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1.
Int J Mol Sci ; 21(23)2020 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-33255398

RESUMO

Adipose-derived mesenchymal stromal cells (Ad-MSCs) are a promising tool for articular cartilage repair and regeneration. However, the terminal hypertrophic differentiation of Ad-MSC-derived cartilage is a critical barrier during hyaline cartilage regeneration. In this study, we investigated the role of matrilin-3 in preventing Ad-MSC-derived chondrocyte hypertrophy in vitro and in an osteoarthritis (OA) destabilization of the medial meniscus (DMM) model. Methacrylated hyaluron (MAHA) (1%) was used to encapsulate and make scaffolds containing Ad-MSCs and matrilin-3. Subsequently, the encapsulated cells in the scaffolds were differentiated in chondrogenic medium (TGF-ß, 1-14 days) and thyroid hormone hypertrophic medium (T3, 15-28 days). The presence of matrilin-3 with Ad-MSCs in the MAHA scaffold significantly increased the chondrogenic marker and decreased the hypertrophy marker mRNA and protein expression. Furthermore, matrilin-3 significantly modified the expression of TGF-ß2, BMP-2, and BMP-4. Next, we prepared the OA model and transplanted Ad-MSCs primed with matrilin-3, either as a single-cell suspension or in spheroid form. Safranin-O staining and the OA score suggested that the regenerated cartilage morphology in the matrilin-3-primed Ad-MSC spheroids was similar to the positive control. Furthermore, matrilin-3-primed Ad-MSC spheroids prevented subchondral bone sclerosis in the mouse model. Here, we show that matrilin-3 plays a major role in modulating Ad-MSCs' therapeutic effect on cartilage regeneration and hypertrophy suppression.

2.
J Am Chem Soc ; 2020 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-33382947

RESUMO

The electrochemical CO2 reduction reaction (CO2RR) using Cu-based catalysts holds great potential for producing valuable multi-carbon products from renewable energy. However, the chemical and structural state of Cu catalyst surfaces during the CO2RR remains a matter of debate. Here, we show the structural evolution of the near-surface region of polycrystalline Cu electrodes under in situ conditions through a combination of grazing incidence X-ray absorption spectroscopy (GIXAS) and X-ray diffraction (GIXRD). The in situ GIXAS reveals that the surface oxide layer is fully reduced to metallic Cu before the onset potential for CO2RR, and the catalyst maintains the metallic state across the potentials relevant to the CO2RR. We also find a preferential surface reconstruction of the polycrystalline Cu surface toward (100) facets in the presence of CO2. Quantitative analysis of the reconstruction profiles reveals that the degree of reconstruction increases with increasingly negative applied potentials, and it persists when the applied potential returns to more positive values. These findings show that the surface of Cu electrocatalysts is dynamic during the CO2RR, and emphasize the importance of in situ characterization to understand the surface structure and its role in electrocatalysis.

3.
Int J Nanomedicine ; 15: 8437-8449, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33162754

RESUMO

Background: Lipid polymer hybrid nanoparticles (LPHNPs) have been widely investigated in drug and gene delivery as well as in medical imaging. A knowledge of lipid-based surface engineering and its effects on how the physicochemical properties of LPHNPs affect the cell-nanoparticle interactions, and consequently how it influences the cytological response, is in high demand. Methods: Herein, we have engineered antibiotic-loaded (doxycycline or vancomycin) LPHNPs with cationic and zwitterionic lipids and examined the effects on their physicochemical characteristics (size and charge), antibiotic entrapment efficiency, and the in vitro intracellular bacterial killing efficiency against Mycobacterium smegmatis or Staphylococcus aureus infected macrophages. Results: The incorporation of cationic or zwitterionic lipids in the LPHNP formulation resulted in a size reduction in LPHNPs formulations and shifted the surface charge of bare NPs towards positive or neutral values. Also observed were influences on the drug incorporation efficiency and modulation of the drug release from the biodegradable polymeric core. The therapeutic efficacy of LPHNPs loaded with vancomycin was improved as its minimum inhibitory concentration (MIC) (2 µg/mL) versus free vancomycin (4 µg/mL). Importantly, our results show a direct relationship between the cationic surface nature of LPHNPs and its intracellular bacterial killing efficiency as the cationic doxycycline or vancomycin loaded LPHNPs reduced 4 or 3 log CFU respectively versus the untreated controls. Conclusion: In our study, modulation of surface charge in the nanomaterial formulation increased macrophage uptake and intracellular bacterial killing efficiency of LPHNPs loaded with antibiotics, suggesting alternate way for optimizing their use in biomedical applications.


