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1.
Int J Mol Sci ; 25(5)2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38474027

RESUMO

Candida spp. periprosthetic joint infections are rare but difficult-to-treat events, with a slow onset, unspecific symptoms or signs, and a significant relapse risk. Treatment with antifungals meets with little success, whereas prosthesis removal improves the outcome. In fact, Candida spp. adhere to orthopedic devices and grow forming biofilms that contribute to the persistence of this infection and relapse, and there is insufficient evidence that the use of antifungals has additional benefits for anti-biofilm activity. To date, studies on the direct antifungal activity of silver against Candida spp. are still scanty. Additionally, polycaprolactone (PCL), either pure or blended with calcium phosphate, could be a good candidate for the design of 3D scaffolds as engineered bone graft substitutes. Thus, the present research aimed to assess the antifungal and anti-biofilm activity of PCL-based constructs by the addition of antimicrobials, for instance, silver, against C. albicans and C. auris. The appearance of an inhibition halo around silver-functionalized PCL scaffolds for both C. albicans and C. auris was revealed, and a significant decrease in both adherent and planktonic yeasts further demonstrated the release of Ag+ from the 3D constructs. Due to the combined antifungal, osteoproliferative, and biodegradable properties, PCL-based 3D scaffolds enriched with silver showed good potential for bone tissue engineering and offer a promising strategy as an ideal anti-adhesive and anti-biofilm tool for the reduction in prosthetic joints of infections caused by Candida spp. by using antimicrobial molecule-targeted delivery.


Assuntos
Candida albicans , Candidíase , Poliésteres , Antifúngicos/farmacologia , Candida auris , Prata , Candida , Candidíase/microbiologia , Biofilmes , Fosfatos de Cálcio , Recidiva , Testes de Sensibilidade Microbiana
2.
J Biomed Mater Res B Appl Biomater ; 112(4): e35402, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38520704

RESUMO

There is an ever-evolving need of customized, anatomic-specific grafting materials for bone regeneration. More specifically, biocompatible and osteoconductive materials, that may be configured dynamically to fit and fill defects, through the application of an external stimulus. The objective of this study was to establish a basis for the development of direct inkjet writing (DIW)-based shape memory polymer-ceramic composites for bone tissue regeneration applications and to establish material behavior under thermomechanical loading. Polymer-ceramic (polylactic acid [PLA]/ß-tricalcium phosphate [ß-TCP]) colloidal gels were prepared of different w/w ratios (90/10, 80/20, 70/30, 60/40, and 50/50) through polymer dissolution in acetone (15% w/v). Cytocompatibility was analyzed through Presto Blue assays. Rheological properties of the colloidal gels were measured to determine shear-thinning capabilities. Gels were then extruded through a custom-built DIW printer. Space filling constructs of the gels were printed and subjected to thermomechanical characterization to measure shape fixity (Rf) and shape recovery (Rr) ratios through five successive shape memory cycles. The polymer-ceramic composite gels exhibited shear-thinning capabilities for extrusion through a nozzle for DIW. A significant increase in cellular viability was observed with the addition of ß-TCP particles within the polymer matrix relative to pure PLA. Shape memory effect in the printed constructs was repeatable up to 4 cycles followed by permanent deformation. While further research on scaffold macro-/micro-geometries, and engineered porosities are warranted, this proof-of-concept study suggested suitability of this polymer-ceramic material and the DIW 3D printing workflow for the production of customized, patient specific constructs for bone tissue engineering.


Assuntos
Fosfatos de Cálcio , Poliésteres , Engenharia Tecidual , Humanos , Poliésteres/farmacologia , Polímeros , Regeneração Óssea , Géis , Tecidos Suporte , Impressão Tridimensional
3.
Methods Mol Biol ; 2754: 551-560, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38512689

RESUMO

The study of Tau protein in disease-relevant neuronal cells in culture requires efficient delivery systems for transfection of exogenous Tau and also modulators and interactors of Tau. Transfection of cultivated cells using calcium phosphate precipitation is a simple and cost-effective approach, also for difficult-to-transfect and sensitive cells such as primary neurons. Because of its low cell toxicity and ease of use, the Ca2+-phosphate transfection method is one of the most widely used gene transfer procedures in neuroscience. However, Ca2+-phosphate transfection efficacy in neurons is poor, often in the range of 1-5%, limiting its use in functional investigations. Here, we outline our improved Ca2+-phosphate transfection methodology for human iPSC-derived neurons that yields a reasonable efficiency (20-30% for bright volume markers) without apparent effects on cell health. We have used it to introduce wild-type and mutant human Tau with and without co-transfection of a volume marker (used here: tdTomato). In sum, our procedure can deliver neuronal genes (e.g., MAPT) using typical eukaryotic expression vectors (e.g., using CMV promoter) and is optimized for transfection of human iPSC-derived neurons.


