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1.
Biomed Res Int ; 2024: 1741539, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38628498

RESUMO

Background: Dental implantation has become a standard procedure with high success rates, relying on achieving osseointegration between the implant surface and surrounding bone tissue. Polyether ether ketone (PEEK) is a promising alternative to traditional dental implant materials like titanium, but its osseointegration capabilities are limited due to its hydrophobic nature and reduced surface roughness. Objective: The aim of the study is to increase the surface roughness and hydrophilicity of PEEK by treating the surface with piranha solution and then coating the surface with epigallocatechin-3-gallate (EGCG) by electrospraying technique. Materials and Methods: The study includes four groups intended to investigate the effect of piranha treatment and EGCG coating: a control group of PEEK discs with no treatment (C), PEEK samples treated with piranha solution (P), a group of PEEK samples coated with EGCG (E), and a group of PEEK samples treated with piranha solution and coated with EGCG (PE). Surface roughness, wettability, and microhardness were assessed through statistical analysis. Results: Piranha treatment increased surface roughness, while EGCG coating moderated it, resulting in an intermediate roughness in the PE group. EGCG significantly improved wettability, as indicated by the reduced contact angle. Microhardness increased by about 20% in EGCG-coated groups compared to noncoated groups. Statistical analysis confirmed significant differences between groups in all tests. Conclusion: This study demonstrates the potential of EGCG coating to enhance the surface properties of PEEK as dental implants. The combined piranha and EGCG modification approach shows promise for improved osseointegration, although further vivo research is necessary. Surface modification techniques hold the key to optimizing biomaterial performance, bridging the gap between laboratory findings and clinical implementation in dental implantology.


Assuntos
Catequina/análogos & derivados , Polietilenoglicóis , Polímeros , Polímeros/química , Polietilenoglicóis/química , Benzofenonas , Cetonas/farmacologia , Cetonas/química , Propriedades de Superfície , Éteres , Titânio/química
2.
J Mech Behav Biomed Mater ; 154: 106501, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38531182

RESUMO

OBJECTIVE: The influence of various aging protocols, representing and accelerating influences present in the dental context, on possible changes in the microstructure and mechanical properties of thermoplastics was investigated. In order to minimize the complexity of the systems, first pure polymers and then later the equivalent dental polymeric materials were analyzed. MATERIALS AND METHODS: Pure polymers (Poly(methyl methacrylate) - PMMA, Polyoxymethylene homopolymer - POM-H, Polyether ether ketone - PEEK, Nylon 12 - PA12, Polypropylene - PP) were analyzed before as well as after applying different aging protocols relevant to the oral environment (ethanol, thermocycling, alkaline and acidic setting) by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). The thermoanalytical parameters used were glass transition temperature (Tg), melting peak and crystallization peak temperature (Tpm, Tpc) and decomposition behavior. In a second step selected commercially available dental products (Telio CAD - PMMAD, Zirlux Acetal - POMD, Juvora Natural Dental Disc - PEEKD) aged by the protocol that previously showed strong effects were examined and additionally tested for changes in their Vickers and Martens hardness by Mann-Whitney-U test. RESULTS: The combinations of pure polymers and viable aging protocols analyzed within this study were identified via TGA or DSC as PA12 & thermocycling, POM-H & denture cleanser/lactic acid/ethanol, PP & lactic acid. The dental polymeric materials PMMAD and POMD due to aging in lactic acid showed slight but significantly (p < 0.01) reduced Vickers and partly Martens hardness. PEEK showed the greatest material resistance within this study.


