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1.
Adv Healthc Mater ; 13(15): e2304595, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38424663

RESUMO

The rapid multiplication of residual tumor cells and poor reconstruction quality of new bone are considered the major challenges in the postoperative treatment of osteosarcoma. It is a promising candidate for composite bone scaffold which combines photothermal therapy (PTT) and bone regeneration induction for the local treatment of osteosarcoma. However, it is inevitable to damage the normal tissues around the tumor due to the hyperthermia of PTT, while mild heat therapy shows a limited effect on antitumor treatment as the damage can be easily repaired by stress-induced heat shock proteins (HSP). This study reports a new type of single-atom Cu nanozyme-loaded bone scaffolds, which exhibit exceptional photothermal conversion properties as well as peroxidase and glutathione oxidase mimicking activities in vitro experiments. This leads to lipid peroxidation (LPO) and reactive oxygen species (ROS) upregulation, ultimately causing ferroptosis. The accumulation of LPO and ROS also contributes to HSP70 inactivation, maximizing PTT efficiency against tumors at an appropriate therapeutic temperature and minimizing the damage to surrounding normal tissues. Further, the bone scaffold promotes bone regeneration via a continuous release of bioactive ions (Ca2+, P5+, Si4+, and Cu2+). The results of in vivo experiments reveal that scaffolds inhibit tumor growth and promote bone repair.


Assuntos
Neoplasias Ósseas , Cobre , Ferroptose , Osteossarcoma , Terapia Fototérmica , Espécies Reativas de Oxigênio , Alicerces Teciduais , Osteossarcoma/terapia , Osteossarcoma/patologia , Osteossarcoma/metabolismo , Osteossarcoma/tratamento farmacológico , Ferroptose/efeitos dos fármacos , Cobre/química , Animais , Alicerces Teciduais/química , Terapia Fototérmica/métodos , Humanos , Camundongos , Linhagem Celular Tumoral , Neoplasias Ósseas/terapia , Neoplasias Ósseas/patologia , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Regeneração Óssea/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Osso e Ossos/patologia , Osso e Ossos/metabolismo , Osso e Ossos/efeitos dos fármacos , Camundongos Nus
2.
J Adv Res ; 2023 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-38030127

RESUMO

INTRODUCTION: The electro-actuated shape memory polymer scaffold has gained increasing attentions on the utilization of minimally invasive surgery for bone defect repair, which requires to construct an efficient conductive network to accomplish electrical-to-thermal conversion from conductive fillers to the entire matrix evenly. OBJECTIVES: In this study, multiwall carbon nanotube (MWCNT) was convective self-assembled on the ZnO tetrapod (t-ZnO) template, where MWCNT was controlled to disperse uniformly and regulated to contact with each other effectively due to the immersion capillary force during the evaporation loss of the convective self-assembly process, leading to an interwoven layer on the t-ZnO surface. METHODS: The prepared t-ZnO@MWCNT assembly was embedded in the poly(L-lactic acid)/thermoplastic polyurethane (PLLA/TPU) scaffold fabricated via selective laser sintering to construct a 3D conductive MWCNT network for improving the electro-actuated shape memory properties. RESULTS: It was observed that the interconnected MWCNT formed a 3D conductive network in the matrix without significant aggregation, which boosted the electrical-to-thermal properties of the scaffold, and the scaffold containing t-ZnO@MWCNT assembly possessed better electro-actuated shape memory properties with shape fixity of 98.0% and shape recovery of 98.8%. CONCLUSION: The scaffold exhibited improved electro-actuated shape memory properties and mechanical properties and the osteogenic inductivity was promoted with the combined effect of t-ZnO and electrical stimulation.