Assuntos
Células-Tronco Pluripotentes Induzidas , Proteínas tau , Humanos , Proteínas tau/genética , Proteínas tau/metabolismo , Cálcio/metabolismo , Transfecção , Fosfatos de Cálcio , Fosfatos/metabolismo , Neurônios/metabolismo
4.
J Dent ; 143: 104906, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38428715

RESUMO

OBJECTIVE: Remineralising composites with antibacterial properties may seal the cavity and prevent secondary caries. This study aimed at developing experimental flowable composites containing different concentrations of fluoride-doped calcium phosphate fillers and evaluating their remineralising and antibacterial properties. METHODS: Experimental resin-based composites containing different concentrations (0-20 %) of fluoride-doped calcium phosphate fillers (VS10/VS20) were formulated. The release of calcium (Ca), phosphate (PO) and fluoride (F) ions was assessed for 30 days. Remineralisation properties were evaluated through ATR-FTIR and SEM/EDX after storage in simulated body fluid (SBF). The metabolic activity and viability of Streptococcus gordonii was also evaluated through ATP, CFU and live/dead confocal microscopy. The evaluation of specific monomer elution from the experimental composites was conducted using high-performance liquid chromatography (HPLC). RESULTS: The composites containing VS10 showed the highest release of Ca, those containing VS20 released more F over time (p < 0.05), while there was no significant difference in terms of PO ions release between the groups (p > 0.05). A quick 7-day mineral precipitation was observed in the tested composites containing VS10 or VS20 at 10 %; these materials also showed the greatest antibacterial activity (p < 0.05). Moreover, the tested composites containing VS10 presented the lowest elution of monomers (p < 0.05). CONCLUSIONS: Innovative composites were developed with low monomers elution, evident antibacterial activity against S. gordonii and important remineralisation properties due to specific ions release. CLINICAL SIGNIFICANCE: Novel composites containing fluoride-doped calcium phosphates may be promising to modulate bacteria growth, promote remineralisation and reduce the risk of cytotoxicity related to monomers' elution.


Assuntos
Fluoretos , Fosfatos , Fosfatos/farmacologia , Fosfatos/química , Fluoretos/farmacologia , Fluoretos/química , Teste de Materiais , Resinas Compostas/farmacologia , Resinas Compostas/química , Fosfatos de Cálcio/farmacologia , Fosfatos de Cálcio/química , Fluoreto de Cálcio , Antibacterianos/farmacologia
5.
J Dent ; 143: 104909, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38428717

RESUMO

OBJECTIVES: This in vitro study aimed to evaluate the effect of resin infiltration combined with casein phosphopeptide-amorphous calcium phosphate with fluoride (CPP-ACPF) or bioactive glass (BAG) on the stability of enamel white spot lesions (WSLs) treatment. MATERIALS AND METHODS: Eighty-four enamel blocks were prepared from the buccal surfaces of sound human premolars. All enamel blocks were placed in a demineralisation solution for 3 days to establish the artificial enamel WSLs. Enamel blocks with WSLs were randomly divided into three groups (n = 28 each group): RI/B: one-off resin infiltration followed by twice daily BAG treatment; RI/C: one-off resin infiltration followed by twice daily CPP-ACPF treatment; RI: one-off resin infiltration treatment only (as control) and subjected to pH cycling for 7 days. Surface morphology, elemental analysis, crystal characteristics, surface roughness and microhardness of enamel surfaces were investigated by scanning electron microscopy and energy-dispersive spectrometry observation, X-ray diffraction (XRD), atomic force microscope and Vickers' hardness testing, respectively. RESULTS: Mean values of the surface roughness (mean±standard deviation (nm)) were 24.52±5.07, 27.39±5.87 and 34.36±4.55 for groups RI/B, RI/C and RI respectively (p = 0.003). The calcium to phosphate ratios were 1.32±0.16, 1.22±0.26 and 0.69±0.24 for groups RI/B, RI/C and RI respectively (p < 0.001). XRD revealed apatite formation in all three groups. The mean enamel surface microhardness (kg/mm2) of the groups were 353.93±28.49, 339.00±27.32 and 330.38±22.55 for groups RI/B, RI/C and RI respectively (p = 0.216). CONCLUSIONS: Resin infiltration combined with CPP-ACPF or BAG remineralisation appears to improve the surface properties of WSLs. CLINICAL SIGNIFICANCE: The combination of resin infiltration and CPP-ACPF/BAG remineralisation may be a potential treatment for the management of the WSLs.


Assuntos
Cárie Dentária , Esmalte Dentário , Humanos , Esmalte Dentário/patologia , Fluoretos/farmacologia , Fluoretos/uso terapêutico , Fluoretos/análise , Fosfatos de Cálcio/farmacologia , Fosfatos de Cálcio/uso terapêutico , Cárie Dentária/patologia
6.
Sci Rep ; 14(1): 6660, 2024 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-38509314