Assuntos
Benzofenonas , Mustelidae , Polimetil Metacrilato , Animais , Polimetil Metacrilato/química , Teste de Materiais , Dureza , Polímeros/química , Polietilenoglicóis/química , Cetonas/química , Etanol , Ácido Láctico , Materiais Dentários , Propriedades de Superfície
3.
Biomacromolecules ; 25(4): 2261-2276, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38490188

RESUMO

Polysaccharides are biodegradable, abundant, sustainable, and often benign natural polymers. The achievement of selective modification of polysaccharides is important for targeting specific properties and structures and will benefit future development of highly functional, sustainable materials. The synthesis of polysaccharides containing aldehyde or ketone moieties is a promising tool for achieving this goal because of the rich chemistry of aldehyde or ketone groups, including Schiff base formation, nucleophilic addition, and reductive amination. The obtained polysaccharide aldehydes or ketones themselves have rich potential for making useful materials, such as self-healing hydrogels, polysaccharide-protein therapeutic conjugates, or drug delivery vehicles. Herein, we review recent advances in synthesizing polysaccharides containing aldehyde or ketone moieties and briefly introduce their reactivity and corresponding applications.


Assuntos
Aldeídos , Cetonas , Aldeídos/química , Cetonas/química , Polissacarídeos/química , Sistemas de Liberação de Medicamentos , Polímeros/química , Hidrogéis/química
4.
Acta Biomater ; 177: 243-252, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38367656

RESUMO

Porous structures are frequently used in surgical implants to strengthen the interlocking power produced by bone ingrowth. Therefore, we aimed to elucidate the mechanism underlying bone ingrowth into a porous structure accompanied by vascularization. A nonbioactive polyetheretherketone implant with a 3D-printed porous structure was prepared and implanted in a bone hole created in the tibias of rabbits. We observed bone ingrowth in the same individual specimens immediately and at 2, 4, 8, and 12 weeks post-implantation using in-vivo computed tomography (CT). Furthermore, a detailed evaluation with blood vessels of each specimen at 2, 4, and 12 weeks was performed with ex-vivo CT and histological specimen. Additional histological evaluation was performed using thin sections of an implant made with thermoplastic polyurethane having the same structure. As a result, the bone invasion began after four weeks, when the construction of fibrous tissue and the spread of new blood vessels within the voids matured. As the bone matured in the load-bearing area, new blood vessels outside the bone matrix regressed. This longitudinal evaluation study suggests that preceding fibrogenesis and vascularization may be key in developing bone ingrowth. STATEMENT OF SIGNIFICANCE: A porous structure is an essential structure for dental and orthopedic implants because it provides strong fixation through bone invasion. Although it was known that vascularization was involved in this, the details were not known. This in vivo study revealed that in order for bone ingrowth to begin, a preparatory period of approximately 4 weeks was required to establish blood flow inside and outside the implant. Furthermore, it was confirmed that by spreading the fibrous structure in advance, it has an advantageous effect on the migration of cells involved in the formation of bones and blood vessels. We pointed out that it is necessary to consider fibrogenesis and vascularization when creating future implants.


Assuntos
Osso e Ossos , Próteses e Implantes , Animais , Coelhos , Porosidade , Polietilenoglicóis/química , Cetonas/farmacologia , Cetonas/química , Neovascularização Patológica , Titânio/química , Osseointegração/fisiologia
5.
Dent Mater ; 40(4): 674-688, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38388252