3.
Colloids Surf B Biointerfaces ; 225: 113251, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36931045

RESUMO

Ascorbic acid (AA) is a promising antitumor agent, yet its autooxidation is too slow which constrains the further application. Fortunately, the autoxidation process can be accelerated by transition metal catalysts, especially Fe3+ ions. In this study, AA was loaded to Fe-doped mesoporous silica (designated as AA@Fe-SiO2), which was introduced into poly-L-lactic acid (PLLA) and then prepared into a scaffold. Mechanistically, AA@Fe-SiO2 degraded in acidic tumor microenvironment because excessive H+ substituted Fe atoms in the iron silicate framework, releasing Fe3+ and AA. The Fe3+ boosted the pro-oxidation reaction of AA, generating numerous hydrogen peroxide (H2O2) and Fe2+. Then, Fe2+ reacted with H2O2 to initiate Fenton reactions favoring hydroxyl radical generation, triggering oxidative damage on tumor cells to implement tumor-specific therapy. Results showed that the release amount of AA in acidic solution was about 3 times higher than that in neutral solution, which was attributed to the pH-dependency of the degradation of AA@Fe-SiO2 in scaffold. Furthermore, the scaffold generated numerous ascorbate radical intermediate and increased the H2O2 concentration by 120.2%, demonstrating that Fe3+ remarkably accelerated the oxidation rate of AA. Cell experimental results showed that the scaffold caused massive apoptosis of tumor cells, while no obvious cytotoxicity to normal cells, confirming the antitumor specificity of scaffold. This work paves a promising way to construct a biodegradable and catalytic scaffold, featuring effective tumor-specific therapy.


Assuntos
Ácido Ascórbico , Dióxido de Silício , Peróxido de Hidrogênio/metabolismo , Oxirredução , Ferro , Ácidos
4.
J Colloid Interface Sci ; 632(Pt A): 95-107, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36410298

RESUMO

The movement towards the clinical application of iron (Fe) has been hindered by the slow degradation rate in physiological environments. Herein, manganese dioxide (MnO2) particles were compounded with titanium dioxide (TiO2) particles by mechanical ball milling, and then the mixed powders were incorporated into Fe and fabricated into an implant using selective laser melting. On the one hand, MnO2 had a higher work function (5.21 eV) than Fe (4.48 eV), which inclined electrons to transfer from Fe to MnO2 to accelerate the anode reaction. On the other hand, MnO2 catalysed the oxygen reduction reaction (ORR) through a four-step proton-electron-coupled reaction, which caused more oxygen to flow into the sample to improve the cathode performance. Besides, anatase TiO2 with high conductivity was compounded with MnO2 to construct a composite cathode, which facilitated electron transport from the cathode to the electrolyte, further consuming electrons and promoting cathode reaction. Results showed that Fe-MnO2-TiO2 had a high limiting current density of 5.32 mA·cm-2 and a large half-wave potential of -767.4 mV, indicating an enhanced ORR activity. More significantly, Fe-MnO2-TiO2 had a higher average electron transfer number (2.9) than Fe-MnO2 (2.5), demonstrating a faster electronic consumption reaction and higher cathode performance. In addition, the Fe-MnO2-TiO2 also exhibited fast instantaneous and long-term degradation rates (0.33 ± 0.03 and 0.19 ± 0.02 mm/year), suggesting a high anode dissolution rate. In conclusion, introducing the cathode with high work function and ORR activity provides novel pathways for accelerating the degradation rate of Fe-based implants.


Assuntos
Compostos de Manganês , Óxidos , Elétrons , Ferro , Eletrodos , Oxigênio
5.
Int J Bioprint ; 8(1): 432, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35187274

RESUMO

Graphene oxide (GO) is recognized as a promising antibacterial material that is expected to be used to prepare a new generation of high-efficiency antibacterial coatings. The propensity of GO to agglomeration makes it difficult to apply it effectively. A new method of preparing GO-loaded nickel (GNC) with excellent antibacterial property is proposed in this paper. In this work, GNC was prepared on a titanium sheet by magnetic field-assisted scanning jet electrodeposition. The massive introduction of GO on the coating was proven by energy disperse spectroscopy and Raman spectroscopy. The antibacterial performance of GNC was proven by agar plate assessment and cell living/dead staining. The detection of intracellular reactive oxygen species (ROS) and the concentration of nickel ions, indicate that the antibacterial property of GNC are not entirely derived from the nickel ions released by the coating and the intracellular ROS induced by nickel ions, but rather are due to the synergistic effect of nickel ions and GO.