Assuntos
Antibacterianos/farmacologia , Sistemas de Liberação de Medicamentos , Espaço Intracelular/microbiologia , Macrófagos/microbiologia , Nanopartículas/química , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Liberação Controlada de Fármacos , Lipídeos/química , Macrófagos/efeitos dos fármacos , Camundongos , Testes de Sensibilidade Microbiana , Mycobacterium smegmatis/efeitos dos fármacos , Tamanho da Partícula , Polímeros/química , Staphylococcus aureus/efeitos dos fármacos , Vancomicina/farmacologia
4.
Adv Sci (Weinh) ; 7(17): 2001365, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32995130

RESUMO

Human pluripotent stem cells (hPSCs) are a potent source of clinically relevant mesenchymal stem cells (MSCs) that confer functional and structural benefits in cell therapy and tissue regeneration. Obtaining sufficient numbers of MSCs in a short period of time and enhancing the differentiation potential of MSCs can be offered the potential to improve the regenerative activity of MSCs therapy. In addition, the underlying processes in the isolation and derivation of MSCs from hPSCs are still poorly understood and controlled. To overcome these clinical needs, an efficient and simplified technique on the isolation of MSCs from spontaneously differentiated human embryonic stem cells (hESCs) via integrin α5ß1 (fibronectin (FN) receptor)-to-FN interactions (hESC-FN-MSCs) is successfully developed. It is demonstrated that hESC-FN-MSCs exhibit a typical MSC surface phenotype, cellular morphology, with the whole transcriptome similar to conventional adult MSCs; but show higher proliferative capacity, more efficient trilineage differentiation, enhanced cytokine secretion, and attenuated cellular senescence. In addition, the therapeutic potential and regenerative capacity of the isolated hESC-FN-MSCs are confirmed by in vitro and in vivo multilineage differentiation. This novel method will be useful in the generation of abundant amounts of clinically relevant MSCs for stem cell therapeutics and regenerative medicine.

5.
J Control Release ; 328: 596-607, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32946872

RESUMO

A high level of reactive oxygen species (ROS) such as hydrogen peroxide (H2O2) upregulates pro-inflammatory cytokines and inhibits the osteogenic differentiation of mesenchymal stem cells (MSCs), which are key factors in bone regeneration. Ursodeoxycholic acid (UDCA), a hydrophilic bile acid, has antioxidant and anti-inflammatory activities and also plays beneficial roles in bone regeneration by stimulating the osteogenic differentiation of MSCs while suppressing their adipogenic differentiation. Despite its remarkable capacity for bone regeneration, multiple injections of UDCA induce adverse side effects such as mechanical stress and contamination in bone defects. To fully exploit the beneficial roles of UDCA, a concept polymeric prodrug was developed based on the hypothesis that removal of overproduced H2O2 will potentiate the osteogenic functions of UDCA. In this work, we report bone regenerative nanoparticles (NPs) formulated from a polymeric prodrug of UDCA (PUDCA) with UDCA incorporated in its backbone through H2O2-responsive peroxalate linkages. The PUDCA NPs displayed potent antioxidant and anti-inflammatory activities in MSCs and induced osteogenic rather than adipogenic differentiation of the MSCs. In rat models of bone defect, the PUDCA NPs exhibited significantly better bone regeneration capacity and anti-inflammatory effects than equivalent amounts of UDCA. We anticipate that PUDCA NPs have tremendous translational potential as bone regenerative agents.

