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1.
Int J Mol Sci ; 25(17)2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39273239

RESUMEN

5-fluorouracil (5-FU), a chemotherapeutic agent against oral squamous cell carcinoma (OSCC), is limited by poor pharmacokinetics and toxicity. The pH-sensitive zeolite imidazolate framework-8 (ZIF-8) may increase the selectivity and length of 5-FU released into the acidic tumor microenvironment. This study examined the in vitro 5-FU absorption and release profiles of ZIF-8, and then progressed to cytotoxicity assays using the OSCC primary cell line SCC7. The 5-FU loading capacity of ZIF-8 was calculated with UV-vis spectroscopy (λ = 260 nm). 5-FU release was quantified by submerging 5-FU@ZIF-8 in pH 7.4 and 5.5 acetate buffer over 48 h. For the cytotoxicity assays, 5-FU, ZIF-8, and 5-FU@ZIF-8 were added to SCC7 cultures at 25, 50, and 100 µg/mL. Cell viability was assessed through toluidine blue staining and further quantified through transcriptomic RNA sequencing. ZIF-8 stabilized at a maximum absorption of 2.71 ± 0.22 mg 5-FU, and released 0.66 mg more 5-FU at pH 5.5 than 7.4 for at least 72 h. The cytotoxicity assays showed that 5-FU@ZIF-8 had a synergistic inhibitory effect at 50 µg/mL. The RNA sequencing analysis further revealed the molecular targets of 5-FU@ZIF-8 in SCC7. 5-FU@ZIF-8 may release 5-FU based on the pH of the surrounding microenvironments and synergistically inhibit OSCC.


Asunto(s)
Carcinoma de Células Escamosas , Fluorouracilo , Neoplasias de la Boca , Fluorouracilo/farmacología , Humanos , Concentración de Iones de Hidrógeno , Neoplasias de la Boca/tratamiento farmacológico , Neoplasias de la Boca/patología , Neoplasias de la Boca/metabolismo , Línea Celular Tumoral , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Supervivencia Celular/efectos de los fármacos , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/farmacología , Zeolitas/química , Microambiente Tumoral/efectos de los fármacos , Liberación de Fármacos , Portadores de Fármacos/química , Sistemas de Liberación de Medicamentos/métodos , Nanopartículas/química , Imidazoles
2.
J Dent Res ; 103(1): 42-50, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37990799

RESUMEN

Biomimetic mineralization of dentin collagen appears to be a promising strategy to optimize dentin bonding durability. However, traditional postbonding mineralization strategies based on Ca/P ion release still have some drawbacks, such as being time-consuming, having a spatiotemporal mismatch, and having limited intrafibrillar minerals. To tackle these problems, a prebonding rapid intrafibrillar mineralization strategy was developed in the present study. Specifically, polyacrylic acid-stabilized amorphous calcium fluoride (PAA-ACF) was found to induce rapid intrafibrillar mineralization of the single-layer collagen model and dentin collagen at just 1 min and 10 min, as identified by transmission electron microscopy, scanning electron microscopy, and atomic force microscopy. This strategy has also been identified to strengthen the mechanical properties of demineralized dentin within a clinically acceptable timeframe. Significantly, the bonding strength of the PAA-ACF-treated groups outperformed the control group irrespective of aging modes. In addition, the endogenous matrix metalloproteinases as well as exogenous bacterial erosion were inhibited, thus reducing the degradation of dentin collagen. High-quality integration of the hybrid layer and the underlying dentin was also demonstrated. On the basis of the present results, the concept of "prebonding rapid intrafibrillar mineralization" was proposed. This user-friendly scheme introduced PAA-ACF-based intrafibrillar mineralization into dentin bonding for the first time. As multifunctional primers, PAA-ACF precursors have the potential to shed new light on prolonging the service life of adhesive restorations, with promising significance.


Asunto(s)
Cementos Dentales , Dentina , Colágeno , Minerales , Microscopía Electrónica de Transmisión
3.
J Dent Res ; 101(13): 1613-1619, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-35923076

