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1.
Mater Sci Eng C Mater Biol Appl ; 128: 112236, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34474814

RESUMO

In the present study, the synergistic effect of the bioactive glass (BG) and halloysite nanotubes (HNTs) (i.e. BG@HNT) was evaluated on physicochemical and bioactive properties of polyacrylamide/poly (vinyl alcohol) (PMPV) based nanocomposite hydrogels. Here, a double-network hydrogel composed of organic-inorganic components was successfully developed by using in-situ free-radical polymerization and freeze-thawing process. Structural analyses confirmed the successful formation of the nanocomposite hydrogels through physical and chemical interactions. Morphological analysis showed that all hydrogel scaffolds are containing highly porous 3D microstructure and pore-interconnectivity. The equilibrium swelling ratio of the hydrogels was decreased by the addition of BG or BG@HNT and thereby the lower porosity and pore-size reduced the penetration of media and slow down the degradation process. Enhanced biomineralization ability of PMPV/BG@HNT was observed via apatite-forming ability (Ca/P: 1.21 ± 0.14) after immersion in the simulated body fluid as well as significantly enhanced dynamic mechanical properties (compressive strength: 102.1 kPa at 45% of strain and stiffness: 3115.0 N/m at 15% of strain). Furthermore, an enhanced attachment and growth of hFOB1.19 osteoblast cells on PMPV/BG@HNT was achieved compared to PMPV or PMPV/BG hydrogels over 14 days. The PMPV/BG@HNT nanocomposite hydrogel could have a promising application in low-load bearing bone tissue regeneration.


Assuntos
Biomineralização , Nanotubos , Regeneração Óssea , Argila , Vidro , Hidrogéis/farmacologia , Nanogéis , Engenharia Tecidual , Tecidos Suporte
2.
Mater Sci Eng C Mater Biol Appl ; 128: 112287, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34474838

RESUMO

As an emerging 3D printing technique, melt electrospinning writing (MEW) has been used to fabricate scaffolds with controllable structure and good mechanical strength for bone regeneration. However, how to further improve MEW scaffolds with nanoscale extracellular matrix (ECM) mimic structure and bioactivity is still challenging. In this study, we proposed a simple composite process by combining MEW and solution electrospinning (SE) to fabricate a micro/nano hierarchical scaffold for bone tissue engineering. The morphological results confirmed the hierarchical structure with both well-defined MEW microfibrous grid structure and SE random nanofiber morphology. The addition of gelatin nanofibers turned the scaffolds to be hydrophilic, and led to a slight enhancement of mechanical strength. Compared with PCL MEW scaffolds, higher cell adhesion efficiency, improved cell proliferation and higher osteoinductive ability were achieved for the MEW/SE composite scaffolds. Finally, multilayer composite scaffolds were fabricated by alternately stacking of MEW layer and SE layer and used to assess the effect on cell ingrowth in the scaffolds. The results showed that gelatin nanofibers did not inhibit cell penetration, but promoted the three-dimensional growth of bone cells. Thus, the strategy of the combined use of MEW and SE is a potential method to fabricate micro/nano hierarchical scaffolds to improve bone regeneration.


Assuntos
Gelatina , Tecidos Suporte , Regeneração Óssea , Poliésteres , Redação
3.
Mater Sci Eng C Mater Biol Appl ; 128: 112288, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34474839

RESUMO

The bone extracellular matrix (ECM) is a composite scaffold having inorganic hydroxyapatite and organic collagen fibers. Synthetic bone repair scaffolds that mimic the chemical composition of the native ECM and capable of delivering therapeutics are beneficial. In this study, we prepared intrinsically fluorescent organic-inorganic hybrid microparticle biomaterials by sol-gel process. Unlike the conventional Stöber process which requires an alkaline condition for microparticle formation, an acidic condition in the presence of a biodegradable poly(ester amide) (PEA) polymer was used to prepare silica and tertiary bioactive glass hybrids. During their preparation, one or two model drugs were loaded in the microparticles. Our results showed that a gelation temperature between 40 °C-60 °C and the inclusion of PEA were critical for microparticle formation. Unexpectedly, the hybrid microparticles were fluorescent with tunable emission by changing the excitation wavelengths ranging from 300 to 565 nm for potential multiplex imaging. Gene expression studies showed that the hybrid materials induce osteogenic differentiation of 10T1/2 cells without adding exogenous biochemical factors. The bioactivity of the inorganic phase and the dual drug release from homogenous, biodegradable, biocompatible, osteoinductive, and intrinsically fluorescent microparticles may offer a unique platform for bone regeneration and therapy.