6.
J Bone Miner Metab ; 40(2): 177-188, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35091784

RESUMO

The differentiation of stem cells into osteoblasts is a key link in the treatment of bone defects and other orthopedic diseases. N6-methyladenosine (m6A) modification, an important post-transcriptional modification, is a methylation that occurs at the N6 site of RNA adenylate. The modification plays a regulatory role in the growth and development of biological individuals, the directional differentiation of stem cells and the occurrence of diseases. It is involved in various processes of the fate decision of stem cells. And it regulates the development and constant renewal of bone and keeps bone homeostasis by controlling and maintaining the balance between osteogenesis and adipogenesis. Meanwhile, it also affects the progress of orthopedic-associated diseases such as degenerative osteoporosis and bone tumor. In this review, we mainly summarize the new findings of three key molecules including Writers, Erasers and Readers which regulate m6A modification, and the emerging role of m6A modification in determining the fate and directed differentiation potential of stem cells, especially highlight the regulatory mechanism of osteogenic differentiation, the balance between osteogenesis and adipogenesis and the occurrence and development of bone-related diseases. It may provide some important ideas about finding new strategies to recover from bone defect and degenerative bone disease.


Assuntos
Adenosina , Osteogênese , Adenosina/genética , Adenosina/metabolismo , Diferenciação Celular , Metilação , Células-Tronco/metabolismo
7.
Front Bioeng Biotechnol ; 9: 783821, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34926428

RESUMO

A too slow degradation of iron (Fe) limits its orthopedic application. In this study, calcium chloride (CaCl2) was incorporated into a Fe-based biocomposite fabricated by laser additive manufacturing, with an aim to accelerate the degradation. It was found that CaCl2 with strong water absorptivity improved the hydrophilicity of the Fe matrix and thereby promoted the invasion of corrosive solution. On the other hand, CaCl2 could rapidly dissolve once contacting the solution and release massive chloride ion. Interestingly, the local high concentration of chloride ion effectively destroyed the corrosion product layer due to its strong erosion ability. As a result, the corrosion product layer covered on the Fe/CaCl2 matrix exhibited an extremely porous structure, thus exhibiting a significantly reduced corrosion resistance. Besides, in vivo cell testing proved that the Fe/CaCl2 biocomposite also showed favorable cytocompatibility.

8.
Mater Sci Eng C Mater Biol Appl ; 120: 111592, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33545810

RESUMO

Bone defects caused by tumors are difficult to repair clinically because of their poor morphology and residual tumor cell-induced recurrence. Scaffolds with the dual function of bone repair and bone tumor treatment are urgently needed to resolve this problem. In this study, a poly(L-lactic acid) (PLLA)/nanoscale hydroxyapatite (nHA)/metformin (MET) nanocomposite scaffold was constructed via selective laser sintering. The scaffolds were expected to combine the excellent mechanical strength and biodegradability of PLLA, the good bioactivity of nHA, and the water solubility and antitumor properties of MET. The PLLA/nHA/MET scaffolds showed improved cell adhesion, appropriate porosity, good biocompatibility and osteogenic-induced ability in vitro because metformin improves water solubility and promotes the osteogenic differentiation of cells within the scaffold. The PLLA/nHA/MET scaffold had an extended drug release time because the MET particles were wrapped in the biodegradable polymer PLLA and the wrapped MET particles were slowly released into body fluids as the PLLA was degraded. Moreover, the scaffold induced osteosarcoma (OS) cell apoptosis by upregulating apoptosis-related gene expression and showed excellent tumor inhibition characteristics in vitro. In addition, the scaffold induced osteogenic differentiation of bone marrow mesenchymal cells (BMSCs) by promoting osteogenic gene expression. The results suggest that the PLLA/nHA/MET composite scaffold has the dual function of tumor inhibition and bone repair and therefore it provides a promising new approach for the treatment of tumor-induced bone defects.