RESUMO

The aim of this preliminary study was to assess the impact of injecting recombinant human bone morphogenetic protein-2 (rhBMP-2) with ß-tricalcium phosphate (ß-TCP) carrier into the uppermost instrumented vertebra (UIV) during surgery to prevent the development of proximal junctional kyphosis (PJK) and proximal junctional failure (PJF). The 25 patients from study group had received 0.5 mg rhBMP-2 mixed with 1.5 g ß-TCP paste injection into the UIV during surgery. The control group consisted of 75 patients who underwent surgery immediately before the start of the study. The incidences of PJK and PJF were analyzed as primary outcomes. Spinopelvic parameters and patient-reported outcomes were analyzed as secondary outcomes. Hounsfield unit (HU) measurements were performed to confirm the effect of rhBMP-2 with ß-TCP on bone formation at preoperative and postoperative at computed tomography. PJK and PJF was more occurred in control group than study group (p = 0.02, 0.29, respectively). The HU of the UIV significantly increased 6 months after surgery. And the increment at the UIV was also significantly greater than that at the UIV-1 6 months after surgery. Injection of rhBMP-2 with ß-TCP into the UIV reduced PJK and PJF rates 6 months after surgery with new bone formation.


Assuntos
Proteína Morfogenética Óssea 2 , Fosfatos de Cálcio , Cifose , Proteínas Recombinantes , Fusão Vertebral , Fator de Crescimento Transformador beta , Adulto , Humanos , Estudos Retrospectivos , Complicações Pós-Operatórias/etiologia , Cifose/etiologia , Fusão Vertebral/métodos
7.
Nan Fang Yi Ke Da Xue Xue Bao ; 44(2): 370-380, 2024 Feb 20.
Artigo em Chinês | MEDLINE | ID: mdl-38501423

RESUMO

OBJECTIVE: To investigate the release kinetics of Zn2+ from nZCP-loaded polylactic acid/hydroxyapatite (PLA/HA) composite scaffold (PHZ) and determine the optimal nZCP content in the scaffold. METHODS: The particle size of nZCP was measured by DLS measurement, and PXRD, FTIR, and SEM were used to characterize the scaffolds and nZCP distribution; EDS was used to analyze element composition of the scaffold. Compression strength of the scaffold was determined, and ion release profile was investigated using ICP-MS. The biocompatibility of the materials was evaluated by CCK-8 assay and dead/alive staining of rat bone marrow stem cells (BMSCs) incubated with their aqueous extracts. ALP staining, alizarin red staining, RT-qPCR, and Western blotting were used to assess the osteogenic potential of the treated cells. In a rat model of bilateral ovariectomy (OVX) with femoral condylar bone defect, PHZ-1, PHZ-2, PHZ-3 or PLA/HA scaffold was implanted into the bone defect, and bone repair was observed using a microCT scanner and histological staining at 6 and 12 weeks. RESULTS: DLS, PXRD, SEM, FTIR, and EDS confirmed successful synthesis of 10-nm ZCP and efficient nZCP loading in the scaffold. PHZ-2 and PHZ-3 had significantly greater compression strength than PLA/HA. ICP-MS showed that Zn2+ release from PHZ-1, PHZ-2 and PHZ-3 were all optimal for promoting osteogenesis. In rat BMSCs, all the 4 scaffolds showed good biocompatibility, and their extracts enhanced ALP activity and extracellular matrix mineralization and promoted expressions of ALP, RUNX2, and OCN in the cells. In the rat models, nZCP in the implants improved bone graft integration at 6 weeks, and PHZ-2 and PHZ-3 more effectively induced new bone formation at 12 weeks (P < 0.05). CONCLUSION: PHZ scaffold is capable of stable Zn2+ release to promote osteoporotic bone defect healing, and PHZ-2 and PHZ-3 scaffolds with nZCP mass fraction of 4.5%-7.5% have better osteogenic activity.


Assuntos
Fosfatos de Cálcio , Durapatita , Minerais , Osteoporose , Feminino , Ratos , Animais , Durapatita/farmacologia , Tecidos Suporte , Diferenciação Celular , Osteogênese , Poliésteres/farmacologia , Regeneração Óssea
8.
Clin Exp Dent Res ; 10(2): e876, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38506322

RESUMO

OBJECTIVES: This study evaluated the remineralization potential of calcium sodium phosphosilicate and functionalized tri-calcium phosphate (f-TCP) dentifrices in deeper incipient carious lesions (ICLs). MATERIALS AND METHODS: Artificial ICLs were created by placing premolars into demineralizing solutions. Teeth were randomly assigned into four groups: calcium sodium phosphosilicate (Group 1), f-TCP (Group 2), 1450 ppm fluoride (Group 3), and distilled water (Group 4), which were subjected to 10-day pH cycling. Mineral density (MD) was assessed using microcomputed tomography (Micro-CT), while hardness (H) and elastic modulus (EM) were assessed using nanomechanical testing. RESULTS: MD % gain was higher in Groups 1-3 than in Group 4. In addition, Groups 1 and 2 exhibited significantly higher MD % gain than Group 3. Also, Groups 1-3 showed significantly higher EM and H values than Group 4 in the outer enamel area; yet, Groups 1 and 2 displayed significantly higher EM and H values than Groups 3 and 4 in the inner enamel. CONCLUSIONS: The MD, EM, and H of ICLs significantly increased with the addition of calcium sodium phosphosilicate or f-TCP to fluoridated dentifrices compared to standard fluoride dentifrices. The added active ingredients remineralized the deeper parts of the ICLs, while remineralization at the lesion surface was similar between tested dentifrices.