Assuntos
Preparações Farmacêuticas , Tecidos Suporte , Amidas , Materiais Biocompatíveis/farmacologia , Regeneração Óssea , Ésteres , Osteogênese
4.
Mater Sci Eng C Mater Biol Appl ; 128: 112295, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34474846

RESUMO

It is of great significance to develop osteoinductive artificial scaffold for bone repair and regeneration. We constructed a biomimetic apatite interface on electrospun polycaprolactone fibers by combining layer-by-layer (LbL) nanocoating with mineralization to fabricate an osteoinductive artificial scaffold. After polydopamine modification, cationic type-І collagen and anionic chondroitin sulfate were sequentially adsorbed on the fiber surface. The fibers coated with the multilayer components served as the precursor matrix to induce apatite deposition. By adjusting the number of the layers and duration of mineralization, the nanoscale morphology of composite fibers was optimized. When ten bilayers of the collagen and chondroitin sulfate were deposited onto the fibers followed by one day-mineralization, the obtained polycaprolactone-apatite composite scaffolds significantly promoted the adhesion, proliferation, and osteogenic differentiation of MC3T3-E1 cells. In a subcutaneous implantation in mice, this composite fiber membrane enhanced in vivo ectopic osteogenesis. Our nano-architectural scaffolds were able to mimic the composition and structure of the bone matrix to a certain extent, holding great potential for bone repair and regeneration.


Assuntos
Sulfatos de Condroitina , Osteogênese , Animais , Regeneração Óssea , Diferenciação Celular , Colágeno , Camundongos , Tecidos Suporte
5.
Mater Sci Eng C Mater Biol Appl ; 128: 112298, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34474849

RESUMO

Guided Bone Regeneration (GBR) is a widely used process for the treatment of periodontal defects to prevent the formation of surrounding soft tissue at the periodontal defect and to provide hard tissue regeneration. Recently GBR designs have focused on the development of resorbable natural polymer-based barrier membranes due to their biodegradability and excellent biocompatibility. The aim of this study is to fabricate a novel bilayer nanocomposite membrane with microporous sublayer composed of chitosan and Si doped nanohydroxyapatite particles (Si-nHap) and chitosan/PEO nanofiber upper layer. Bilayer membrane was designed to prevent epithelial and fibroblastic cell migration and growth impeding bone formation with its upper layer and to support osteogenic cell bioactivity at the defect site with its sublayer. Microporous and nanofiber layers were fabricated by using freeze-drying and electrospinning techniques respectively. The effect of Si-nHap content on the morphological, mechanical and physical properties of the composites were investigated using SEM, AFM, micro-Ct, compression test, water uptake capacity and enzymatic degradation study. Antimicrobial properties of nanocomposite membranes were investigated with tube dilution and disk diffusion methods. In vitro cytotoxicity of bilayer membranes was evaluated. Saos-2 and NIH/3T3 proliferation studies were carried out on each layer. In vitro bioactivity of Saos-2 and NIH/3T3 cells were evaluated with ALP activity and hydroxyproline content respectively. Results showed that Si-nHap incorporation enhanced the mechanical and physical properties as well as controlling biodegradability of the polymer matrix. Besides, Si-nHap loading induced the bioactivity of Saos-2 cells by enhancing cell attachment, spreading and biomineralization on the material surface. Thus, results supported that designed bilayer nanocomposite membranes can be used as a potential biomaterial for guided bone regeneration in periodontal applications.


Assuntos
Quitosana , Nanocompostos , Animais , Materiais Biocompatíveis/farmacologia , Regeneração Óssea , Durapatita , Membranas Artificiais , Camundongos
6.
Mater Sci Eng C Mater Biol Appl ; 128: 112347, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34474897

RESUMO

Although the use of bioactive ions and proteins are crucial for bone defect repair, delivering them in a stable and controlled manner remains challenging. To achieve controlled delivery of osteogenic active factor, we developed a novel double network (DN) hydrogel capable of co-delivering Mg2+ ions and BMP2 in a controlled localized manner. This DN hydrogel was composed of poly (acrylamide) and chitosan, in which the poly (acrylamide) was cross-linked via covalent bond and the chitosan was grafted using bisphosphonate (BP) to form metal coordination bonds with Mg2+ ions. Due to this dynamic dissociation and re-association of the "BP-Mg2+" coordination bond, it was possible to deliver Mg2+ ions in a stable and controlled manner. Additionally, the obtained DN hydrogel exhibited an effective tensile strength (0.62 MPa), perfect stretchability (973% fracture strain), and good creep and recovery properties due to the dynamic cross-linking effect of "BP-Mg2+". Additionally, the hydrogel could synergistically promote the proliferation and differentiation of mouse embryo osteoblast precursor cells (MC3T3-E1 cells) in vitro via the BMP2/Wnt pathway. In the skull defect rat model, this positive delivery government of Mg2+ ions and BMP2 synergistically accelerated bone regeneration. In conclusion, this dynamic cross-linked hydrogel containing Mg2+ ions established a new platform for the sustained release of osteogenesis factor and accelerated the bone regeneration process.