Assuntos
Neoplasias Ósseas , Metformina , Neoplasias Ósseas/tratamento farmacológico , Durapatita , Humanos , Ácido Láctico , Metformina/farmacologia , Osteogênese , Poliésteres , Engenharia Tecidual , Alicerces Teciduais
9.
ACS Appl Bio Mater ; 4(6): 5304-5311, 2021 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-35007011

RESUMO

Magnetite (Fe3O4) nanoparticles as drug carriers can achieve precise drug target due to their magnetic property. However, they are easy to aggregate in the physiological environment, which obviously limits their application in drug delivery. The development of the Fe-MIL-88B-derived method to construct the Fe3O4-loaded mesoporous carbon (Fe3O4/carbon) system is a feasible strategy to solve the issue. First, iron atoms evenly distribute in the organic links through coordination bonds in Fe-MIL-88B. After the carbonization of Fe-MIL-88B, mesoporous carbon acts as a barrier to prevent the aggregation of Fe3O4 nanoparticles. Herein, Fe-MIL-88B particles were fabricated by the hydrothermal method and then pyrolyzed to construct Fe3O4/carbon systems. Results showed that Fe3O4 nanoparticles uniformly in situ grew on mesoporous carbon generated by the carbonization of organic components. More encouragingly, the Fe3O4/carbon system loaded with DOX demonstrated pH-responsive DOX release, efficient delivery of DOX into cancer cells, and significant cancer cell killing ability. Therefore, the Fe3O4/carbon systems prepared by the Fe-MIL-88B-derived method might open up a way for targeted and controlled drug delivery.


Assuntos
Carbono , Nanopartículas , Portadores de Fármacos , Óxido Ferroso-Férrico/química , Ferro/química
10.
Differentiation ; 116: 16-25, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33157509

RESUMO

Osteoporosis is a systemic bone disease with bone fragility and increased fracture risk. The non-coding RNAs (ncRNAs) have appeared as important regulators of cellular signaling and pertinent human diseases. Studies have demonstrated that circular RNAs (circRNAs) and long non-coding RNAs (lncRNAs) are involved in the progression of osteoporosis through a variety of pathways, and are considered as targets for the prophylaxis and treatment of osteoporosis. Based on an in-depth understanding of their roles and mechanisms in osteoporosis, we summarize the functions and molecular mechanisms of circRNAs and lncRNAs involved in the progression of osteoporosis and provide some new insights for the prognosis, diagnosis and treatment of osteoporosis.


Assuntos
Osteogênese/genética , Osteoporose/genética , RNA Circular/genética , RNA Longo não Codificante/genética , Densidade Óssea/genética , Osso e Ossos/citologia , Progressão da Doença , Humanos , Macrófagos/imunologia , Osteoporose/patologia
11.
ACS Appl Mater Interfaces ; 12(41): 46743-46755, 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-32940994

RESUMO

Hydroxyapatite (HAP) can endow a biopolymer scaffold with good bioactivity and osteoconductive ability, while the interfacial bonding is fairly weak between HAP and biopolymers. In this study, HAP was in situ generated on poly(l-lactic acid) (PLLA) particles, and then they were used to fabricate a scaffold by selective laser sintering. Detailedly, PLLA particles were first functionalized by dopamine oxide polymerization, which introduced abundance active catechol groups on the particle surface, and subsequently, the catechol groups concentrated Ca2+ ions by chelation in a simulated body fluid solution, and then, Ca2+ ions absorbed PO43- ions through electrostatic interactions for in situ nucleation of HAP. The results indicated that HAP was homogeneously generated on the PLLA particle surface, and HAP and PLLA exhibited good interfacial bonding in the HAP/PLLA scaffolds. Meanwhile, the scaffolds displayed excellent bioactivity by inducing apatite precipitation and provided a good environment for human bone mesenchymal stem cell attachment, proliferation, and osteogenic differentiation. More importantly, the ingrowth of blood vessel and the formation of new bone could be stimulated by the scaffolds in vivo, and the bone volume fraction and bone mineral density increased by 44.44 and 41.73% compared with the pure PLLA scaffolds, respectively. Serum biochemical indexes fell within the normal range, which indicated that there was no harmful effect on the normal functioning of the body after implanting the scaffold.


