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1.
Int J Mol Sci ; 25(18)2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39337259

RESUMEN

The low-cost daily monitoring of C-reactive protein (CRP) levels is crucial for screening acute inflammation or infections as well as managing chronic inflammatory diseases. In this study, we synthesized novel 2-Methacryloyloxy ethyl phosphorylcholine (MPC)-based biomimetic nanoparticles with a large surface area to develop a visual CRP-quantification assay using affordable glass capillaries. The PMPC nanoparticles, synthesized via reflux precipitation polymerization, demonstrated multivalent binding capabilities, enabling rapid and specific CRP capture. In the presence of CRP, PMPC nanoparticles formed sandwich structures with magnetic nanoparticles functionalized with CRP antibodies, thereby enhancing detection sensitivity and specificity. These sandwich complexes were magnetically accumulated into visible and quantifiable stacks within the glass capillaries, allowing for the rapid, sensitive, and specific quantification of CRP concentrations with a detection limit of 57.5 pg/mL and a range spanning from 0 to 5000 ng/mL. The proposed visual distance-based capillary biosensor shows great potential in routine clinical diagnosis as well as point-of-care testing (POCT) in resource-limited settings.


Asunto(s)
Proteína C-Reactiva , Nanopartículas , Polímeros , Proteína C-Reactiva/análisis , Inmunoensayo/métodos , Nanopartículas/química , Humanos , Polímeros/química , Materiales Biomiméticos/química , Técnicas Biosensibles/métodos , Límite de Detección , Fosforilcolina/química , Fosforilcolina/análogos & derivados
2.
Bioconjug Chem ; 35(9): 1417-1428, 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39225485

RESUMEN

Electrostatic self-assembly between negatively charged nucleic acids and cationic materials is the basis for the formulation of the delivery systems. Nevertheless, structural disintegration occurs because their colloidal stabilities are frequently insufficient in a hostile biological environment. To overcome the sequential biological barriers encountered during transcellular gene delivery, we attempted to use in situ polymerization onto plasmid DNA (pDNA) with a variety of functional monomers, including N-(3-aminopropyl)methacrylate, (aminopropyl)methacrylamide hydrochloride, 1-vinylimidazole, and 2-methacryloyloxyethylphosphorylcholine and N,N'-bis(acryloyl) cystamine. The covalently linked monomers could polymerize into a network structure on top of pDNA, providing excellent structural stability. Additionally, the significant proton buffering capacity of 1-vinylimidazole is expected to aid in the release of pDNA payloads from acidic and digestive endolysosomes. In addition, the redox-mediated cleavage of the disulfide bond in N,N'-bis(acryloyl)cystamine allows for the selective cleavage of the covalently linked network in the cytosolic microenvironment. This is due to the high intracellular level of glutathione, which promotes the liberation of pDNA payloads in the cell interiors. The proposed polymerization strategies resulted in well-defined nanoscale pDNA delivery systems. Excellent colloidal stabilities were observed, even when incubated in the presence of high concentrations of heparin (10 mg/mL). In contrast, the release of pDNA was confirmed upon incubation in the presence of glutathione, mimicking the intracellular microenvironment. Cell transfection experiments verified their efficient cellular uptake and gene expression activities in the hard-transfected MCF-7 cells. Hence, the polymerization strategy used in the fabrication of covalently linked nonviral gene delivery systems shows promise in creating high-performance gene delivery systems with diverse functions. This could open new avenues in cellular microenvironment engineering.


Asunto(s)
ADN , Plásmidos , Polimerizacion , Humanos , ADN/administración & dosificación , ADN/química , Plásmidos/administración & dosificación , Técnicas de Transferencia de Gen , Metacrilatos/química , Transfección/métodos , Células MCF-7 , Fosforilcolina/química , Fosforilcolina/análogos & derivados
3.
Proc Natl Acad Sci U S A ; 121(37): e2404542121, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39240968

RESUMEN

Human C-reactive protein (CRP) is a pentameric complex involved in immune defense and regulation of autoimmunity. CRP is also a therapeutic target, with both administration and depletion of serum CRP being pursued as a possible treatment for autoimmune and cardiovascular diseases, among others. CRP binds to phosphocholine (PC) moieties on membranes to activate the complement system via the C1 complex, but it is unknown how CRP, or any pentraxin, binds to C1. Here, we present a cryoelectron tomography (cryoET)-derived structure of CRP bound to PC ligands and the C1 complex. To gain control of CRP binding, a synthetic mimotope of PC was synthesized and used to decorate cell-mimetic liposome surfaces. Structure-guided mutagenesis of CRP yielded a fully active complex able to bind PC-coated liposomes that was ideal for cryoET and subtomogram averaging. In contrast to antibodies, which form Fc-mediated hexameric platforms to bind and activate the C1 complex, CRP formed rectangular platforms assembled from four laterally associated CRP pentamers that bind only four of the six available globular C1 head groups. Potential residues mediating lateral association of CRP were identified from interactions between unit cells in existing crystal structures, which rationalized previously unexplained mutagenesis data regarding CRP-mediated complement activation. The structure also enabled interpretation of existing biochemical data regarding interactions mediating C1 binding and identified additional residues for further mutagenesis studies. These structural data therefore provide a possible mechanism for regulation of complement by CRP, which limits complement progression and has consequences for how the innate immune system influences autoimmunity.