6.
Stem Cell Res Ther ; 11(1): 363, 2020 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-32831130

RESUMO

BACKGROUND: Chronic low back pain is a prevalent disability, often caused by intervertebral disc (IVD) degeneration. Mesenchymal stem cell (MSC) therapy could be a safe and feasible option for repairing the degenerated disc. However, for successful translation to the clinic, various challenges need to be overcome including unwanted adverse effects due to acidic pH, hypoxia, and limited nutrition. Matrilin-3 is an essential extracellular matrix (ECM) component during cartilage development and ossification and exerts chondrocyte protective effects. METHODS: This study evaluated the effects of matrilin-3-primed adipose-derived MSCs (Ad-MSCs) on the repair of the degenerated disc in vitro and in vivo. We determined the optimal priming concentration and duration and developed an optimal protocol for Ad-MSC spheroid generation. RESULTS: Priming with 10 ng/ml matrilin-3 for 5 days resulted in the highest mRNA expression of type 2 collagen and aggrecan in vitro. Furthermore, Ad-MSC spheroids with a density of 250 cells/microwell showed the increased secretion of favorable growth factors such as transforming growth factor beta (TGF-ß1), TGF-ß2, interleukin-10 (IL-10), granulocyte colony-stimulating factor (G-CSF), and matrix metalloproteinase 1 (MMP1) and decreased secretion of hypertrophic ECM components. In addition, matrilin-3-primed Ad-MSC spheroid implantation was associated with optimal repair in a rabbit model. CONCLUSION: Our results suggest that priming MSCs with matrilin-3 and spheroid formation could be an effective strategy to overcome the challenges associated with the use of MSCs for the treatment of IVD degeneration.

8.
Int J Mol Sci ; 21(12)2020 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-32560070

RESUMO

Tauroursodeoxycholic acid (TUDCA) is a US FDA-approved hydrophilic bile acid for the treatment of chronic cholestatic liver disease. In the present study, we investigate the effects of TUDCA on the proliferation and differentiation of osteoblasts and its therapeutic effect on a mice model of osteoporosis. Following treatment with different concentrations of TUDCA, cell viability, differentiation, and mineralization were measured. Three-month-old female C57BL/6 mice were randomly divided into three groups (n = 8 mice per group): (i) normal mice as the control group, (ii) ovariectomy (OVX) group (receiving phosphate-buffered saline (PBS) treatment every other day for 4 weeks), and (iii) OVX group with TUDCA (receiving TUDCA treatment every other day for 4 weeks starting 6 weeks after OVX). At 11 weeks post-surgery, serum levels of procollagen type I N-terminal propeptides (PINP) and type I collagen crosslinked C-telopeptides (CTX) were measured, and all mice were sacrificed to examine the distal femur by micro-computed tomography (CT) scans and histology. TUDCA (100 nM, 1 µM) significantly increased the proliferation and viability of osteoblasts and osteoblast differentiation and mineralization when used in vitro. Furthermore, TUDCA neutralized the detrimental effects of methylprednisolone (methylprednisolone-induced osteoblast apoptosis). In the TUDCA treatment group the PINP level was higher and the CTX level was lower, but these levels were not significantly different compared to the PBS treatment group. Micro-CT and histology showed that the TUDCA treatment group preserved more trabecular structures in the distal femur compared to the PBS treatment group. In addition, the TUDCA treatment group increased the percentage bone volume with respect to the total bone volume, bone mineral density, and mice distal femur trabeculae compared with the PBS treatment group. Taken together, our findings suggest that TUDCA may provide a favorable effect on bones and could be used for the prevention and treatment of osteoporosis.