Assuntos
Durapatita/química , Células-Tronco Mesenquimais/citologia , Poliésteres/química , Alicerces Teciduais/química , Densidade Óssea , Regeneração Óssea , Durapatita/síntese química , Humanos , Estrutura Molecular , Osteogênese , Tamanho da Partícula , Propriedades de Superfície , Engenharia Tecidual
12.
Int J Biol Sci ; 16(11): 1941-1953, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32398961

RESUMO

Ovarian cancer (OC) is one of the malignant tumors that seriously threaten women's health, with the highest mortality rate in gynecological malignancies. The prognosis of patients with advanced OC is still poor, and the 5-year survival rate is only 20-30%. Therefore, how to improve the early diagnosis rate and therapeutic effect are urgent for patients with OC. In this research, we found that Lin28A can promote the expression of stem cell marker molecules CD133, CD44, OCT4 and Nanog. We later confirmed that Lin28A can enrich the mRNA of ras-related nuclear protein (RAN) and heat shock factor binding protein 1 (HSBP1) through RIP assay, and that Lin28A can regulate their protein expression. We also identified that RAN and HSBP1 are highly expressed in OC tissues, and that they are significantly positively correlated with the expression of Lin28A and negatively correlated with the survival prognosis of OC patients. After stable knockdown of RAN or HSBP1 in OC cells with high expression of Lin28A, the expression of the stem cell marker molecules such as OCT4, CD44 and Nanog are reduced. And after knocking down of RAN or HSBP1 in Lin28A highly expressed OC cells, the survival and invasion of OC cells and tumor size of OC xenograft in nude mice were markedly inhibited and apoptosis was increased. Our data also showed that knock down of RAN or HSBP1 can inhibit the invasion ability of OC cells by decreasing the expression of N-cadherin, Vimentin and promoting the expression of E-cadherin. Meanwhile, knockdown of RAN or HSBP1 induced cell apoptosis by inhibiting the expression of PARP. Our results indicated that Lin28A could regulate the biological behaviors in OC cells through RAN/HSBP1. These findings suggest that Lin28A/RAN/HSBP1 can be used as a marker for diagnosis and prognosis of OC patients, and RAN/HSBP1 may be a potential new target for gene therapy of OC.


Assuntos
Regulação Neoplásica da Expressão Gênica/fisiologia , Proteínas de Choque Térmico/metabolismo , Neoplasias Ovarianas/metabolismo , Proteína ran de Ligação ao GTP/metabolismo , Animais , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Proteínas de Choque Térmico/genética , Humanos , Camundongos , Neoplasias Experimentais , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Regulação para Cima , Proteína ran de Ligação ao GTP/genética
14.
Cell Prolif ; 53(5): e12814, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32346990

RESUMO

OBJECTIVES: Increasing evidences suggest that inducing mesenchymal stem cells to differentiate into osteoblasts has been as an especially important component in the prevention and therapy for degenerative bone disease. Here, we identify a novel lncRNA, linc02349, which increases significantly during osteogenic differentiation. MATERIALS AND METHODS: Human umbilical cord-derived stem cells (hUC-MSCs) and dental pulp mesenchymal stem cells were used. Overexpression and knockdown of linc02349 in cell lines were generated using lentiviral-mediated gene delivery method. Bioinformatics prediction, Ago2-RIP assay and dual-luciferase reporter system were employed to examine miRNA which interacts with linc02349. The RNA FISH assay was performed to identify the subcelluar location of linc02349. Alizarin Red S staining, ALP staining and qPCR were applied to identify the osteogenic differentiation. The potential linc02349-regulated genes, miR-25-3p and miR-33b-5p, were explored by ChIP, RIP and Western blotting assays. Micro-CT was used to measure the osteogenic content in bone formation assay in vivo. RESULTS: Linc02349 overexpression improves osteogenic differentiation by in vitro and in vivo analysis. Mechanistically, linc02349 acts as a molecular sponge for miR-25-3p and miR-33b-5p to control expression abundance of SMAD5 and Wnt10b, respectively, which eventually activated Dlx5/OSX pathway and hence promoted osteogenic differentiation. In addition, we revealed that STAT3 interacts with linc02349 promoter region and positively regulates the linc02349 transcriptional activity. CONCLUSION: These findings identify that linc02349 modulates the osteogenic differentiation through acting as a sponge RNA of miR-25-3p and miR-33b-5p and regulating SMAD5 and Wnt10b, and proposed a new interaction between STAT3 and linc02349, which could be a potential target in the process the osteogenesis of hUC-MSCs for future clinical application.


