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1.
Head Face Med ; 15(1): 27, 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31711509

RESUMO

BACKGROUND: Controlled release of proteins bound to conventional bone substitutes is still insufficient. Therefore, this study evaluates in-vitro release kinetics of the model protein FITC-BSA (fluorescein conjugated bovine serum albumine) from insoluble bovine collagenous bone matrices (ICBM) with different polymer coatings. Analyzes aim at comparing FITC-BSA release from uncoated versus coated ICBM over time to find bone substitute coatings with consistent release profiles. METHODS: Release kinetics of FITC-BSA from uncoated as well as coated ICBM with five different polymers (RESOMER R 203 H, RG 503 H, RG 504 H, RG 505, L 206 S) were measured over a period of 11 days (d). Measurements were conducted after 6 h (h), 12 h, 24 h, 3 d, 5 d, 7 d, 9 d and 11 d with six samples for each coated ICBM. Two groups were formed (1) with and (2) without medium change at times of measurement. For each group ANOVA with post-hoc Bonferroni testing was used. Scanning electron microscopy assessed morphologic differences between ICBM coating. RESULTS: In group 1 approx. 70% of FITC-BSA release from uncoated ICBM occurred after 6 h compared to approx. 50% in group 2. Only polymers with medium inherent viscosity, i.e. RESOMER RG 503 H, constantly showed significantly more FITC-BSA release throughout 11 d than uncoated ICBM (p = 0.007). The same was found for group 2 (p = 0.005). No significant differences between PLA and PLGA polymers were found. Scanning electron microscopy results indicate a weak adhesion of polymer coatings to ICBM explaining its rather weak retentive effect on overall FITC-BSA release. CONCLUSIONS: Medium molecular size polymers reduce the overall released FITC-BSA from ICBM over time. In clinical practice these polymers may prove ideal for bone substitute materials.


Assuntos
Substitutos Ósseos , Fluoresceína-5-Isotiocianato/análogos & derivados , Polímeros , Soroalbumina Bovina , Animais , Substitutos Ósseos/farmacocinética , Bovinos , Fluoresceína-5-Isotiocianato/farmacocinética , Cinética , Microscopia Eletrônica de Varredura , Soroalbumina Bovina/farmacocinética
2.
Rev. esp. cir. oral maxilofac ; 41(3): 126-137, jul.-sept. 2019. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-191776

RESUMO

OBJETIVO: El propósito de esta revisión fue evaluar sistemáticamente la literatura científica sobre los resultados que se obtienen al combinar la fibrina rica en plaquetas (PRF) y rellenos óseos en la regeneración ósea guiada. MATERIALES Y MÉTODOS: Búsqueda detallada en las bases de datos PubMed, Scopus, Web of Science, ScienceDirect, Cochrane y SciELO para obtener la información más actualizada de los resultados (grado de relleno óseo, éxito de la cirugía, movilidad del implante, complicaciones posquirúrgicas, supervivencia del implante) entre los casos tratados con PRF y los casos donde se combinó PRF con algún tipo de relleno óseo. RESULTADOS: De las 965 publicaciones identificadas inicialmente, se excluyeron reportes clínicos, revisiones, estudios observacionales, etc. Se incluyeron 12 ensayos clínicos que contrastaron las variables entre la técnica con PRF solo y la combinación con un relleno óseo. CONCLUSIÓN: La combinación entre PRF más rellenos óseos promueve la neoformación ósea, aumenta el trabeculado y mejora los tiempos de cicatrización; sin embargo, al cabo de 6 meses de control los resultados no son diferentes significativamente de los de los grupos que no utilizaron PRF en el procedimiento de levantamiento de piso de seno maxilar con técnica de ventana lateral. Respecto a la preservación de reborde alveolar, los distintos estudios no son concluyentes: algunos indican que la mezcla de PRF con un relleno óseo parece mejorar las proporciones volumétricas; sin embargo, otros refirieron pérdidas óseas en anchura e incluso mayor grado de inflamación


OBJECTIVE: To evaluate systematically the results obtained by combining platelet rich fibrin (PRF) and bone fill in guided bone regeneration, according to scientific literature. MATERIALS AND METHOD: Detailed search of database from PubMed, Scopus, Web of Science, ScienceDirect, Cochrane and SciELO to obtain the most updated information of clinical results (bone filling degree, surgical success, implant mobility, post-surgical complications, and implant survival) of the cases treated with PRF and the cases where the platelet rich fibrin was combined with a bone filler. Those results registered and compared. RESULTS: From the 965 files initially identified, were excluded clinical reports, reviews, observational studies, comments, studies with pediatric patients and so on. There were included 12 clinical essays where the variables of the technique with PRF and the technique where the PRF was combined with a bone filler were contrasted. CONCLUSION: The combination of PRF plus bone filler promotes bone neoformation, increased trabecular bones, and improved healing times; however, after 6 months of monitoring, the results were not significantly different with the groups that did not use the PRF in the procedure of maxillary sinus floor lift with lateral window technique. Regarding the preservation of alveolar ridge the different studies are not conclusive: some indicate that the mixture of a concentrate with a bone filling seems to improve the volumetric proportions; however, other studies report bone loss in width and even greater degree of inflammation


Assuntos
Humanos , Fibrina Rica em Plaquetas/fisiologia , Substitutos Ósseos/farmacocinética , Regeneração Tecidual Guiada Periodontal/métodos , Plasma Rico em Plaquetas/fisiologia , Regeneração Óssea/efeitos dos fármacos , Perda do Osso Alveolar/cirurgia , Aumento do Rebordo Alveolar/métodos , Implantação Dentária Endo-Óssea/métodos
3.
J Mater Sci Mater Med ; 30(8): 94, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31414232