Assuntos
Cárie Dentária , Dentifrícios , Compostos de Flúor , Humanos , Fluoretos , Cariostáticos , Dentifrícios/farmacologia , Cálcio , Microtomografia por Raio-X , Fosfatos de Cálcio , Minerais , Sódio
9.
J Mater Sci Mater Med ; 35(1): 17, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38507150

RESUMO

3D borosilicate bioactive glass (1393B20 and B12.5MgSr) scaffolds were prepared by robocasting, with and without a dense layer at the top. Pore graded scaffolds are promising as they allow for membrane deposition and could limit the risk of soft tissue infiltration. In vitro dissolution was studied in tris(hydroxymethyl)aminomethane (TRIS) and Simulated Body Fluid (SBF). 1393B20 scaffolds dissolved faster than B12.5MgSr in TRIS whereas they dissolved slower in SBF. The difference in dissolution profiles, as a function of the medium used, is assigned to the different rates of precipitation of hydroxyapatite (HA). While the precipitation of calcium phosphate (CaP) in the form of HA, first sign of bioactivity, was confirmed by ICP, FTIR-ATR and SEM-EDX analysis for both compositions, 1393B20 was found to precipitate HA at a faster rate. The presence of a dense top layer did not significantly impact the dissolution rate and CaP precipitation. In vitro cell culture was performed using human adipose-derived stem cells (hADSCs). Prior to cell plating, a preincubation of 3 days was found optimum to prevent burst ion release. In direct contact, cells proliferate and spread on the scaffolds while maintaining characteristic spindle morphology. Cell plated on 1393B20 scaffolds showed increased viability when compared to cell plated on B12.5MgSr. The lower cell viability, when testing B12.5MgSr, was assigned to the depletion of Ca2+ ions from culture medium and higher pH. Static cell culture leads to believe that the scaffold produced from the 1393B20 glass composition are promising in bone regeneration applications.


Assuntos
Vidro , Tecidos Suporte , Humanos , Vidro/química , Tecidos Suporte/química , Durapatita/química , Fosfatos de Cálcio/química
10.
Int J Nanomedicine ; 19: 2709-2732, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38510794

RESUMO

Purpose: Given the escalating prevalence of diabetes, the demand for specific bone graft materials is increasing, owing to the greater tendency towards bone defects and more difficult defect repair resulting from diabetic bone disease (DBD). Melatonin (MT), which is known for its potent antioxidant properties, has been shown to stimulate both osteogenesis and angiogenesis. Methods: MT was formulated into MT@PLGA nanoparticles (NPs), mixed with sodium alginate (SA) hydrogel, and contained within a 3D printing polycaprolactone/ß-Tricalcium phosphate (PCL/ß-TCP) scaffold. The osteogenic capacity of the MT nanocomposite scaffold under diabetic conditions was demonstrated via in vitro and in vivo studies and the underlying mechanisms were investigated. Results: Physicochemical characterization experiments confirmed the successful fabrication of the MT nanocomposite scaffold, which can achieve long-lasting sustained release of MT. The in vitro and in vivo studies demonstrated that the MT nanocomposite scaffold exhibited enhanced osteogenic capacity, which was elucidated by the dual angiogenesis effects activated through the NF-E2-related factor 2/Heme oxygenase 1 (Nrf2/HO-1) signaling pathway, including the enhancement of antioxidant enzyme activity to reduce the oxidative stress damage of vascular endothelial cells (VECs) and directly stimulating vascular endothelial growth factor (VEGF) production, which reversed the angiogenesis-osteogenesis uncoupling and promoted osteogenesis under diabetic conditions. Conclusion: This study demonstrated the research prospective and clinical implications of the MT nanocomposite scaffold as a novel bone graft for treating bone defect and enhancing bone fusion in diabetic individuals.


Assuntos
Fosfatos de Cálcio , Diabetes Mellitus , Melatonina , Nanocompostos , Humanos , Tecidos Suporte/química , Melatonina/farmacologia , Fator 2 Relacionado a NF-E2 , Células Endoteliais , Antioxidantes/farmacologia , Fator A de Crescimento do Endotélio Vascular/farmacologia , Heme Oxigenase-1 , Indutores da Angiogênese/farmacologia , Estudos Prospectivos , Osteogênese , Transdução de Sinais , Regeneração Óssea
11.
Poult Sci ; 103(4): 103558, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38442559