Asunto(s)
Proteína C-Reactiva , Humanos , Proteína C-Reactiva/química , Proteína C-Reactiva/metabolismo , Proteína C-Reactiva/inmunología , Activación de Complemento , Complemento C1/metabolismo , Complemento C1/química , Vía Clásica del Complemento/inmunología , Microscopía por Crioelectrón , Liposomas/metabolismo , Liposomas/química , Modelos Moleculares , Fosforilcolina/química , Fosforilcolina/metabolismo , Unión Proteica
4.
Acta Biomater ; 186: 185-200, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39103136

RESUMEN

Thrombosis and plasma leakage are two of the most frequent dysfunctions of polypropylene (PP) hollow fiber membrane (PPM) used in extracorporeal membrane oxygenation (ECMO) therapy. In this study, a superhydrophilic endothelial membrane mimetic coating (SEMMC) was constructed on polydopamine-polyethyleneimine pre-coated surfaces of the PPM oxygenator and its ECMO circuit to explore safer and more sustainable ECMO strategy. The SEMMC is fabricated by multi-point anchoring of a phosphorylcholine and carboxyl side chained copolymer (PMPCC) and grafting of heparin (Hep) to form PMPCC-Hep interface, which endows the membrane superior hemocompatibility and anticoagulation performances. Furthermore, the modified PPM reduces protein adsorption amount to less than 30 ng/cm2. More significantly, the PMPCC-Hep coated ECMO system extends the anti-leakage and non-clotting oxygenation period to more than 15 h in anticoagulant-free animal extracorporeal circulation, much better than the bare and conventional Hep coated ECMO systems with severe clots and plasma leakage in 4 h and 8 h, respectively. This SEMMC strategy of grafting bioactive heparin onto bioinert zwitterionic copolymer interface has great potential in developing safer and longer anticoagulant-free ECMO systems. STATEMENT OF SIGNIFICANCE: A superhydrophilic endothelial membrane mimetic coating was constructed on surfaces of polypropylene hollow fiber membrane (PPM) oxygenator and its ECMO circuit by multi-point anchoring of a phosphorylcholine and carboxyl side chain copolymer (PMPCC) and grafting of heparin (Hep). The strong antifouling nature of the PMPCC-Hep coating resists the adsorption of plasma bio-molecules, resulting in enhanced hemocompatibility and anti-leakage ability. The grafted heparin on the zwitterionic PMPCC interface exhibits superior anticoagulation property. More significantly, the PMPCC-Hep coating achieves an extracorporeal circulation in a pig model for at least 15 h without any systemic anticoagulant. This endothelial membrane mimetic anticoagulation strategy shows great potential for the development of safer and longer anticoagulant-free ECMO systems.


Asunto(s)
Materiales Biocompatibles Revestidos , Oxigenación por Membrana Extracorpórea , Animales , Materiales Biocompatibles Revestidos/química , Materiales Biocompatibles Revestidos/farmacología , Heparina/química , Heparina/farmacología , Humanos , Polipropilenos/química , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología , Fibrinolíticos/farmacología , Fibrinolíticos/química , Membranas Artificiales , Adsorción , Trombosis/prevención & control , Fosforilcolina/química , Fosforilcolina/análogos & derivados , Polímeros/química
5.
Molecules ; 29(15)2024 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-39124916

RESUMEN

Poly[2-(methacryloyloxy)ethyl phosphorylcholine] liposomes (pMPC liposomes) gained attention during the last few years because of their potential use in treating osteoarthritis. pMPC liposomes that serve as boundary lubricants are intended to restore the natural lubrication properties of articular cartilage. For this purpose, it is important that the liposomes remain intact and do not fuse and spread as a lipid film on the cartilage surface. Here, we investigate the stability of the liposomes and their interaction with two types of solid surfaces, gold and carbon, by using cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). With the aid of a hydrophilic species used as an electroactive probe in the solution, the charge transfer characteristics of the electrode surfaces are obtained. Additionally, from EIS, the capacitance characteristics of the surfaces are derived. No decrease of the peak currents and no displacement of the peak potentials to greater overpotentials are observed in the CV experiments. No decrease in the apparent capacitance and increase in the charge transfer resistance is observed in the EIS experiments. On the contrary, all parameters in both CV and EIS do change in the opposite direction. The obtained results confirm that there is only physical adsorption without fusion and spreading of the pMPC liposomes and without the formation of lipid films on the surfaces of both gold and carbon electrodes.