RESUMEN

Bisphenol A (BPA), as an endocrine disruptor derived from petroleum-based chemicals, has been prohibited by several regulatory agencies for use in a wide variety of consumer products. For the sake of reducing human exposure to BPA derivatives and in the context of sustainability, it is far-reaching to develop high-performance and low-toxic materials from bountiful biomass sources. The objective of this work was to synthesize 2 bio-based dimethacrylate monomers, 2,2'-dially-4,4'-dimethoxy-5,5'-diglycerolate acrylatediphenylmethane (BEF-EA) and 2,2'-dially-4,4'-dimethoxy-5,5'-diglycerolate methacrylatediphenylmethane (BEF-GMA), using eugenol as the raw material. The estrogenic activity of bio-based bisphenol 2,2'-dially-4,4'-dimethoxy-5,5'-dihydroxydiphenylmethane (BEF) was evaluated and compared with estrogen and commercial bisphenols. After photopolymerization of the di(meth)acrylates diluted with tri(ethyleneglycol) dimethacrylate (TEGDMA), bio-based visible light-curing materials were prepared, and their properties were systematically investigated. Notably, di(meth)acrylates BEF-GMA and BEF-EA derived from these nonestrogenic bio-based phenols exhibited improved biocompatibility and low viscosity (down to 220-280 Pa.s). BEF-GMA and BEF-EA resin matrix exhibits lower volumetric polymerization shrinkage (about 8.5%), high photopolymerization reactivity (>50% in 60 s), and mechanical properties (fracture energy >5.5 N mm; flexural strength of 87-91 MPa, etc), which were comparable or superior to commercial Bis-GMA. The respective bio-based composites still exhibit adequate properties. Therefore, introducing eugenol-based visible light-curable dimethacrylate monomers into dental materials is a potential strategy to establish green sustainability and biocompatible dental materials without BPA.


Asunto(s)
Syzygium , Humanos , Resinas Compuestas/química , Eugenol , Ensayo de Materiales , Bisfenol A Glicidil Metacrilato/química , Materiales Biocompatibles/química
4.
J Pharm Sci ; 111(8): 2389-2396, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35500670

RESUMEN

We demonstrated the antibiotic impregnation and release properties of four porous hydroxyapatite (HAp) materials with 40% or 50% porosity and different pore structures for infectious control in neurotrauma surgery. The antibiotics used were meropenem (MEPM), ceftriaxone sodium hydrate (CTRX), gentamicin sulfate (GM), and linezolid (LZD). Greater amounts of antibiotics could be impregnated into each HAp material by increasing the volume of the antibiotics using a simple impregnation method for 15 min at atmospheric pressure. Each material showed two antibiotic release patterns based on the type of antibiotic and their interaction with the material. The first was non-reactive release of MEPM and LZD, which plateaued on day 2 after an initial burst; the second was reactive release of CTRX and GM, which showed a two-phase release comprising an initial burst followed by sustained release from day 2. Almost all eluates showed antibacterial activity against Staphylococcus aureus, suggesting that any combination of materials and antibiotics examined can be used to prevent intraoperative infection during surgery. Notably, CTRX and GM, which showed sustained release for several days, may also be useful for infected cases, including control of wound infection around 48 h postoperatively.


Asunto(s)
Antibacterianos , Durapatita , Antibacterianos/química , Preparaciones de Acción Retardada , Durapatita/química , Gentamicinas , Porosidad
5.
J Dent Res ; 101(9): 1015-1024, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35319289

RESUMEN

Oral tissue regeneration following chronic diseases and injuries is limited by the natural endogenous wound-healing process. Current regenerative approaches implement exogenous systems, including stem cells, scaffolds, growth factors, and plasmid DNA/viral vectors, that induce variable clinical outcomes. An innovative approach that is safe, effective, and inexpensive is needed. The lipid nanoparticle-encapsulated nucleoside-modified messenger RNA (mRNA) platform has proven to be a successful vaccine modality against coronavirus disease 2019, demonstrating safety and high efficacy in humans. The same fundamental technology platform could be applied to facilitate the development of mRNA-based regenerative therapy. While the platform has not yet been studied in the field of oral tissue regeneration, mRNA therapeutics encoding growth factors have been evaluated and demonstrated promising findings in various models of soft and hard tissue regeneration such as myocardial infarction, diabetic wound healing, and calvarial and femoral bone defects. Because restoration of both soft and hard tissues is crucial to oral tissue physiology, this new therapeutic modality may help to overcome challenges associated with the reconstruction of the unique and complex architecture of oral tissues. This review discusses mRNA therapeutics with an emphasis on findings and lessons in different regenerative animal models, and it speculates how we can apply mRNA-based platforms for oral tissue regeneration.


