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1.
Int J Nanomedicine ; 15: 10059-10073, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33335394

RESUMO

Introduction: Vertical bone augmentation without osseous walls to support the stability of clots and bone grafts remains a challenge in dental implantology. The objectives of this study were to confirm that cortical perforation of the recipient bed is necessary and to evaluate whether nanohydroxyapatite (nHA) block grafts coated with recombinant human vascular endothelial growth factor165 (rhVEGF165) and cortical perforation can improve vertical bone regeneration. Materials and Methods: We prepared nHA blocks coated with or without rhVEGF165 on the rabbit calvarium through cortical perforation, and designated the animals as the nonperforated group (N-nHA), rhVEGF165 group (NV-nHA), perforated group (P-nHA) and rhVEGF165 on perforated group (PV-nHA). Micro-computed tomography (micro-CT) and fluorescence microscopy were selected to evaluate parameters of vertical bone regeneration at 4 and 6 weeks. Results: The ratio of the newly formed bone volume to the titanium dome volume (BV/TV) and the bone mineral density (BMD) were significantly higher in the PV-nHA group than in the N-nHA group at 4 and 6 weeks, as determined using micro-CT. The fluorescence analysis showed slightly greater increases in new bone regeneration (NB%) and vertical height (VH%) gains in the P-nHA group than in the N-nHA group. Greater increases in NB% and VH% were observed in groups treated with rhVEGF165 and perforation than in the blank groups, with significant differences detected at 4 and 6 weeks (N-nHA compared with PV-nHA, p<0.05). A greater VH% that was observed at the midline of the block in the PV-nHA group than in the other three groups at both time points (0.75±0.53% at 4 weeks and 0.83±0.42% at 6 weeks). Conclusion: According to the present study, cortical perforation is necessary and nHA blocks coated with rhVEGF165 and decoration could work synergistically to improve vertical bone regeneration by directly affecting primary osteoblasts and promoting angiogenesis and osteoinduction.


Assuntos
Regeneração Óssea/efeitos dos fármacos , Durapatita/farmacologia , Regeneração Tecidual Guiada/métodos , Nanoestruturas/química , Crânio/efeitos dos fármacos , Crânio/fisiologia , Fator A de Crescimento do Endotélio Vascular/química , Animais , Durapatita/química , Osteoblastos/efeitos dos fármacos , Porosidade , Coelhos , Proteínas Recombinantes/química , Crânio/citologia , Crânio/diagnóstico por imagem , Titânio/química , Microtomografia por Raio-X
2.
Arch Oral Biol ; 117: 104779, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32559508

RESUMO

OBJECTIVE: The aim of this study was to investigate the effects of the long-term alendronate administration on bone healing in defects created in rat calvarias. MATERIALS AND METHODS: Female Wistar rats were randomly distributed into 2 groups: Control (CTL): animals received saline solution once a week; and Alendronate (ALD): rats underwent alendronate treatment (1 mg/kg/weekly). After 120 days from the commencement of treatment, a critical size defect was created in all animals, and 10 animals from each group were sacrificed at 5, 10, 15, 20, 25, 30, 45 and 60-days after the defect creation. On the day of sacrifice, urine and blood samples were collected for determination of the serum levels of bone resorption and formation markers by enzyme linked immunosorbent assay, and the urinary concentration of deoxypyridinoline. Bone mineral density (BMD) in the femurs, descriptive histology, tartrate-resistant acid-phosphatase staining and immunohistochemical analyzes were assessed in the calvaria. RESULTS: Alendronate group showed increased BMD compared to the test group. The concentration of C-terminal telopeptide of type I collagen and deoxypyridinoline decreased significantly, and the concentration of aminoterminal propeptide of procollagen type 1 and osteocalcin were significant lower in the alendronate group. Immunohistochemical analysis showed significant downregulation in the inducible nitric oxide synthase, runt-related transcription factor-2, cathepsin-K and receptor activator of nuclear factor kappa-B ligand expression in the alendronate group. Vascular endothelial growth factor and osteopontin were upregulated in the later periods of alendronate group. CONCLUSIONS: Our results suggest that long-term treatment with alendronate did not compromise the repair processing of critical size defects in rat.