RESUMO

Iron is routinely supplemented in broiler feeds aiming to prevent dietary deficiencies. Limestone and phosphates are very rich in Fe; however, its contribution from these sources have not been thoroughly investigated with chickens. The present research was conducted to evaluate live performance and blood parameters of broilers when using limestone and dicalcium phosphate as sources of Fe. A total of 576 one-day-old male Cobb x Cobb 500 were allocated into a total of 72 battery cages, 6 treatments with 12 replication cages of 8 chicks at placement. Chicks were fed diets formulated with corn, soybean meal (SBM) with laboratory grade calcium carbonate and phosphoric acid (having traces of Fe). All chicks were fed a common prestarter without Fe supplementation (analyzed total 58.2 ± 2.4 mg/kg Fe) from placement to 7 d. Allocation of birds to dietary treatments was completely randomized on day 8. Treatments had increasing Fe derived from commercial limestone and dicalcium phosphate (analyzed Fe 7,218 and 4,783 mg/kg, respectively) progressively replacing calcium carbonate and phosphoric acid to provide graded increases in total Fe (analyzed Fe in the feeds were 57.6 ± 2.1, 92.0 ± 2.3, 124.1 ± 2.7, 159.3 ± 3.1, 187.2 ± 3.2, 223.7 ± 3.6 mg/kg, respectively). There were no effects of dietary Fe on live performance, hematocrit, and hemoglobin the end of the study on day 28 (P > 0.05). Increasing dietary Fe from commercial limestone and dicalcium phosphate led to a linear reduction in the percent ileal digestible Fe. However, linear increments in Fe retention, serum ferritin and liver Fe occurred when compared to feeds without Fe derived from limestone and phosphate dicalcium. It is concluded that Fe from limestone and dicalcium phosphate can be partially utilized by broiler chickens. It was estimated that the Fe retained from limestone and dicalcium phosphate is of 1.9%. Broilers fed corn-soy feeds (58.2 mg/kg Fe) do not require supplemental Fe.


Assuntos
Carbonato de Cálcio , Fosfatos de Cálcio , Galinhas , Ácidos Fosfóricos , Animais , Masculino , Ferro , Dieta/veterinária , Suplementos Nutricionais , Fosfatos , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Digestão
12.
Iran Biomed J ; 28(1): 38-45, 2024 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-38477251

RESUMO

Background: The surface properties of dental and orthopedic implants are directly related to their osseointegration rate. Coating and/or modifying the implant surface might reduce the time of healing. In this study, we aimed to examine the effects of a hybrid surface consisting of a brushite surface coating and cross-linked water-soluble eggshell membrane protein on the osseointegration of titanium (Ti) screws under in vivo conditions. Methods: Twenty Ti alloy screws were implanted monocortically in anteromedial regions of New Zealand rabbit tibiae. Ten screws were untreated and used as controls. The remaining 10 screws were coated with calcium phosphate and following cross-linked with ostrich eggshell membrane protein. All rabbits were sacrificed six weeks after the surgery. Peri-screw tissues were evaluated by micro-computed tomography (µ-CT), histological and histomorphometrical methods. Results: The µ-CT assessments indicated that the experimental group had significantly higher mean bone surface area (BSA) and trabeculae number (TbN) than those of the control group (p ˂ 0.05). Bone surface area (BV), trabecular separation (TbSp), trabecular thickness (TbTh), and bone mineral density (BMD) scores of the control and experimental groups were quite similar (p > 0.05). The vascularization score of the experimental group was significantly higher than the control group (4.29 vs. 0.92%). No sign of the graft-versus-host reaction was observed. Conclusion: Our findings reveal that coating Ti alloy implants with calcium phosphate cross-linked with ostrich eggshell membrane protein increases the osseointegration of Ti alloy screws by increasing the bone surface area, number of trabeculae and vascularization in the implant site.


Assuntos
Osseointegração , Titânio , Coelhos , Animais , Titânio/farmacologia , Água , Ligas/farmacologia , Microtomografia por Raio-X , Casca de Ovo , Materiais Revestidos Biocompatíveis/farmacologia , Fosfatos de Cálcio/farmacologia , Proteínas de Membrana , Propriedades de Superfície
13.
J Biomed Mater Res B Appl Biomater ; 112(3): e35397, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38456309

RESUMO

In this study, we have formulated a novel apatite bone cements derived from natural sources (i.e. eggshell and fishbone) with improved qualities that is, porosity, resorbability, biological activity, and so forth. The naturally-derived apatite bone cement (i.e. FBDEAp) was prepared by mixing hydroxyapatite (synthesized from fishbone) and tricalcium phosphate (synthesized from eggshell) as a solid phase with a liquid phase (a dilute acidic blend of cement binding accelerator and biopolymers like gelatin and chitosan) with polysorbate (as liquid porogen) to get a desired bone cement paste. The prepared cement paste sets within the clinically acceptable setting time (≤20 min), easily injectable (>85%) through hands and exhibits physiological pH stability (7.3-7.4). The pure apatite phased bone cement was confirmed by x-ray diffraction and Fourier transform infrared spectroscopy analyses. The FBDEAp bone cement possesses acceptable compressive strength (i.e. 5-7 MPa) within trabecular bone range and is resorbable up to 28% in simulated body fluid solution within 12 weeks of incubation at physiological conditions. The FBDEAp is macroporous in nature (average pore size ~50-400 µm) with interconnected pores verified by SEM and micro-CT analyses. The FBDEAp showed significantly increased MG63 cell viability (>125% after 72 h), cell adhesion, proliferation, and key osteogenic genes expression levels (up to 5-13 folds) compared to the synthetically derived, synthetic and eggshell derived as well as synthetic and fishbone derived bone cements. Thus, we strongly believe that our prepared FBDEAp bone cement can be used as potential trabecular bone substitute in orthopedics.