Assuntos
Hidrogéis , Magnésio , Animais , Proteína Morfogenética Óssea 2 , Regeneração Óssea , Diferenciação Celular , Íons , Camundongos , Osteogênese , Ratos
7.
Mater Sci Eng C Mater Biol Appl ; 128: 112359, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34474906

RESUMO

Lipid metabolism in macrophages has been increasingly emphasized in exerting an anti-inflammatory effect and accelerating fracture healing. 12-lipoxygenase (12-LOX) is expressed in several cell types, including macrophages, and oxidizes polyunsaturated fatty acids (PUFAs) to generate both pro- and anti-inflammatory lipid mediators, of which the n-3 PUFAs play an important part in tissue homeostasis/fibrosis. Although mechanical factor regulates the lipid metabolic axis of inflammatory cells, specifically matrix stiffness influences macrophages metabolic responses, little is known about how matrix stiffness affects the 12-LOX-mediated early inflammation in bone repair. In the present study, demineralized bone matrix (DBM) scaffolds with different matrix stiffness were constructed by controlling the duration of decalcification (0 h (control), 1 h (high), 12 h (medium), and 5 d (low)) to repair the defected rat skull. The expression of inflammatory cytokines and macrophages polarization were analyzed. The lipid metabolites and lipid mediators' biosynthesis by matrix stiffness-regulated were further detected. The results showed that the low matrix stiffness could polarize macrophages into an anti-inflammatory phenotype, promote the expression of anti-inflammatory cytokines and specialized pro-resolving lipid mediators (SPMs) biosynthesis beneficial for the osteogenesis of mesenchymal stem cells (MSCs). After treated with ML355, the expression of anti-inflammatory cytokines/proteins and SPMs biosynthesis in macrophages cultured on low-matrix stiffness scaffolds were repressed, and there were almost no statistical differences among all groups. Findings from this study support that matrix stiffness regulates bone repair by modulating 12-LOX-mediated early inflammation, which suggest a direct mechanical impact of matrix stiffness on macrophages lipid metabolism and provide a new insight into the clinical application of SPMs for bone regeneration.


Assuntos
Araquidonato 12-Lipoxigenase , Células-Tronco Mesenquimais , Animais , Regeneração Óssea , Inflamação , Osteogênese , Ratos
8.
Int J Mol Sci ; 22(15)2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34360864

RESUMO

This study evaluated the new bone formation potential of micro-macro biphasic calcium phosphate (MBCP) and Bio-Oss grafting materials with and without dental pulp-derived mesenchymal stem cells (DPSCs) and bone marrow-derived mesenchymal stem cells (BMSCs) in a rabbit calvarial bone defect model. The surface structure of the grafting materials was evaluated using a scanning electron microscope (SEM). The multipotent differentiation characteristics of the DPSCs and BMSCs were assessed. Four circular bone defects were created in the calvarium of 24 rabbits and randomly allocated to eight experimental groups: empty control, MBCP, MBCP+DPSCs, MBCP+BMSCs, Bio-Oss+DPSCs, Bio-Oss+BMSCs, and autogenous bone. A three-dimensional analysis of the new bone formation was performed using micro-computed tomography (micro-CT) and a histological study after 2, 4, and 8 weeks of healing. Homogenously porous structures were observed in both grafting materials. The BMSCs revealed higher osteogenic differentiation capacities, whereas the DPSCs exhibited higher colony-forming units. The micro-CT and histological analysis findings for the new bone formation were consistent. In general, the empty control showed the lowest bone regeneration capacity throughout the experimental period. By contrast, the percentage of new bone formation was the highest in the autogenous bone group after 2 (39.4% ± 4.7%) and 4 weeks (49.7% ± 1.5%) of healing (p < 0.05). MBCP and Bio-Oss could provide osteoconductive support and prevent the collapse of the defect space for new bone formation. In addition, more osteoblastic cells lining the surface of the newly formed bone and bone grafting materials were observed after incorporating the DPSCs and BMSCs. After 8 weeks of healing, the autogenous bone group (54.9% ± 6.1%) showed a higher percentage of new bone formation than the empty control (35.3% ± 0.5%), MBCP (38.3% ± 6.0%), MBCP+DPSC (39.8% ± 5.7%), Bio-Oss (41.3% ± 3.5%), and Bio-Oss+DPSC (42.1% ± 2.7%) groups. Nevertheless, the percentage of new bone formation did not significantly differ between the MBCP+BMSC (47.2% ± 8.3%) and Bio-Oss+BMSC (51.2% ± 9.9%) groups and the autogenous bone group. Our study results demonstrated that autogenous bone is the gold standard. Both the DPSCs and BMSCs enhanced the osteoconductive capacities of MBCP and Bio-Oss. In addition, the efficiency of the BMSCs combined with MBCP and Bio-Oss was comparable to that of the autogenous bone after 8 weeks of healing. These findings provide effective strategies for the improvement of biomaterials and MSC-based bone tissue regeneration.