Assuntos
Alendronato , Regeneração Óssea/efeitos dos fármacos , Crânio/efeitos dos fármacos , Alendronato/farmacologia , Animais , Densidade Óssea , Feminino , Osteopontina , Ratos , Ratos Wistar , Crânio/patologia , Fator A de Crescimento do Endotélio Vascular
3.
J Bone Miner Metab ; 38(5): 639-647, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32303916

RESUMO

INTRODUCTION: Collagen from marine esponges has been used as a promising material for tissue engineering proposals. Similarly, photobiomodulation (PBM) is able of modulating inflammatory processes after an injury, accelerating soft and hard tissue healing and stimulating neoangiogenesis. However, the effects of the associated treatments on bone tissue healing have not been studied yet. In this context, the present study aimed to evaluate the biological temporal modifications (using two experimental periods) of marine sponge collagen or sponging (SPG) based scaffold and PBM on newly formed bone using a calvaria bone defect model. MATERIAL AND METHODS: Wistar rats were distributed into two groups: SPG or SPG/PBM and euthanized into two different experimental periods (15 and 45 days post-surgery). A cranial critical bone defect was used to evaluate the effects of the treatments. Histology, histomorfometry and immunohistological analysis were performed. RESULTS: Histological findings demonstrated that SPG/PBM-treated animals, 45 days post-surgery, demonstrated a higher amount of connective and newly formed bone tissue at the region of the defect compared to CG. Notwithstanding, no difference among groups were observed in the histomorphometry. Interestingly, for both anti-transforming growth factor-beta (TGF-ß) and anti-vascular endothelial growth factor (VEGF) immunostaining, higher values for SPG/PBM, at 45 days post-surgery could be observed. CONCLUSION: It can be concluded that the associated treatment can be considered as a promising therapeutical intervention.


Assuntos
Organismos Aquáticos/química , Colágeno/farmacologia , Terapia com Luz de Baixa Intensidade , Crânio/patologia , Tecidos Suporte/química , Cicatrização/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Masculino , Ratos Wistar , Crânio/efeitos dos fármacos , Fator de Crescimento Transformador beta/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
4.
J Craniofac Surg ; 31(5): 1477-1482, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32195836

RESUMO

Tideglusib is a glycogen synthase kinase 3 (GSK-3) inhibitor which has shown the effects of bone regeneration, used for the treatment of Alzheimer disease. The aim of the study was to determine the effects of Tideglusib in the apoptosis and the bone regeneration in rats with calvarial defects. Twenty male Wistar rats (aged 11-13 weeks) were used for the study. Full-thickness flap elevated to exposure calvarial bone. Two 5 mm critical size calvarial defects were created on each rat calvarium. The defects were divided into 4 study groups: 1-Control (n = 10); 2- Gelatin sponge+Tideglusib (Gs+TDG; n = 10); 3- Autogenous bone (AB; n = 10); 4-Autogenous bone+Tideglusib (AB+TDG; n = 10). Then, the rats were sacrificed at fourth week. Three-dimensional imaging, histopathologic and immunohistochemical examinations were performed to evaluate the samples. The most increased bone formation and interaction between graft and new bone were observed in AB+TDG group. Bone morphogenic protein-2 (BMP-2), alkaline phosphatase (ALP), collagen type 1 (Col 1) and osteocalcin (OCN) was determined significantly higher in Tideglusib received groups compared with those of Control and AB groups (P < 0.05). Osteoclast numbers found to be higher in Gs+TDG and AB+TDG groups as well as RANKL expression dis not affected in Gs+TDG group but decreased in AB+TDG group comparing those of Control and AB groups. In addition, Tideglusib increased the Bcl-2 levels (P < 0.05) and decreased Bax levels (P > 0.05) in Tideglusib received groups compared with their controls. The administration of Tideglusib in calvarial bone defects increased bone mineral density, new bone area and total bone area by decreasing apoptosis and increasing osteoblastogenesis.


Assuntos
Regeneração Óssea/efeitos dos fármacos , Quinase 3 da Glicogênio Sintase/antagonistas & inibidores , Inibidores de Proteínas Quinases/farmacologia , Crânio/efeitos dos fármacos , Tiadiazóis/farmacologia , Animais , Masculino , Ratos , Ratos Wistar , Crânio/cirurgia
5.
Acta Cir Bras ; 35(1): e202000102, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32215463

RESUMO

PURPOSE: To evaluate the local effect of simvastatin (SVT) combined with deproteinized bovine bone (DBB) with hydroxyapatite/ß-tricalcium phosphate biphasic ceramics (HA/TCP) and with collagen sponge (CS) on bone repair in critical size defects (CSDs) in rat calvaria. METHODS: Forty-two 5-mm diameter CSDs were made bilaterally in the calvaria of 18 rats. The animals were allocated according to the type of biomaterial and associations used to fill the CSD. After 8 weeks, the animals were euthanized, and their calvaria were evaluated for repaired tissue composition using histologic and histometric analyses. RESULTS: In the histometric analysis, the use of SVT showed to increase bone formation in the CSDs when combined with all the bone substitutes tested in this study (p<0.05). Greater bone formation was observed in the groups with SVT compared to the groups without SVT. CONCLUSIONS: The use of SVT without the need for a vehicle and combined with a commercially available biomaterial may be a cheaper way to potentiate the formation of bone tissue without the need to produce new biomaterials. Therefore, SVT combined with DBB induced significantly greater new bone formation than did the other treatments.