9.
Int J Biol Macromol ; 159: 474-486, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32437816

RESUMO

Poly(acrylamide-co-acrylamidoglycolic acid)/guar gum@ Ag-nanocomposite (AgNC@PAAG) hydrogels has been fabricated by a green protocol utilizing rhubarb stem-extract as bioreductant. The prepared nanocomposites (NCs) are formulated by varying guar gum (GG) polymer and cross-linker content, and used remarkably to study the release of an anticancer drug, 5-fluorouracil (FU). The AgNC@PAAG has demonstrated its potential in bacterial inactivation and p-nitrophenol (PNP) reduction. The AgNC@PAAG hydrogels showed extended FU release time, which was up to 23 h in pH 7.4. The higher zone of inhibition was documented for AgNC@PAAG against B. subtilis and E. coli. It was noticed that, the inhibition activity of AgNC@PAAG, was directly proportional to cross-linker content than the GG polymer. The efficiency of AgNC@PAAG as a nanocatalyst was evaluated for a model reduction reaction of p-nitrophenol (PNP) reduction by aqueous sodium borohydride (NaBH4), with an apparent rate constant of 121.8 × 10-3 min-1 at ambient temperature. The proposed nanocatalysts are reliable and recyclable, demonstrated its catalytic recycle efficacy of 85% after the third successive run. These NCs robust its biological and catalytic activity after embedding silver nanoparticles (AgNPs) by the bioreduction process; these optimized nanocatalysts can be remarkably used in biomedical healthcare sectors and industrial catalysis.

10.
Tissue Eng Part B Rev ; 26(2): 164-180, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31910095

RESUMO

Health care and medicine were revolutionized in recent years by the development of biomaterials, such as stents, implants, personalized drug delivery systems, engineered grafts, cell sheets, and other transplantable materials. These materials not only support the growth of cells before transplantation but also serve as replacements for damaged tissues in vivo. Among the various biomaterials available, those made from natural biological sources such as extracellular proteins (collagen, fibronectin, laminin) have shown significant benefits, and thus are widely used. However, routine biomaterial-based research requires copious quantities of proteins and the use of pure and intact extracellular proteins could be highly cost ineffective. Gelatin is a molecular derivative of collagen obtained through the irreversible denaturation of collagen proteins. Gelatin shares a very close molecular structure and function with collagen and thus is often used in cell and tissue culture to replace collagen for biomaterial purposes. Recent technological advancements such as additive manufacturing, rapid prototyping, and three-dimensional printing, in general, have resulted in great strides toward the generation of functional gelatin-based materials for medical purposes. In this review, the structural and molecular similarities of gelatin to other extracellular matrix proteins are compared and analyzed. Current strategies for gelatin crosslinking and production are described and recent applications of gelatin-based biomaterials in cell culture and tissue regeneration are discussed. Finally, recent improvements in gelatin-based biomaterials for medical applications and future directions are elaborated. Impact statement In this study, we described gelatin's biochemical properties and compared its advantages and drawbacks over other extracellular matrix proteins and polymers used for biomaterial application. We also described how gelatin can be used with other polymers in creating gelatin composite materials that have enhanced mechanical properties, increased biocompatibility, and boosted bioactivity, maximizing its benefits for biomedical purposes. The article is relevant, as it discussed not only the chemistry of gelatin, but also listed the current techniques in gelatin/biomaterial manufacturing and described the most recent trends in gelatin-based biomaterials for biomedical applications.

11.
J Nanosci Nanotechnol ; 20(1): 161-167, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31383151

RESUMO

In this literature, we discussed the effect of anti-reflection coating of silicon heterojunction (SHJ) solar cells with different characteristics of double layered indium tin oxide (ITO/ITO) structure. Firstly, the OPAL 2 simulation was performed to optimize the values of the photo generation-current density of ITO/ITO/Si device structures. Afterwards, experimental work was conducted by depositing ITO on the SHJ solar cell to analyze the anti-reflection coating effect. ITO was deposited on the SHJ solar cell for 90 to 180 seconds by varying the oxygen flow rate. The highest short-circuit current density of 39.25 mA/cm² was obtained when ITO was deposited for 150 seconds, which was higher than the short-circuit current density of non-deposited cell of ITO (38 mA/cm²). The efficiency of the SHJ solar cell increased by about 2% after additional ITO deposition to 20.75%, which was due to the improvement of short-circuit current density by ITO deposition. The double layer ITO helped to improve the efficiency of SHJ solar cell by increasing light absorption in a silicon wafer.