Asunto(s)
COVID-19 , Ingeniería de Tejidos , Animales , Regeneración Ósea/genética , Humanos , Péptidos y Proteínas de Señalización Intercelular , Liposomas , Nanopartículas , ARN Mensajero , Tecnología , Cicatrización de Heridas/genética
6.
J Periodontol ; 93(3): 343-353, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34245016

RESUMEN

BACKGROUND: The aim of this study was to examine osseous changes following lateral bone augmentation using a novel scaffold (OV) alone and compare it to combination therapy using freeze-dried bone allograft (FDBA) and resorbable collagen membrane (FDBA/CM). METHODS: Thirty patients completed this 9-months prospective two-center cohort clinical trial. Before surgery and 9-months re-entry, linear measurements were performed, and impressions taken. Cone-beam computed tomography (CBCT) were done at baseline and 9 months. DICOM slice data were converted into volumetric images using 3D Slicer. Following 3D volumetric image construction, pre- and post-op Standard Triangle Language files were superimposed and volumetric data were extracted for a 10-mm region of interest. Linear measurements were compared similarly. RESULTS: Baseline clinical parameters were similar in both groups (4.22 and 4.53 mm for OV and FDBA/CM at -2 mm, respectively). Following treatment, vertical distance from the stent had changed minimally (-0.36 and -0.12 mm, respectively). Similarly, lateral bone gain ranged from 0 to 0.4 mm, for both groups. To the contrary, the CBCT measurements showed a significantly greater increase in horizontal width in the control at -2 mm (0.95 ± 0.2 mm) compared with -0.62 mm for the OV (P = 0.000). Similar changes were observed at -5 mm (0.63 and -0.41 mm, respectively, P = 0.01). Sites volume had increased from 266 ± 149 mm3 to 360 ± 138 mm3 (P = 0.001) for FDBA/CM with negligible changes for OV (from 334 to 335 mm3 , P = 0.952). these between-group changes being statistically significant (P = 0.023). CONCLUSION: FDBA/CM yielded better albeit moderate increase in the volume of the edentulous ridge, while OV scaffolds failed to produce similar results.


Asunto(s)
Aumento de la Cresta Alveolar , Aloinjertos/cirugía , Proceso Alveolar/diagnóstico por imagen , Proceso Alveolar/cirugía , Regeneración Ósea , Trasplante Óseo/métodos , Colágeno/uso terapéutico , Humanos , Estudios Prospectivos , Extracción Dental , Alveolo Dental/cirugía
7.
J Periodontol ; 93(10): 1578-1588, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-34855256

RESUMEN

BACKGROUND: A weak implant-soft tissue interface may lead to bacterial ingression, breakdown of underlying tissues, and eventually implant failure. This study proposes a surface modification technique of titanium alloy (Ti), using a nano-biopolymer scaffold to enhance soft tissue attachment in dental implants. METHODS: Gelatin (20% w/v) embedded with 10 ± 2 nm silver nanoparticles (AgNPs) was electrospun to form a gelatin electrospun mat (GEM) scaffold, bonded to Ti alloy surface using chemical surface functionalization. Antimicrobial activity of AgNPs was tested against representative Gram-positive (Staphylococcus aureus) and Gram-negative bacteria (Escherichia coli) at 4, 24, and 48 hours and after embedding in scaffold at 48 hours. Cytotoxicity analysis (MTT assay) was performed using the 3T3 mouse fibroblast cell line at 24 and 72 hours for two groups: control (unmodified Ti disc) and experimental (GEM embedded with AgNPs); and further validated by scanning electron microscopy. RESULTS: The AgNPs-embedded GEM showed good antimicrobial activity at 48 hours, with the AgNPs showing complete (99.99%) inhibition of bacterial colony counts at 24 and 48 hours. Cell viability and proliferation over the GEM modified Ti discs were seen to be significantly increased (P < 0.05) at 72 hours as compared with control. SEM images revealed intimate spreading of fibroblasts, with differentiated cell morphology and pseudopodial processes, indicative of enhanced fibroblastic adhesion, growth, and differentiation over the scaffold. CONCLUSION: Results show good antifouling properties and biocompatibility of the fabricated coating, making it a promising strategy to reduce postoperative infections and peri-implant diseases in Ti dental implants.