RESUMO

Clinically, S53P4 bioactive glass (BAG) has shown very promising results in bone infection treatment, but it is also known to degrade very slowly in vivo. To evaluate which mechanisms (cellular or dissolution) can play a role in the degradation of S53P4 BAG and S53P4 BAG putty, in vitro degradation experiments at different pH (7.4 and 4.6) were performed. Micro computed tomography showed a rapid dissolution of the synthetic binder in the putty formulation, within 12 h is simulated body fluid (pH = 7.4), leaving behind only loose granules. Therefore the degradation of the loose granules was investigated further. Significant weight loss was observed and ion chromatography showed that Ca2+, Na+ and PO43- ions were released from S54P4 BAG granules in the two fluids. It was observed that the weight loss and ion release were increased when the pH of the fluid was decreased to 4.6. Osteoclasts are known to create such a low pH when resorbing bone and therefore their capacity to degrade S53P4 surfaces were studied as well. Scanning electron microscopy and energy-dispersive X-ray spectroscopy confirmed that osteoclasts were able to create resorption pits in the calcium phosphate layer on S53P4 BAG surfaces. The silica of the BAG, located underneath the calcium phosphate, seemed to hinder further osteclastic resorption of the material. To our knowledge we were the first to observe actively resorbing osteoclasts on S53P4 bioactive glass surfaces, in vitro. Future research is needed to define the specific role osteoclasts play in the degradation of BAG in vivo.


Assuntos
Implantes Absorvíveis , Substitutos Ósseos/farmacocinética , Fosfatos de Cálcio/farmacocinética , Vidro , Osteoclastos/fisiologia , Adsorção , Substitutos Ósseos/química , Fosfatos de Cálcio/química , Diferenciação Celular , Células Cultivadas , Vidro/química , Humanos , Teste de Materiais , Monócitos/fisiologia
4.
Acta Biomater ; 75: 463-471, 2018 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-29859366

RESUMO

There is increasing interest in biodegradable ceramic scaffolds for bone tissue engineering capable of in situ delivery of ionic species favoring bone formation. Strontium has been shown to be osteogenic, but strontium-containing drugs such as strontium ranelate, used in Europe for the treatment of osteoporosis, are now restricted due to clinical evidence of systemic effects. By doping fluorapatite-based glasses with strontium, we developed ceramic scaffolds with fully interconnected macroporosity and cell size similar to that of cancellous bone, that are also capable of releasing strontium. The crystallization behavior, investigated by XRD and SEM, revealed the formation of akermanite and fluorapatite at the surface of strontium-free glass-ceramic scaffolds, and strontium-substituted fluorapatite at the surface of the strontium-doped scaffolds. At 8 weeks after implantation in a rat calvarial critical size defect, scaffolds doped with the highest amount of strontium led to the highest mineral apposition rate. A significantly higher amount of newly-formed bone was found with the strontium-free glass-ceramic scaffold, and possibly linked to the presence of akermanite at the scaffold surface. We demonstrate by energy dispersive XRF analyses of skull sections that strontium was present in newly formed bone with the strontium-doped scaffolds, while a significant amount of fluorine was incorporated in newly formed bone, regardless of composition or crystallization state. STATEMENT OF SIGNIFICANCE: The present work demonstrates the in vivo action of strontium-containing glass-ceramic scaffolds. These bone graft substitutes are targeted at non load-bearing bone defects. Results show that strontium is successfully incorporated in newly formed bone. This is associated with a significantly higher Mineral Apposition Rate. The benefits of in situ release of strontium are demonstrated. The broader scientific impact of this works builds on the concept of resorbable ceramic scaffolds as reservoirs of ionic species capable of enhancing bone regeneration.


Assuntos
Apatitas , Substitutos Ósseos , Cerâmica , Osteogênese/efeitos dos fármacos , Crânio , Estrôncio , Tecidos Suporte/química , Animais , Apatitas/química , Apatitas/farmacocinética , Apatitas/farmacologia , Substitutos Ósseos/química , Substitutos Ósseos/farmacocinética , Substitutos Ósseos/farmacologia , Cerâmica/química , Cerâmica/farmacocinética , Cerâmica/farmacologia , Ratos , Crânio/lesões , Crânio/metabolismo , Crânio/patologia , Estrôncio/química , Estrôncio/farmacocinética , Estrôncio/farmacologia
5.
J Biomed Mater Res B Appl Biomater ; 106(1): 80-87, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27860210

RESUMO

Patients with inadequate volume of alveolar processes or bone defects commonly require graft substitutes in oral, maxillofacial or orthopedic surgery. Ridge augmentation and reconstruction of facial bony defects with bone graft materials achieve better outcomes in functional and aesthetic rehabilitation. The injectable calcium sulfate filler is used widely in intra-operative applications. Calcium sulfate bone filler has been shown to upregulate bone formation-related mRNA genes in vitro and improve osseointegration in vivo. In addition, the bone graft substitute can be used as a drug delivery system for antibiotics to treat or prevent infections based on the clinical experiences. However, the influences of antibiotics addition on the calcium sulfate are not fully understood. In this study, calcium sulfate impregnated with gentamycin in different weight ratios was characterized. The results showed that gentamycin prolonged the hydration process and extended initial/final setting times of calcium sulfate. The addition of gentamycin slowed the conversion from calcium sulfate hemihydrate to dihydrate and changed the crystalline phase and microstructure. Higher amounts of gentamycin added resulted in faster degradation and lower mechanical strength of calcium sulfate. This study reveals that the extended setting time, decreased compressive strength, and the accelerated degradation of the gentamycin-impregnated calcium sulfate bone graft substitutes should be considered during intra-operative applications. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 80-87, 2018.