12.
J Prosthet Dent ; 123(6): 850-859, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31590981

RESUMO

STATEMENT OF PROBLEM: Patients with partial tooth loss treated with implant-supported fixed partial dentures (FPDs) have difficulty using conventional mandibular advancement devices (MADs) because of the risk of side effects. Also, which design factors affect biomechanical stability when designing MADs with better stability is unclear. PURPOSE: The purpose of this finite element (FE) analysis study was to analyze the effect of the MAD design on biomechanical behavior and to propose a new design process for improving the stability of MADs. MATERIAL AND METHODS: Each 3D model consisted of the maxillofacial bones, teeth, and implant-supported FPDs located in the left tooth loss area from the first premolar to the second molar and a MAD. Three types of custom-made MADs were considered: a complete-coverage MAD covering natural tooth-like conventional MADs, a shortened MAD excluding the coverage on the implant-supported FPD, and a newly designed MAD without anterior coverage. For the new MAD design, topology optimization was conducted to reduce the stress exerted on the teeth and to improve retention of the MAD. The new MAD design was finished by excluding the coverage of the maxillary and mandibular central incisors based on the results of the topology optimization. A mandibular posterior restorative force for a protrusion amount of 40% was used as the loading condition. The principal stress and pressure of the cancellous bone and periodontal ligaments (PDLs) were identified. RESULTS: Considering the load concentration induced by the complete-coverage MAD, bone resorption risk and root resorption risk were observed at both ends of the mandibular teeth. The shortened MAD resulted in the highest stress concentration and pressure with the worst stability. However, in the case of the complete-coverage MAD, the pressure in the PDLs was reduced to the normal range, and the risk of root resorption was reduced. CONCLUSIONS: For patients with implant-supported FPDs, MAD designs with different extents of coverage had an influence on biomechanical behavior in terms of stress distribution in cancellous bone and PDLs. A MAD design without anterior coverage provided improved stability compared with complete-coverage or shortened designs. The presented method for MAD design, which combined FE analysis and topology optimization, could be effectively applied in the design of such improved MADs.


Assuntos
Implantes Dentários , Prótese Dentária Fixada por Implante , Prótese Parcial Fixa , Análise de Elementos Finitos , Humanos , Placas Oclusais
13.
Cells ; 8(12)2019 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-31842346

RESUMO

Owing to the importance of stem cell culture systems in clinical applications, researchers have extensively studied them to optimize the culture conditions and increase efficiency of cell culture. A spheroid culture system provides a similar physicochemical environment in vivo by facilitating cell-cell and cell-matrix interaction to overcome the limitations of traditional monolayer cell culture. In suspension culture, aggregates of adjacent cells form a spheroid shape having wide utility in tumor and cancer research, therapeutic transplantation, drug screening, and clinical study, as well as organic culture. There are various spheroid culture methods such as hanging drop, gel embedding, magnetic levitation, and spinner culture. Lately, efforts are being made to apply the spheroid culture system to the study of drug delivery platforms and co-cultures, and to regulate differentiation and pluripotency. To study spheroid cell culture, various kinds of biomaterials are used as building forms of hydrogel, film, particle, and bead, depending upon the requirement. However, spheroid cell culture system has limitations such as hypoxia and necrosis in the spheroid core. In addition, studies should focus on methods to dissociate cells from spheroid into single cells.


Assuntos
Técnicas de Cultura de Células/métodos , Células-Tronco Mesenquimais/citologia , Esferoides Celulares/citologia , Animais , Materiais Biocompatíveis/química , Diferenciação Celular , Hipóxia Celular , Células Cultivadas , Humanos
14.
J Am Chem Soc ; 141(35): 13829-13840, 2019 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-31382746