Asunto(s)
Antiinfecciosos , Implantes Dentales , Nanopartículas del Metal , Nanofibras , Ratones , Animales , Plata/química , Plata/farmacología , Nanopartículas del Metal/química , Biomimética , Gelatina , Antibacterianos/farmacología , Antiinfecciosos/farmacología , Titanio , Aleaciones , Escherichia coli , Propiedades de Superficie , Materiales Biocompatibles Revestidos/química , Materiales Biocompatibles Revestidos/farmacología
8.
Clin Oral Implants Res ; 32(11): 1263-1273, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34448240

RESUMEN

OBJECTIVES: Soft-tissue volume augmentation treatments do not provide the satisfactory long-term functional and esthetic outcomes. The aim of the study was to develop a standardized digital procedure to design individual soft-tissue substitutes (STS) and apply mathematical modeling to obtain average shape STS for single posterior tooth defects. MATERIAL AND METHODS: Thirty-three casts from 30 patients were scanned. STS were designed with a computer-aided design software and a systematic procedure standardized the measurements across all STS using 3D-analysis software. The occlusal, mesial-distal, and buccal-lingual planes were defined to partition, each STS and produce a mesh. The thickness values of each 3D slice were documented in a coordinate system chart to generate a scatter graph. Graphs were embedded into images (Orange software) and images were analyzed via hierarchical clustering. RESULTS: Three STS groups were identified according to shape. Two shapes corresponded to the maxilla defects: a square (n = 13) with dimensions of 10 mm in a lingual-buccal (length) and 7-10 mm in a mesial-distal (width) direction; a rectangle (n = 11) of 11 mm in length and 4-7 mm in width. The average shape for mandible defects (n = 9) was smaller (6-8 mm in length, 5-10 mm in width). The highest thickness in all STS was in the buccal portion, above the alveolar ridge, with median values of 2 mm. The lowest thickness of 0.2 mm was at the edges. CONCLUSIONS: The study developed novel methodology to design customized, as well as average shape STS for volume augmentation. Future STS harboring adapted geometry might increase volume augmentation efficiency and accuracy, while reducing surgical time.


Asunto(s)
Aumento de la Cresta Alveolar , Diente , Diseño Asistido por Computadora , Estética Dental , Humanos , Mandíbula/cirugía , Maxilar/cirugía
9.
Clin Oral Implants Res ; 32(8): 916-927, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34031931

RESUMEN

OBJECTIVES: Compared to autografts, bone graft substitutes are slower to consolidate. If we understood why, this might open strategies to accelerate new bone formation and thus shorten the time to implant placement. In this study, we aimed at comparing autologous bone graft with a bovine bone graft substitute in a preclinical sinus lift model. MATERIALS AND METHODS: The mouse posterior paranasal sinus served as a recipient site for grafting. Autograft from the oral cavity was compared against bone graft substitute using molecular, cellular, and histological analyses conducted on post-grafting days (PSD) 0, 9, 18, and 120. RESULTS: Either autografts or bone graft substitutes were positioned on the sinus floor and remained in situ throughout the study. At the time of grafting and until day 9, bone graft substitutes were devoid of cells and alkaline phosphatase (ALP) activity while autografts were comprised of viable cells and showed strong ALP (mineralization) activity. Consequently, new bone formed faster in autografts compared to bone graft substitutes (140.21 ± 41.21 µm vs. 41.70 ± 10.09 µm, respectively, PSD9, p = .0143). By PSD18, osteogenesis was evident in autografted and xenografted sites. Osteoclasts identified by tartrate resistant acid phosphatase attached to, but did not resorb the bone graft substitute matrix. Autograft matrix, however, underwent extensive resorption. Transgenic mice revealed that Wnt-responsive osteoprogenitor cells originated primarily from the internal periosteum of the maxillary bone, and not from the Schneiderian membrane. CONCLUSION: Autografts produce new bone sooner, but bovine bone graft substitutes eventually consolidate and then resist resorption. Enhancing osteoprogenitor cell recruitment to a bone graft substitute constitutes a viable strategy for accelerating bone formation in a sinus lift procedure.


Asunto(s)
Sustitutos de Huesos , Elevación del Piso del Seno Maxilar , Animales , Autoinjertos , Biología , Sustitutos de Huesos/farmacología , Trasplante Óseo , Bovinos , Implantación Dental Endoósea , Seno Maxilar/cirugía , Ratones , Modelos Teóricos , Osteogénesis
10.
J Pharm Sci ; 110(8): 2946-2954, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-33785350

