear localization of the transcription factor YAP. YAP/TAZ could further inhibit the phosphorylation of AKT and mTOR proteins in MSCs, leading to higher LC3-II protein expression and osteogenic differentiation of MSCs. Ti-SSNs also showed a higher level of autophagosome formation, ALP activity and mineralization capability compared to the other groups. Our results showed that the surface elasticity modulus of an implant plays an important role in the regulation of MSC behaviors. Therefore, designing an implant with an optimal elastic modulus at the surface might have great clinical potential in the bone repair field.
Asunto(s)
Autofagia/efectos de los fármacos , Materiales Biocompatibles Revestidos/química , Células Madre Mesenquimatosas/efectos de los fármacos , Nanopartículas del Metal/química , Osteogénesis/efectos de los fármacos , Animales , Proteínas Reguladoras de la Apoptosis/metabolismo , Materiales Biocompatibles Revestidos/toxicidad , Módulo de Elasticidad , Femenino , Nanopartículas del Metal/toxicidad , Ratones Endogámicos BALB C , Proteínas Asociadas a Microtúbulos/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas Sprague-Dawley , Dióxido de Silicio/química , Dióxido de Silicio/toxicidad , Serina-Treonina Quinasas TOR/metabolismo , Titanio/química , Titanio/toxicidad , Proteínas Señalizadoras YAPRESUMEN
Herein, thermo- and pH-sensitive pectin-graft-poly(dimethylaminoethyl methacrylate) copolymer-coated magnetic nanoparticles were synthesized via a green and rapid synthetic approach based on microwave irradiation. Firstly, a novel thermo- and pH-sensitive pectin-graft-poly(dimethylaminoethyl methacrylate) copolymer (Pec-g-PolyDMAEMA) was synthesized and then, Pec-g-PolyDMAEMA based magnetic nanoparticles (Pec-g-PolyDMAEMA@Fe3O4) were produced via microwave-assisted co-precipitation method. The thermo/pH/magnetic field multi-sensitive hybrid nanoparticle was characterized by techniques like TEM, VSM, FT-IR, and TGA/DSC. In vitro release studies of 5-Fluorouracil (FL) were carried out by altering the temperature (37 and 44°C), pH (5.5 and 7.4) and presence of an AMF. The FL release of Pec-g-PolyDMAEMA@Fe3O4@FL exhibited pH-sensitive behavior. They showed thermo/pH-sensitive FL release features with the greatest release of FL at 37°C (56%) than at 44°C (40%) and at pH of 7.4 (63%) than at pH of 5.5 (45%) within 48h. The FL release was also significantly increased (100%) with the presence of a 50 mT magnetic field. These results indicate that the developed Pec-g-PolyDMAEMA@Fe3O4 nanoparticles are promising in the application of multi-stimuli-sensitive delivery of drugs.
Asunto(s)
Materiales Biocompatibles Revestidos , Portadores de Fármacos , Nanopartículas de Magnetita , Metacrilatos/química , Pectinas/química , Ácidos Polimetacrílicos/química , Animales , Antimetabolitos Antineoplásicos/administración & dosificación , Antimetabolitos Antineoplásicos/farmacología , Antimetabolitos Antineoplásicos/toxicidad , Materiales Biocompatibles Revestidos/farmacología , Materiales Biocompatibles Revestidos/toxicidad , Liberación de Fármacos , Ensayos de Selección de Medicamentos Antitumorales , Fibroblastos/efectos de los fármacos , Fluorouracilo/administración & dosificación , Fluorouracilo/farmacología , Fluorouracilo/toxicidad , Humanos , Concentración de Iones de Hidrógeno , Células MCF-7 , Campos Magnéticos , Nanopartículas de Magnetita/administración & dosificación , Nanopartículas de Magnetita/toxicidad , Ratones , Transición de Fase , Ácidos Polimetacrílicos/síntesis química , Ácidos Polimetacrílicos/farmacología , Ácidos Polimetacrílicos/toxicidad , Solubilidad , Espectroscopía Infrarroja por Transformada de Fourier , TemperaturaRESUMEN