Assuntos
Regeneração Óssea , Substitutos Ósseos/uso terapêutico , Anormalidades Craniofaciais/cirurgia , Minerais/uso terapêutico , Engenharia Tecidual/métodos , Tecidos Suporte , Animais , Transplante Ósseo , Masculino , Osteogênese , Coelhos , Cicatrização
9.
Int J Oral Implantol (Berl) ; 14(3): 285-302, 2021 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-34415129

RESUMO

PURPOSE: To investigate the effect of platelet-rich fibrin on bone formation by investigating its use in guided bone regeneration, sinus elevation and implant therapy. MATERIALS AND METHODS: This systematic review and meta-analysis were conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The eligibility criteria comprised human controlled clinical trials comparing the clinical outcomes of platelet-rich fibrin with those of other treatment modalities. The outcomes measured included percentage of new bone formation, percentage of residual bone graft, implant survival rate, change in bone dimension (horizontal and vertical), and implant stability quotient values. RESULTS: From 320 articles identified, 18 studies were included. Owing to the heterogeneity of the investigated parameters, a meta-analysis was only possible for sinus elevation. There is a general lack of data from comparative randomised clinical trials evaluating platelet-rich fibrin for guided bone regeneration procedures (only two studies), with no quantifiable advantages in terms of new bone formation or dimensional bone gain found in the platelet-rich fibrin group. For sinus elevation, the meta-analysis demonstrated no advantage in terms of histological new bone formation in the control group (bone graft alone) compared with the test group (bone graft and platelet-rich fibrin). Two studies demonstrated that platelet-rich fibrin may shorten healing periods prior to implant placement. Platelet-rich fibrin was also shown to slightly enhance primary implant stability (implant stability quotient value < 5) as assessed using implant stability quotients and resonance frequency analysis parameters, with no histological data evaluating bone-implant contact yet available on this topic. In one study, platelet-rich fibrin was shown to improve the clinical parameters when utilised as an adjunct for the treatment of peri-implantitis. CONCLUSIONS: In the majority of studies, platelet-rich fibrin offered little or no clear advantage in terms of new bone formation as evaluated in various studies on guided bone regeneration and sinus elevation, nor in implant stability and treatment of peri-implantitis. Various authors and systematic reviews on the topic have now expressed criticism of the various study designs and protocols, and the lack of appropriate controls and available information regarding patient selection. Well-controlled human studies on these specific topics are required.


Assuntos
Implantes Dentários , Fibrina Rica em Plaquetas , Regeneração Óssea , Transplante Ósseo , Humanos , Osteogênese
10.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 39(4): 482-488, 2021 Aug 01.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-34409807

RESUMO

Long-term missing teeth can lead to alveolar bone loss in the edentulous area. Guided bone regeneration (GBR) is a bone augmentation method. It is widely used in clinical practice and broadens the indications of orthodontic treatment to a certain extent. This article reports a case of an adult patient with edentulous space in the maxillary central incisor, which was successfully closed through orthodontic treatment combined with GBR. This study will provide a re-ference for future clinical work.


Assuntos
Perda do Osso Alveolar , Anodontia , Adulto , Regeneração Óssea , Humanos , Incisivo , Maxila , Fechamento de Espaço Ortodôntico
11.
Int J Oral Maxillofac Implants ; 36(4): 633-639, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34411202

RESUMO

PURPOSE: To evaluate the effect of bovine-derived anorganic bone graft (ABB) in combination with hemostatic plant extract (ABS) on bone regeneration. MATERIALS AND METHODS: Three bone defects were created via an extraoral approach on the mandibles of nine domestic pigs. The first defects were filled with ABS solution (0.3 mL/defect) in a transporting agent of ABB (0.3 cc/defect), whereas the second defects were filled with ABS (0.3 mL/defect) in microcapsules for controlled drug release, combined with ABB (0.3 cc/defect) again. The third defects were left empty. After a 10-week healing period and the sacrification, undecalcified sections were prepared for histomorphometric analysis. RESULTS: The mean total area of hard tissue was 29.54% ± 3.2% in the control group, 59.78% ± 5.4% in the conventional group, and 63.67% ± 4.2% in the microsphere group (P < .001). The mean area of newly formed bone was 29.54% ± 3.2% in the control group, 34.79% ± 3.9% in the conventional group, and 37.95% ± 5.3% in the microsphere group (P = .003). The mean residual graft area was 24.99% ± 2.4% in the conventional group and 25.71% ± 4.4% in the microsphere group (P = .730). CONCLUSION: The combined usage of ABS and ABB in both ways increased bone regeneration statistically. However, there was no significant difference between the two methods for ABS delivery systems in terms of new bone regeneration.