RESUMEN

Glioma-targeted drug delivery is a hugely challenging task because of the multibarrier in the brain. In this study, we report a magnetic T7 peptide&AS1411 aptamer-modified microemulsion for triple glioma-targeted delivery of shikonin and docetaxel (Fe3O4@T7/AS1411/DTX&SKN-M). Such a system comprises two tumor-targeted ligands (T7 peptide and AS1411 aptamer), ultra-small superparamagnetic iron oxide nanoparticle (Fe3O4), and shikonin&docetaxel-coloaded microemulsion (SKN&DTX-M). Fe3O4@T7/AS1411/DTX&SKN-M is capable of stably circulating in the blood, accumulating around the brain under an external magnetic field, distributing inside the glioma via the affinity to nucleolin/transferrin receptor, and retarding the growth of orthotopic glioma. Fe3O4@T7/AS1411/DTX&SKN-M encapsulated Fe3O4 nanoparticles in the core to obtain the superparamagnetism, which did not influence the main surface properties. Introducing 6% (wt%) of DSPE-PEG2000-T7 and 180 nM of AS1411 collaboratively enhanced the murine glioma (G422) cellular uptake of Fe3O4@T7/AS1411/DTX&SKN-M and thereby achieved the strongest antiproliferation among all the groups. Notably, the drug distribution at the brain sites of orthotopic Luc-G422 glioma tumor-bearing nude mice treated with Fe3O4@T7/AS1411/DTX&SKN-M was overwhelming among all the treatments. Most importantly, Fe3O4@T7/AS1411/DTX&SKN-M not only significantly reduced the luminescence signal at the brain areas of orthotopic Luc-G422 glioma mice but also prolonged the overall survival period. The enhancement of anti-glioma efficacy was associated with down-regulating the population of CD133- and CD44-positive cells within the tumors. In summary, such a triple glioma-targeted delivery of shikonin and docetaxel using combinational magnetism and T7/AS1411 modification strategies provides a promising method for synergistic and precise glioma therapy.


Asunto(s)
Antineoplásicos , Glioma , Nanopartículas , Animales , Antineoplásicos/uso terapéutico , Aptámeros de Nucleótidos , Línea Celular Tumoral , Colágeno Tipo IV , Docetaxel , Sistemas de Liberación de Medicamentos , Glioma/tratamiento farmacológico , Fenómenos Magnéticos , Ratones , Ratones Desnudos , Naftoquinonas , Oligodesoxirribonucleótidos , Fragmentos de Péptidos
11.
J Dent ; 107: 103609, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33610589

RESUMEN

OBJECTIVE: The aim of this paper is to present the results of a consensus meeting on the threshold property requirements for the clinical use of conventional glass-ionomer cements (GICs) for restorative indications. METHODS: Twenty-one experts on GICs evaluated the results of tests on mechanical and optical properties of 18 different brands of restorative GICs: Bioglass R [B], Chemfil Rock [CR], Equia Forte [EF], Gold Label 2 [GL2], Gold Label 9 [GL9], Glass Ionomer Cement II [GI], Ionglass [IG], Ion Z [IZ], Ionomaster [IM], Ionofil Plus [IP], Ionostar Plus [IS], Ketac Molar Easymix [KM], Magic Glass [MG], Maxxion R [MA], Riva Self Cure [R], Vidrion R [V], Vitro Fil [VF] and Vitro Molar [VM]. All experiments were carried out by a team of researchers from Brazil and England following strict protocols, under the same laboratory conditions throughout, and maintaining data integrity. RESULTS: There was consensus on: determining as primary properties of the material: compressive strength, microhardness, acid erosion and fluoride release, and as secondary properties: contrast ratio and translucency parameter, in order to rank the materials. Seven brands were below the thresholds for restorative indications: IZ, IM, IG, MA, VF, B and MG. CONCLUSIONS: Based on the primary properties adopted as being essential for restorative indications, the conventional restorative GICs that met the thresholds and could be considered suitable as long-term restorative materials were: EF, GI, GL9, KM, IP, GL2, IS, CR, V, VM and R. A decision-making process to select the best GIC must also include results from clinical trials. CLINICAL SIGNIFICANCE: This study provides a ranking of GICs that could be considered suitable as long-term restorative materials based on their main properties.


Asunto(s)
Cementos de Ionómero Vítreo , Brasil , Fuerza Compresiva , Consenso , Ensayo de Materiales
12.
Biomaterials ; 269: 120671, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33493771