Assuntos
Substitutos Ósseos , Quitosana , Apatitas/farmacologia , Apatitas/química , Substitutos Ósseos/química , Cimentos Ósseos/farmacologia , Cimentos Ósseos/química , Fosfatos de Cálcio/química , Durapatita , Quitosana/farmacologia , Quitosana/química , Difração de Raios X , Força Compressiva
14.
J Mech Behav Biomed Mater ; 152: 106455, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38335647

RESUMO

Electrospun fibres have emerged as vital components in developing tissue engineering scaffolds. Calcium phosphate-based materials, renowned for their bioactivity and biocompatibility, have garnered considerable attention in biomedical applications. This study focuses on the incorporation of amorphous calcium phosphate (ACP) nanoparticles into poly(L-lactic acid) (PLLA) to produce electrospun PLLA/ACP fibrous membranes. Subsequent treatment with acetone yielded a hierarchical porous structure, boasting an ultra-high surface area of 94.7753 ± 0.3884 m2/g. The ACP nanoparticles, initially encapsulated by PLLA, were exposed on the fibre surface after acetone treatment. Furthermore, the porous PLLA/ACP fibrous membrane exhibited superior mechanical properties (Young's modulus = 0.148 GPa, tensile strength = 3.05 MPa) and enhanced wettability. In a 7-day in vitro cell culture with human osteoblast-like cells, the porous PLLA/ACP fibrous membrane demonstrated a significant improvement in osteoblast adhesion and proliferation, with a proliferation rate increase of 252.0% and 298.7% at day 4 and day 7, respectively. These findings underscore the potential of the porous PLLA/ACP fibrous membrane as a promising candidate for bone tissue scaffolds.


Assuntos
Acetona , Tecidos Suporte , Humanos , Porosidade , Fosfatos de Cálcio
15.
Biomater Adv ; 158: 213795, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38335762

RESUMO

The grand discovery of morphogens, or "form-generating substances", revealed that tissue morphogenesis is initiated by soluble molecular signals or morphogens primarily belonging to the transforming growth factor-ß (TGF-ß) supergene family. The regenerative potential of bone rests on its extracellular matrix, which is the repository of several morphogens that tightly control cellular differentiating pathways, cellular matrix deposition and remodeling. Alluringly, the matrix also contains specific factors transferred from the heterotopic implanted bone matrices initiating "Tissue Induction", as provocatively described in Nature in 1945. Later, it was found that selected genes and gene products of the TGF-ß supergene family singly, synchronously, and synergistically mastermind the induction of bone formation. This review describes the phenomenon of the spontaneous and/or intrinsic osteoinductivity of calcium phosphate-based biomaterials and titanium' constructs without the applications of soluble osteogenetic molecular signals. The review shows the spontaneous induction of bone formation initiated by Ca++ activating stem cell differentiation and up-regulation of bone morphogenetic proteins genes. Expressed gene products are embedded into the concavities of the calcium phosphate-based substrata, initiating bone formation as a secondary response. Pure titanium's substrata do not initiate the spontaneous induction of bone formation. The induction of bone is solely dependent on acid, alkali and heat treatments to form apatite layers on the treated titanium surfaces. The induction of bone formation is achieved exclusively by apatite-based biomaterial surfaces. The hydroxyapatite, in its various forms and geometric configurations, finely tunes the induction of bone formation in heterotopic sites. Cellular differentiation by fine-tuning of the cellular molecular machinery is initiated by specific geometric modularity of the hydroxyapatite substrata that push cellular buttons that start the ripple-like cascade of "Tissue Induction", generating newly formed ossicles with bone marrow in heterotopic extraskeletal sites. The highlighted mechanistic insights into the spontaneous induction of bone formation are a research platform invocating selected molecular elements to construct the induction of bone formation.


Assuntos
Fosfatos de Cálcio , Osteogênese , Titânio , Osteogênese/genética , Apatitas , Materiais Biocompatíveis , Durapatita , Fator de Crescimento Transformador beta
16.
ACS Appl Mater Interfaces ; 16(8): 10601-10622, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38376231