RESUMO

OBJECTIVE: Polyetheretherketone (PEEK), a biomaterial with appropriate bone-like mechanical properties and excellent biocompatibility, is widely applied in cranio-maxillofacial and dental applications. However, the lack of antibacterial effect is an essential drawback of PEEK material and might lead to infection and osseointegration issues. This study aims to apply a natural antibacterial agent, totarol coating onto the 3D printed PEEK surface and find an optimized concentration with balanced cytocompatibility, osteogenesis, and antibacterial capability. METHODS: In this study, a natural antibacterial agent, totarol, was applied as a coating to fused filament fabrication (FFF) 3D printed PEEK surfaces at a series of increasing concentrations (1 mg/ml, 5 mg/ml, 10 mg/ml, 15 mg/ml, and 20 mg/ml). The samples were then evaluated for cytocompatibility with L929 fibroblast and SAOS-2 osteoblast using live/dead staining and CCK-8 assay. The antibacterial capability was assessed by crystal violet staining, live/dead staining, and scanning electron microscopy (SEM) utilizing the oral primary colonizer S. gordonii and isolates of mixed oral bacteria in a stirring system simulating the oral environment. The appropriate safe working concentration for totarol coating is selected based on the results of the cytocompatibility and antibacterial test. Subsequently, the influence on osteogenic differentiation was evaluated by alkaline phosphatase (ALP) and alizarin red staining (ARS) analysis of pre-osteoblasts. RESULTS: Our results showed that the optimal concentration of totarol solution for promising antibacterial coating was approximately 10 mg/ml. Such surfaces could play an excellent antibacterial role by inducing a contact-killing effect with an inhibitory effect against biofilm development without affecting the healing of soft and hard tissues around FFF 3D printed PEEK implants or abutments. SIGNIFICANCE: This study indicates that the totarol coated PEEK has an improved antibacterial effect with excellent biocompatibility providing great clinical potential as an orthopedic/dental implant/abutment material.


Assuntos
Abietanos , Benzofenonas , Implantes Dentários , Osteogênese , Polímeros , Polietilenoglicóis/farmacologia , Polietilenoglicóis/química , Cetonas/farmacologia , Cetonas/química , Antibacterianos/farmacologia , Antibacterianos/química , Impressão Tridimensional , Propriedades de Superfície
6.
J Am Chem Soc ; 146(7): 5005-5010, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38329236

RESUMO

Radical hydrofunctionalizations of electronically unbiased dienes are challenging to render regioselective, because the products are nearly identical in energy. Here, we report two engineered FMN-dependent "ene"-reductases (EREDs) that catalyze regiodivergent hydroalkylations of cyclic and linear dienes. While previous studies focused exclusively on the stereoselectivity of alkene hydroalkylation, this work highlights that EREDs can control the regioselectivity of hydrogen atom transfer, providing a method for selectively preparing constitutional isomers that would be challenging to prepare using traditional synthetic methods. Engineering the ERED from Gluconabacter sp. (GluER) furnished a variant that favors the γ,δ-unsaturated ketone, while an engineered variant from a commercial ERED panel favors the δ,ε-unsaturated ketone. The effect of beneficial mutations has been investigated using substrate docking studies and the mechanism probed by isotope labeling experiments. A variety of α-bromo ketones can be coupled with cyclic and linear dienes. These interesting building blocks can also be further modified to generate difficult-to-access heterocyclic compounds.


Assuntos
Oxirredutases , Polienos , Biocatálise , Oxirredutases/química , Catálise , Isomerismo , Cetonas/química
7.
J Agric Food Chem ; 72(9): 4587-4595, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38408430

RESUMO

4-Hydroxyphenylpyruvate dioxygenase (EC 1.13.11.27, HPPD) is one of the most widely studied herbicide targets and has gained significant attention. To identify potential effective HPPD inhibitors, a rational multistep virtual screening workflow was built, which included CBP models (based on the receptor-ligand interactions in the crystal complex), Hypogen models with activity prediction ability (according to the derivation of structure-activity relationships from a set of molecules with reported activity values), and a consensus docking procedure (consisting of LibDock, Glide, and CDOCKER). About 1 million molecules containing diketone or ß-keto-enol substructures were filtered by Lipinski's rules, CBP model, and Hypogen model. A total of 12 compounds with similar docking postures were generated by consensus docking. Eventually, four molecules were screened based on the specific binding pattern and affinity of the HPPD inhibitor. The biological evaluation in vivo displayed that compounds III-1 and III-2 exhibited comparable herbicidal activity to isoxaflutole and possessed superior safety on various crops (wheat, rice, sorghum, and maize). The ADMET prediction (absorption, distribution, metabolism, excretion, and toxicity) showed that compound III possessed relatively good toxicological results. This work provides a theoretical basis and valuable reference for the virtual screening and molecular design of novel HPPD inhibition herbicides.