RESUMEN

Dimensionally stable vertical bone regeneration outside of the existing bony envelope is a major challenge in the field of orofacial surgery. In this study, we demonstrate that a highly porous, resorbable scaffold fabricated using additive manufacturing techniques enables reproducible extra-skeletal bone formation and prevents bone resorption. An additively manufactured medical grade polycaprolactone (mPCL) biphasic scaffold mimicking the architecture of the jaw bone, consisting of a 3D-printed outer shell overlying an inner highly porous melt electrowritten scaffold, was assessed for its ability to support dimensionally stable bone regeneration in an extraskeletal ovine calvarial model. To investigate bone formation capacity (stage 1), 7 different constructs placed under a protective dome were assessed 8 weeks post-implantation: Empty control, Biphasic scaffold with hydrogel (PCL-Gel), PCL-Gel with 75 or 150 µg of BMP-2 (PCL-BMP-75 and PCL-BMP-150), hydrogel only (Gel), Gel containing 75 or 150 µg of BMP-2 (Gel-BMP-75 and Gel-BMP-150). To assess dimensional stability (stage 2), in a separate cohort, 5 animals were similarly implanted with 2 samples of each of the Gel-BMP-150 and PCL-BMP-150 groups, and after 8 weeks of healing, the protective domes were removed and titanium implants were placed in the regenerated bone and allowed to heal for a further 8 weeks. Bone formation and osseointegration were assessed using micro-computed tomography, histology and histomorphometry. In stage 1, enhanced bone formation was found in the BMP-2 containing groups, especially the PCL-BMP constructs whereby regeneration of full bone height was achieved in a reproducible manner. There was no significant bone volume increase with the higher dose of BMP-2. In the dimensional stability assessment (stage 2), after the rtemoval of the protective dome, the biphasic scaffold prevented bone resorption whereas in the absence of the scaffold, the bone previously formed in the hydrogel underwent extensive resorption. This was attributed to the space maintenance properties and dimensional stability of the biphasic scaffold. Titanium implants osseointegrated into the newly formed bone within the biphasic scaffolds. In conclusion, additively manufactured biphasic scaffolds functionalized with BMP-2 facilitated dimensionally stable bone regeneration that supported dental implant osseointegration.


Asunto(s)
Regeneración Ósea , Huesos , Andamios del Tejido , Animales , Proteína Morfogenética Ósea 2 , Osteogénesis , Ovinos , Microtomografía por Rayos X
13.
J Dent Res ; 100(3): 268-275, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33043768

RESUMEN

New strategies for tissue engineering have great potential for restoring and revitalizing impaired tissues and organs, including the use of smart hydrogels that can be modified to enhance organization and functionality of the salivary glands. For instance, monomers of laminin-111 peptides chemically conjugated to fibrin hydrogel (L1pM-FH) promote cell cluster formation in vitro and salivary gland regeneration in vivo when compared with fibrin hydrogel (FH) alone; however, L1pM-FH produce only weak expression of acinar differentiation markers in vivo (e.g., aquaporin-5 and transmembrane protein 16). Since previous studies demonstrated that a greater impact can be achieved when trimeric forms were used as compared with monomeric or dimeric forms, we investigated the extent to which trimers of laminin-111 chemically conjugated to FH (L1pT-FH) can increase the expression of acinar differentiation markers and elevate saliva secretion. In vitro studies using Par-C10 acinar cells demonstrated that when compared with L1pM-FH, L1pT-FH induced similar levels of acinar-like cell clustering, polarization, lumen formation, and calcium signaling. To assess the performance of the trimeric complex in vivo, we compared the ability of L1pM-FH and L1pT-FH to increase acinar differentiation markers and restore saliva flow rate in a salivary gland wound model of C57BL/6 mice. Our results show that L1pT-FH applied to wounded mice significantly improved the expression of the acinar differentiation markers and saliva secretion when compared with the monomeric form. Together, these positive effects of L1pT-FH warrant its future testing in additional models of hyposalivation with the ultimate goal of applying this technology in humans.


Asunto(s)
Fibrina , Hidrogeles , Animales , Laminina , Ratones , Ratones Endogámicos C57BL , Glándulas Salivales
14.
Clin Implant Dent Relat Res ; 23(1): 86-95, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33295137

RESUMEN

BACKGROUND: Lateral maxillary sinus augmentation (MSA) is a predictable bone regeneration technique in case of atrophy of the posterior-upper maxilla. Aimed at obtaining quantity and quality of bone suitable for receiving osseointegrated implants, its success is largely due to the skill of the surgeon, but also to the characteristics of the biomaterial used. METHODS: Twenty-four patients needing MSA were included in the study. The patients were randomly allocated to three different groups: anorganic bovine bone mineral as control, tricalcium phosphate with or without hyaluronic acid (HA) as test groups. Nine months after MSA, bone biopsies were harvested for the histomorphometric analysis. Secondary outcomes were mean bone gain, intraoperative and postoperative complications, implant insertion torque, implant failure, and patient-reported outcome measures. RESULTS: Although the percentage of new bone was not statistically different between the three groups (P = .191), the percentages of residual biomaterial was significantly higher (P < .000) and nonmineralized tissue significantly lower (P < .000) in the control than in the test groups. Test groups did not differ significantly from each other for all histomorphometric parameters. The implant insertion torque was significantly higher in the control group (P < .0005). The rest of the secondary outcomes were not significantly different between the groups. CONCLUSION: MSA is a safe and predictable procedure in terms of histological, clinical, and PROAMs, regardless of the biomaterial used. The addition of HA did not influence the outcomes.