Assuntos
Antibacterianos , Substitutos Ósseos , Sulfato de Cálcio , Gentamicinas , Streptococcus mutans/crescimento & desenvolvimento , Antibacterianos/química , Antibacterianos/farmacocinética , Antibacterianos/farmacologia , Substitutos Ósseos/química , Substitutos Ósseos/farmacocinética , Substitutos Ósseos/farmacologia , Sulfato de Cálcio/química , Sulfato de Cálcio/farmacocinética , Sulfato de Cálcio/farmacologia , Implantes de Medicamento , Gentamicinas/química , Gentamicinas/farmacocinética , Gentamicinas/farmacologia
6.
J Biomed Mater Res B Appl Biomater ; 106(4): 1546-1557, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-28755493

RESUMO

The bone-induction capacity of a porous biphasic calcium phosphate (pBCP) using heterotopic implantation in mouse (mHI-model) and its efficacy as substitute for autograft in mandibular critical-size defect in rabbit (rabMCSD-model) was investigated. In mHI-model, pBCP was implanted into the thigh muscles and bone formation was histomorphometrically and immunohistochemically evaluated. In rabMCSD-model, 13 mm bone defects were treated with pBCP or autograft and bone repair comparatively evaluated by radiographic and histomorphometric methods. In mHI-model, formed bone and immunolabeling for bone morphogenetic protein-2 and osteopontin were observed in 90% of pBCP implanted samples after 12 weeks. In rabMCSD-model neither statistically significant difference was found in newly formed bone between pBCP and autograft groups at 4 weeks (18.8 ± 5.5% vs 27.1 ± 5.6%), 8 weeks (22.3 ± 2.7% vs 26.2 ± 5.1), and 12 weeks (19.6 ± 4.7% vs 19.6 ± 2.3%). At 12 weeks, the stability and contour of the mandible were restored in both treatments. Near tooth remaining, pBCP particles were covered by small amount of mineralized tissue exhibiting perpendicular attachments of collagen fiber bundles with histological characteristic of acellular cementum. Within the limitations of this study, it was concluded that pBCP is osteoinductive and able to stimulate the new formation of bone and cementum-like tissues in rabMCSD-model, suggesting that it may be an alternative to treatment of large bone defect and in periodontal regenerative therapy. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1546-1557, 2018.


Assuntos
Substitutos Ósseos , Cerâmica , Hidroxiapatitas , Mandíbula , Traumatismos Mandibulares , Osteogênese/efeitos dos fármacos , Animais , Proteína Morfogenética Óssea 2/química , Proteína Morfogenética Óssea 2/farmacocinética , Proteína Morfogenética Óssea 2/farmacologia , Substitutos Ósseos/química , Substitutos Ósseos/farmacocinética , Substitutos Ósseos/farmacologia , Transplante Ósseo , Cerâmica/química , Cerâmica/farmacocinética , Cerâmica/farmacologia , Modelos Animais de Doenças , Hidroxiapatitas/química , Hidroxiapatitas/farmacocinética , Hidroxiapatitas/farmacologia , Masculino , Mandíbula/metabolismo , Mandíbula/patologia , Traumatismos Mandibulares/metabolismo , Traumatismos Mandibulares/patologia , Traumatismos Mandibulares/terapia , Camundongos , Camundongos Endogâmicos BALB C , Coelhos
7.
Acta Biomater ; 58: 550-560, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28571692

RESUMO

Prevention of orthopedic device related infection (ODRI) using antibiotics has met with limited amount of success and is still a big concern during post-surgery. As an alternative, use of silver as an antibiotic treatment to prevent surgical infections is being used due to the well-established antimicrobial properties of silver. However, in most cases silver is used in particulate form with wound dressings or with short-term devices such as catheters but not with load-bearing implants. We hypothesize that strongly adherent silver to load-bearing implants can offer longer term solution to infection in vivo. Keeping that in mind, the focus of this study was to understand the long term release study of silver ions for a period of minimum 6months from silver coated surface modified porous titanium implants. Implants were fabricated using a LENS™ system, a powder based additive manufacturing technique, with at least 25% volume porosity, with and without TiO2 nanotubes in phosphate buffer saline (pH 7.4) to see if the total release of silver ions is within the toxic limit for human cells. Considering the fact that infection sites may reduce the local pH, silver release was also studied in acetate buffer (pH 5.0) for a period of 4weeks. Along with that, the osseointegrative properties as well as cytotoxicity of porous titanium implants were assessed in vivo for a period of 12weeks using a rat distal femur model. In vivo results indicate that porous titanium implants with silver coating show comparable, if not better, biocompatibility and bonding at the bone-implant interface negating any concerns related to toxicity related to silver to normal cells. The current research is based on our recently patented technology, however focused on understanding longer-term silver release to mitigate infection related problems in load-bearing implants that can even arise several months after the surgery. STATEMENT OF SIGNIFICANCE: Prevention of orthopedic device related infection using antibiotics has met with limited success and is still a big concern during post-surgery. Use of silver as an antibiotic treatment to prevent surgical infections is being explored due to the well-established antimicrobial properties of silver. However, in most cases silver is used in particulate form with wound dressings or with short-term devices such as catheters but not with load-bearing implants. We hypothesize that strongly adherent silver to load-bearing implants can offer longer-term solution towards infection in vivo. Keeping that in mind, the focus of this study was to understand the long-term release of silver ions, for a period of minimum 6months, from silver coated surface modified porous titanium implants.