Assuntos
Materiais Biocompatíveis/farmacologia , Substitutos Ósseos/farmacologia , Colágeno/farmacologia , Osteogênese/efeitos dos fármacos , Sinvastatina/farmacologia , Crânio/efeitos dos fármacos , Animais , Anticolesterolemiantes/farmacologia , Regeneração Óssea/efeitos dos fármacos , Transplante Ósseo/métodos , Bovinos , Modelos Animais de Doenças , Feminino , Ratos , Ratos Wistar , Crânio/cirurgia
6.
Cell Prolif ; 53(4): e12796, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32202021

RESUMO

OBJECTIVES: Bone regeneration is a complex process modulated by multiple growth factors and hormones during long regeneration period; thus, designing biomaterials with the capacity to deliver multiple bioactive molecules and obtain sustained release has gained an increasing popularity in recent years. This study is aimed to evaluate the effect of a novel core-shell electrospun fibre loaded with dexamethasone (DEX) and bone morphogenetic protein-2 (BMP-2) on bone regeneration. MATERIALS AND METHODS: The core-shell electrospun fibres were fabricated by coaxial electrospinning technology, which were composed of poly-D, L-lactide (PLA) shell and poly (ethylene glycol) (PEG) core embedded with BMP-2 and DEX-loaded micelles. Morphology, hydrophilicity, gradation, release profile of BMP-2 and DEX, and cytological behaviour on bone marrow mesenchymal stem cells (BMSCs) were characterized. Furthermore, the effect on bone regeneration was evaluated via critical-sized calvarial defect model. RESULTS: The electrospun fibres were featured by the core-shell fibrous architecture and a suitable degradation rate. The sustained release of DEX and BMP-2 was up to 562 hours. The osteogenic gene expression and calcium deposition of BMSCs were significantly enhanced, indicating the osteoinduction capacity of electrospun fibres. This core-shell fibre could accelerate repair of calvarial defects in vivo via synergistic effect. CONCLUSIONS: This core-shell electrospun fibre loaded with DEX and BMP-2 can act synergistically to enhance bone regeneration, which stands as a strong potential candidate for repairing bone defects.


Assuntos
Anti-Inflamatórios/uso terapêutico , Proteína Morfogenética Óssea 2/uso terapêutico , Regeneração Óssea/efeitos dos fármacos , Dexametasona/uso terapêutico , Tecidos Suporte/química , Animais , Anti-Inflamatórios/administração & dosagem , Materiais Biocompatíveis/química , Proteína Morfogenética Óssea 2/administração & dosagem , Células Cultivadas , Dexametasona/administração & dosagem , Sinergismo Farmacológico , Feminino , Humanos , Osteogênese/efeitos dos fármacos , Ratos Sprague-Dawley , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/uso terapêutico , Crânio/efeitos dos fármacos , Crânio/lesões
7.
Int J Nanomedicine ; 15: 647-659, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32099357

RESUMO

Background: Graphene and its derivatives have recently gained popularity in the biomedical field. Previous studies have confirmed that both the mechanical strength and wear resistance of graphene-containing polyethylene have been greatly improved. Therefore, it is being considered as an alternative for artificial joint replacement liners. Based on the literature, the wear debris generated from the traditional polymers used for orthopedic liners could lead to particle-induced osteolysis and, consequently, failure of joint replacement. However, the biological response of this novel graphene-based polymer is still unclear. Therefore, the current study aimed to investigate the in vitro and in vivo biological effects of graphene and graphene oxide (GO) particles on bone. Materials and Methods: The biological responses of graphene and GO particles were tested via in vitro and murine calvarial in vivo models. In the in vitro model, murine macrophage cells were mixed with particles and hydrogel and printed into two differently designed scaffolds; the induced proinflammatory cytokines were then tested. In the murine in vivo model, the particle size distribution was measured via SEM, and these particles were then administrated in the calvarial area, referring to our established model. A micro-CT and histological analysis were performed to examine the biological effects of the particles on bone health. The data were analyzed via the one-way analysis of variance to determine the differences between the groups. Results: Both graphene and GO induced significantly higher TNF-α and IL-6 secretion compared with the control in the three-dimensional in vitro model. In the murine calvarial in vivo test, the graphene and GO particles increased the bone mass compared with the sham groups in the micro-CT analysis. Bone formation was also observed in the histological analysis. Conclusion: In these in vivo and in vitro studies, the graphene and GO wear debris did not seem to induce harmful biological response effect to bone. Bone formation around the skull was observed in the calvarial model instead. Graphene-containing biomaterials could be a suitable new material for application in orthopedic prostheses due to their benefit of eliminating the risk of particle-induce osteolysis.