Assuntos
4-Hidroxifenilpiruvato Dioxigenase , Herbicidas , Herbicidas/farmacologia , Herbicidas/química , Relação Estrutura-Atividade , Cetonas/química , 4-Hidroxifenilpiruvato Dioxigenase/química , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química
8.
Biomed Mater ; 19(2)2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38364280

RESUMO

As a thermoplastic and bioinert polymer, polyether ether ketone (PEEK) serves as spine implants, femoral stems, cranial implants, and joint arthroplasty implants due to its mechanical properties resembling the cortical bone, chemical stability, and radiolucency. Although there are standards and antibiotic treatments for infection control during and after surgery, the infection risk is lowered but can not be eliminated. The antibacterial properties of PEEK implants should be improved to provide better infection control. This review includes the strategies for enhancing the antibacterial properties of PEEK in four categories: immobilization of functional materials and functional groups, forming nanocomposites, changing surface topography, and coating with antibacterial material. The measuring methods of antibacterial properties of the current studies of PEEK are explained in detail under quantitative, qualitative, andin vivomethods. The mechanisms of bacterial inhibition by reactive oxygen species generation, contact killing, trap killing, and limited bacterial adhesion on hydrophobic surfaces are explained with corresponding antibacterial compounds or techniques. The prospective analysis of the current studies is done, and dual systems combining osteogenic and antibacterial agents immobilized on the surface of PEEK are found the promising solution for a better implant design.


Assuntos
Benzofenonas , Osseointegração , Polímeros , Polímeros/farmacologia , Polietilenoglicóis/química , Cetonas/química , Cetonas/farmacologia , Antibacterianos/farmacologia , Propriedades de Superfície
9.
Nat Commun ; 15(1): 71, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38167391

RESUMO

Chemoenzymatic cascade catalysis has emerged as a revolutionary tool for streamlining traditional retrosynthetic disconnections, creating new possibilities for the asymmetric synthesis of valuable chiral compounds. Here we construct a one-pot concurrent chemoenzymatic cascade by integrating organobismuth-catalyzed aldol condensation with ene-reductase (ER)-catalyzed enantioselective reduction, enabling the formal asymmetric α-benzylation of cyclic ketones. To achieve this, we develop a pair of enantiocomplementary ERs capable of reducing α-arylidene cyclic ketones, lactams, and lactones. Our engineered mutants exhibit significantly higher activity, up to 37-fold, and broader substrate specificity compared to the parent enzyme. The key to success is due to the well-tuned hydride attack distance/angle and, more importantly, to the synergistic proton-delivery triade of Tyr28-Tyr69-Tyr169. Molecular docking and density functional theory (DFT) studies provide important insights into the bioreduction mechanisms. Furthermore, we demonstrate the synthetic utility of the best mutants in the asymmetric synthesis of several key chiral synthons.


Assuntos
Aldeídos , Cetonas , Estrutura Molecular , Simulação de Acoplamento Molecular , Aldeídos/química , Catálise , Cetonas/química , Estereoisomerismo
10.
J Mech Behav Biomed Mater ; 150: 106258, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38000162