Asunto(s)
Espectroscopía Dieléctrica , Liposomas , Liposomas/química , Oro/química , Técnicas Electroquímicas , Electrodos , Carbono/química , Fosforilcolina/química , Fosforilcolina/análogos & derivados
6.
Biomacromolecules ; 25(9): 5860-5872, 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39113312

RESUMEN

19F magnetic resonance imaging (19F MRI) is gaining attention as an emerging diagnostic technology. Effective 19F MRI contrast agents (CAs) for in vivo applications require a long transverse (or spin-spin) relaxation time (T2), short longitudinal (or spin-lattice) relaxation time (T1), high fluorine content, and excellent biocompatibility. Here, we present a novel hyperbranched polymeric 19F MRI CA based on ß-cyclodextrin and phosphorylcholine. The influence of the branching degree and fluorine content on T2 was thoroughly investigated. Results demonstrated a maximum fluorine content of 11.85% and a T2 of 612 ms. This hyperbranched polymeric 19F MRI CA exhibited both great biocompatibility against cells and organs of mice and high-performance imaging capabilities both in vitro and in vivo. The research provides positive insights into the synthesis strategies, topological design, and selection of fluorine tags for 19F MRI CAs.


Asunto(s)
Medios de Contraste , beta-Ciclodextrinas , beta-Ciclodextrinas/química , Medios de Contraste/química , Animales , Ratones , Fosforilcolina/química , Fosforilcolina/análogos & derivados , Imagen por Resonancia Magnética/métodos , Flúor/química , Polímeros/química , Humanos , Imagen por Resonancia Magnética con Fluor-19/métodos
7.
ACS Appl Mater Interfaces ; 16(30): 39104-39116, 2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39036941

RESUMEN

Surface modification using zwitterionic 2-methacryloyloxyethylphosphorylcholine (MPC) polymers is one of the most reasonable ways to prepare medical devices that can suppress undesired biological reactions such as blood coagulation. Usable MPC polymers are hydrophilic and water soluble, and their surface modification strategy involves exploiting the copolymer structures by adding physical or chemical bonding moieties. In this study, we developed copolymers composed of MPC, hydrophobic anchoring moiety, and chemical cross-linking unit to clarify the role of hydrophobic interactions in achieving biocompatible and long-term stable coatings. The four kinds of MPC copolymers with cross-linking units, such as 3-methacryloxypropyl trimethoxysilane (MPTMSi), and four different hydrophobic anchoring moieties, such as 3-(methacryloyloxy)propyltris(trimethylsiloxy)silane (MPTSSi) named as PMMMSi, n-butyl methacrylate (BMA) as PMBSi, 2-ethylhexyl methacrylate (EHMA) as PMESi, and lauryl methacrylate as PMLSi, were synthesized and coated on polydimethylsiloxane, polypropylene (PP), and polymethyl pentene. These copolymers were uniformly coated on the substrate materials PP and poly(methyl pentene) (PMP), to achieve hydrophilic and electrically neutral coatings. The results of the antibiofouling test showed that PMBSi repelled the adsorption of fluorescence-labeled bovine serum albumin the most, whereas PMLSi repelled it the least. Notably, all four copolymers suppressed platelet adhesion similarly. The variations in protein adsorption quantities among the four copolymer coatings were attributed to their distinct swelling behaviors in aqueous environments. Further investigations, including 3D scanning force microscopy and neutron reflectivity measurements, revealed that the PMLSi coating exhibited a higher water intake under aqueous conditions in comparison to the other coatings. Consequently, all copolymer coatings effectively prevented the invasion of platelets but the proteins penetrated the PMLSi network. Subsequently, the dynamic stability required to induce shear stress was evaluated using a circulation system. The results demonstrated that the PMMMSi and PMLSi coatings on PMP and PP exhibited exceptional platelet repellency and maintained high stability during circulation. This study highlights the potential of hydrophobic moieties to improve hemocompatibility and stability, offering potential applications in medical devices.


Asunto(s)
Interacciones Hidrofóbicas e Hidrofílicas , Fosforilcolina/química , Fosforilcolina/análogos & derivados , Polímeros/química , Animales , Reactivos de Enlaces Cruzados/química , Materiales Biocompatibles Revestidos/química , Adhesividad Plaquetaria/efectos de los fármacos , Propiedades de Superficie , Albúmina Sérica Bovina/química , Humanos , Metacrilatos/química , Fosfolípidos/química , Bovinos
8.
Biomacromolecules ; 25(8): 5251-5259, 2024 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-39074380

RESUMEN

Efficiently delivering mRNA to the deep-seated cells of diseased tissues for therapeutic purposes remains a significant challenge. To address this, we leveraged the dual hydrophobic properties of fluorine atoms to conjugate fluorinated polyethylenimine (FPEI) with fluorinated choline phosphate (FCP) lipids. When one adjusted the ratio of N/F atoms to 2/1 and a 15% FCP content, the mRNA@FPEI-FCP carrier was optimized, achieving significant circulation and accumulation in deep tumor regions. Compared to control carriers lacking FCP or FPEI, mRNA@FPEI-FCP exhibited a 3.94-fold increase in tumor targeting and a 3.0-fold increase in deep delivery. Delivery of IL-2 mRNA to 4T1 breast tumors resulted in a tumor inhibition rate of 91.9%, with IL-2 levels reaching 149.2 pg/mL and 12.1% of CD4+ cells throughout the tumor, with no abnormal blood indexes. This FPEI and FCP composite delivery system demonstrates potent targeting of mRNA delivery to deep tumor tissues.