Nosocomial infections resulting from bacterial attachment on blood-contacting medical devices, as well as biofilm and thrombus formation caused by fibrin crosslinking and platelet accumulation/activation are a major health concern and may lead to severe morbidity and mortality. Therefore, there is an urgent need to develop facile and efficient surface coatings with both antibiofilm and antithrombotic properties to prevent medical-device associated infections as well as thrombus formation. In this study, the copolymers containing quaternary ammonium (QA) and phosphorylcholine (PC) groups were synthesized through traditional free-radical copolymerization. The cationic group of QA provides bactericidal properties, and the cell membrane-mimicking group of PC provides antithrombotic and antifouling properties. Long-term stability of the copolymer coating was achieved via simple dip coating. X-ray photoelectron spectroscopy and water contact angle measurement demonstrated that the QA and PC groups possessed inversion properties once in contact with water allowing for long-term stability. Scanning electron microscopy and confocal laser scanning microscopy demonstrated that the copolymer coating could maintain antibiofilm properties for one week in a nutrient-rich environment. Furthermore, the copolymer coating significantly decreased platelet adhesion/activation and did not cause hemolysis. The ex vivo blood circulation showed no thrombus formation which confirmed the excellent antithrombotic property of the copolymer coating. Such coatings that maintain high cell viability and exhibit both antibiofilm and antithrombotic properties present potential applications for blood-contacting devices.
Asunto(s)
Biopelículas/efectos de los fármacos , Materiales Biocompatibles Revestidos/farmacología , Fibrinolíticos/farmacología , Fosforilcolina/análogos & derivados , Fosforilcolina/farmacología , Compuestos de Amonio Cuaternario/farmacología , Animales , Materiales Biocompatibles Revestidos/química , Materiales Biocompatibles Revestidos/toxicidad , Fibrinolíticos/química , Fibrinolíticos/toxicidad , Células Endoteliales de la Vena Umbilical Humana , Humanos , Pruebas de Sensibilidad Microbiana , Fosforilcolina/toxicidad , Adhesividad Plaquetaria/efectos de los fármacos , Compuestos de Amonio Cuaternario/química , Compuestos de Amonio Cuaternario/toxicidad , Conejos , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/fisiologíaRESUMEN
Polydimethylsiloxane (PDMS) is commonly used in medical devices because it is non-toxic and stable against oxidative stress. Relatively high blood platelet adhesion and the need for chemical crosslinking through curing, however, limit its utility. In this research, a biostable PDMS-based polyurethane-urea bearing zwitterion sulfobetaine (PDMS-SB-UU) was synthesized for potential use in the fabrication or coating of blood-contacting devices, such as a conduits, artificial lungs, and microfluidic devices. The chemical structure and physical properties of synthesized PDMS-SB-UU were confirmed by 1H-nuclear magnetic resonance (1H-NMR), X-ray diffraction (XRD), and uniaxial stress-strain curve. In vitro stability of PDMS-SB-UU was confirmed against lipase and 30% H2O2 for 8 weeks, and PDMS-SB-UU demonstrated significantly higher resistance to fibrinogen adsorption and platelet deposition compared to control PDMS. Moreover, PDMS-SB-UU showed a lack of hemolysis and cytotoxicity with whole ovine blood and rat vascular smooth muscle cells (rSMCs), respectively. The PDMS-SB-UU was successfully processed into small-diameter (0.80 ± 0.05 mm) conduits by electrospinning and coated onto PDMS- and polypropylene-based blood-contacting biomaterials due to its unique physicochemical characteristics from its soft- and hard- segments.