RESUMO

Stainless steel (316L SS) has been widely used in orthopedic, cardiovascular stents, and other biomedical implant applications due to its strength, corrosion resistance, and biocompatibility. To address the weak interaction between steel implants and tissues, it is a widely adopted strategy to enhance implant performance through the application of bioactive coatings. In this study, Cu-doped brushite coatings were deposited successfully through pulse electrodeposition on steel substrates facilitated with a biosurfactant (BS) (i.e., surfactin). Further, the combined effect of various concentrations of Cu ions and BS on the structural, electrochemical, and biological properties was studied. The X-ray diffraction (XRD) confirms brushite composition with Cu substitution causing lattice contraction and a reduced crystallite size. The scanning electron microscopy (SEM) and energy-dispersive spectroscopy (EDS) studies reveal the morphological changes of the coatings with the incorporation of Cu, which is confirmed by X-ray photoelectron spectroscopy (XPS) and elemental mapping. The Fourier transform infrared (FTIR) and Raman spectroscopy confirm the brushite and Cu doping in the coatings, respectively. Increased surface roughness and mechanical properties of Cu-doped coatings were analyzed by using atomic force microscopic (AFM) and nanohardness tests, respectively. Electrochemical assessments demonstrate corrosion resistance enhancement in Cu-doped coatings, which is further improved with the addition of biosurfactants. In vitro biomineralization studies show the Cu-doped coating's potential for osseointegration, with added stability. The cytocompatibility of the coatings was analyzed using live/dead and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assays; cell adhesion, proliferation, and migration studies were evaluated using SEM. Antibacterial assays highlight significant improvement in the antibacterial properties of Cu-doped coatings with BS. Thus, the developed Cu-doped brushite coatings with BS demonstrate their potential in the realm of biomedical implant technologies, paving the way for further exploration.


Assuntos
Fosfatos de Cálcio , Aço Inoxidável , Fosfatos de Cálcio/química , Aço Inoxidável/química , Antibacterianos/química , Corrosão , Stents , Materiais Revestidos Biocompatíveis/farmacologia , Materiais Revestidos Biocompatíveis/química
17.
BMC Oral Health ; 24(1): 279, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38413983

RESUMO

BACKGROUND: Several methods were introduced for enamel biomimetic remineralization that utilize a biomimetic analogue to interact and absorb bioavailable calcium and phosphate ions and induce crystal nucleation on demineralized enamel. Amelogenin is the most predominant enamel matrix protein that is involved in enamel biomineralization. It plays a major role in developing the enamel's hierarchical microstructure. Therefore, this study was conducted to evaluate the ability of an amelogenin-inspired peptide to promote the remineralization potential of fluoride and a supersaturated calcium phosphate solution in treating artificially induced enamel carious lesions under pH-cycling regimen. METHODS: Fifty enamel slices were prepared with a window (4*4 mm2 ) on the surface. Five samples were set as control healthy enamel and 45 samples were subjected to demineralization for 3 days. Another 5 samples were set as control demineralized enamel and 40 enamel samples were assigned into 8 experimental groups (n=5) (P/I, P/II, P/III, P/AS, NP/I, NP/II, NP/III and NP/AS) according to peptide treatment (peptide P or non-peptide NP) and remineralizing solution used (I; calcium phosphate solution, II; calcium phosphate fluoride solution, III; fluoride solution and AS; artificial saliva). Samples were then subjected to demineralization/remineralization cycles for 9 days. Samples in all experimental groups were evaluated using Raman spectroscopy for mineral content recovery percentage, microhardness and nanoindentation as healthy, demineralized enamel and after pH-cycling. Data were statistically analysed using two-way repeated measures Anova followed by Bonferroni-corrected post hoc test for pairwise multiple comparisons between groups. Statistical significance was set at p= 0.05. Additionally, XRD, FESEM and EDXS were used for crystal orientation, surface morphology and elemental analysis after pH-cycling. RESULTS: Nanocrystals clumped in a directional manner were detected in peptide-treated groups. P/II showed the highest significant mean values in mineral content recovery (63.31%), microhardness (268.81±6.52 VHN), elastic modulus (88.74±2.71 GPa), nanohardness (3.08±0.59 GPa) and the best crystal orientation with I002/I300 (1.87±0.08). CONCLUSION: Despite pH changes, the tested peptide was capable of remineralizing enamel with ordered crystals. Moreover, the supplementary use of calcium phosphate fluoride solution with peptide granted an enhancement in enamel mechanical properties after remineralization.


Assuntos
Cárie Dentária , Fluoretos , Humanos , Fluoretos/farmacologia , Amelogenina/farmacologia , Amelogenina/uso terapêutico , Cariostáticos/farmacologia , Cariostáticos/uso terapêutico , Biomimética , Fosfatos de Cálcio/farmacologia , Fosfatos de Cálcio/uso terapêutico , Minerais , Fosfatos , Remineralização Dentária/métodos , Concentração de Íons de Hidrogênio
18.
Int J Nanomedicine ; 19: 993-1016, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38299194