RESUMO

Nanoparticles have been extensively used to deliver therapeutic drugs to tumor tissues through the extravasation of a leaky vessel via enhanced permeation and retention effect (EPR, passive targeting) or targeted interaction of tumor-specific ligands (active targeting). However, the therapeutic efficacy of drug-loaded nanoparticles is hampered by its heterogeneous distribution owing to limited penetration in tumor tissue. Inspired by the fact that cancer cells can recruit inflammatory immune cells to support their survival, we developed a click reaction-assisted immune cell targeting (CRAIT) strategy to deliver drug-loaded nanoparticles deep into the avascular regions of the tumor. Immune cell-targeting CD11b antibodies are modified with trans-cyclooctene to enable bioorthogonal click chemistry with mesoporous silica nanoparticles functionalized with tetrazines (MSNs-Tz). Sequential injection of modified antibodies and MSNs-Tz at intervals of 24 h results in targeted conjugation of the nanoparticles onto CD11b+ myeloid cells, which serve as active vectors into tumor interiors. We show that the CRAIT strategy allows the deep tumor penetration of drug-loaded nanoparticles, resulting in enhanced therapeutic efficacy in an orthotopic 4T1 breast tumor model. The CRAIT strategy does not require ex vivo manipulation of cells and can be applied to various types of cells and nanovehicles.


Assuntos
Antibióticos Antineoplásicos/farmacologia , Doxorrubicina/farmacologia , Nanopartículas/química , Dióxido de Silício/química , Animais , Antibióticos Antineoplásicos/administração & dosagem , Antígeno CD11b/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Química Click , Ciclo-Octanos/química , Modelos Animais de Doenças , Doxorrubicina/administração & dosagem , Portadores de Fármacos/química , Ensaios de Seleção de Medicamentos Antitumorais , Camundongos , Imagem Óptica , Tamanho da Partícula , Porosidade , Propriedades de Superfície
15.
Biomater Sci ; 7(8): 3178-3189, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31143889

RESUMO

Cholesterol and lipid metabolism are associated with osteoarthritis (OA) in human cartilage. High cholesterol levels in OA chondrocytes leads to decreased membrane fluidity and blocks the signaling cascade associated with the expression of chondrogenic genes. It is known that bile acid plays a role in regulating cholesterol homeostasis and the digestion of fats in the human body. Tauroursodeoxycholic acid (TUDCA), as a member of the bile acid family, also aids in the transport of cellular cholesterol. In this study, we hypothesized that TUDCA might be able to promote the restoration of OA cartilage by reducing membrane cholesterol levels in OA chondrocytes and by stimulating the chondrogenic signaling cascade. To assess this hypothesis, we investigated the effects of TUDCA on degenerated chondrocytes isolated from patients with OA. Importantly, treatment with TUDCA at sub-micellar concentrations (2500 µM) significantly increased cell proliferation and Cyclin D1 expression compared with the controls. In addition, the expression of chondrogenic marker genes (SOX9, COL2, and ACAN), proteins (SOX9 and COL2), and glycosaminoglycan (Chondroitin sulfate) was much higher in the TUDCA-treated group compared to the controls. We also found that TUDCA treatment significantly reduced the intracellular cholesterol levels in the chondrocytes and increased membrane fluidity. Furthermore, the stability of TGF receptor 1 and activity of focal adhesion proteins were also increased following TUDCA treatment. Together, these results demonstrated that TUDCA could be used as an alternative treatment for the restoration of OA cartilage.


Assuntos
Colesterol/metabolismo , Condrócitos/efeitos dos fármacos , Espaço Intracelular/efeitos dos fármacos , Espaço Intracelular/metabolismo , Fluidez de Membrana/efeitos dos fármacos , Osteoartrite/tratamento farmacológico , Ácido Tauroquenodesoxicólico/farmacologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Condrócitos/metabolismo , Condrócitos/patologia , Condrogênese/efeitos dos fármacos , Relação Dose-Resposta a Droga , Adesões Focais/efeitos dos fármacos , Humanos , Osteoartrite/metabolismo , Osteoartrite/patologia , Receptores de Fatores de Crescimento Transformadores beta/metabolismo , Transdução de Sinais/efeitos dos fármacos , Ácido Tauroquenodesoxicólico/química , Ácido Tauroquenodesoxicólico/uso terapêutico
16.
ACS Appl Mater Interfaces ; 11(23): 20615-20627, 2019 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-31050404