Asunto(s)
Incrustaciones Biológicas/prevención & control , Materiales Biocompatibles Revestidos/química , Dimetilpolisiloxanos/química , Poliuretanos/química , Compuestos de Amonio Cuaternario/química , Ácidos Sulfónicos/química , Adsorción , Animales , Plaquetas/efectos de los fármacos , Materiales Biocompatibles Revestidos/síntesis química , Materiales Biocompatibles Revestidos/toxicidad , Dimetilpolisiloxanos/síntesis química , Dimetilpolisiloxanos/toxicidad , Fibrinógeno/química , Fibrinógeno/metabolismo , Hemólisis/efectos de los fármacos , Adhesividad Plaquetaria/efectos de los fármacos , Poliuretanos/síntesis química , Poliuretanos/toxicidad , Compuestos de Amonio Cuaternario/síntesis química , Compuestos de Amonio Cuaternario/toxicidad , Ratas , Ovinos , Ácidos Sulfónicos/síntesis química , Ácidos Sulfónicos/toxicidadRESUMEN
The deposition of polyelectrolyte multilayers, obtained by the layer-by-layer (LbL) method, is a well-established technology to design biocompatible and antibacterial coatings aimed at preventing implant-associated infections. Several types of LbL films have been reported to exhibit antiadhesive and/or antibacterial (contact-killing or release-killing) properties governed not only by the incorporated compounds but also by their buildup conditions or their postbuildup treatments. Tannic acid (TA), a natural polyphenol, is known to inhibit the growth of several bacterial strains. In this work, we developed TA/collagen (TA/COL) LbL films built in acetate or citrate buffers at pH 4. Surprisingly, the used buffer impacts not only the physicochemical but also the antibacterial properties of the films. When incubated in physiological conditions, both types of TA/COL films released almost the same amount of TA depending on the last layer and showed an antibacterial effect against Staphylococcus aureus only for citrate-built films. Because of their granular topography, TA/COL citrate films exhibited an efficient release-killing effect with no cytotoxicity toward human gingival fibroblasts. Emphasis is put on a comprehensive evaluation of the physicochemical parameters driving the buildup and the antibacterial property of citrate films. Specifically, complexation strengths between TA and COL are different in the presence of the two buffers affecting the LbL deposition. This work constitutes an important step toward the use of polyphenols as an antibacterial agent when incorporated in LbL films.
Asunto(s)
Antibacterianos/farmacología , Materiales Biocompatibles Revestidos/farmacología , Colágeno/química , Taninos/farmacología , Antibacterianos/toxicidad , Ácido Cítrico/química , Ácido Cítrico/toxicidad , Materiales Biocompatibles Revestidos/toxicidad , Colágeno/toxicidad , Sistemas de Liberación de Medicamentos , Escherichia coli/efectos de los fármacos , Fibroblastos/efectos de los fármacos , Humanos , Pruebas de Sensibilidad Microbiana , Staphylococcus aureus/efectos de los fármacos , Taninos/toxicidadRESUMEN
One of the leading causes of failure for any bone implant is implant-associated infections. The implant-bone interface is in fact the crucial site of infection where both the microorganisms and cells compete to populate the newly introduced implant surface. Most of the work dealing with this issue has focused on the design of implant coatings capable of preventing infection while ignoring cell proliferation or vice versa. The present study is therefore focused on investigating the antibacterial and biological properties of nanocomposite coatings based on an amorphous hydrocarbon (a-C:H) matrix containing silver nanoparticles (AgNPs). a-C:H coatings with varying silver concentrations were generated directly on medical grade titanium substrates using a combination of a gas aggregation source (GAS) and a plasma-enhanced chemical vapor deposition (PE-CVD) process. The obtained results revealed that the surface silver content increased from 1.3 at % to 5.3 at % by increasing the used DC magnetron current in the GAS from 200 to 500 mA. The in vitro antibacterial assays revealed that the nanocomposites with the highest number of silver content exhibited excellent antibacterial activities resulting in a 6-log reduction of Escherichia coli and a 4-log reduction of Staphylococcus aureus after 24 h of incubation. An MTT assay, fluorescence live/dead staining, and SEM microscopy observations of MC3T3 cells seeded on the uncoated and coated Ti substrates also showed that increasing the amount of AgNPs in the nanocomposites had no notable impact on their cytocompatibility, while improved cell proliferation was especially observed for the nanocomposites possessing a low amount of AgNPs. These controllable Ag/a-C:H nanocomposites on Ti substrates, which simultaneously provide an excellent antibacterial performance and good biocompatibility, could thus have promising applications in orthopedics and other biomedical implants.