Assuntos
Grafite/farmacologia , Osteólise/tratamento farmacológico , Crânio/efeitos dos fármacos , Animais , Materiais Biocompatíveis/farmacologia , Feminino , Interleucina-6/metabolismo , Macrófagos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Nanopartículas/química , Osteogênese/efeitos dos fármacos , Osteólise/patologia , Tamanho da Partícula , Células RAW 264.7 , Crânio/citologia , Crânio/diagnóstico por imagem , Tecidos Suporte , Fator de Necrose Tumoral alfa/metabolismo , Microtomografia por Raio-X
9.
Sci Rep ; 10(1): 2277, 2020 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-32042021

RESUMO

Megakaryocytes (MKs) play key roles in regulating bone metabolism. To test the roles of MK-secreted factors, we investigated whether MK and promegakaryocyte (pro-MK) conditioned media (CM) may affect bone formation and resorption. K562 cell lines were differentiated into mature MKs. Mouse bone marrow macrophages were differentiated into mature osteoclasts, and MC3T3-E1 cells were used for osteoblastic experiments. Bone formation was determined by a calvaria bone formation assay in vivo. Micro-CT analyses were performed in the femurs of ovariectomized female C57B/L6 and Balb/c nude mice after intravenous injections of MK or pro-MK CM. MK CM significantly reduced in vitro bone resorption, largely due to suppressed osteoclastic resorption activity. Compared with pro-MK CM, MK CM suppressed osteoblastic differentiation, but stimulated its proliferation, resulting in stimulation of calvaria bone formation. In ovariectomized mice, treatment with MK CM for 4 weeks significantly increased trabecular bone mass parameters, such as bone volume fraction and trabecular thickness, in nude mice, but not in C57B/L6 mice. In conclusion, MKs may secrete anti-resorptive and anabolic factors that affect bone tissue, providing a novel insight linking MKs and bone cells in a paracrine manner. New therapeutic agents against metabolic bone diseases may be developed from MK-secreted factors.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Meios de Cultivo Condicionados/farmacologia , Megacariócitos/metabolismo , Osteogênese/efeitos dos fármacos , Comunicação Parácrina , Animais , Reabsorção Óssea/diagnóstico por imagem , Reabsorção Óssea/tratamento farmacológico , Reabsorção Óssea/etiologia , Diferenciação Celular/fisiologia , Meios de Cultivo Condicionados/metabolismo , Modelos Animais de Doenças , Feminino , Fêmur/diagnóstico por imagem , Fêmur/fisiologia , Humanos , Injeções Intravenosas , Células K562 , Macrófagos/efeitos dos fármacos , Macrófagos/fisiologia , Células Progenitoras de Megacariócitos/metabolismo , Camundongos , Osteoclastos/fisiologia , Osteoporose Pós-Menopausa/diagnóstico por imagem , Osteoporose Pós-Menopausa/tratamento farmacológico , Osteoporose Pós-Menopausa/etiologia , Ovariectomia , Crânio/efeitos dos fármacos , Crânio/fisiologia , Microtomografia por Raio-X
10.
Braz Oral Res ; 34: e007, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32049108

RESUMO

The aim of this study was to assess the influence of cyclosporine administration on the repair of critical-sized calvaria defects (CSDs) in rat calvaria filled with diverse biomaterials. Sixty animals were divided into two groups: the control (CTR) group (saline solution) and the cyclosporine (CCP) group (cyclosporine, 10 mg/kg/day). These medications were administered daily by gavage, beginning 15 days before the surgical procedure and lasting until the day the animals were euthanized. A CSD (5 mm Ø) was made in the calvaria of each animal, which was allocated to one of 3 subgroups, according to the biomaterial used to fill the defect: coagulum (COA), deproteinized bovine bone (DBB), or biphasic calcium phosphate ceramics of hydroxyapatite and ß-phosphate tricalcium (HA/TCP). Euthanasia of the animals was performed 15 and 60 days after the surgical procedure (n = 5 animals/period/subgroup). Bone repair (formation) assessment was performed through microtomography and histometry, while the analyses of the expression of the BMP2, Osteocalcin, and TGFß1 proteins were performed using immunohistochemistry. The CSDs not filled with biomaterials demonstrated lower bone formation in the CCP group. At 15 days, less bone formation was observed in the CSDs filled with DBB, a smaller volume of mineralized tissue was observed in the CSDs filled with HA/TCP, and the expression levels of BMP2 and osteocalcin were lower in the CCP group compared to the CTR group. The use of cyclosporine impaired bone repair in CSD, and this effect can be partially explained by the suppression of BMP2 and osteocalcin expression.