Asunto(s)
Sustitutos de Huesos , Elevación del Piso del Seno Maxilar , Animales , Trasplante Óseo , Bovinos , Implantación Dental Endoósea , Humanos , Maxilar/cirugía , Seno Maxilar/cirugía , Medición de Resultados Informados por el Paciente
15.
Front Bioeng Biotechnol ; 8: 559494, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33117779

RESUMEN

Periodontal disease is one of the most common diseases worldwide. It has a significant impact on oral health and subsequently the individual's quality of life. However, optimal regeneration of periodontal tissues, using current treatments, has yet to be achieved. Peptide self-assembly has provided a step-change in nanobiotechnology and regenerative medicine fields. Our aim was to investigate the effects of a self-assembling peptide (SAP; P11-4) on periodontal regeneration in a preclinical model. Twenty-six bilateral maxillary critical-sized periodontal defects were created surgically in 13 rats. Defects on one side of the mouth were filled with P11-4 hydrogel; the contra-lateral defect was untreated (control). Rats were sacrificed immediately post-surgery (time 0) and after 2 and 4 weeks. Retrieved maxillae were processed for histological, immunohistochemical, and histomorphometric assessments. The results of histological analysis showed greater organization of periodontal fibers in defects treated with P11-4, at both time points, when compared to untreated defects. Histomorphometry showed that treated defects had both a significant increase in functional periodontal ligament length and a reduction in epithelial down growth after 4 weeks. At 2 weeks, treated defects showed a significant increase in expression of osteocalcin and osteoprotegerin as judged by immunohistochemistry. Also, a significantly higher osteoprotegerin/RANKL ratio was shown in treated defects. In conclusion, the results demonstrated enhanced regeneration of periodontal tissues when SAP P11-4 was used to fill periodontal defects in rats. The findings of this study suggest that SAP P11-4 is a promising novel candidate for periodontal regenerative therapy. Further investigations are required for optimization before clinical use.

16.
Dent Mater J ; 39(6): 1080-1086, 2020 Dec 03.
Artículo en Inglés | MEDLINE | ID: mdl-33028788

RESUMEN

Silicon nitride (Si3N4) is one of the promising ceramics for dental restoration due to providing significant benefits during the application. This study aimed to investigate the potential use of Si3N4 for all-ceramic dental restorations by characterizing some critical properties as color shade, mechanical resistance, shear-bond strength and radiolucency. For our study, porous Si3N4 ceramic was produced by partial sintering process with limited amounts of sintering additives and low temperature. A commercial ZrO2 ceramic was prepared according to manufacturer's instructions and results were compared with Si3N4. Si3N4 is an attractive ceramic for dental applications with good mechanical properties even in porous form, it has additional advantages over the conventional ceramics used as restorative material, such as, inherent antibacterial/anti-infective activity, radiolucency, and lower hardness. It is expected that Si3N4 will become popular in dental applications as well.


Asunto(s)
Cerámica , Compuestos de Silicona , Materiales Dentales , Porcelana Dental , Ensayo de Materiales , Propiedades de Superficie
17.
Clin Adv Periodontics ; 10(4): 195-199, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32862550

RESUMEN

INTRODUCTION: Guided tissue regeneration (GTR) has been well documented with combination of bone graft substitutes and biologic modifiers to improve the outcomes of periodontal regenerative procedures. Amnion-chorion allograft membrane (ACM) is a placenta-derived resorbable allograft membrane which contains growth factors found in the placenta. The primary purpose of the barrier membranes for GTR was to exclude the epithelial down-growth along with the root surface, however, the ACM can be used as an additional biologic modifier because of the release of growth factors from the ACM after placement. The aim of this case report is to evaluate the efficacy and the application of ACM on the previously diseased root surface to treat periodontal intrabony defect. CASE PRESENTATION: A 60-year-old Caucasian male with deep and wide intrabony defect on mesial #19 was treated with a regenerative procedure with combination of application of ACM on the root surface and filling the intrabony defect with the corticocancellous freeze-dried bone allograft. The bone substitute was covered with another layer of ACM and primary closure was achieved. Wound healing process was uneventful, and the clinical and radiographic outcomes were favorable up to 18 months after the surgical procedure. CONCLUSION: This case report demonstrated that the application of ACM on the root surface with a combination of bone substitute might enhance to the radiographic bone fill and the clinical attachment level gain and minimize the risk of post-operative gingival recession.