RESUMO

Biocompatible, electrically conductive microfibers with superior mechanical properties have received a great attention due to their potential applications in various biomedical applications such as implantable medical devices, biosensors, artificial muscles, and microactuators. Here, we developed an electrically conductive and mechanically stable carbon nanotube-based microactuator with a low degradability that makes it usable for an implantable device in the body or biological environments. The microfiber was composed of hyaluronic acid (HA) hydrogel and single-wall carbon nanotubes (SWCNTs) (HA/SWCNT). HA hydrogel acts as biosurfactant and ion-conducting binder to improve the dispersion of SWCNTs resulting in enhanced electrical and mechanical properties of the hybrid microfiber. In addition, HA was crosslinked to prevent the leaking of the nanotubes from the composite. Crosslinking of HA hydrogel significantly enhances Young's modulus, the failure strain, the toughness, the stability of the electrical conductivity, and the resistance to biodegradation and creep of hybrid microfibers. The obtained crosslinked HA/SWCNT hybrid microfibers show an excellent capacitance and actuation behavior under mechanical loading with a low potential of ±1 V in a biological environment. Furthermore, the HA/SWCNT microfibers exhibit an excellent in vitro viability. Finally, the biocompatibility is shown through the resolution of an early inflammatory response in less than 3 weeks after the implantation of the microfibers in the subcutaneous tissue of mice.

17.
Tissue Eng Part A ; 25(23-24): 1646-1657, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-30982407

RESUMO

The directed differentiation of human adipose-derived stem cells (hASCs) into different cell types has shown great therapeutic potential in treating various diseases. To maximize the therapeutic potentials, researchers have tried manipulating master transcriptional genes that promote efficient differentiation of mesenchymal stem cells (MSCs) such as the MAPK/ERK signaling pathway. Sprouty (SPRY) is a family of proteins that are known to inhibit the MAPK/ERK signaling pathway. Although the role of some SPRY isoforms in MSC differentiation is known, the function of SPRY4 isoform has not been fully elucidated. In the present study, the role of SPRY4 in the multilineage differentiation of hASCs has been elucidated. To investigate the role of SPRY4 in hASC differentiation and tissue regeneration, we performed a transient knockdown of SPRY expression via a small interfering RNA (siSPRY4). Western blot and quantitative polymerase chain reaction results revealed that the treatment of siSPRY4 before induction of differentiation had no significant effect on adipogenic, but reduced chondrogenic, differentiation of hASCs. Interestingly, SPRY4 transient knockdown had a significant effect on the osteogenic differentiation as indicated by the increased messenger RNA (mRNA) and protein expression of osteogenic markers such as alkaline phosphatase (ALP; 2.3-fold) and osteopontin (OPN; 3.5-fold) and increased calcium deposition measured via Alizarin red staining (3.3-fold). Moreover, in vivo tissue regeneration of siSPRY4-treated hASCs in ectopic bone formation and calvarial defect mouse models showed higher bone volume (5.24-fold) and trabecular number (4.59-fold) assessed via histological and microcomputed tomography analyses. We also determined that the enhanced osteogenic differentiation in SPRY4-treated hASCs was due to the induction of ERK1/2 phosphorylation. Taken together, our results suggest that the regulation of SPRY4 through MAPK signaling is a potentially critical aspect on the osteogenic differentiation of hASCs and for bone tissue regeneration, and thus, may be utilized as a potent technique in the development of effective bone therapeutics. Impact Statement This study tried to expand our current understanding of the osteogenic differentiation of mesenchymal stem cells. The transient downregulation of the SPRY4 expression via small interfering RNA (siRNA) showed significant enhancement of the osteogenic differentiation of adipose-derived stem cells via the induction of ERK 1/2 phosphorylation. This suggests the possible mechanism to maximize the potential of stem cell as therapeutics and has a great potential in treating various bone-related diseases.