Assuntos
Regeneração Óssea/efeitos dos fármacos , Substitutos Ósseos/farmacologia , Inibidores de Calcineurina/farmacologia , Ciclosporina/farmacologia , Osteogênese/efeitos dos fármacos , Animais , Proteína Morfogenética Óssea 2/análise , Imuno-Histoquímica , Masculino , Osteocalcina/análise , Distribuição Aleatória , Ratos , Reprodutibilidade dos Testes , Crânio/efeitos dos fármacos , Crânio/patologia , Fatores de Tempo , Fator de Crescimento Transformador beta1/análise , Microtomografia por Raio-X
11.
Plast Reconstr Surg ; 145(2): 337e-347e, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31985634

RESUMO

BACKGROUND: Three-dimensionally-printed bioceramic scaffolds composed of ß-tricalcium phosphate delivering the osteogenic agent dipyridamole can heal critically sized calvarial defects in skeletally mature translational models. However, this construct has yet to be applied to growing craniofacial models. In this study, the authors implanted three-dimensionally-printed bioceramic/dipyridamole scaffolds in a growing calvaria animal model and evaluated bone growth as a function of geometric scaffold design and dipyridamole concentration. Potential adverse effects on the growing suture were also evaluated. METHODS: Bilateral calvarial defects (10 mm) were created in 5-week-old (approximately 1.1 kg) New Zealand White rabbits (n = 16 analyzed). Three-dimensionally-printed bioceramic scaffolds were constructed in quadrant form composed of varying pore dimensions (220, 330, and 500 µm). Each scaffold was coated with collagen and soaked in varying concentrations of dipyridamole (100, 1000, and 10,000 µM). Controls consisted of empty defects. Animals were killed 8 weeks postoperatively. Calvariae were analyzed using micro-computed tomography, three-dimensional reconstruction, and nondecalcified histologic sectioning. RESULTS: Scaffold-induced bone growth was statistically greater than bone growth in empty defects (p = 0.02). Large scaffold pores, 500 µm, coated in 1000 µM dipyridamole yielded the most bone growth and lowest degree of scaffold presence within the defect. Histology showed vascularized woven and lamellar bone along with initial formation of vascular canals within the scaffold lattice. Micro-computed tomographic and histologic analysis revealed patent calvarial sutures without evidence of ectopic bone formation across all dipyridamole concentrations. CONCLUSION: The authors present an effective pediatric bone tissue-engineering scaffold design and dipyridamole concentration that is effective in augmentation of calvarial bone generation while preserving cranial suture patency.


Assuntos
Regeneração Óssea/efeitos dos fármacos , Fosfatos de Cálcio/uso terapêutico , Dipiridamol/uso terapêutico , Fraturas Cranianas/cirurgia , Engenharia Tecidual/métodos , Tecidos Suporte , Animais , Dipiridamol/administração & dosagem , Modelos Animais de Doenças , Coelhos , Crânio/efeitos dos fármacos , Crânio/lesões , Fraturas Cranianas/tratamento farmacológico
12.
J Craniofac Surg ; 31(1): 158-161, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31842076

RESUMO

The aim of this study was to evaluate the effect of Concentrated Growth Factor (CGF) on bone healing in diabetic rat model. Experimental diabetes was induced in 24 male Sprague-Dawley rats by streptozotocin. Twenty-four animals served as healthy controls. The animals were divided into 4 subgroups; empty bone defect, grafting with xenogenous graft (Geno-os, OsteoBiol, Turin-Italy), CGF administration, and combined application of the CGF with the xenogenous graft in critical-sized defects in the calvaria of the rats. The diabetic group was given 4 units of Neutral Protamin Hagedorn per day. After 6 weeks, all animals were sacrificed and bone healing was histologically and histomorphometrically analyzed, and the evaluation revealed that the new bone formation in diabetic animals was significantly lower than in healthy group (P: 0.001, P: 0.023). In both groups, the highest rate of ossification was observed in the combined use of xenogenous graft and CGF. When the new bone formation was examined in the graft and CGF group, no significant difference was found between control and diabetic group (P = 0.562; P > 0.05). In conclusion, in patients with diabetes mellitus, combination therapy of CGF with graft is expected to contribute positively to the healing of bone defect.


Assuntos
Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Crânio/efeitos dos fármacos , Animais , Masculino , Osteogênese/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Crânio/patologia , Cicatrização/efeitos dos fármacos
13.
World Neurosurg ; 134: 548, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31785440

RESUMO

We present an image of a patient's skull characterized by dark, irregular discoloration. This was discovered incidentally in a 66-year-old man who underwent craniotomy for resection of a glioblastoma. This image demonstrates cranial black bone disease. This is an abnormal bone pigmentation associated with long-term tetracycline use, as occurred in this patient.