Assuntos
Células-Tronco Mesenquimais/patologia , MicroRNAs/genética , Osteogênese/genética , RNA Longo não Codificante/genética , Cordão Umbilical/patologia , Diferenciação Celular/genética , Células Cultivadas , Células HEK293 , Humanos , Osteoblastos/patologia , Regiões Promotoras Genéticas/genética , Fator de Transcrição STAT3/genética , Transcrição Gênica/genética
15.
ACS Appl Mater Interfaces ; 12(20): 23464-23473, 2020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-32345014

RESUMO

Graphene oxide (GO) can improve the degradation resistance of biomedical Mg alloy because of its excellent impermeability and outstanding chemical inertness. However, the weak interfacial bonding between GO and Mg matrix leads to easily detaching during degradation. In this study, in situ reaction induced by TiO2 took place in the AZ61-GO biocomposite to enhance the interfacial bonding between GO and Mg matrix. For the specific process, TiO2 was uniformly and tightly deposited onto the GO surface by hydrothermal reaction (TiO2/GO) first and then used for fabricating AZ61-TiO2/GO biocomposites by selective laser melting (SLM). Results showed that TiO2 was in situ reduced by magnesiothermic reaction during SLM process, and the reduzate Ti, on the one hand, reacted with Al in the AZ61 matrix to form TiAl2 and, on the other hand, reacted with GO to form TiC at the AZ61-GO interface. Owing to the enhanced interfacial bonding, the AZ61-TiO2/GO biocomposite showed 12.5% decrease in degradation rate and 10.1% increase in compressive strength as compared with the AZ61-GO biocomposite. Moreover, the AZ61-TiO2/GO biocomposite also showed good cytocompatibility because of the slowed degradation. These findings may provide guidance for the interfacial enhancement in GO/metal composites for biomedical applications.


Assuntos
Ligas/química , Materiais Revestidos Biocompatíveis/química , Grafite/química , Titânio/química , Ligas/toxicidade , Linhagem Celular Tumoral , Materiais Revestidos Biocompatíveis/toxicidade , Grafite/toxicidade , Humanos , Magnésio/química , Magnésio/toxicidade , Titânio/toxicidade
16.
Mater Sci Eng C Mater Biol Appl ; 108: 110486, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31924055

RESUMO

The poor interfacial bonding and resultant agglomeration of nanoparticles in polymer-based composite severely deteriorated their reinforcement effect. In this work, MgO nanoparticles (MgO-NPs) were surface modified with Poly (L-lactic acid-co-malic acid) (PLMA) to improve the interfacial compatibility in Poly-l-lactic acid (PLLA) scaffold manufactured by selective laser sintering. PLMA possess a hydrophilic end with carboxyl group (comes from the malic acid) and an l-lactic acid chain. On one hand, the carboxyl group was able to form hydrogen bonding with the hydroxyl groups of MgO-NPs. On the other hand, the l-lactic acid chain containing the hydroxyl groups could react with the carboxyl group of PLLA. Results revealed that the scaffold exhibited significantly enhanced compressive strength and modulus by 47.1% and 237.7%, respectively, which could be ascribed to the enhanced interfacial bonding between PLLA and MgO-NPs, as well as the rigid particle reinforcement. In addition, the scaffold was favorable for cell adhesion, proliferation and differentiation, owing to the improved hydrophilic and suitable pH environment. It was suggested the scaffold was a promising material for bone repair application.