Asunto(s)
Polietileneimina , ARN Mensajero , Polietileneimina/química , Animales , ARN Mensajero/genética , Femenino , Ratones , Fosforilcolina/química , Fosforilcolina/análogos & derivados , Lípidos/química , Halogenación , Ratones Endogámicos BALB C , Línea Celular Tumoral , Portadores de Fármacos/química , Humanos , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Neoplasias de la Mama/tratamiento farmacológico
9.
J Prosthet Dent ; 132(2): 465.e1-465.e8, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38890060

RESUMEN

STATEMENT OF PROBLEM: Studies on the effect of barium silicate on the material properties of additively manufactured (AM) resins containing 2-methacryloyloxyethyl phosphorylcholine (MPC) for dental applications are lacking. PURPOSE: The purpose of this in vitro study was to evaluate the mechanical properties, transmittance, and protein adsorption of MPC-containing AM resin incorporated with different barium silicate contents and to compare these findings with those of a commercially available unfilled AM resin marketed for definitive restorations. MATERIAL AND METHODS: Resins incorporating 6 wt% MPC and 4 different concentrations of barium silicate (10 wt%, MB10; 20 wt%, MB20; 30 wt%, MB30; and 40 wt%, MB40) were prepared. An MPC-containing resin with no filler was also prepared (0 wt%, MBN). Surface roughness (n=15), Vickers hardness (n=15), flexural strength and modulus (n=15), fracture toughness (n=15), transmittance (n=15), and protein adsorption (n=3) of the filled resin specimens were measured and compared with those of commercially available unfilled resin specimens. All data were analyzed using the Kruskal-Wallis and Dunn tests (α=.05). RESULTS: All experimental resins had higher surface roughness than the unfilled resin (P≤.048). MB40 had higher hardness, flexural strength, flexural modulus, and fracture toughness than most other groups (P≤.047). MB10 had higher transmittance than most other groups (P≤.012). All experimental resins had lower protein adsorption than the unfilled resin, regardless of the barium silicate content (P≤.023). CONCLUSIONS: The experimental resin containing 6 wt% MPC and 40 wt% barium silicate showed better mechanical properties and lower protein adsorption than the resin with no MPC or ceramic fillers. Transmittance decreased with the increase of barium silicate in the resins.


Asunto(s)
Ensayo de Materiales , Silicatos , Propiedades de Superficie , Silicatos/química , Adsorción , Polímeros/química , Compuestos de Bario/química , Metacrilatos/química , Fosforilcolina/química , Fosforilcolina/análogos & derivados , Proteínas/química , Técnicas In Vitro , Resistencia Flexional , Dureza , Materiales Dentales/química
10.
Biomaterials ; 311: 122661, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38875883

RESUMEN

Abdominal adhesion, a serious complication of abdominal surgery, often resists mitigation by current drug administration and physical barriers. To address this issue, we developed an injectable, antifouling hydrogel through the free-radical polymerization of methacrylate chondroitin sulfate (CS-GMA) and 2-methacryloyloxyethyl phosphorylcholine (MPC) monomers, dubbed the CGM hydrogel. We systematically analyzed its physicochemical properties, including rheological strength, biocompatibility, and antifouling capabilities. A rat abdominal cecum adhesion model was constructed to assess the effectiveness of CGM hydrogel in preventing postoperative adhesion and recurrent adhesion. In addition, multi-omics analyses identified the relationship between adhesion development and CCL2/CCR2 interaction. Notably, CGM hydrogel can thwart the recruitment and aggregation of fibroblasts and macrophages by inhibiting the CCL2/CCR2 interaction. Moreover, CGM hydrogel significantly dampens the activity of fibrosis-linked cytokines (TGF-ßR1) and recalibrates extracellular matrix deposition-related cytokines (t-PA and PAI-1, Col Ⅰ and MMP-9). Cumulatively, the dual action of CGM hydrogel-as a physical barrier and cytokine regulator-highlights its promising potential in clinical application for abdominal adhesion prevention.