Assuntos
Doenças Ósseas/tratamento farmacológico , Glioblastoma/tratamento farmacológico , Crânio/efeitos dos fármacos , Tetraciclina/farmacologia , Idoso , Antibacterianos/farmacologia , Doenças Ósseas/cirurgia , Craniotomia/métodos , Humanos , Masculino , Crânio/cirurgia , Tempo , Tomografia Computadorizada por Raios X
14.
Drug Deliv Transl Res ; 10(1): 108-121, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31428941

RESUMO

Bone tissue engineering aims to develop bone graft structure that can heal bone defects without using autografts or allografts. The current study was conducted to promote bone regeneration using a collagen type I hydrogel containing tacrolimus. For this purpose, different amounts of tacrolimus (10 µg/ml, 100 µg/ml, and 1000 µg/ml) were loaded into the hydrogel. The resulting drug-loaded hydrogels were characterized for their porosity, swelling capacity, weight loss, drug release, blood compatibility, and cell proliferation (MTT). For functional analysis, the developed hydrogel surrounded by a film made of gelatin and polycaprolactone (PCL) was administrated in the calvarias defect of Wistar rats. The results indicated that the hydrogel has a porosity of 89.2 ± 12.5% and an appropriate swelling, drug release, and blood compatibility behavior. The in vitro results indicated that the collagen hydrogel containing 1000 µg tacrolimus was adequate in terms of cell proliferation. Finally, in vivo studies provided some evidence of the potential of the developed hydrogel for bone healing.


Assuntos
Colágeno Tipo I/química , Consolidação da Fratura/efeitos dos fármacos , Crânio/lesões , Tacrolimo/administração & dosagem , Engenharia Tecidual/métodos , Animais , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Humanos , Hidrogéis , Masculino , Porosidade , Ratos , Ratos Wistar , Crânio/efeitos dos fármacos , Tacrolimo/química , Tacrolimo/farmacologia , Tecidos Suporte
15.
Int J Mol Sci ; 20(23)2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31801223

RESUMO

Matrix metalloproteinase (MMP)-2 and MMP-9 are well-known gelatinases that disrupt the extracellular matrix, including gelatin. However, the advantages of modulating MMP expression in gelatin-based materials for applications in bone regenerative medicine have not been fully clarified. In this study, we examined the effects of epigallocatechin gallate (EGCG), a major polyphenol catechin isolated from green tea, on MMP expression in gelatin sponges and its association with bone formation. Four gelatin sponges with or without EGCG were prepared and implanted into bone defects for up to 4 weeks. Histological and immunohistological staining were performed. Micro-computed tomography was used to estimate the bone-forming capacity of each sponge. Our results showed that EGCG integration attenuated MMP-2 (70.6%) and -9 expression (69.1%) in the 1 week group, increased residual gelatin (118.7%), and augmented bone formation (101.8%) in the 4 weeks group in critical-sized bone defects of rat calvaria compared with vacuum-heated gelatin sponges without EGCG. Moreover, vacuum-heated gelatin sponges with EGCG showed superior bone formation compared with other sponges. The results indicated that integration of EGCG in gelatin-based materials modulated the production and activity of MMP-2 and -9 in vivo, thereby enhancing bone-forming capacity.


Assuntos
Materiais Biocompatíveis/síntese química , Regeneração Óssea/efeitos dos fármacos , Reabsorção Óssea/prevenção & controle , Catequina/análogos & derivados , Gelatina/química , Inibidores de Metaloproteinases de Matriz/farmacologia , Engenharia Tecidual/métodos , Implantes Absorvíveis , Aldeídos/antagonistas & inibidores , Aldeídos/metabolismo , Animais , Reabsorção Óssea/diagnóstico por imagem , Catequina/farmacologia , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Osteoblastos/citologia , Osteoblastos/efeitos dos fármacos , Osteoblastos/fisiologia , Ratos , Ratos Sprague-Dawley , Crânio/diagnóstico por imagem , Crânio/efeitos dos fármacos , Crânio/lesões , Crânio/fisiologia , Tecidos Suporte , Microtomografia por Raio-X
16.
Sci Rep ; 9(1): 18439, 2019 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-31804544