RESUMO

Background: The M1/M2 polarization of intestinal macrophages exerts an essential function in the pathogenesis of ulcerative colitis (UC), which can be adjusted to alleviate the UC symptoms. Purpose: A kind of pH-sensitive lipid calcium phosphate core-shell nanoparticles (NPs), co-loading with dexamethasone (Dex) and its water-soluble salts, dexamethasone sodium phosphate (Dsp), was constructed to comprehensively regulate macrophages in different states towards the M2 phenotype to promote anti-inflammatory effects. Methods: Dex and Dsp were loaded in the outer lipid shell and inner lipid calcium phosphate (Cap) core of the LdCaPd NPs, respectively. Then, the morphology of NPs and methods for determining drug concentration were investigated, followed by in vitro protein adsorption, stability, and release tests. Cell experiments evaluated the cytotoxicity, cellular uptake, and macrophage polarization induction ability of NPs. The in vivo distribution and anti-inflammatory effect of NPs were evaluated through a 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced BALB/c mice ulcerative colitis model. Results: The LdCaPd NPs showed a particle size of about 200 nm and achieved considerable loading amounts of Dex and Dsp. The in vitro and in vivo studies revealed that in the acidic UC microenvironment, the cationic lipid shell of LdCaPd underwent protonated dissociation to release Dex first for creating a microenvironment conducive to M2 polarization. Then, the exposed CaP core was further engulfed by M1 macrophages to release Dsp to restrict the pro-inflammatory cytokines production by inhibiting the activation and function of the nuclear factor kappa-B (NF-κB) through activating the GC receptor and the NF kappa B inhibitor α (I-κBα), respectively, ultimately reversing the M1 polarization to promote the anti-inflammatory therapy. Conclusion: The LdCaPd NPs accomplished the sequential release of Dex and Dsp to the UC site and the inflammatory M1 macrophages at this site, promoting the regulation of macrophage polarization to accelerate the remission of UC symptoms.


Assuntos
Colite Ulcerativa , Colite , Nanopartículas , Camundongos , Animais , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/patologia , Colite/induzido quimicamente , Colite/tratamento farmacológico , Macrófagos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Dexametasona/farmacologia , Dexametasona/uso terapêutico , Fosfatos de Cálcio/farmacologia , Lipídeos/efeitos adversos
19.
Sci Rep ; 14(1): 2804, 2024 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-38307930

RESUMO

This work aimed at tailoring of different properties of antibacterial drug delivery Ca-phosphate cements by incorporation of bioactive glass (BG). The cements were prepared from beta-tricalcium phosphate cement (ß-TCP) and BG based on 50 SiO2-20 CaO-15 Na2O-7 B2O3-4 P2O5-4 Al2O3 wt% with different percentages of BG [5, 10, 15, and 20% (w/w)]. The composite cements were characterized by XRD, FTIR, and TEM. Moreover, in vitro bioactivity and biodegradation were evaluated in the simulated body fluid (SBF) at 37 °C. In addition, physical properties and mechanical strength were determined. Also, the effect of glass addition on the drug release profile was examined using gentamicin. Finally, the antimicrobial activity was studied against Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella pneumonia bacteria, one unicellular fungal strain (Candida albicans), and one multicellular fungal strain (Mucor racemosus). The results showed that after soaking in SBF, the compression strength values ranged from 14 to 36 MPa, the bulk densities and porosities were within 1.35 to 1.49 g/cm3 and 51.3 to 44.71%, respectively. Furthermore, gentamicin was released in a sustained manner, and BG decreased the released drug amount from ~ 80% (in pure ß-TCP) to 47-53% in the composite cements. A drug release profile that is sustained by all samples was achieved. The antimicrobial test showed good activity of gentamicin-conjugated cements against bacteria and fungi used in this study. Additionally, cytotoxicity results proved that all samples were safe on MG-63 cells up to 50 µg/mL with no more than 7-12% dead cells. From the view of the physico-mechanical properties, bioactivity, biodegradation, and drug release rate, 20BG/ß-TCP sample was nominated for practical bone grafting material, where it showed appropriate setting time and a relatively high mechanical strength suitable for cancellous bone.


Assuntos
Antibacterianos , Cimentos Ósseos , Cimentos Ósseos/farmacologia , Antibacterianos/farmacologia , Dióxido de Silício , Fosfatos de Cálcio , Vidro , Gentamicinas/farmacologia , Teste de Materiais
20.
J Biomed Mater Res B Appl Biomater ; 112(2): e35388, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38334714

RESUMO

The trace element strontium (Sr) enhances new bone formation. However, delivering Sr, like other materials, in a sustained manner from a ceramic bone graft substitute (BGS) is difficult. We developed a novel ceramic BGS, polyphosphate dicalcium phosphate dehydrate (P-DCPD), which delivers embedded drugs in a sustained pattern. This study assessed the in vitro and in vivo performance of Sr-doped P-DCPD. In vitro P-DCPD and 10%Sr-P-DCPD were nontoxic and eluents from 10%Sr-P-DCPD significantly enhanced osteoblastic MC3T3 cell differentiation. A sustained, zero-order Sr release was observed from 10%Sr-P-DCPD for up to 70 days. When using this BGS in a rat calvaria defect model, both P-DCPD and 10% Sr-P-DCPD were found to be biocompatible and biodegradable. Histologic data from decalcified and undecalcified tissue showed that 10%Sr-P-DCPD had more extensive new bone formation compared with P-DCPD 12-weeks after surgery and the 10%Sr-P-DCPD had more organized new bone and much less fibrous tissue at the defect margins. The new bone was formed on the surface of the degraded ceramic debris within the bone defect area. P-DCPD represented a promising drug-eluting BGS for repair of critical bone defects.


Assuntos
Substitutos Ósseos , Fosfatos de Cálcio , Fosfatos , Polifosfatos , Ratos , Animais , Polifosfatos/farmacologia , Substitutos Ósseos/farmacologia , Estrôncio/farmacologia , Cerâmica/farmacologia , Crânio
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