Asunto(s)
Quimiocina CCL2 , Hidrogeles , Ratas Sprague-Dawley , Receptores CCR2 , Animales , Adherencias Tisulares/prevención & control , Adherencias Tisulares/metabolismo , Hidrogeles/química , Hidrogeles/farmacología , Quimiocina CCL2/metabolismo , Ratas , Receptores CCR2/metabolismo , Fosforilcolina/análogos & derivados , Fosforilcolina/química , Fosforilcolina/farmacología , Metacrilatos/química , Metacrilatos/farmacología , Incrustaciones Biológicas/prevención & control , Sulfatos de Condroitina/química , Sulfatos de Condroitina/farmacología , Ratones , Abdomen/cirugía , Inyecciones , Masculino , Macrófagos/metabolismo , Macrófagos/efectos de los fármacos
11.
J Pharm Biomed Anal ; 248: 116269, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-38906072

RESUMEN

Corrections to the article based on comments published by Dr Acree, various models, including the modified Apelblat model, the λh model, the Jouyban-Acree model, the SUN model and the CNIBS/R-K model, recalculated, obtained new parameters and relative absolute percentage deviations.


Asunto(s)
Solubilidad , Solventes , Termodinámica , Solventes/química , Modelos Químicos , Fosforilcolina/análogos & derivados , Fosforilcolina/química
12.
ACS Nano ; 18(25): 16113-16125, 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38857428

RESUMEN

Urinary extracellular vesicles (uEVs) are regarded as highly promising liquid-biopsy biomarkers for the early diagnosis and prognosis of bladder cancer (BC). However, detection of uEVs remains technically challenging owing to their huge heterogeneity and ultralow abundance in real samples. We herein present a choline phosphate-grafted platinum nanozyme (Pt@CP) that acts as a universal EV probe for the construction of a high-throughput and high-sensitivity immunoassay, which allowed multiplex profiling of uEV protein markers for BC detection. With the Pt@CP-based immunoassays, three uEV protein markers (MUC-1, CCDC25, and GLUT1) were identified for BC, by which the BC cases (n = 48), cystitis patients (n = 27), and healthy donors (n = 24) were discriminated with high clinical sensitivity and specificity (area under curve = 98.3%). For the BC cases (n = 9) after surgery, the Pt@CP-based immunoassay could report the postoperative residual tumor that cannot be observed by cystoscopy, which is clinically significant for assessing BC recurrence. This work provides generally high sensitivity for EV detection, facilitating the discovery and clinical use of EV-based biomarkers.


Asunto(s)
Biomarcadores de Tumor , Vesículas Extracelulares , Neoplasias de la Vejiga Urinaria , Neoplasias de la Vejiga Urinaria/diagnóstico , Neoplasias de la Vejiga Urinaria/patología , Humanos , Vesículas Extracelulares/química , Biomarcadores de Tumor/análisis , Fosforilcolina/química , Inmunoensayo/métodos , Platino (Metal)/química , Femenino
13.
PLoS One ; 19(6): e0301901, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38870204

RESUMEN

Herein we report the design and the synthesis of a library of new and more hydrophilic bisindole analogues based on our previously identified antileishmanial compound URB1483 that failed the preliminary in vivo test. The novel bisindoles were phenotypically screened for efficacy against Leishmania infantum promastigotes and simultaneously for toxicity on human macrophage-like THP-1 cells. Among the less toxic compounds, eight bisindoles showed IC50 below 10 µM. The most selective compound 1h (selectivity index = 10.1, comparable to miltefosine) and the most potent compound 2c (IC50 = 2.7 µM) were tested for their efficacy on L. infantum intracellular amastigotes. The compounds also demonstrated their efficacy in the in vitro infection model, showing IC50 of 11.1 and 6.8 µM for 1h and 2c, respectively. Moreover, 1h showed a better toxicity profile than the commercial drug miltefosine. For all these reasons, 1h could be a possible new starting point for hydrophilic antileishmanial agents with low cytotoxicity on human macrophage-like cells.


Asunto(s)
Antiprotozoarios , Leishmania infantum , Leishmania infantum/efectos de los fármacos , Humanos , Antiprotozoarios/farmacología , Antiprotozoarios/química , Células THP-1 , Indoles/farmacología , Indoles/química , Interacciones Hidrofóbicas e Hidrofílicas , Fosforilcolina/análogos & derivados , Fosforilcolina/farmacología , Fosforilcolina/química , Macrófagos/efectos de los fármacos , Macrófagos/parasitología , Concentración 50 Inhibidora
14.
J Dent ; 147: 105134, 2024 08.
Artículo en Inglés | MEDLINE | ID: mdl-38885733