RESUMO

This study investigates a comprehensive model of bone regeneration capacity of dypiridamole-loaded 3D-printed bioceramic (DIPY-3DPBC) scaffolds composed of 100% beta-tricalcium phosphate (ß -TCP) in an immature rabbit model through the time of facial maturity. The efficacy of this construct was compared to autologous bone graft, the clinical standard of care in pediatric craniofacial reconstruction, with attention paid to volume of regenerated bone by 3D reconstruction, histologic and mechanical properties of regenerated bone, and long-term safety regarding potential craniofacial growth restriction. Additionally, long-term degradation of scaffold constructs was evaluated. At 24 weeks in vivo, DIPY-3DPBC scaffolds demonstrated volumetrically significant osteogenic regeneration of calvarial and alveolar defects comparable to autogenous bone graft with favorable biodegradation of the bioactive ceramic component in vivo. Characterization of regenerated bone reveals osteogenesis of organized, vascularized bone with histologic and mechanical characteristics comparable to native bone. Radiographic and histologic analyses were consistent with patent craniofacial sutures. Lastly, through application of 3D morphometric facial surface analysis, our results support that DIPY-3DPBC scaffolds do not cause premature closure of sutures and preserve normal craniofacial growth. Based on this novel evaluation model, this DIPY-3DPBC scaffold strategy is a promising candidate as a safe, efficacious pediatric bone tissue engineering strategy.


Assuntos
Regeneração Óssea/efeitos dos fármacos , Dipiridamol/administração & dosagem , Regeneração Tecidual Guiada/métodos , Crânio/lesões , Tecidos Suporte/química , Animais , Bioimpressão/métodos , Fosfatos de Cálcio/efeitos adversos , Fosfatos de Cálcio/química , Cerâmica/efeitos adversos , Cerâmica/química , Criança , Desenvolvimento Infantil/efeitos dos fármacos , Dipiridamol/efeitos adversos , Modelos Animais de Doenças , Humanos , Desenvolvimento Maxilofacial/efeitos dos fármacos , Modelos Animais , Impressão Tridimensional , Coelhos , Crânio/efeitos dos fármacos , Crânio/crescimento & desenvolvimento , Engenharia Tecidual/métodos , Tecidos Suporte/efeitos adversos
17.
Theranostics ; 9(24): 7140-7155, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31695758

RESUMO

Rationale: Peri-prosthetic osteolysis (PPO) is mainly induced by wear particles and represents the leading cause of implant failure and revision surgery. Previous studies have identified mitigation of wear particle-induced inflammation and bone resorption as the main approaches to treat PPO. Recently, wear particle-induced reduction of bone formation around the prosthesis was identified as a major factor in the development of PPO. Acetyl-11-keto-ß-boswellic acid (AKBA), a derivative of frankincense, has been shown to play a potential role in bone metabolism. However, whether AKBA enhances bone formation in wear particle-induced osteolysis remains unknown. In this study, we examined whether AKBA attenuates titanium particle-induced osteogenic reduction. Methods: Titanium particles were used to induce osteolysis in murine calvaria, and micro-CT and histological analyses were used to evaluate the results. Mouse osteoblast cells, MC3T3-E1 were co-cultured with titanium particles to determine their effect on osteoblast formation in vitro. Results: We demonstrated that AKBA treatment significantly inhibited titanium particle-induced osteogenic inhibition by enhancing osteogenesis both in vivo and in vitro. AKBA treatment also enhanced the phosphorylation of GSK-3ß, decreased the degradation of ß-catenin, and increased the translocation of ß-catenin from the cytoplasm to the nucleus. Taken together, these results showed that AKBA treatment attenuated titanium-induced osteogenic inhibition by activating the GSK-3ß/ß-catenin signaling pathway. Conclusion: These findings suggest that AKBA is a promising new target in the prevention and treatment of PPO.


Assuntos
Glicogênio Sintase Quinase 3 beta/metabolismo , Osteogênese/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Titânio/toxicidade , Triterpenos/farmacologia , beta Catenina/metabolismo , Animais , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Calcificação Fisiológica/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Masculino , Camundongos Endogâmicos C57BL , Osteólise/patologia , Pirimidinonas/farmacologia , Crânio/efeitos dos fármacos , Crânio/patologia
18.
BMC Oral Health ; 19(1): 263, 2019 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-31775860