RESUMO

In bone tissue engineering (BTE), defects in large bones remain the greatest issue which can be addressed using bone scaffolds. In this work, blends of heat cured polymethylmethacrylate (HC PMMA) and various weight percentages of poly-ether-ketone-ketone (PEKK) (0, 2, 4, 8, and 10%) were made using a porogen leaching process. The blends were then subjected to tensile, compression and bending tests to select the optimum blend. Based on the results obtained, HC PMMA blended with 2 wt% PEKK was selected to produce the bio-porous blends. Here, the porosity was imparted using tartaric acid (C4H6O6) and sodium hydrogen carbonate (NaHCO3) as porogen leaching components. Porous blends resulted were then reinforced with a nano titanium dioxide powder (nTiO2) at different weight percentages of (0, 1, 3, and 5). The results showed that porous composites made of (HC PMMA: 2 wt% PEKK) blend reinforced with 5 wt % nTiO2 exhibit the highest strength values under various loadings. The FTIR identified the functional groups of the bone scaffold components. The mean pore size and pore depth were measured using atomic force microscopy (AFM) analysis and the values are 92.6 nm and 42.78 nm, respectively. The good distribution of the PEKK and nTiO2 within the HC PMMA and the uniform porous structure with multi-scale pores between 535 nm and 1.187 mm were confirmed by the AFM data and SEM images, respectively. This research expected that the porous composite (HC PMMA: 2% PEKK: 5% nTiO2) is a good candidate for bone scaffold applications.


Assuntos
Cetonas , Polimetil Metacrilato , Polimetil Metacrilato/química , Cetonas/química , Éter , Temperatura Alta , Engenharia Tecidual , Porosidade , Etil-Éteres , Éteres , Tecidos Suporte/química
11.
Int J Mol Sci ; 24(21)2023 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-37958636

RESUMO

Recently, polyetheretherketone (PEEK) has shown promising dental applications. Surface treatment is essential for dental applications owing to its poor surface energy and wettability; however, no consensus on an effective treatment method has been achieved. In this study, we attempted to carboxylate PEEK sample surfaces via Friedel-Crafts acylation using succinic anhydride and AlBr3. The possibility of further chemical modifications using carboxyl groups was examined. The samples were subjected to dehydration-condensation reactions with 1H,1H-pentadecafluorooctylamine and N,N'-dicyclohexylcarbodiimide. Furthermore, the sample's surface properties at each reaction stage were evaluated. An absorption band in the 3300-3500 cm-1 wavenumber region was observed. Additionally, peak suggestive of COOH was observed in the sample spectra. Secondary modification diminished the absorption band in 3300-3500 cm-1 and a clear F1s signal was observed. Thus, Friedel-Crafts acylation with succinic anhydride produced carboxyl groups on the PEEK sample surfaces. Further chemical modification of the carboxyl groups by dehydration-condensation reactions is also possible. Thus, a series of reactions can be employed to impart desired chemical structures to PEEK surfaces.


Assuntos
Desidratação , Anidridos Succínicos , Humanos , Polietilenoglicóis/química , Cetonas/química , Propriedades de Superfície , Acilação
12.
Phys Chem Chem Phys ; 25(45): 31292-31300, 2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-37955422

RESUMO

Alcohol dehydrogenases (ADH) are a family of enzymes that catalyse the interconversion between ketones/aldehydes and alcohols in the presence of NADPH cofactor. It is challenging to desymmetrise the substituted cyclopentane-1,3-dione by engineering an ADH, while the reaction mechanism of the metal independent ADH remains elusive. Here we measured the conversion of a model substrate 2-benzyl-2-methylcyclopentane-1,3-dione by LbADH and found it predominately gave the (2R,3R) product. Binding mode analysis of the substrate in LbADH from molecular dynamics simulations disclosed the origin of the enantioselectivity of the enzyme; the opening and closing of the loop 191-205 above the substrate are responsible for shaping the binding pocket to orientate the substrate, so as to give different stereoisomer products. Using QM/MM calculations, we elucidated the reaction mechanism of LbADH. Furthermore, we demonstrated the reaction profile corresponding to the production of different stereoisomers, which is in accordance with our experimental observations. This research here will shed a light on the rational engineering of ADH to achieve stereodivergent stereoisomer products.