Assuntos
Materiais Revestidos Biocompatíveis , Fêmur/cirurgia , Implantes Experimentais/microbiologia , Prata , Infecção da Ferida Cirúrgica/prevenção & controle , Titânio/química , Animais , Substitutos Ósseos/química , Substitutos Ósseos/farmacocinética , Materiais Revestidos Biocompatíveis/farmacocinética , Masculino , Porosidade , Ratos , Ratos Sprague-Dawley , Prata/química , Prata/farmacocinética
8.
J Periodontal Res ; 52(4): 772-786, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28261803

RESUMO

BACKGROUND AND OBJECTIVE: In regenerative dentistry, platelet preparations are applied to stimulate bone healing and periodontal regeneration. Here, we pursue a strategy where bone substitutes are used as carriers for platelet-released supernatants. The mitogenic capacity and release kinetics of loaded bone substitutes were assessed. MATERIAL AND METHODS: Platelet-released supernatants of washed platelets (washed PRS) and platelet-released supernatants of unwashed platelets (unwashed PRS) were lyophilized onto the bone substitutes deproteinized bovine bone mineral, hydroxyapatite and ß-tricalcium phosphate. Scanning electron microscopy images were taken. Supernatants of bone substitutes were collected at hours 1, 3, 6, 24, and 48 and medium was replaced. We evaluated the protein content with the bicinchoninic acid assay and the effect on proliferation using bioassays with human periodontal fibroblasts. Release of growth factors from the loaded bone substitutes was measured based on the platelet-derived growth factor isoform (PDGF-BB) and thrombin immunoassays. Furthermore, we assessed DNA and RNA content of washed PRS and unwashed PRS. RESULTS: Unwashed PRS showed higher total protein concentrations than washed PRS, while the concentration of PDGF-BB, thrombin, DNA, RNA and their mitogenic effect was not significantly different. The bone substitute materials adsorbed protein over time but no significant changes in overall appearance was found. Supernatants collected from unwashed PRS-loaded bone substitute after 1 h induced a potent mitogenic response in periodontal fibroblasts. This pro-mitogenic capacity of the supernatants decreased over the observation period. Supernatants of washed PRS-loaded bone substitutes did not induce a substantial mitogenic effect. Levels of PDGF-BB, thrombin and protein were higher in supernatants of unwashed PRS-loaded bone substitutes than of washed PRS-loaded bone substitutes. CONCLUSION: Bone substitutes loaded with unwashed PRS, but not bone substitutes loaded with washed PRS show continuously declining release kinetics. These data suggest that plasma components in platelet preparations can modify the release kinetics profile.


Assuntos
Plaquetas/fisiologia , Substitutos Ósseos/farmacocinética , Minerais/farmacocinética , Animais , Fosfatos de Cálcio/farmacocinética , Bovinos , Durapatita/farmacocinética , Fibroblastos/metabolismo , Humanos , Microscopia Eletrônica de Varredura , Fator de Crescimento Derivado de Plaquetas/farmacocinética
9.
Mater Sci Eng C Mater Biol Appl ; 68: 603-612, 2016 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-27524060

RESUMO

Despite the attractive characteristics of three-dimensional pure hydroxyapatite (HA) scaffolds, due to their weak mechanical properties, researches have focused on the development of composite scaffolds via introducing suitable secondary components. The aim of this study was to develop, for the first time, three-dimensional HA-bredigite (Ca7MgSi4O16) scaffolds containing various amounts of bredigite nanopowder (0, 5, 10 and 15wt.%) using space holder technique. Transmission electron microscopy, scanning electron microscopy, energy-dispersive X-ray spectroscopy and X-ray diffraction spectroscopy were applied in order to study the morphology, fracture surface and phase compositions of nanopowders and scaffolds. Furthermore, the effects of scaffold composition on the mechanical properties, bioactivity, biodegradability, and cytotoxicity were also evaluated. Results showed that the composite scaffolds with average pore size in the range of 220-310µm, appearance porosity of 63.1-75.9% and appearance density of 1.1±0.04g/cm(3) were successfully developed, depending on bredigite content. Indeed, the micropore size of the scaffolds reduced with increasing bredigite content confirming that the sinterability of the scaffolds was improved. Furthermore, the compression strength and modulus of the scaffolds significantly enhanced via incorporation of bredigite content from 0 to 15wt.%. The composite scaffolds revealed superior bioactivity and biodegradability with increasing bredigite content. Moreover, MTT assay confirmed that HA-15wt.% bredigite scaffold significantly promoted cell proliferation compared to tissue culture plate (control) and HA scaffold. Based on these results, three-dimensional HA-bredigite scaffolds could be promising replacements for HA scaffolds in bone regeneration.