Asunto(s)
Antibacterianos/farmacología , Materiales Biocompatibles Revestidos/química , Nanocompuestos/química , Prótesis e Implantes , Plata/farmacología , Titanio/química , Animales , Antibacterianos/química , Antibacterianos/toxicidad , Adhesión Celular/efectos de los fármacos , Línea Celular , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Materiales Biocompatibles Revestidos/toxicidad , Escherichia coli/efectos de los fármacos , Hidrocarburos/química , Hidrocarburos/toxicidad , Nanopartículas del Metal/química , Nanopartículas del Metal/toxicidad , Ratones , Pruebas de Sensibilidad Microbiana , Nanocompuestos/toxicidad , Plata/química , Plata/toxicidad , Staphylococcus aureus/efectos de los fármacos , HumectabilidadRESUMEN
The purpose of this work is the development of Ag/a:C and Ag-Au/a:C coatings for ureteral stents, to provide them with antimicrobial characteristics. Silver was selected because of its well-known antibacterial properties, while gold was included to assess its capacity to accelerate the silver ion release forming a galvanic couple between Au and Ag. Thus, the metallic (Ag) and bimetallic clusters (Ag-Au) were produced by three different configurations: (i) unbalanced magnetron sputtering (conventional sputtering), (ii) plasma gas condensation process, and by (iii) a combination between both previous approaches. Coatings with Ag-Au bimetallic clusters were characterized by transmission electron microscopy (TEM) in order to study the arrangement (alloy, core-shell, and galvanic couple) of these particles in the carbon matrix. Inductively coupled plasma optical emission spectroscopy (ICP-OES) was used to quantify the Ag ions released through artificial urine from the different coatings deposited on thermoplastic polyurethane tape (one of the materials used in the manufacture of the ureteral stent ). Then, the antibacterial and cytotoxicity properties of Ag and Ag-Au/a:C coatings were evaluated. TEM shows that a biphasic structure was not detected, thus not allowing to anticipate the establishment of a galvanic couple. The ICP-OES results demonstrate that the silver ionization is mainly a function of the amount of silver incorporated in the amorphous carbon (a:C) matrix, and the formation of a bimetallic alloy has a detrimental effect on release of the silver ions. The antibacterial activity was regulated by the silver ionization mechanisms because the coatings with higher Ag release had a higher antibacterial activity.
Asunto(s)
Antibacterianos/farmacología , Carbono/química , Materiales Biocompatibles Revestidos/química , Nanopartículas del Metal/química , Plata/farmacología , Stents , Antibacterianos/toxicidad , Materiales Biocompatibles Revestidos/toxicidad , Escherichia coli/efectos de los fármacos , Escherichia coli/fisiología , Fibroblastos/efectos de los fármacos , Oro/química , Oro/toxicidad , Plata/toxicidadRESUMEN
Graphene oxide (GO) can improve the degradation resistance of biomedical Mg alloy because of its excellent impermeability and outstanding chemical inertness. However, the weak interfacial bonding between GO and Mg matrix leads to easily detaching during degradation. In this study, in situ reaction induced by TiO2 took place in the AZ61-GO biocomposite to enhance the interfacial bonding between GO and Mg matrix. For the specific process, TiO2 was uniformly and tightly deposited onto the GO surface by hydrothermal reaction (TiO2/GO) first and then used for fabricating AZ61-TiO2/GO biocomposites by selective laser melting (SLM). Results showed that TiO2 was in situ reduced by magnesiothermic reaction during SLM process, and the reduzate Ti, on the one hand, reacted with Al in the AZ61 matrix to form TiAl2 and, on the other hand, reacted with GO to form TiC at the AZ61-GO interface. Owing to the enhanced interfacial bonding, the AZ61-TiO2/GO biocomposite showed 12.5% decrease in degradation rate and 10.1% increase in compressive strength as compared with the AZ61-GO biocomposite. Moreover, the AZ61-TiO2/GO biocomposite also showed good cytocompatibility because of the slowed degradation. These findings may provide guidance for the interfacial enhancement in GO/metal composites for biomedical applications.