RESUMEN

OBJECTIVE: To evaluate the mechanical and biological properties of three-dimensionally (3D) printable resins filled with 2-methacryloyloxyethyl phosphorylcholine (MPC) and silicate-based composites and compare with those of a commercially available 3D-printable resin for definitive restorations. METHODS: A group of 3D-printable hybrid resins (HRs) filled with 6 wt% MPC and three different compositions of silicate-based composites (barium silicate to zirconium silicate ratios: 1.50:1 for HR1, 0.67:1 for HR2, and 0.25:1 for HR3) were prepared. The HR groups were compared with the commercially available unfilled 3D-printable resin (CR) marketed for definitive restorations in terms of flexural strength and modulus, fracture toughness, surface roughness, Vickers hardness, light transmittance (all, n = 15), cytotoxicity, and protein adsorption (both, n = 3). All data were analyzed by using non-parametric Kruskal-Wallis and Dunn's tests (α=0.05). RESULTS: The HR groups had significantly higher flexural strength, modulus, fracture toughness, and hardness values than the CR (P < 0.001). HR3 had the highest surface roughness and light transmittance among the groups (P ≤ 0.006). None of tested resins showed cytotoxicity. Both HR2 and HR3 showed significantly lower protein adsorption than the CR, with a difference of approximately 60% (P ≤ 0.026). CONCLUSION: Both HR2 and HR3 exhibited superior mechanical properties (flexural strength, flexural modulus, fracture toughness, and Vickers hardness), light transmittance, and protein-repellent activity than the CR, with no impact on cytotoxicity. CLINICAL SIGNIFICANCE: The MPC/silicate-based composite-filled resins may be a suitable alternative for definitive restorations, given their higher mechanical properties and promising biological properties to prevent microbial adhesion and subsequent biofilm formation, as well as their non-cytotoxic properties.


Asunto(s)
Resinas Compuestas , Dureza , Ensayo de Materiales , Metacrilatos , Silicatos , Propiedades de Superficie , Silicatos/química , Resinas Compuestas/química , Adsorción , Metacrilatos/química , Fosforilcolina/análogos & derivados , Fosforilcolina/química , Materiales Dentales/química , Restauración Dental Permanente/métodos , Resistencia Flexional , Módulo de Elasticidad , Animales , Polímeros/química , Humanos , Circonio/química
15.
Clin Oral Investig ; 28(6): 323, 2024 May 18.
Artículo en Inglés | MEDLINE | ID: mdl-38761310

RESUMEN

OBJECTIVES: White spot lesions are the most common iatrogenic effect observed during orthodontic treatment. This study aimed to compare the surface characteristics and antibacterial action of uncoated and coated orthodontic brackets. MATERIALS AND METHODS: Sixty commercially available stainless steel brackets were coated with TiO2 nanotubes and methacryloyloxyethylphosphorylcholine. The sample was divided into Group 1: uncoated orthodontic brackets, Group 2: Stainless steel brackets with TiO2 nanotubes coating, Group 3: Stainless steel brackets with methacryloyloxyethylphosphorylcholine coating, and Group 4: Stainless steel brackets with TiO2 nanotubes combined with methacryloyloxyethylphosphorylcholine coating. Surface characterization was assessed using atomic force microscopy and scanning electron microscopy. Streptococcus mutans was selected to test the antibacterial ability of the orthodontic brackets, total bacterial adhesion and bacterial viability were assessed. The brackets were subjected to scanning electron microscopy to detect the presence of biofilm. RESULTS: The surface roughness was the greatest in Group 1 and least in Group 2 followed by Group 4 and Group 3 coated brackets. The optical density values were highest in Group 1 and lowest in Group 4. Comparison of colony counts revealed high counts in Group 1 and low counts in Group 4. A positive correlation between surface roughness and colony counts was obtained, however, was not statistically significant. CONCLUSIONS: The coated orthodontic brackets exhibited less surface roughness than the uncoated orthodontic brackets. Group 4 coated orthodontic brackets showed the best antibacterial properties. CLINICAL RELEVANCE: Coated orthodontic brackets prevent adhesion of streptococcus mutans and reduces plaque accumulation around the brackets thereby preventing formation of white spot lesions during orthodontic treatment.


Asunto(s)
Antibacterianos , Adhesión Bacteriana , Microscopía Electrónica de Rastreo , Nanotubos , Soportes Ortodóncicos , Fosforilcolina , Streptococcus mutans , Propiedades de Superficie , Titanio , Titanio/química , Fosforilcolina/análogos & derivados , Fosforilcolina/farmacología , Fosforilcolina/química , Streptococcus mutans/efectos de los fármacos , Antibacterianos/farmacología , Nanotubos/química , Adhesión Bacteriana/efectos de los fármacos , Microscopía de Fuerza Atómica , Ensayo de Materiales , Acero Inoxidable/química , Metacrilatos/farmacología , Metacrilatos/química , Biopelículas/efectos de los fármacos , Materiales Biocompatibles Revestidos/farmacología , Materiales Biocompatibles Revestidos/química
16.
ACS Appl Mater Interfaces ; 16(22): 28162-28171, 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38767334