Assuntos
Amiantos Anfibólicos , Regeneração Óssea/efeitos dos fármacos , Substitutos Ósseos , Durapatita , Nanoestruturas/química , Tecidos Suporte/química , Amiantos Anfibólicos/química , Amiantos Anfibólicos/farmacocinética , Amiantos Anfibólicos/farmacologia , Substitutos Ósseos/química , Substitutos Ósseos/farmacocinética , Substitutos Ósseos/farmacologia , Linhagem Celular Tumoral , Avaliação Pré-Clínica de Medicamentos , Durapatita/química , Durapatita/farmacocinética , Durapatita/farmacologia , Humanos
10.
Mater Sci Eng C Mater Biol Appl ; 67: 440-452, 2016 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-27287141

RESUMO

The release of inorganic ions from biomaterials could provide an alternative approach to the use of growth factors for improving tissue healing. In the present study, the release of copper (Cu) ions from bioactive silicate (13-93) glass scaffolds on the response of cells in vitro and on bone regeneration and angiogenesis in vivo was studied. Scaffolds doped with varying concentrations of Cu (0-2.0wt.% CuO) were created with a grid-like microstructure by robotic deposition. When immersed in simulated body fluid in vitro, the Cu-doped scaffolds released Cu ions into the medium in a dose-dependent manner and converted partially to hydroxyapatite. The proliferation and alkaline phosphatase activity of pre-osteoblastic MC3T3-E1 cells cultured on the scaffolds were not affected by 0.4 and 0.8wt.% CuO in the glass but they were significantly reduced by 2.0wt.% CuO. The percent new bone that infiltrated the scaffolds implanted for 6weeks in rat calvarial defects (46±8%) was not significantly affected by 0.4 or 0.8wt.% CuO in the glass whereas it was significantly inhibited (0.8±0.7%) in the scaffolds doped with 2.0wt.% CuO. The area of new blood vessels in the fibrous tissue that infiltrated the scaffolds increased with CuO content of the glass and was significantly higher for the scaffolds doped with 2.0wt.% CuO. Loading the scaffolds with bone morphogenetic protein-2 (1µg/defect) significantly enhanced bone infiltration and reduced fibrous tissue in the scaffolds. These results showed that doping the 13-93 glass scaffolds with up to 0.8wt.% CuO did not affect their biocompatibility whereas 2.0wt.% CuO was toxic to cells and detrimental to bone regeneration.


Assuntos
Regeneração Óssea/efeitos dos fármacos , Substitutos Ósseos , Cobre , Vidro/química , Neovascularização Fisiológica/efeitos dos fármacos , Osteoblastos/metabolismo , Crânio , Tecidos Suporte/química , Animais , Substitutos Ósseos/química , Substitutos Ósseos/farmacocinética , Substitutos Ósseos/farmacologia , Linhagem Celular , Cobre/química , Cobre/farmacocinética , Cobre/farmacologia , Camundongos , Osteoblastos/patologia , Ratos , Crânio/irrigação sanguínea , Crânio/lesões , Crânio/metabolismo
11.
Mater Sci Eng C Mater Biol Appl ; 62: 429-38, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26952443

RESUMO

The increasing interest in the effect of strontium in bone tissue repair has promoted the development of bioactive materials with strontium release capability. According to literature, hybrid materials based on the system PDMS-SiO2 have been considered a plausible alternative as they present a mechanical behavior similar to the one of the human bone. The main purpose of this study was to obtain a biocompatible hybrid material with simultaneous calcium and strontium release capability. A hybrid material, in the system PDMS-SiO2-CaO-SrO, was prepared with the incorporation of 0.05 mol of titanium per mol of SiO2. Calcium and strontium were added using the respective acetates as sources, following a sol-gel technique previously developed by the present authors. The obtained samples were characterized by FT-IR, solid-state NMR, and SAXS, and surface roughness was analyzed by 3D optical profilometry. In vitro studies were performed by immersion of the samples in Kokubo's SBF for different periods of time, in order to determine the bioactive potential of these hybrids. Surfaces of the immersed samples were observed by SEM, EDS and PIXE, showing the formation of calcium phosphate precipitates. Supernatants were analyzed by ICP, revealing the capability of the material to simultaneously fix phosphorus ions and to release calcium and strontium, in a concentration range within the values reported as suitable for the induction of the bone tissue repair. The material demonstrated to be cytocompatible when tested with MG63 osteoblastic cells, exhibiting an inductive effect on cell proliferation and alkaline phosphatase activity.


Assuntos
Materiais Biocompatíveis , Substitutos Ósseos , Cálcio , Osteoblastos/metabolismo , Estrôncio , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacocinética , Materiais Biocompatíveis/farmacologia , Substitutos Ósseos/química , Substitutos Ósseos/farmacocinética , Substitutos Ósseos/farmacologia , Cálcio/química , Cálcio/farmacocinética , Cálcio/farmacologia , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/farmacologia , Dimetilpolisiloxanos/química , Dimetilpolisiloxanos/farmacocinética , Dimetilpolisiloxanos/farmacologia , Humanos , Estrôncio/química , Estrôncio/farmacocinética , Estrôncio/farmacologia
12.
Sci Rep ; 6: 23422, 2016 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-26996657

RESUMO

The present study was performed to determine whether simvastatin improves bone regeneration when combined with calcium silicate/gypsum and gelatin (CS-GEL). The surface morphology was determined using field-emission scanning electron microscopy (FSEM). Degradation in vitro was evaluated by monitoring the weight change of the composites soaked in phosphate buffered saline (PBS). Drug release was evaluated using high-performance liquid chromatography (HPLC). Cytotoxicity testing was performed to assess the biocompatibility of composites. Four 5 mm-diameter bone defects were created in rabbit calvaria. Three sites were filled with CS-GEL, 0.5 mg simvastatin-loaded CS-GEL (SIM-0.5) and 1.0 mg simvastatin-loaded CS-GEL (SIM-1.0), respectively, and the fourth was left empty as the control group. Micro-computed tomography (micro-CT) and histological analysis were carried out at 4 and 12 weeks postoperatively. The composites all exhibited three-dimensional structures and showed the residue with nearly 80% after 4 weeks of immersion. Drug release was explosive on the first day and then the release rate remained stable. The composites did not induce any cytotoxicity. The results in vivo demonstrated that the new bone formation and the expressions of BMP-2, OC and type I collagen were improved in the simvastatin-loaded CS-GEL group. It was concluded that the simvastatin-loaded CS-GEL may improve bone regeneration.