Assuntos
Materiais Biocompatíveis/química , Osso e Ossos/química , Óxido de Magnésio/química , Poliésteres/química , Propriedades de Superfície , Alicerces Teciduais/química , Osso e Ossos/fisiologia , Adesão Celular , Linhagem Celular Tumoral , Força Compressiva , Humanos , Ligação de Hidrogênio , Concentração de Íons de Hidrogênio , Lasers , Microscopia Eletrônica de Transmissão , Porosidade , Pós , Estresse Mecânico , Engenharia Tecidual/métodos
17.
Colloids Surf B Biointerfaces ; 185: 110587, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31648118

RESUMO

Piezoelectric effect of polyvinylidene fluoride (PVDF) plays a crucial role in restoring the endogenous electrical microenvironment of bone tissue, whereas more ß phase in PVDF leads to higher piezoelectric performance. Nanoparticles can induce the nucleation of the ß phase. However, they are prone to aggregate in PVDF matrix, resulting in weakened nucleation ability of ß phase. In this work, the hydroxylated BaTiO3 nanoparticles were functionalized with polydopamine to promote their dispersion in PVDF scaffolds fabricated via selective laser sintering. On one hand, the catechol groups of polydopamine could form hydrogen bonding with the hydroxyl groups of the BaTiO3. On the other hand, the amino groups of polydopamine were able to bond with CF group of PVDF. As a result, the functionalized BaTiO3 nanoparticles homogeneously distributed in PVDF matrix, which significantly increased the ß phase fraction from 46% to 59% with an enhanced output voltage by 356%. Cell testing confirmed the enhanced surface electric cues significantly promoted cell adhesion, proliferation and differentiation. Furthermore, the scaffolds exhibited enhanced tensile strength and modulus, which was ascribed to the rigid particle strengthening effect and the improved interfacial adhesion. This study suggested that the piezoelectric scaffolds shown a potential application in bone repair.


Assuntos
Compostos de Bário/química , Materiais Biocompatíveis/química , Indóis/química , Nanopartículas/química , Osteossarcoma/patologia , Polímeros/química , Polivinil/química , Alicerces Teciduais/química , Titânio/química , Neoplasias Ósseas/patologia , Adesão Celular , Diferenciação Celular , Proliferação de Células , Eletricidade , Humanos , Células Tumorais Cultivadas
18.
Cell Death Dis ; 10(12): 947, 2019 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-31827076

RESUMO

Long noncoding RNAs (lncRNAs) have been demonstrated to be important regulators during the osteogenic differentiation of mesenchymal stem cells (MSCs). We analyzed the lncRNA expression profile during osteogenic differentiation of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) and identified a significantly downregulated lncRNA RP11-527N22.2, named osteogenic differentiation inhibitory lncRNA 1, ODIR1. In hUC-MSCs, ODIR1 knockdown significantly promoted osteogenic differentiation, whereas overexpression inhibited osteogenic differentiation in vitro and in vivo. Mechanistically, ODIR1 interacts with F-box protein 25 (FBXO25) and facilitates the proteasome-dependent degradation of FBXO25 by recruiting Cullin 3 (CUL3). FBXO25 increases the mono-ubiquitination of H2BK120 (H2BK120ub) which subsequently promotes the trimethylation of H3K4 (H3K4me3). Both H2BK120ub and H3K4me3 form a loose chromatin structure, inducing the transcription of the key transcription factor osterix (OSX) and increasing the expression of the downstream osteoblast markers, osteocalcin (OCN), osteopontin (OPN), and alkaline phosphatase (ALP). In summary, ODIR1 acts as a key negative regulator during the osteogenic differentiation of hUC-MSCs through the FBXO25/H2BK120ub/H3K4me3/OSX axis, which may provide a novel understanding of lncRNAs that regulate the osteogenesis of MSCs and a potential therapeutic strategy for the regeneration of bone defects.