Assuntos
Substitutos Ósseos , Hemostáticos , Animais , Regeneração Óssea , Substitutos Ósseos/farmacologia , Substitutos Ósseos/uso terapêutico , Transplante Ósseo , Bovinos , Hemostáticos/farmacologia , Hemostáticos/uso terapêutico , Osteogênese , Extratos Vegetais/farmacologia
12.
Int J Oral Maxillofac Implants ; 36(4): 690-701, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34411207

RESUMO

PURPOSE: To determine the profile of gene expression of soft connective tissue covering bone grafted with deproteinized bovine bone mineral (DBBM) or demineralized freeze-dried bone allograft (DFDBA) in comparison to that without grafting. MATERIALS AND METHODS: Calvaria defects of mice were created and treated as follows: (1) defect without a graft as a control, (2) grafted with DBBM, or (3) grafted with DFDBA. After 1 month, the animals were sacrificed. Soft connective tissue covering the defect area was collected by a punch technique. RNA was isolated and processed to cDNA. Gene expression was evaluated with the microarray technique. Pathway analyses were performed via the PANTHER Overrepresentation test and WikiPathway analysis. Inflammatory marker genes were chosen for mRNA expression using reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR). Tissue sections were used for the histologic and immunohistologic evaluation. RESULTS: The numbers of genes that were significantly differently expressed were 312 (DBBM vs control), 82 (DFDBA vs control), and 113 (DBBM vs DFDBA). Inflammation-related genes were upregulated in DBBM vs control (16 genes), DFDBA vs control (3 genes), and DBBM vs DFDBA (15 genes). Two of these genes, Bcl2a1 and Cxcl9, were significantly upregulated in both the DBBM and DFDBA groups compared with the control. Pathway analysis indicated that Bcl2a1 and Cxcl9 are dominantly expressed in inflammation-related pathways. RT-qPCR and immunohistochemistry showed upregulation of Bcl2a1 and Cxcl9 in DBBM compared with the control and DFDBA groups. Cxcl9 showed a significantly higher expression in the DBBM group. Bcl2a1 at the protein level was equally expressed in all groups. Any sign of inflammation, however, was not seen by histology in any of the groups. CONCLUSION: After a 1-month healing period, soft tissue covering bone grafted with DBBM expressed a higher number of inflammation-related genes compared with those non-grafted or grafted with DFDBA. DFDBA resulted in a decreased expression of inflammation-related genes.


Assuntos
Transplante Ósseo , Tecido Conjuntivo , Aloenxertos , Animais , Regeneração Óssea , Bovinos , Liofilização , Imuno-Histoquímica , Inflamação/genética , Camundongos , Minerais
13.
J Biomed Nanotechnol ; 17(7): 1330-1338, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34446136

RESUMO

The best way in which to prepare scaffolds with good biological properties is an urgent problem in the field of tissue engineering. In this paper we discuss the preparation of nano-hydroxyapatite scaffold of recombinant human bone morphogenetic protein-2 (rhBMP-2) and its application in bone defect repair. rhBMP-2 reagent was dissolved in 1 mol/L sodium dihydrogen phosphate solution, and the rhBMP-2 solution was added to the nano-hydroxyapatite artificial bone with a 100 µL glass micro dropper at the rate of 10 drops/min to obtain Nano-HA/rhBMP-2 composite artificial bone. In in vivo experiments, rabbits were fixed on an operating table, a 2 cm longitudinal incision was made in the middle part of the radial forearm, and the radius was cut with a wire saw and periosteum, 2.5 cm away from the distal radius. After washing the wound with normal saline, Adv-hBMP-2/MC3T3-E1 nano-HA composite artificial bone, MC3T3-E1 nan-HA composite artificial bone, or Nano-HA artificial bone were implanted in different groups. The artificial bone scaffold prepared in this study has a stronger ability to repair bone defects than the alternatives, and is a promising prospect for the clinical treatment of bone defects.


Assuntos
Proteína Morfogenética Óssea 2 , Durapatita , Animais , Regeneração Óssea , Humanos , Osteogênese , Periósteo , Coelhos , Proteínas Recombinantes , Engenharia Tecidual , Tecidos Suporte , Fator de Crescimento Transformador beta
14.
Arch Oral Biol ; 130: 105243, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34416564