Assuntos
Regeneração Óssea/efeitos dos fármacos , Substitutos Ósseos/administração & dosagem , Compostos de Cálcio/administração & dosagem , Sulfato de Cálcio/administração & dosagem , Gelatina/administração & dosagem , Silicatos/administração & dosagem , Sinvastatina/administração & dosagem , Crânio/efeitos dos fármacos , Animais , Substitutos Ósseos/farmacocinética , Compostos de Cálcio/farmacocinética , Sulfato de Cálcio/farmacocinética , Gelatina/farmacocinética , Masculino , Teste de Materiais , Coelhos , Silicatos/farmacocinética , Sinvastatina/farmacocinética , Crânio/lesões , Crânio/ultraestrutura
13.
J R Soc Interface ; 12(110): 0509, 2015 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-26269233

RESUMO

This work aimed to develop novel composite biomaterials for bone tissue engineering (BTE) made of bioactive glass nanoparticles (Nbg) and alginate cross-linked with Cu(2+) or Ca(2+) (AlgNbgCu, AlgNbgCa, respectively). Two-dimensional scaffolds were prepared and the nanocomposite biomaterials were characterized in terms of morphology, mechanical strength, bioactivity, biodegradability, swelling capacity, release profile of the cross-linking cations and angiogenic properties. It was found that both Cu(2+) and Ca(2+) are released in a controlled and sustained manner with no burst release observed. Finally, in vitro results indicated that the bioactive ions released from both nanocomposite biomaterials were able to stimulate the differentiation of rat bone marrow-derived mesenchymal stem cells towards the osteogenic lineage. In addition, the typical endothelial cell property of forming tubes in Matrigel was observed for human umbilical vein endothelial cells when in contact with the novel biomaterials, particularly AlgNbgCu, which indicates their angiogenic properties. Hence, novel nanocomposite biomaterials made of Nbg and alginate cross-linked with Cu(2+) or Ca(2+) were developed with potential applications for preparation of multifunctional scaffolds for BTE.


Assuntos
Cálcio , Cobre , Células Endoteliais da Veia Umbilical Humana/metabolismo , Células-Tronco Mesenquimais/metabolismo , Nanocompostos/química , Engenharia Tecidual , Tecidos Suporte/química , Animais , Substitutos Ósseos/química , Substitutos Ósseos/farmacocinética , Cálcio/química , Cálcio/farmacocinética , Cobre/química , Cobre/farmacocinética , Células Endoteliais da Veia Umbilical Humana/citologia , Humanos , Teste de Materiais , Células-Tronco Mesenquimais/citologia , Ratos , Ratos Sprague-Dawley
14.
Int J Nanomedicine ; 10: 517-26, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25609957

RESUMO

The regeneration of large bone defects is an osteoinductive, osteoconductive, and osteogenic process that often requires a bone graft for support. Limitations associated with naturally autogenic or allogenic bone grafts have demonstrated the need for synthetic substitutes. The present study investigates the feasibility of using novel hollow hydroxyapatite microspheres as an osteoconductive matrix and a carrier for controlled local delivery of bone morphogenetic protein 2 (BMP2), a potent osteogenic inducer of bone regeneration. Hollow hydroxyapatite microspheres (100±25 µm) with a core (60±18 µm) and a mesoporous shell (180±42 m(2)/g surface area) were prepared by a glass conversion technique and loaded with recombinant human BMP2 (1 µg/mg). There was a gentle burst release of BMP2 from microspheres into the surrounding phosphate-buffered saline in vitro within the initial 48 hours, and continued at a low rate for over 40 days. In comparison with hollow hydroxyapatite microspheres without BMP2 or soluble BMP2 without a carrier, BMP2-loaded hollow hydroxyapatite microspheres had a significantly enhanced capacity to reconstitute radial bone defects in rabbit, as shown by increased serum alkaline phosphatase; quick and complete new bone formation within 12 weeks; and great biomechanical flexural strength. These results indicate that BMP2-loaded hollow hydroxyapatite microspheres could be a potential new option for bone graft substitutes in bone regeneration.


Assuntos
Proteína Morfogenética Óssea 2 , Regeneração Óssea/efeitos dos fármacos , Durapatita , Microesferas , Osteogênese/efeitos dos fármacos , Fator de Crescimento Transformador beta , Animais , Proteína Morfogenética Óssea 2/química , Proteína Morfogenética Óssea 2/farmacocinética , Proteína Morfogenética Óssea 2/farmacologia , Substitutos Ósseos/química , Substitutos Ósseos/farmacocinética , Substitutos Ósseos/farmacologia , Durapatita/química , Durapatita/farmacocinética , Durapatita/farmacologia , Humanos , Coelhos , Proteínas Recombinantes/química , Proteínas Recombinantes/farmacocinética , Proteínas Recombinantes/farmacologia , Fator de Crescimento Transformador beta/química , Fator de Crescimento Transformador beta/farmacocinética , Fator de Crescimento Transformador beta/farmacologia
15.
J Nanosci Nanotechnol ; 15(10): 7976-9, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26726450

RESUMO

Hydroxyapatite (HA) is widely used as a bioactive ceramics as it forms a chemical bond with bone. However, the drawback to using this material is its inferior mechanical properties. In this research, surface corrosion and disintegration of nanoscaled HA in a dog were studied, and the mechanism by which phase-pure HA dissolved in vivo was investigated. Biological properties of HA in vivo are affected by the grain-boundary dissolution followed by a surface corrosion and microstructural disintegration. This kind of dissolution process, apparently evidenced at the grain boundary, causes particle generation, which indicates that both long-term bone in-growth and mechanical properties can dramatically deteriorate. Implant dissolution by osteoclasts in vivo is also observed on the surface of hydroxyapatite. Implant surface showed an aggressive corrosion by an osteoclast resorption. Severe and deeper dissolution underwent close to osteoclast resulting in formation of smaller and more round particle shape.