Assuntos
Proteínas F-Box/genética , Histonas/genética , Proteínas do Tecido Nervoso/genética , Osteogênese/genética , RNA Longo não Codificante/genética , Fator de Transcrição Sp7/genética , Diferenciação Celular/genética , Células Cultivadas , Regulação da Expressão Gênica no Desenvolvimento/genética , Humanos , Células-Tronco Mesenquimais/citologia , Osteoblastos/metabolismo , Osteocalcina/genética , Osteopontina/genética , Transdução de Sinais/genética , Cordão Umbilical/citologia
19.
J Appl Biomater Funct Mater ; 17(2): 2280800019857064, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31597509

RESUMO

BACKGROUND: Rapid corrosion rates are a major impediment to the use of magnesium alloys in bone tissue engineering despite their good mechanical properties and biodegradability. Zinc is a promising alloy element, and it is an effective grain refiner for magnesium. ß-Ca3(PO4)2 (ß-TCP) is widely used for bone regeneration because of its good biocompatibility, and it also has a similar chemical and crystal structure to human bone. METHODS: In this research, the magnesium alloy was reinforced by adding 3%Zn (wt.%) and 5%ß-TCP (wt.%) particles in order to improve the corrosion resistance and biocompatibility. Furthermore, the biomaterial was prepared through powder metallurgy technology using NH4HCO3 as space-holding particles to construct porous Mg-3%Zn/5%ß-TCP scaffolds. RESULTS: The results revealed that the magnesium-zinc phase and calcium phosphate phase were uniformly distributed in the α-magnesium matrix. Mechanical and corrosion tests indicated that the scaffolds had mechanical strengths similar to that of human bone, and their corrosion resistance decreased with an increase in the porosity. The scaffolds had cytotoxicity grades of 0-1 against MG63 cells, SaoS2 cells, and HK-2 cells, which suggested that they were appropriate for cellular applications. In addition, the scaffolds demonstrated excellent biocompatibility when tested in rabbits. CONCLUSIONS: These results indicate that porous Mg-3%Zn/5%ß-TCP scaffolds are promising biodegradable implants for bone tissue engineering.


Assuntos
Implantes Absorvíveis , Ligas , Regeneração Óssea/efeitos dos fármacos , Fosfatos de Cálcio , Magnésio , Alicerces Teciduais/química , Zinco , Ligas/química , Ligas/farmacologia , Animais , Osso e Ossos/metabolismo , Osso e Ossos/patologia , Fosfatos de Cálcio/química , Fosfatos de Cálcio/farmacologia , Linhagem Celular Tumoral , Corrosão , Humanos , Magnésio/química , Magnésio/farmacologia , Porosidade , Coelhos , Engenharia Tecidual , Zinco/química , Zinco/farmacologia
20.
Mater Sci Eng C Mater Biol Appl ; 104: 109935, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31500057

RESUMO

The slow degradation of Fe severely restricts its application in bone repair although it possesses good biocompatibility and high mechanical properties. In this study, carbon nanotubes (CNTs) were introduced to accelerate Fe biodegradation: (I) CNTs acted as cathodes to induce galvanic corrosion owing to their differences in corrosion potential; (II) The large specific surface area of CNTs increased area ratios of cathode to anode; (III) The excellent electrical conductivity of CNTs allowed significant levels of electron transfer through the cathode in galvanic corrosion. Consequently, the degradation rate of Fe/CNTs composites greatly increased by 74% with the increase of CNTs (0.3-0.9 wt%). Further addition of CNTs would lead to corrosion holes and cracks due to localized corrosion. Besides, cell culture experiments showed that MG-63 cells could normally proliferate to maintain their population, indicating good cytocompatibility of Fe/CNTs composites. The results proved that the incorporation of CNTs into Fe was an effective approach to develop Fe-based bone implants with enhanced degradation rates.


Assuntos
Ferro/química , Nanotubos de Carbono/química , Biodegradação Ambiental , Linhagem Celular Tumoral , Sobrevivência Celular , Corrosão , Eletroquímica , Dureza , Humanos , Nanotubos de Carbono/ultraestrutura , Tamanho da Partícula , Difração de Raios X
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