RESUMO

BACKGROUND: Low-molecular-weight chitosan oligosaccharide (LMCOS), a chitosan degradation product, is water-soluble and easily absorbable, rendering it a popular biomaterial to study. However, its effect on bone remodelling remains unknown. Therefore, we evaluated the effect of LMCOS on lipopolysaccharide (LPS)-induced bone resorption in mice. METHODS: Six-week-old male C57BL/6 mice (n = five per group) were randomly divided into five groups: PBS, LPS, LPS + 0.005% LMCOS, LPS + 0.05% LMCOS, and LPS + 0.5% LMCOS. Then, the corresponding reagents (300 µL) were injected into the skull of the mice. To induce bone resorption, LPS was administered at 10 mg/kg per injection. The mice were injected three times a week with PBS alone or LPS without or with LMCOS and sacrificed 2 weeks later. The skull was removed for micro-computed tomography, haematoxylin-eosin staining, and tartrate-resistant acid phosphatase staining. The area of bone damage and osteoclast formation were evaluated and recorded. RESULTS: LMCOS treatment during LPS-induced skull resorption led to a notable reduction in the area of bone destruction; we observed a dose-dependent decrease in the area of bone destruction and number of osteoclasts with increasing LMCOS concentration. CONCLUSIONS: Our findings showed that LMCOS could inhibit skull bone damage induced by LPS in mice, further research to investigate its therapeutic potential for treating osteolytic diseases is required.


Assuntos
Reabsorção Óssea , Quitosana , Animais , Reabsorção Óssea/tratamento farmacológico , Quitosana/farmacologia , Lipopolissacarídeos/toxicidade , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Oligossacarídeos , Osteoclastos , Crânio/efeitos dos fármacos , Crânio/patologia , Microtomografia por Raio-X
19.
Acta Cir Bras ; 34(9): e201900904, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31778526

RESUMO

PURPOSE: Ganoderma lucidum, a kind of mushroom used for its antioxidant, anti-inflammatory, and immunomodulatory activities, was investigated in the present study for its possible healing effect on calvarial defects with bone grafts. METHODS: Wistar male rats (n = 30) were divided into 3 groups: 1) the control (defect) group (n = 10), 2) defect and graft group (n = 10), and 3) defect, graft, and G. lucidum treated group (n = 10). The G. lucidum was administered to the rats at 20 mL/kg per day via gastric lavage. RESULTS: In the defect and graft group, osteonectin positive expression was observed in osteoblast and osteocyte cells at the periphery of the small bone trabeculae within the graft area. In the defect, graft, and G. lucidum treated group, osteonectin expression was positive in the osteoblast and osteocyte cells and positive osteonectin expression in new bone trabeculae. The expression of matrix metalloproteinase-9 (MMP-9) was positive in the inflammatory cells, fibroblast cells, and degenerated collagen fibril areas within the defect area. CONCLUSION: This study shows that, with its antioxidant and anti-inflammatory properties, G. Lucidum is an important factor in the treatment of calvarial bone defects.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Regeneração Óssea/efeitos dos fármacos , Transplante Ósseo , Reishi/química , Crânio/cirurgia , Animais , Modelos Animais de Doenças , Imuno-Histoquímica , Masculino , Osseointegração/efeitos dos fármacos , Ratos , Ratos Wistar , Crânio/efeitos dos fármacos
20.
Mater Sci Eng C Mater Biol Appl ; 105: 109879, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31546456

RESUMO

In this study, a porous Ti-alloy based implant with an interconnected channel structure (MAO-CaP-BMP2) is fabricated using a method combining 3D printing, microarc oxidation (MAO) treatment, and co-precipitation of Ca,P layer with BMP-2 technique. The macroporous structure with pore size of 600 µm made by 3D printing not only enhances the ingrowth of cells but also allows the formation of blood vessels inside the implant. As a result, the new bond formation is promoted. In addition, the microporous dioxide layer formed on the implant surface by MAO provides the sites for co-precipitation of Ca,P layer with BMP-2. The microstructure allows the prolonged release of BMP-2. Our results show that a sustained release of BMP-2 over 35 days is achieved for MAO-CaP-BMP2 group longer than Ti without MAO modification group and without Ca,P electrochemical deposition group. The slow release of BMP-2 at the bone/implant interface for a long period of time leads to enhancement of the osseointegration between the implant and surrounding bones. This result indicates that MAO-CaP-BMP2 is a good candidate of growth factor carrier. Successful regeneration of bone requires the concomitant processes of osteogenesis and neovascularization. MAO-CaP-BMP2 modified Ti-alloy implant is both osteoinductive and osteoconductive which can create better osteogenesis and angiogenesis. As a result, it can enhance bone formation.


Assuntos
Proteína Morfogenética Óssea 2/farmacologia , Galvanoplastia , Osteogênese/efeitos dos fármacos , Titânio/química , Fator de Crescimento Transformador beta/farmacologia , Ligas/farmacologia , Animais , Fosfatos de Cálcio/farmacologia , Materiais Revestidos Biocompatíveis/farmacologia , Preparações de Ação Retardada/farmacologia , Liberação Controlada de Fármacos , Humanos , Camundongos , Neovascularização Fisiológica/efeitos dos fármacos , Oxirredução , Próteses e Implantes , Coelhos , Proteínas Recombinantes/farmacologia , Crânio/efeitos dos fármacos , Crânio/patologia
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