Asunto(s)
Aleaciones/química , Materiales Biocompatibles Revestidos/química , Grafito/química , Titanio/química , Aleaciones/toxicidad , Línea Celular Tumoral , Materiales Biocompatibles Revestidos/toxicidad , Grafito/toxicidad , Humanos , Magnesio/química , Magnesio/toxicidad , Titanio/toxicidadRESUMEN
The management of thrombosis and bacterial infection is critical to ensure the functionality of medical devices. While administration of anticoagulants is the current antithrombotic clinical practice, a variety of complications, such as uncontrolled hemorrhages or heparin-induced thrombocytopenia, can occur. Additionally, infection rates remain a costly and deadly complication associated with use of these medical devices. It has been hypothesized that if a synthetic surface could mimic the biochemical mechanisms of the endothelium of blood vessels, thrombosis could be reduced, anticoagulant use could be avoided, and infection could be prevented. Herein, the interfacial biochemical effects of the endothelium were mimicked by altering the surface of medical grade silicone rubber (SR). Surface modification was accomplished via heparin surface immobilization (Hep) and the inclusion of a nitric oxide (NO) donor into the SR polymeric matrix to achieve synergistic effects (Hep-NO-SR). An in vitro bacteria adhesion study revealed that Hep-NO-SR exhibited a 99.46 ± 0.17% reduction in viable bacteria adhesion compared to SR. An in vitro platelet study revealed Hep-NO-SR reduced platelet adhesion by 84.12 ± 6.19% compared to SR, while not generating a cytotoxic response against fibroblast cells. In a 4 h extracorporeal circuit model without systemic anticoagulation, all Hep-NO-SR samples were able to maintain baseline platelet count and device patency; whereas 66% of SR samples clotted within the first 2 h of study. Results indicate that Hep-NO-SR creates a more hemocompatible and antibacterial surface by mimicking two key biochemical functions of the native endothelium.
Asunto(s)
Materiales Biomiméticos/química , Fármacos Hematológicos/uso terapéutico , Heparina/uso terapéutico , Donantes de Óxido Nítrico/uso terapéutico , S-Nitroso-N-Acetilpenicilamina/uso terapéutico , Animales , Adhesión Bacteriana/efectos de los fármacos , Materiales Biomiméticos/toxicidad , Coagulación Sanguínea/efectos de los fármacos , Plaquetas/metabolismo , Materiales Biocompatibles Revestidos/química , Materiales Biocompatibles Revestidos/toxicidad , Endotelio/química , Fármacos Hematológicos/farmacología , Fármacos Hematológicos/toxicidad , Heparina/farmacología , Heparina/toxicidad , Proteínas Inmovilizadas/farmacología , Proteínas Inmovilizadas/uso terapéutico , Proteínas Inmovilizadas/toxicidad , Ratones , Óxido Nítrico/metabolismo , Donantes de Óxido Nítrico/farmacología , Donantes de Óxido Nítrico/toxicidad , Adhesividad Plaquetaria/efectos de los fármacos , Conejos , S-Nitroso-N-Acetilpenicilamina/farmacología , S-Nitroso-N-Acetilpenicilamina/toxicidad , Elastómeros de Silicona/química , Elastómeros de Silicona/toxicidad , Staphylococcus aureus/efectos de los fármacos , Propiedades de SuperficieRESUMEN
Titanium-based endosseous implants with high antibacterial and osseointegration activities are extremely required in clinics. To achieve this line, herein the doped coatings with three kinds of Zn doses were micro-arc oxidized (MAOed) on Ti. They were examined to reveal a bilayered structure, in which the outer layer consisted completely of the amorphism comprising elements of Ti, O and Zn with Zn doped in the form of weaken Zn-O bonds, and the underlying layer was partially crystallized with nanocrystalline TiO2 and Zn2TiO4 to embed an amorphous matrix. While the Zn doped doses of the surface amorphous layers increased with elevating the MAOed voltages, the weaken Zn-O bonds in the amorphism were identified to act as both the contributor of Zn2+ controllable release and the generator of reactive oxide species (ROS) on the coatings. The enhanced HO⢠and O2-⢠formation on the elevated voltage MAOed coatings caused serious break of the cell walls and plasma membranes of S. aureus. In parallel, the enhanced Zn2+ release and extracellular H2O2 formation led to the enhanced intracellular ROS level of S. aureus, further aggravating the damage of plasma membrane, resulting in bacteria death. On contrary to the overdose of Zn doped coating, the moderate doses of Zn doped coatings did not induce additional intracellular ROS and attenuate viability and proliferation of osteoblasts in vitro, and promoted osseointegration in both S. aureus-uninfected and infected rat tibias, which ascribed to the strong antibacterial activity and un-attenuated cell function of the coatings in the infected case. STATEMENT OF SIGNIFICANCE: (1) The Zn-doped coatings revealed a bilayered structure of the surface layer comprising the Ti, O and Zn constructed amorphism with Zn in the form of weaken Zn-O bonds, and the underlying layer comprising nanocrystalline TiO2 and Zn2TiO4 to embed amorphous matrix. (2) The weaken Zn-O bonds in the amorphism were identified to act as both the contributor of Zn2+ controllable release and the generator of ROS on the coatings. (3) The enhanced Zn2+ release and ROS formation on the coatings killed S. aureus by inducing serious break of their cell walls and plasma membranes. This effect in combination of un-attenuated osteoblast proliferation endowed the moderate Zn doped coatings with enhanced osseointegration in S. aureus-infected rat tibias.