RESUMO

OBJECTIVES: The aims of this study were to explore: (ⅰ) the effect of the polypeptide OP 3-4 on bone regeneration in vivo; (ⅱ) the effect of OP 3-4 on osteogenic differentiation of bone marrow mesenchymal stem cells in vitro; and (ⅲ) the potential mechanism of OP 3-4 in promoting osteogenic differentiation of bone marrow mesenchymal stem cells. DESIGNS: 30 Wistar rats (8-week, male) were randomly divided into Control group (n = 5), Hydrogel group (n = 5), and Hydrogel loaded OP 3-4 group (n = 5). Hematoxylin and eosin staining was used to evaluate the level of bone regeneration in mandibular defect. Immunohistochemistry staining was used to evaluate the expression of alkaline phosphatase, runt-related transcription factor 2, and type Ⅰ collagen. Flow cytometry was applied to identify the phenotype of bone marrow mesenchymal stem cells. Furthermore, LY294002, the inhibitor of protein kinase B, was applied to verify the role of OP 3-4 in promoting osteogenic differentiation via protein kinase B/glycogen synthase kinase 3ß/ß-catenin pathway through western blot. RESULTS: OP 3-4 promoted bone regeneration of rat mandibular defect. The expression of osteogenic differentiation related markers were increased after adding OP 3-4 to bone marrow mesenchymal stem cells. OP 3-4 promoted osteogenic differentiation of bone marrow mesenchymal stem cells via protein kinase B/glycogen synthase kinase 3ß/ß-catenin pathway. CONCLUSION: OP 3-4 could promote bone regeneration of mandibular defect and improve osteogenic differentiation through protein kinase B/glycogen synthase kinase 3ß/ß-catenin pathway.


Assuntos
Células-Tronco Mesenquimais , Osteogênese , Animais , Células da Medula Óssea/metabolismo , Regeneração Óssea , Cateninas , Diferenciação Celular , Células Cultivadas , Glicogênio Sintase Quinase 3 beta , Masculino , Células-Tronco Mesenquimais/metabolismo , Proteínas Proto-Oncogênicas c-akt , Ratos , Ratos Wistar , Via de Sinalização Wnt , beta Catenina/metabolismo
15.
Int J Mol Sci ; 22(15)2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34360979

RESUMO

Bone cancer is a demanding challenge for contemporary medicine due to its high frequency of presentation and significant heterogeneity of malignant lesions developing within the bone. To date, available treatments are rarely curative and are primarily aimed at prolonging patients' survival and ameliorating their quality of life. Furthermore, both pharmacological and surgical therapies are aggravated by a consistent burden of adverse events and subsequent disability due to the loss of healthy bone structural and functional properties. Therefore, great research efforts are being made to develop innovative biomaterials able to selectively inhibit bone cancer progression while reducing the loss of bone structural properties secondary to local tissue invasion. In this review, we describe the state of the art of innovative biomaterials for the treatment of bone cancer. Along with physiological bone remodeling, the development of bone metastasis and osteosarcoma will be depicted. Subsequently, recent advances on nanocarrier-based drug delivery systems, as well as the application of novel, multifunctional biomaterials for the treatment of bone cancer will be discussed. Eventually, actual limitations and promising future perspectives regarding the employment of such approaches in the clinical scenario will be debated.


Assuntos
Antineoplásicos/uso terapêutico , Materiais Biocompatíveis/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Animais , Antineoplásicos/química , Materiais Biocompatíveis/química , Regeneração Óssea , Humanos
16.
Int J Mol Sci ; 22(15)2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34360988

RESUMO

Replacement and inflammatory resorption are serious complications associated with the delayed replantation of avulsed teeth. In this study, we aimed to assess whether deferoxamine (DFO) can suppress inflammation and osteoclastogenesis in vitro and attenuate inflammation and bone resorption in a replanted rat tooth model. Cell viability and inflammation were evaluated in RAW264.7 cells. Osteoclastogenesis was confirmed by tartrate-resistant acid phosphatase staining, reactive oxygen species (ROS) measurement, and quantitative reverse transcriptase-polymerase chain reaction in teeth exposed to different concentrations of DFO. In vivo, molars of 31 six-week-old male Sprague-Dawley rats were extracted and stored in saline (n = 10) or DFO solution (n = 21) before replantation. Micro-computed tomography (micro-CT) imaging and histological analysis were performed to evaluate inflammation and root and alveolar bone resorption. DFO downregulated the genes related to inflammation and osteoclastogenesis. DFO also reduced ROS production and regulated specific pathways. Furthermore, the results of the micro-CT and histological analyses provided evidence of the decrease in inflammation and hard tissue resorption in the DFO group. Overall, these results suggest that DFO reduces inflammation and osteoclastogenesis in a tooth replantation model, and thus, it has to be further investigated as a root surface treatment option for an avulsed tooth.