Assuntos
Diferenciação Celular , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Osteogênese , Adipogenia , Animais , Proliferação de Células , Condrogênese , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Regulação da Expressão Gênica , Humanos , Sistema de Sinalização das MAP Quinases , Células-Tronco Mesenquimais/enzimologia , Camundongos Endogâmicos BALB C , Camundongos Nus , Fosforilação
18.
J Am Chem Soc ; 141(5): 2035-2045, 2019 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-30620877

RESUMO

The effect of porous structures on the electrocatalytic activity of N-doped carbon is studied by using electrochemical analysis techniques and the result is applied to synthesize highly active and stable Fe-N-C catalyst for oxygen reduction reaction (ORR). We developed synthetic procedures to prepare three types of N-doped carbon model catalysts that are designed for systematic comparison of the porous structures. The difference in their catalytic activity is investigated in relation to the surface area and the electrochemical parameters. We found that macro- and mesoporous structures contribute to different stages of the reaction kinetics. The catalytic activity is further enhanced by loading the optimized amount of Fe to prepare Fe-N-C catalyst. In both N-doped carbon and Fe-N-C catalysts, the hierarchical porous structure improved electrocatalytic performance in acidic and alkaline media. The optimized catalyst exhibits one of the best ORR performance in alkaline medium with excellent long-term stability in anion exchange membrane fuel cell and accelerated durability test. Our study establishes a basis for rationale design of the porous carbon structure for electrocatalytic applications.

19.
Stem Cell Res Ther ; 10(1): 32, 2019 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-30654843

RESUMO

BACKGROUND: Ell3 is a RNA polymerase II elongation factor that has various cell type-dependent functions, such as regulating the differentiation efficiency of embryonic stem cells and sensitizing cancer cells to anticancer drugs. However, there has been little research on the role of Ell3 on the regulation of senescence and apoptosis of stem cells. METHODS: We analyzed the senescence of Ell3-suppressed stem cells by mitochondrial activity, ß-gal (+) cells, and lineage differentiation efficiency. The apoptosis of Ell3-overexpressing stem cells was analyzed by Annexin V staining, Immunoblot, and Live&dead assay. In addition, chromatin immunoprecipitation and luciferase assays were used to demonstrate p53 functions as a direct transcriptional activator of Ell3. RESULTS: Suppression of Ell3 expression induced senescence in stem cells by increasing Bcl-2 expression. Unlike the effect of Ell3 suppression, the ectopic expression of Ell3 induces apoptosis of stem cells and induces apoptosis of adjacent cells. In addition, p53 functions as a direct transcriptional activator of Ell3 during the stem cell apoptosis. CONCLUSIONS: We suggest that the function of Ell3 is associated with the p53-Bcl2 axis in both senescent and apoptotic ADSCs.


Assuntos
Células-Tronco Adultas/citologia , Fatores de Elongação da Transcrição/metabolismo , Adipócitos/citologia , Adipócitos/metabolismo , Células-Tronco Adultas/metabolismo , Apoptose/fisiologia , Diferenciação Celular/fisiologia , Células Cultivadas , Senescência Celular/fisiologia , Humanos , Células MCF-7 , Osteócitos/citologia , Osteócitos/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ativação Transcricional , Fatores de Elongação da Transcrição/antagonistas & inibidores , Fatores de Elongação da Transcrição/biossíntese , Fatores de Elongação da Transcrição/genética , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
20.
J Ind Eng Chem ; 77: 12-24, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32288512

RESUMO

Most traditional vaccines are composed either of a whole pathogen or its parts; these vaccines, however, are not always effective and can even be harmful. As such, additional agents known as adjuvants are necessary to increase vaccine safety and efficacy. This review summarizes the potential of biodegradable materials, including synthetic and natural polymers, for vaccine delivery. These materials are highly biocompatible and have minimal toxicity, and most biomaterial-based vaccines delivering antigens or adjuvants have been shown to improve immune response, compared to formulations consisting of the antigen alone. Therefore, these materials can be applied in modern vaccine development.

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