RESUMEN

This study investigated the suitability of surface modification for a long-range surface plasmon (LRSP) aptasensor using two different hydrogels, aiming at real-time monitoring of vancomycin (VCM) in undiluted serum and blood. Three different layer structures were formed on a gold surface of LRSP sensor chip using poly[2-methacryloyloxyethyl phosphorylcholine (MPC)-co-N-methacryloyl-(L)-tyrosinemethylester (MAT)] (PMM) and poly[MPC-co-2-ethylhexyl methacrylate (EHMA)-co-MAT] (PMEM). The peptide aptamer for VCM was immobilized in PMM and PMEM via MAT. Among four differently prepared sensor chips, the LRSP hydrogel aptasensor with PMM, referred to as the PMM hydrogel, exhibited the highest sensor output and superior antifouling properties. Following the optimization of the PMM hydrogel preparation conditions, the shelf life of the PMM hydrogel was determined to exceed 2 weeks, and the same sensor chip could be used for 102 days without significant performance deterioration. The PMM hydrogel was then applied for VCM measurement in undiluted serum in vitro, where it demonstrated a limit of detection of 0.098 µM and a dynamic range of 0.18-100 µM, covering the therapeutic range. Additionally, the PMM hydrogel enabled the continuous measurement of various VCM concentrations in serum without rinsing and showed a concentration-dependent output in undiluted blood. These findings underscore the potential of the PMM hydrogel for real-time and direct monitoring of VCM in body fluids.


Asunto(s)
Hidrogeles , Resonancia por Plasmón de Superficie , Vancomicina , Vancomicina/sangre , Vancomicina/química , Vancomicina/farmacología , Humanos , Hidrogeles/química , Técnicas Biosensibles/métodos , Técnicas Biosensibles/instrumentación , Aptámeros de Péptidos/química , Oro/química , Aptámeros de Nucleótidos/química , Antibacterianos/sangre , Antibacterianos/química , Antibacterianos/farmacología , Fosforilcolina/química , Fosforilcolina/análogos & derivados , Metacrilatos/química
17.
J Dent ; 148: 105054, 2024 09.
Artículo en Inglés | MEDLINE | ID: mdl-38796091

RESUMEN

OBJECTIVES: To create bacteria-resistant dental CAD-CAM blocks with a biofilm-resistant effect by incorporating Nano-crystalline ceramic and polymer (NCP) with 2-methacryloyloxyethyl phosphorylcholine (MPC) and sulfobetaine methacrylate (SBMA) and at an equimolar ratio, referred to as MS. METHODS: Experimental groups comprised NCP blocks containing zwitterions at 0.15wt% (MS015) and 0.45wt% (MS045). NCP blocks without MS served as control (CTRL). Flexural strength, surface hardness, water sorption and solubility, photometric properties, and cytotoxicity were assessed for all samples. Additionally, the resistance to single and multi-species bacterial adhesion was investigated. RESULTS: MS045 showed significant reduction in flexural strength (P < 0.01) compared to both CTRL and MS015. Both MS015 and MS045 showed significantly increased water sorption and significant reduction in water solubility compared to CTRL. Light transmission remained consistent across all MS content levels, but the irradiance value decreased by 12 % in the MS045 group compared to the MS015 group. Notably, compared to the CTRL group, the MS015 group exhibited enhanced resistance to adhesion by Porphyromonas gingivalis and a multi-species salivary biofilm, with biofilm thickness and biomass reduced by 45 % and 56 %, respectively. CONCLUSIONS: NCP containing 0.15 % MS can effectively reduce adhesion of multiple species of bacteria while maintaining physical and mechanical properties. CLINICAL SIGNIFICANCE: NCP integrating zwitterions is clinically advantageous in resisting bacterial adhesion at internal and external margins of milled indirect restoration.


Asunto(s)
Adhesión Bacteriana , Biopelículas , Cerámica , Diseño Asistido por Computadora , Resistencia Flexional , Ensayo de Materiales , Metacrilatos , Fosforilcolina , Propiedades de Superficie , Cerámica/química , Metacrilatos/química , Adhesión Bacteriana/efectos de los fármacos , Biopelículas/efectos de los fármacos , Fosforilcolina/análogos & derivados , Fosforilcolina/química , Fosforilcolina/farmacología , Materiales Dentales/química , Polímeros/química , Humanos , Dureza , Solubilidad , Porphyromonas gingivalis/efectos de los fármacos
18.
Langmuir ; 40(21): 10957-10965, 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38752656

RESUMEN

Zwitterionic coatings provide a promising antifouling strategy against biofouling adhesion. Quaternary ammonium cationic polymers can effectively kill bacteria on the surface, owing to their positive charges. This strategy can avoid the release of toxic biocides, which is highly desirable for constructing coatings for biomedical devices. The present work aims to develop a facile method by covalently grafting zwitterionic and cationic copolymers containing aldehydes to the remaining amine groups of self-polymerized dopamine. Reversible addition-fragmentation chain transfer polymerization was used to copolymerize either zwitterionic 2-methacryloyloxyethyl phosphorylcholine monomer (MPC) or cationic 2-(methacryloyloxy)ethyl trimethylammonium monomer (META) with 4-formyl phenyl methacrylate monomer (FPMA), and the formed copolymers poly(MPC-st-FPMA) and poly(META-st-FPMA) are denoted as MPF and MTF, respectively. MPF and MTF copolymers were then covalently grafted onto the amino groups of polydopamine-coated surfaces. PDA/MPF/MTF-coated surfaces exhibited antibacterial and antifouling properties against S. aureus, E. coli, and bovine serum albumin protein. In addition, they showed excellent viability of normal human lung fibroblast cells MRC-5. We expect the facile surface modification strategy discussed here to be applicable to medical device manufacturing.