Assuntos
Perda do Osso Alveolar/tratamento farmacológico , Anti-Inflamatórios/uso terapêutico , Desferroxamina/uso terapêutico , Osteogênese , Avulsão Dentária/tratamento farmacológico , Perda do Osso Alveolar/etiologia , Animais , Anti-Inflamatórios/farmacologia , Regeneração Óssea , Desferroxamina/farmacologia , Masculino , Camundongos , Osteoclastos/citologia , Osteoclastos/efeitos dos fármacos , Osteoclastos/metabolismo , Células RAW 264.7 , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Avulsão Dentária/complicações
17.
Int J Mol Sci ; 22(15)2021 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-34360701

RESUMO

Solid platelet-rich fibrin (PRF), consisting of coagulated plasma from fractionated blood, has been proposed to be a suitable carrier for recombinant bone morphogenetic protein 2 (BMP2) to target mesenchymal cells during bone regeneration. However, whether solid PRF can increase the expression of BMPs in mesenchymal cells remains unknown. Proteomics analysis confirmed the presence of TGF-ß1 but not BMP2 in PRF lysates. According to the existing knowledge of recombinant TGF-ß1, we hypothesized that PRF can increase BMP2 expression in mesenchymal cells. To test this hypothesis, we blocked TGF-ß receptor 1 kinase with SB431542 in gingival fibroblasts exposed to PRF lysates. RT-PCR and immunoassays confirmed that solid PRF lysates caused a robust SB431542-dependent increase in BMP2 expression in gingival fibroblasts. Additionally, fractions of liquid PRF, namely platelet-poor plasma (PPP) and the buffy coat (BC) layer, but not heat-denatured PPP (Alb-gel), greatly induced the expression of BMP2 in gingival fibroblasts. Even though PRF has no detectable BMPs, PRF lysates similar to recombinant TGF-ß1 had the capacity to provoke canonical BMP signaling, as indicated by the nuclear translocation of Smad1/5 and the increase in its phosphorylation. Taken together, our data suggest that PRF can activate TGF-ß receptor 1 kinase and consequently induce the production of BMP2 in cells of the mesenchymal lineage.


Assuntos
Proteína Morfogenética Óssea 2/genética , Fibroblastos/metabolismo , Fibrina Rica em Plaquetas/metabolismo , Transdução de Sinais , Adulto , Regeneração Óssea , Células Cultivadas , Feminino , Fibroblastos/fisiologia , Regulação da Expressão Gênica , Gengiva/citologia , Humanos , Masculino , Proteômica , Fator de Crescimento Transformador beta/metabolismo , Adulto Jovem
18.
Beijing Da Xue Xue Bao Yi Xue Ban ; 53(4): 776-784, 2021 Aug 18.
Artigo em Chinês | MEDLINE | ID: mdl-34393244

RESUMO

OBJECTIVE: To examine the morphology and biocompatibility of a native acellular porcine pericardium (APP) in vitro and to evaluate its barrier function and effects on osteogenesis when used in guided bone regeneration (GBR) in vivo. METHODS: First, the morphology of APP (BonanGenⓇ) was detected using a scanning electron microscope (SEM). Next, for biocompatibility test, proliferation of human bone marrow mesenchymal stem cells (hBMSCs) were determined using cell counting kit-8 (CCK-8) after being seeded 1, 3 and 7 days. Meanwhile, the cells stained with phalloidine and 4, 6-diamidino-2-phenylindole (DAPI) were observed using a confocal laser scanning microscopy (CLSM) to view the morphology of cell adhesion and pattern of cell proliferation on day 5. A 3-Beagle dog model with 18 teeth extraction sockets was used for the further research in vivo. These sites were randomly treated by 3 patterns below: filled with Bio-OssⓇand coverd by APP membrane (APP group), filled with Bio-OssⓇand covered by Bio-GideⓇmembrane (BG group) and natural healing (blank group). Micro-CT and hematoxylin-eosin (HE) were performed after 4 and 12 weeks. RESULTS: A bilayer and three-dimensional porous ultrastructure was identified for APP through SEM. In vitro, APP facilitated proliferation and adhesion of hBMSCs, especially after 7 days (P < 0.05). In vivo, for the analysis of the whole socket healing, no distinct difference of new bone ratio was found between all the three groups after 4 weeks (P>0.05), however significantly more new bone regeneration was detected in APP group and BG group in comparison to blank group after 12 weeks (P < 0.05). The radio of bone formation below the membrane was significantly higher in APP group and BG group than blank group after 4 and 12 weeks (P < 0.05), however, the difference between APP group and BG group was merely significant in 12 weeks (P < 0.05). Besides, less resorption of buccal crest after 4 weeks and 12 weeks was observed in APP group of a significant difference compared in blank group (P < 0.05). The resorption in BG group was slightly lower than blank group (P>0.05). CONCLUSION: APP showed considerable biocompatibility and three-dimentional structure. Performing well as a barrier membrane in the dog alveolar ridge preservation model, APP significantly promoted bone regeneration below it and reduced buccal crest resorption. On the basis of this study, APP is a potential osteoconductive and osteoinductive biomaterial.