Assuntos
Álcool Desidrogenase , Álcoois , Álcool Desidrogenase/química , Aldeídos , Catálise , Cetonas/química , Especificidade por Substrato
13.
J Orthop Surg (Hong Kong) ; 31(3): 10225536231217537, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37997347

RESUMO

BACKGROUND: Total knee arthroplasty is the most effective treatment for advanced-stage knee arthritis, and the majority of knee prostheses are made of metal. Nevertheless, metal prostheses still have several problems. The objective of this study is to introduce new metal-free knee prostheses made of polyether-ether-ketone (PEEK) and to compare their cement bond strength with metal prostheses. METHODS: Twelve sets of knee prostheses were divided into four groups (unloaded PEEK, unloaded Metal, 10 million cycles (MC) PEEK, 10 MC Metal, N = 3 each), and then attached to composite bones using bone cement. Both the 10 MC PEEK and 10 MC Metal groups were subjected to dynamic gait simulations of 10 MC, whereas the other two sets were not. Afterwards, a pull-off strength test was performed on the femoral prostheses and a shear strength test was performed on the tibial prostheses. RESULTS: No apparent cracks were observed in the bone cement after subjecting the PEEK and Metal groups to 10 million cycles of dynamic simulation. No statistically significant differences were observed (p > .05) in the strength tests for unloaded PEEK vs. unloaded Metal, 10 MC PEEK vs.10 MC Metal in the femoral pull-off test, and for unloaded PEEK vs. unloaded Metal in the tibial shear test. The shear strength of 10 MC PEEK was significantly lower (p < .05) compared to that of 10 MC Metal. CONCLUSIONS: By comparing the force analysis of previous investigations on knee prostheses with the failure pattern observed in the PEEK knee prosthesis of this study, which replicates that of the metal prosthesis. We believe that the combination of the peek knee prosthesis with bone cement is reliable. We anticipate that metal-free PEEK knee prostheses will find application in Total Knee Arthroplasty (TKA) in the future, thereby benefiting patients.


Assuntos
Prótese do Joelho , Humanos , Cimentos Ósseos , Teste de Materiais , Polietilenoglicóis/química , Cetonas/química , Éteres
14.
J Mech Behav Biomed Mater ; 148: 106188, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37856992

RESUMO

Electrophoretic deposition (EPD) of polyether ether ketone (PEEK) coatings on metallic implants has recently attracted a great deal of interest; however, further investigation into their corrosion, surface, and tribological properties is required for their clinical application. Using Potentiodynamic polarization and Mott-Schottky analysis of PEEK coatings, we analyzed the electrochemical corrosion behavior of electrophoretically deposited PEEK coatings on 316L stainless steel (SS) substrates. In addition, the tribological behavior of the coatings was determined through pin-on-disc and scratch testing. Initially, the EPD parameters were optimized using a Taguchi Design of Experiment (DoE) approach. The coatings exhibited irregular shaped grains along with ∼66 µm of thickness. Fourier transform infrared spectroscopy confirmed the presence of functional groups ascribed with PEEK. The coatings were moderately hydrophobic and had an average roughness of ∼2 µm. The corrosion studies demonstrated promising features of current density and corrosion potential, indicating that corrosion resistance significantly improves with PEEK coating. Electrochemical impedance spectroscopy also confirmed the corrosion resistance of PEEK coating. The coatings exhibited a slightly lower wear resistance than SS samples, but still possessed adequate wear and scratch resistance for biomedical applications. The current study confirmed that the PEEK coatings on metallic implants is effective for orthopedic applications where corrosion and tribology are major concerns.


Assuntos
Materiais Revestidos Biocompatíveis , Aço Inoxidável , Aço Inoxidável/química , Materiais Revestidos Biocompatíveis/química , Corrosão , Polietilenoglicóis/química , Cetonas/química , Éteres
15.
Chem Pharm Bull (Tokyo) ; 71(10): 792-797, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37779082

RESUMO

Chiral lithium binaphtholates prepared from the corresponding binaphthols and lithium tert-butoxide effectively catalyze the asymmetric Michael additions of ketones to poorly reactive acrylamides. The lithium binaphtholate catalyst mediates ketone deprotonation and enantioselective carbon-carbon bond formation to the acrylamide to deliver the Michael adduct in good yield and enantioselectivity. A small excess of lithium tert-butoxide relative to the binaphthol successfully enolizes the ketone in the initial stage of the reaction to promote the Michael reaction. Computational analysis of the transition state suggested that the 3- and 3'-phenyl groups of the binaphtholate catalyst regulate the orientation of the lithium enolate and the subsequent approach of the acrylamide, leading to superior enantioselectivity.