Asunto(s)
Pérdida de Hueso Alveolar , Regeneración Tisular Guiada Periodontal , Aloinjertos , Pérdida de Hueso Alveolar/cirugía , Amnios , Corion/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Pérdida de la Inserción Periodontal/cirugía
18.
J Periodontol ; 91(9): 1213-1224, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-31858607

RESUMEN

BACKGROUND: Gingival tissue attachment is known to be important for long-term prognosis of implants. This in vitro study evaluated the gingival attachment to zirconia implants and zirconia implants modified with sol-gel derived TiO2 coatings. METHODS: Zirconia endodontic posts (n = 23) were used to function as implants that were inserted into the center of full-thickness porcine gingival explants (n = 31). The tissue/implant specimens were then individually placed at an air/liquid interface on a stainless-steel grid in cell culture wells containing a nutrient solution. The tissue cultures were incubated at 37°C in a 5% CO2 environment and at days 7 and 14, the specimens were harvested and analyzed by dynamic mechanical analysis (DMA) measurements under dynamic loading conditions mimicking natural mastication. Specimens were also analyzed by immunohistochemical staining identifying the laminin (Ln) γ2 chain specific for Ln-332, which is known to be a crucial molecule for the proper attachment of epithelium to tooth/implant surface. RESULTS: Tissue attachment to TiO2 -coated zirconia demonstrated higher dynamic modulus of elasticity and higher creep modulus, meaning that the attachment is stronger and more resistant to damage during function over time. Laminin γ2 was identified in the attachment of epithelium to TiO2 -coated zirconia. CONCLUSIONS: Both DMA and histological analysis support each other, so the gingival tissue is more strongly attached to sol-gel derived TiO2 -coated zirconia than uncoated zirconia. Immunohistochemical staining showed that TiO2 coating may enhance the synthesis and deposition of Ln-332 in the epithelial attachment to the implant surface.


Asunto(s)
Implantes Dentales , Animales , Encía , Propiedades de Superficie , Porcinos , Titanio , Circonio
19.
J Pharm Sci ; 108(11): 3684-3694, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31465736

RESUMEN

In this study, we developed an AS1411 aptamer/hyaluronic acid-bifunctionalized microemulsion co-loading shikonin and docetaxel (AS1411/SKN&DTX-M). Such microemulsion was capable of penetrating the blood-brain barrier (BBB), targeting CD44/nucleolin-overexpressed glioma, and inhibiting the orthotopic glioma growth. AS1411/SKN&DTX-M showed a spherical morphology with a diameter around 30 nm and rapidly released drugs in the presence of hyaluronidase and mild acid. In the U87 cellular studies, AS1411/SKN&DTX-M elevated the cytotoxicity, enhanced the cellular uptake, and induced the cell apoptosis. In the artificial blood-brain barrier model, the transepithelial electrical resistance was decreased after the treatment with AS1411/SKN&DTX-M and thereby of increasing the apparent permeability coefficient. Furthermore, AS1411/SKN&DTX-M showed a strong inhibition against the formation of cancer stem cell-enriched U87 cell spheroids, in which the expression of CD133 was downregulated significantly. In the biodistribution studies, AS1411/SKN&DTX-M could selectively accumulate in the brains of orthotopic luciferase-transfected U87 glioma tumor-bearing nude mice. Importantly, AS1411/SKN&DTX-M exhibited the overwhelming inhibition of glioma growth of orthotopic luciferase-transfected U87 glioma models and reached the longest survival period among all the treatments. In summary, the codelivery of shikonin and docetaxel using bifunctionalization with hyaluronic acid and AS1411 aptamer offers a promising strategy for dual drug-based combinational antiglioma treatment.


Asunto(s)
Antineoplásicos/química , Aptámeros de Nucleótidos/química , Docetaxel/química , Emulsiones/química , Ácido Hialurónico/química , Naftoquinonas/química , Oligodesoxirribonucleótidos/química , Animales , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Línea Celular , Línea Celular Tumoral , Docetaxel/farmacología , Sistemas de Liberación de Medicamentos/métodos , Glioma/tratamiento farmacológico , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Nanopartículas/química , Naftoquinonas/farmacología , Fosfoproteínas/metabolismo , Proteínas de Unión al ARN/metabolismo , Distribución Tisular , Nucleolina
20.
JDR Clin Trans Res ; 4(2): 104-105, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30931702
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