Assuntos
Regeneração Óssea , Osteogênese , Animais , Materiais Biocompatíveis , Cães , Humanos , Pericárdio , Suínos , Extração Dentária , Alvéolo Dental
19.
Int J Mol Sci ; 22(15)2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34361087

RESUMO

Silica/biopolymer hydrogel-based materials constitute very attractive platforms for various emerging biomedical applications, particularly for bone repair. The incorporation of calcium phosphates in the hybrid network allows for designing implants with interesting biological properties. Here, we introduce a synthesis procedure for obtaining silica-chitosan (CS)-tricalcium phosphate (TCP) xerogels, with CS nominal content varying from 4 to 40 wt.% and 10 to 20 wt.% TCP. Samples were obtained using the sol-gel process assisted with ultrasound probe, and the influence of ethanol or water as washing solvents on surface area, micro- and mesopore volume, and average pore size were examined in order to optimize their textural properties. Three washing solutions with different soaking conditions were tested: 1 or 7 days in absolute ethanol and 30 days in distilled water, resulting in E1, E7, and W30 washing series, respectively. Soaked samples were eventually dried by evaporative drying at air ambient pressure, and the formation of interpenetrated hybrid structures was suggested by Fourier transformed infrared (FTIR) spectroscopy. In addition the impact that both washing solvent and TCP content have on the biodegradation, in vitro bioactivity and osteoconduction of xerogels were explored. It was found that calcium and phosphate-containing ethanol-washed xerogels presented in vitro release of calcium (2-12 mg/L) and silicon ions (~60-75 mg/L) after one week of soaking in phosphate-buffered saline (PBS), as revealed by inductive coupled plasma (ICP) spectroscopy analysis. However, only the release of silicon was detected for water-washed samples. Besides, all the samples exhibited in vitro bioactivity in simulated body fluid (SBF), as well as enhanced in vitro cell growth and also significant focal adhesion development and maturation.


Assuntos
Regeneração Óssea , Fosfatos de Cálcio/química , Quitosana/química , Géis/química , Osteoblastos/citologia , Dióxido de Silício/química , Solventes/química , Materiais Biocompatíveis/química , Líquidos Corporais , Células Cultivadas , Humanos , Teste de Materiais
20.
Stem Cell Res Ther ; 12(1): 432, 2021 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-34344474

RESUMO

BACKGROUND: Bone tissue engineering is a new concept bringing hope for the repair of large bone defects, which remains a major clinical challenge. The formation of vascularized bone is key for bone tissue engineering. Growth of specialized blood vessels termed type H is associated with bone formation. In vivo and in vitro studies have shown that low level laser therapy (LLLT) promotes angiogenesis, fracture healing, and osteogenic differentiation of stem cells by increasing reactive oxygen species (ROS). However, whether LLLT can couple angiogenesis and osteogenesis, and the underlying mechanisms during bone formation, remains largely unknown. METHODS: Mouse bone marrow mesenchymal stem cells (BMSCs) combined with biphasic calcium phosphate (BCP) grafts were implanted into C57BL/6 mice to evaluate the effects of LLLT on the specialized vessel subtypes and bone regeneration in vivo. Furthermore, human BMSCs and human umbilical vein endothelial cells (HUVECs) were co-cultured in vitro. The effects of LLLT on cell proliferation, angiogenesis, and osteogenesis were assessed. RESULTS: LLLT promoted the formation of blood vessels, collagen fibers, and bone tissue and also increased CD31hiEMCNhi-expressing type H vessels in mBMSC/BCP grafts implanted in mice. LLLT significantly increased both osteogenesis and angiogenesis, as well as related gene expression (HIF-1α, VEGF, TGF-ß) of grafts in vivo and of co-cultured BMSCs/HUVECs in vitro. An increase or decrease of ROS induced by H2O2 or Vitamin C, respectively, resulted in an increase or decrease of HIF-1α, and a subsequent increase and decrease of VEGF and TGF-ß in the co-culture system. The ROS accumulation induced by LLLT in the co-culture system was significantly decreased when HIF-1α was inhibited with DMBPA and was followed by decreased expression of VEGF and TGF-ß. CONCLUSIONS: LLLT enhanced vascularized bone regeneration by coupling angiogenesis and osteogenesis. ROS/HIF-1α was necessary for these effects of LLLT. LLLT triggered a ROS-dependent increase of HIF-1α, VEGF, and TGF-ß and resulted in subsequent formation of type H vessels and osteogenic differentiation of mesenchymal stem cells. As ROS also was a target of HIF-1α, there may be a positive feedback loop between ROS and HIF-1α, which further amplified HIF-1α induction via the LLLT-mediated ROS increase. This study provided new insight into the effects of LLLT on vascularization and bone regeneration in bone tissue engineering.


Assuntos
Terapia com Luz de Baixa Intensidade , Osteogênese , Animais , Regeneração Óssea , Células Endoteliais da Veia Umbilical Humana , Humanos , Peróxido de Hidrogênio , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Camundongos , Camundongos Endogâmicos C57BL , Neovascularização Fisiológica
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