Assuntos
Acrilamidas , Lítio , Lítio/química , Acrilamida , Estereoisomerismo , Cetonas/química , Catálise
16.
Int J Biol Macromol ; 253(Pt 6): 127348, 2023 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-37820904

RESUMO

The application of (R)-ω-transaminases as biocatalysts for chiral amine synthesis has been hampered by inadequate stereoselectivity and narrow substrate spectrum. Herein, an effective evolution strategy for (R)-ω-transaminase designing for the asymmetric synthesis of sitagliptin intermediate is presented. Since natural transaminases lack activity toward bulky prositagliptin ketone, transaminase scaffolds with catalytic machinery and activity toward the truncated prositagliptin ketone were firstly screened based on substrate walking principle. A transaminase chimera was established synchronously conferring catalytic activity and (R)-selectivity toward prositagliptin ketone through motif swapping, followed by stepwise evolution. The process resulted in a "best" engineered variant MwTAM8, which exhibited 79.2-fold higher activity than the chimeric scaffold MwTAMc. Structural analysis revealed that the heightened activity is mainly due to the enlarged and adaptive substrate pocket and tunnel. The novel (R)-transaminase exhibited unsatisfied industrial operation stability, which is expected to further modify the protein to enhance its tolerance to temperature, pH, and organic solvents to meet sustainable industrial demands. This study underscores a useful evolution strategy of engineering biocatalysts to confer new properties and functions on enzymes for synthesizing high-value drug intermediates.


Assuntos
Fosfato de Sitagliptina , Transaminases , Transaminases/química , Domínio Catalítico , Catálise , Cetonas/química , Especificidade por Substrato , Aminas/química
17.
Int J Biol Macromol ; 253(Pt 7): 127414, 2023 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-37838135

RESUMO

Short-chain dehydrogenase/reductase (SDR) acts as a biocatalyst in the synthesis of chiral alcohols with high optical purity. Herein, we achieved immobilization via crosslinking on novel magnetic metal-organic framework nanoparticles with a three-layer shell structure (Fe3O4@PDA@Cu (PABA)). The results of scanning electron microscopy, Fourier-transform infrared spectroscopy, X-ray diffraction, X-ray photoelectron spectroscopy, and energy dispersive X-ray spectroscopy confirmed the morphology and cross-linking property of immobilized SDR, which was more durable, stable, and reusable and exhibited better kinetic performance than free enzyme. The SDR and glucose dehydrogenase (GDH) were co-immobilized and then used for the asymmetric reduction of COBE and ethyl 2-oxo-4-phenylbutanoate (OPBE). These finding suggest that enzymes immobilized on novel MOF nanoparticles can serve as promising biocatalysts for asymmetric reduction prochiral ketones into chiral alcohols.


Assuntos
Cetonas , Estruturas Metalorgânicas , Cetonas/química , Álcoois/química , Enzimas Imobilizadas/química , Fenômenos Magnéticos , Oxirredutases
18.
Adv Healthc Mater ; 12(32): e2301772, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37723927