Asunto(s)
Antibacterianos/uso terapéutico , Materiales Biocompatibles Revestidos/uso terapéutico , Oseointegración/efectos de los fármacos , Tibia/microbiología , Titanio/uso terapéutico , Zinc/uso terapéutico , Animales , Antibacterianos/química , Antibacterianos/toxicidad , Materiales Biocompatibles Revestidos/química , Materiales Biocompatibles Revestidos/toxicidad , Escherichia coli/efectos de los fármacos , Ratones , Pruebas de Sensibilidad Microbiana , Osteoblastos/efectos de los fármacos , Células RAW 264.7 , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismo , Staphylococcus aureus/efectos de los fármacos , Titanio/química , Titanio/toxicidad , Zinc/química , Zinc/toxicidadRESUMEN
Antibiotic-resistant bacteria are frequently involved in implant-associated infections (IAIs), making the treatment of these infections even more challenging. Therefore, multifunctional implant surfaces that simultaneously possess antibacterial activity and induce osseointegration are highly desired in order to prevent IAIs. The incorporation of multiple inorganic antibacterial agents onto the implant surface may aid in generating synergistic antibacterial behavior against a wide microbial spectrum while reducing the occurrence of bacterial resistance. In this study, porous titanium implants synthesized by selective laser melting (SLM) were biofunctionalized with plasma electrolytic oxidation (PEO) using electrolytes based on Ca/P species as well as silver and zinc nanoparticles in ratios from 0 to 100% that were tightly embedded into the growing titanium oxide layer. After the surface bio-functionalization process, silver and zinc ions were released from the implant surfaces for at least 28 days resulting in antibacterial leaching activity against methicillin-resistant Staphylococcus aureus (MRSA). Furthermore, the biofunctionalized implants generated reactive oxygen species, thereby contributing to antibacterial contact-killing. While implant surfaces containing up to 75% silver and 25% zinc nanoparticles fully eradicated both adherent and planktonic bacteria in vitro as well as in an ex vivo experiment performed using murine femora, solely zinc-bearing surfaces did not. The minimum inhibitory and bactericidal concentrations determined for different combinations of both types of ions confirmed the presence of a strong synergistic antibacterial behavior, which could be exploited to reduce the amount of required silver ions by two orders of magnitude (i.e., 120 folds). At the same time, the zinc bearing surfaces enhanced the metabolic activity of pre-osteoblasts after 3, 7, and 11 days. Altogether, implant biofunctionalization by PEO with silver and zinc nanoparticles is a fruitful strategy for the synthesis of multifunctional surfaces on orthopedic implants and the prevention of IAIs caused by antibiotic-resistant bacteria. STATEMENT OF SIGNIFICANCE: Implant-associated infections are becoming increasingly challenging to treat due to growing antibiotic resistance against antibiotics. Here, we propose an alternative approach where silver and zinc nanoparticles are simultaneously used for the biofunctionalization of rationally designed additively manufactured porous titanium. This combination of porous design and tailored surface treatment allows us to reduce the amount of required silver nanoparticles by two orders of magnitude, fully eradicate antibiotic-resistant bacteria, and enhance the osteogenic behavior of pre-osteoblasts. We demonstrate that the resulting implants display antibacterial activity in vitro and ex vivo against methicillin-resistant Staphylococcus aureus.