Asunto(s)
Antibacterianos , Polímeros , Staphylococcus aureus , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/síntesis química , Polímeros/química , Polímeros/farmacología , Staphylococcus aureus/efectos de los fármacos , Animales , Incrustaciones Biológicas/prevención & control , Escherichia coli/efectos de los fármacos , Bivalvos/química , Propiedades de Superficie , Materiales Biocompatibles Revestidos/química , Materiales Biocompatibles Revestidos/farmacología , Fosforilcolina/análogos & derivados , Fosforilcolina/química , Fosforilcolina/farmacología , Albúmina Sérica Bovina/química , Humanos , Metacrilatos/química , Metacrilatos/farmacología , Adhesión Bacteriana/efectos de los fármacos , Indoles
19.
Colloids Surf B Biointerfaces ; 238: 113886, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38608461

RESUMEN

In this work, poly(lactide) nanoparticles were equipped with a bioinspired coating layer based on poly[2-(methacryloyloxy)ethyl phosphorylcholine] and then evaluated when administered to the lungs and after intravenous injection. Compared to the plain counterparts, the chosen zwitterionic polymer shell prevented the coated colloidal formulation from aggregation and conditioned it for lower cytotoxicity, protein adsorption, complement activation and phagocytic cell uptake. Consequently, no interference with the biophysical function of the lung surfactant system could be detected accompanied by negligible protein and cell influx into the bronchoalveolar space after intratracheal administration. When injected into the central compartment, the coated formulation showed a prolonged circulation half-life and a delayed biodistribution to the liver. Taken together, colloidal drug delivery vehicles would clearly benefit from the investigated poly[2-(methacryloyloxy)ethyl phosphorylcholine]-based polymer coatings.


Asunto(s)
Coloides , Sistemas de Liberación de Medicamentos , Fosforilcolina , Coloides/química , Animales , Fosforilcolina/química , Fosforilcolina/análogos & derivados , Nanopartículas/química , Poliésteres/química , Ratones , Polímeros/química , Polímeros/farmacología , Distribución Tisular , Pulmón/metabolismo , Ácidos Polimetacrílicos/química , Activación de Complemento/efectos de los fármacos , Metacrilatos/química , Humanos
20.
Biomater Sci ; 12(10): 2717-2729, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38619816

RESUMEN

Polymeric heart valves (PHVs) present a promising alternative for treating valvular heart diseases with satisfactory hydrodynamics and durability against structural degeneration. However, the cascaded coagulation, inflammatory responses, and calcification in the dynamic blood environment pose significant challenges to the surface design of current PHVs. In this study, we employed a surface-initiated polymerization method to modify polystyrene-block-isobutylene-block-styrene (SIBS) by creating three hydrogel coatings: poly(2-methacryloyloxy ethyl phosphorylcholine) (pMPC), poly(2-acrylamido-2-methylpropanesulfonic acid) (pAMPS), and poly(2-hydroxyethyl methacrylate) (pHEMA). These hydrogel coatings dramatically promoted SIBS's hydrophilicity and blood compatibility at the initial state. Notably, the pMPC and pAMPS coatings maintained a considerable platelet resistance performance after 12 h of sonication and 10 000 cycles of stretching and bending. However, the sonication process induced visible damage to the pHEMA coating and attenuated the anti-coagulation property. Furthermore, the in vivo subcutaneous implantation studies demonstrated that the amphiphilic pMPC coating showed superior anti-inflammatory and anti-calcification properties. Considering the remarkable stability and optimal biocompatibility, the amphiphilic pMPC coating constructed by surface-initiated polymerization holds promising potential for modifying PHVs.


Asunto(s)
Materiales Biocompatibles Revestidos , Hidrogeles , Fosforilcolina , Propiedades de Superficie , Fosforilcolina/química , Fosforilcolina/análogos & derivados , Fosforilcolina/farmacología , Animales , Hidrogeles/química , Hidrogeles/farmacología , Materiales Biocompatibles Revestidos/química , Materiales Biocompatibles Revestidos/farmacología , Ensayo de Materiales , Polihidroxietil Metacrilato/química , Ácidos Polimetacrílicos/química , Ácidos Polimetacrílicos/farmacología , Metacrilatos/química , Polímeros/química , Polímeros/farmacología , Prótesis Valvulares Cardíacas , Válvulas Cardíacas/efectos de los fármacos , Humanos , Ratones , Interacciones Hidrofóbicas e Hidrofílicas
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