RESUMO

Key factors contributing to implantation failures include implant-associated infections (IAIs) and insufficient osseointegration of the implants. Polyetheretherketone (PEEK) is widely used in orthopedics, yet its clinical applications are restricted due to its poor osteogenic and antibacterial properties as well as inadequate immune responses. To overcome these drawbacks, a novel spatiotemporal immunomodulation approach is proposed, chelating Cu-Sr bilayer bioactive glass nanoparticles (CS-BGNs) onto the PEEK surface via polydopamine (PDA). The CS-BGNs possess a bilayer core-shell structure where copper is distributed in the outer layer and strontium is clustered in the inner layer. The results show that CS-BGNs/PDA functionalized PEEK demonstrates a controlled and sequential release of Cu2+ and Sr2+ . In the early stage, Cu2+ from the outer layer releases rapidly, while Sr2+ from the inner layer releases in the late stage. This well-ordered release pattern modulates the phenotypic transition of macrophages, which induces M1 polarization in the early stage and M2 polarization in the late stage. Combined with the direct effects of Cu2+ and Sr2+ , the spatiotemporal immunomodulation not only benefits the early antibacterial and tissue-healing process, but also promotes the long-term process of osseointegration, providing new perspectives on the design of novel immunomodulatory biomaterials.


Assuntos
Cobre , Nanopartículas , Cobre/farmacologia , Cobre/química , Osteogênese , Polietilenoglicóis/química , Cetonas/farmacologia , Cetonas/química , Nanopartículas/química , Antibacterianos/farmacologia , Antibacterianos/química , Osseointegração , Propriedades de Superfície
19.
ACS Appl Bio Mater ; 6(8): 3319-3329, 2023 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-37561906

RESUMO

The issue of spine-related disorders is a global healthcare concern that requires effective solutions to restore normal spine functioning. Spinal fusion implants have become a standard approach for this purpose, making it crucial to develop biomaterials and structures that possess high osteogenic capacities and exhibit mechanical properties and dynamic responses similar to those of the host bone. This study focused on the fabrication of 3D-printed polyether ether ketone/silicon nitride (PEEK/SiN) scaffolds with a triply periodic minimal surface (TPMS) structure, which offers several advantages, such as a large surface area and uniform stress distribution under load. The mechanical properties and dynamic response of PEEK/SiN scaffolds with varying porosities were evaluated through mechanical testing and finite element analysis. The scaffold with 30% porosity exhibited a compressive strength (34.56 ± 1.91 MPa) and elastic modulus (734 ± 64 MPa) similar to those of trabecular bone. In addition, the scaffold demonstrated favorable damping properties. The biological data revealed that incorporating silicon nitride into the PEEK scaffold stimulated osteogenic differentiation. In light of these findings, it can be inferred that PEEK/SiN TPMS scaffolds exhibit significant potential for use in bone tissue engineering and represent a promising option as candidates for spinal fusion implants.


Assuntos
Osteogênese , Fusão Vertebral , Teste de Materiais , Polietilenoglicóis/química , Cetonas/química , Impressão Tridimensional
20.
Biomater Adv ; 154: 213607, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37651963

RESUMO

Polyetheretherketone (PEEK) has emerged as a highly promising orthopedic implantation material due to its elastic modulus which is comparable to that of natural bone. This polymer exhibits impressive properties for bone implantation such as corrosion resistance, fatigue resistance, self-lubrication and chemical stability. Significantly, compared to metal-based implants, PEEK implants have mechanical properties that are closer to natural bone, which can mitigate the "stress shielding" effect in bone implantation. Nevertheless, PEEK is incapable of inducing osteogenesis due to its bio-inert molecular structure, thereby hindering the osseointegration process. To optimize the clinical application of PEEK, researchers have been working on promoting its bioactivity and endowing this polymer with beneficial properties, such as antibacterial, anti-inflammatory, anti-tumor, and angiogenesis-promoting capabilities. Considering the significant growth of research on PEEK implants over the past 5 years, this review aims to present a timely update on PEEK's modification methods. By highlighting the latest advancements in PEEK modification, we hope to provide guidance and inspiration for researchers in developing the next generation bone implants and optimizing their clinical applications.


Assuntos
Polietilenoglicóis , Polímeros , Polietilenoglicóis/química , Polietilenoglicóis/farmacologia , Benzofenonas , Cetonas/uso terapêutico , Cetonas/química , Cetonas/farmacologia
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