Assuntos
Substitutos Ósseos , Cerâmica , Durapatita , Osteoclastos/metabolismo , Animais , Substitutos Ósseos/química , Substitutos Ósseos/farmacocinética , Substitutos Ósseos/farmacologia , Cerâmica/química , Cerâmica/farmacocinética , Cerâmica/farmacologia , Corrosão , Cães , Durapatita/química , Durapatita/farmacocinética , Durapatita/farmacologia , Masculino , Osteoclastos/patologia
16.
J Biomed Mater Res B Appl Biomater ; 103(5): 1099-106, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25258353

RESUMO

UNLABELLED: Studies have shown that strontium (Sr) incorporated into surfaces may enhance osseointegration. Thus, we suggested that a sustained Sr release from implant surfaces could improve bone healing. This study verifies and further investigates the effect of a novel Ti-Sr-O functionalized implant surface prepared from a magnetron co-sputtering platform with a continuous release of Sr. MATERIALS AND METHODS: Four experimental Ti-Sr-O groups, which differed from each other in Sr contents and pre-wash procedures, were tested. Implants were prepared with a Ti-Sr-O coating by means of magnetron co-sputtering and compared to Grade 4 titanium. Composition, morphology and mechanical stability were analyzed; Sr-release data were gained from in vitro washout experiments. In vivo investigations were carried out in a rat model and analyzed histologically regarding bone-to-implant contact and new bone formation 30 days after implantation. RESULTS: Structural differences were detected between the two basis Ti-Sr-O coatings with 6.7 at.% and 8.9 at.% Sr, respectively. Different release profiles were observed with 8.9 at.% Sr coating exhibiting the highest long-term release of Sr. Median values of new bone formation and bone-to-implant contact was found to be 60.1% and 91.6%, respectively, for the best group compared to 16.6% and 70.6% for the Grade 4 titanium reference. The increase in new bone formation was found to correlate with the amount of Sr released in vitro. CONCLUSION: The results show that sputtered Ti-Sr-O coatings with sustained release of Sr may improve osseointegration, and could thus have impact on practical applications for medical implants.


Assuntos
Substitutos Ósseos , Interface Osso-Implante , Consolidação da Fratura/efeitos dos fármacos , Osseointegração , Estrôncio , Animais , Substitutos Ósseos/química , Substitutos Ósseos/farmacocinética , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Feminino , Ratos , Ratos Wistar , Estrôncio/química , Estrôncio/farmacocinética
17.
J Biomed Mater Res B Appl Biomater ; 103(7): 1354-65, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25385691

RESUMO

Iron-bioceramic composites have been developed as biodegradable implant materials with tailored degradation behavior and bioactive features. In the current work, in vivo bioactivity of the composites was comprehensively studied by using sheep animal model. Five groups of specimens (Fe-HA, Fe-TCP, Fe-BCP composites, and pure-Fe and SS316L as controls) were surgically implanted into medio proximal region of the radial bones. Real-time ultrasound analysis showed a decreased echo pattern at the peri-implant biodegradation site of the composites indicating minimal tissue response during the wound healing process. Peripheral whole blood biomarkers monitoring showed a normal dynamic change of blood cellular responses and no stress effect was observed. Meanwhile, the released Fe ion concentration was increasing along the implantation period. Histological analysis showed that the composites corresponded with a lower inflammatory giant cell count than that of SS316L. Analysis of the retrieved implants showed a thicker degradation layer on the composites compared with pure-Fe. It can be concluded that the iron-bioceramic composites are bioactive and induce a preferable wound healing process.


Assuntos
Substitutos Ósseos , Cerâmica , Ferro , Teste de Materiais , Animais , Substitutos Ósseos/química , Substitutos Ósseos/farmacocinética , Substitutos Ósseos/farmacologia , Cerâmica/química , Cerâmica/farmacocinética , Cerâmica/farmacologia , Ferro/química , Ferro/farmacocinética , Ferro/farmacologia , Masculino , Ovinos
18.
Mater Sci Eng C Mater Biol Appl ; 42: 137-45, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25063103

RESUMO

We present a mild one-pot freeze gelation process for fabricating near-net, complex-shaped hydroxyapatite scaffolds and to directly incorporate active proteins during scaffold processing. In particular, the direct protein incorporation enables a simultaneous adjustment and control of scaffold microstructure, porosity, resorbability and enhancement of initial mechanical and handling stability. Two proteins, serum albumin and lysozyme, are selected and their effect on scaffold stability and microstructure investigated by biaxial strength tests, electron microscopy, and mercury intrusion porosimetry. The resulting hydroxyapatite/protein composites feature adjustable porosities from 50% to 70% and a mechanical strength ranging from 2 to 6 MPa comparable to that of human spongiosa without any sintering step. Scaffold degradation behaviour and protein release are assessed by in vitro studies. A preliminary in vivo assessment of scaffold biocompatibility and resorption behaviour in adult domestic pigs is discussed. After implantation, composites were resorbed up to 50% after only 4 weeks and up to 65% after 8 weeks. In addition, 14% new bone formation after 4 weeks and 37% after 8 weeks were detected. All these investigations demonstrate the outstanding suitability of the one-pot-process to create, in a customisable and reliable way, biocompatible scaffolds with sufficient mechanical strength for handling and surgical insertion, and for potential use as biodegradable bone substitutes and versatile platform for local drug delivery.


Assuntos
Materiais Biocompatíveis/química , Substitutos Ósseos/química , Durapatita/química , Nanocompostos/química , Proteínas/química , Implantes Absorvíveis , Animais , Materiais Biocompatíveis/farmacocinética , Materiais Biocompatíveis/farmacologia , Regeneração Óssea/efeitos dos fármacos , Substitutos Ósseos/farmacocinética , Substitutos Ósseos/farmacologia , Bovinos , Galinhas , Durapatita/farmacocinética , Durapatita/farmacologia , Feminino , Teste de Materiais , Muramidase , Proteínas/farmacocinética , Proteínas/farmacologia , Soroalbumina Bovina , Suínos
19.
J Biomed Mater Res B Appl Biomater ; 102(5): 1074-83, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24376164

RESUMO

Infection remains a significant problem associated with biomedical implants and orthopedic surgeries, especially in revision total joint replacements. Recent advances in antibiotic-releasing bone void fillers (BVF) provide new opportunities to address these types of device-related orthopedic infections that often lead to substantial economic burdens and reduced quality of life. We report improvements made in fabrication and scalability of an antibiotic-releasing polycaprolactone-calcium carbonate/phosphate ceramic composite BVF using a new solvent-free, molten-cast fabrication process. This strategy provides the ability to tailor drug release kinetics from the BVF composite based on modifications of the inorganic substrate and/or the polymeric component, allowing extended tobramycin release at bactericidal concentrations. The mechanical properties of the new BVF composite are comparable to many reported BVFs and validate the relative homogeneity of fabrication. Most importantly, fabrication quality controls are correlated with favorable drug release kinetics, providing bactericidal activity to 10 weeks in vitro when the polycaprolactone component exceeds 98% w/w of the total polymer fraction. Furthermore, in a time kill study, tobramycin-releasing composite fragments inhibited S. aureus growth over 48 h at inoculums as high as 10(9) CFU/mL. This customizable antibiotic-releasing BVF polymer-inorganic biomaterial should provide osseointegrative and osteoconductive properties while contributing antimicrobial protection to orthopedic sites requiring the use of bone void fillers.


Assuntos
Antibacterianos , Substitutos Ósseos , Staphylococcus aureus/crescimento & desenvolvimento , Tobramicina , Antibacterianos/química , Antibacterianos/farmacocinética , Antibacterianos/farmacologia , Substitutos Ósseos/química , Substitutos Ósseos/farmacocinética , Substitutos Ósseos/farmacologia , Fosfatos de Cálcio/química , Fosfatos de Cálcio/farmacocinética , Fosfatos de Cálcio/farmacologia , Cerâmica/química , Cerâmica/farmacocinética , Cerâmica/farmacologia , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/farmacologia , Poliésteres/química , Poliésteres/farmacocinética , Poliésteres/farmacologia , Tobramicina/química , Tobramicina/farmacocinética , Tobramicina/farmacologia
20.
J Appl Oral Sci ; 21(1): 37-42, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23559110

RESUMO

OBJECTIVE: The aim of this study was to produce dense granules of tricalcium phosphate (ß-TCP) and magnesium (Mg) substituted ß-TCP, also known as ß-TCMP (Mg/Ca=0.15 mol), in order to evaluate the impact of Mg incorporation on the physicochemical parameters and in vitro biocompatibility of this novel material. MATERIAL AND METHODS: The materials were characterized using X-ray diffraction (XRD), infrared spectroscopy (FTIR), electron microscopy and inductively coupled plasma (ICP). Biocompatibility was assayed according to ISO 10993-12:2007 and 7405:2008, by two different tests of cell survival and integrity (XTT and CVDE). RESULTS: The XRD profile presented the main peaks of ß-TCP (JCPDS 090169) and ß-TCMP (JCPDS 130404). The characteristic absorption bands of TCP were also identified by FTIR. The ICP results of ß-TCMP granules extract showed a precipitation of calcium and release of Mg into the culture medium. Regarding the cytotoxicity assays, ß-TCMP dense granules did not significantly affect the mitochondrial activity and relative cell density in relation to ß-TCP dense granules, despite the release of Mg from granules into the cell culture medium. CONCLUSION: ß-TCMP granules were successfully produced and were able to release Mg into media without cytotoxicity, indicating the suitability of this promising material for further biological studies on its adequacy for bone therapy.


Assuntos
Materiais Biocompatíveis/toxicidade , Fosfatos de Cálcio/toxicidade , Magnésio/toxicidade , Análise de Variância , Materiais Biocompatíveis/farmacocinética , Substitutos Ósseos/farmacocinética , Substitutos Ósseos/toxicidade , Fosfatos de Cálcio/farmacocinética , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas/efeitos dos fármacos , Magnésio/farmacocinética , Teste de Materiais , Microscopia Eletrônica de Varredura , Osteoblastos/efeitos dos fármacos , Análise Espectral , Fatores de Tempo , Testes de Toxicidade , Difração de Raios X
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