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1.
Biomater Sci ; 10(16): 4576-4587, 2022 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-35791864

RESUMO

Piezoelectric poly(vinylidene fluoride-trifluoroethylene) has demonstrated an ability to promote osteogenesis, and biomaterials with a chirality-patterned topological surface could enhance cellular osteogenic differentiation. In this work, we created a chirality-patterned surface potential distribution of CoFe2O4/poly(vinylidene fluoride-trifluoroethylene (CFO/P(VDF-TrFE)) membranes to explore their osteogenic response under no change in surface chemical and topology, attempting to further strengthen the ability of the membranes to promote osteogenesis. The chirality-patterned surface potential distribution was established by microdomain contact polarization with the help of sinistral/dextral-patterned ITO interdigital microelectrodes. In the in vitro evaluations, the mesenchymal stem cells showed a positive response in osteogenic differentiation to CFO/P(VDF-TrFE) membranes with both sinistral- and dextral-patterned surface potential distributions, however, the dextral-patterned distribution gave a stronger response than the sinistral-patterned one. And the in vivo evaluation showed a response tend in new bone tissue formation similar to the in vitro evaluations. The stronger response in osteogenic differentiation and osteogenesis for the CFO/P(VDF-TrFE) membrane with the dextral-patterned distributions may be attributed to that the intense interaction of the cells with the electrophysiological microenvironment appears due to a correspondingly higher expression of integrin α5ß1, which significantly up-regulates the Arp2/3 complex expression, a crucial factor for cytoskeleton reorganization, possibly increases cytoskeleton contractility, and strengthens the transduction of the osteogenesis-related signaling cascade. This work proves that the chirality-patterns in surface potential distributions could provide an osteogenic response similar to a chirality-patterned topological surface.


Assuntos
Osteogênese , Polivinil , Materiais Biocompatíveis/química , Diferenciação Celular , Polivinil/química , Titânio/química
2.
Colloids Surf B Biointerfaces ; 216: 112528, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35525229

RESUMO

Macrophages polarization in bone immune microenvironment is crucial in bone regeneration. In this work, mineralized collagen (MC) coatings with photo-thermal effect were prepared through incorporation of polydopamine (PDA). MC coatings with different thicknesses were deposited on titanium substrate through electrochemical deposition. PDA preformed on the substrate, acting as a photo-thermal agent. The effects of light illumination, i.e., different thermal effects, on the polarization of mouse bone marrow-derived macrophages were explored. It was found that heat can promote the M1 polarization of macrophages and inhibit the M2 polarization. Also, gene expression results revealed that such photo illumination based macrophage modulation is effective and safe. It provides a possible way for the design of functional materials to regulate the bone immune microenvironment.


Assuntos
Colágeno , Temperatura Alta , Animais , Regeneração Óssea , Colágeno/farmacologia , Ativação de Macrófagos , Macrófagos , Camundongos
3.
J Tissue Eng Regen Med ; 16(5): 448-459, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35225425

RESUMO

Macrophages have two functionalized phenotypes, M1 and M2, and the regulation of M1/M2 polarization of macrophages is critical for tissue repair. Tissue-derived immune factors are considered the major drivers of macrophage polarization. Based on the main cytokine-induced polarization pathways, we tested the effect of electrical stimulation (ES) of macrophages on the regulation of M1/M2 polarization and a possible synergistic effect with the cytokines. Indium tin oxide (ITO) planar microelectrodes were used to produce ES under different voltages, frequencies and waveforms. We evaluated the influence of ES on the cytokine-induced M1/M2 polarization using mouse bone marrow-derived macrophages cultured with both lipopolysaccharide (LPS)/IFN-γ factors and IL-4 factors for M1 and M2, respectively. The results showed that ES promoted the cytokine-induced macrophage polarization. Importantly, we found that stimulation with a square waveform selectively promoted LPS/IFN-γ-induced M1 polarization, while stimulation with a sinusoidal waveform promoted both LPS/IFN-γ-induced M1, and IL-4-induced M2 polarization. Mechanistically, stimulation with a square waveform affected the intracellular ion concentration, whereas stimulation with a sinusoidal waveform promoted both the intracellular ion concentration and membrane receptors. We hereby establish an ES-mediated strategy for immunomodulation via macrophage polarization.


Assuntos
Citocinas , Lipopolissacarídeos , Animais , Citocinas/metabolismo , Estimulação Elétrica , Interleucina-4/metabolismo , Interleucina-4/farmacologia , Lipopolissacarídeos/farmacologia , Macrófagos/metabolismo , Camundongos
4.
Colloids Surf B Biointerfaces ; 210: 112227, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34838419

RESUMO

Mechanical stimulation has been considered to be critical to cellular response and tissue regeneration. However, harnessing the direction of mechanical stimulation during osteogenesis still remains a challenge. In this study, we designed a series of novel magnetized collagen coatings (MCCs) (randomly or parallel-oriented collagen fibers) to exert the anisotropic mechanical stimulation using oriented magnetic actuation during osteogenesis. Strikingly, we found the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) were significantly up-regulated when the direction of magnetic actuation was parallel to the randomly-oriented collagen coating surface, in contrast to the down-regulated capacity under the perpendicular magnetic actuation. Moreover, further exerting a parallel mechanical stimulation along the parallel-oriented collagen coating, which cells have been oriented by the oriented collagens, were not only able to up-regulate the osteogenic differentiation of BMSCs but also promote the new bone formation during osteogenesis in vivo. We also demonstrated the anisotropic magneto-mechanical stimulation for the osteogenic differences might be attributed to the stretching or bending tensile status of collagen fibers controlled by the direction of magnetic actuation, driving the α5ß1-dependent integrin signaling cascade. This study therefore got insight of understanding the directional mechanical stimulation on osteogenesis, and also paved a way for sustaining regulation of the biomaterials-host interface.


Assuntos
Células-Tronco Mesenquimais , Osteogênese , Materiais Biocompatíveis , Diferenciação Celular , Células Cultivadas , Colágeno
5.
Colloids Surf B Biointerfaces ; 207: 111996, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34298411

RESUMO

Light-induced surface potential have been demonstrated as an effective bone marrow mesenchymal stem cells (BMSCs) osteogenic differentiation regulator. However, traditional bone repair implants almost were weak or no light-responsive. Fortunately, surface modification was a feasible strategy to realize its light functionalization for bone implants. Herein, a graphene oxide (GO)/titanium dioxide (TiO2) nanodots composite coating on the surface of titanium (Ti) implant was constructed, and GO was reduced to reduced graphene oxide (rGO) with the method of UV-assisted photocatalytic reduction. After rGO deposited on the surface of TiO2, a heterojunction formed at the interface of rGO and TiO2. With visible light illumination, positive charges accumulated on the surface of rGO/TiO2 film, and performed as a positive surface potential change. The light-induced surface potential which was generated under proper light intensity is harmless to the cell adhesion and proliferation behavior, but presented a good BMSCs osteogenic differentiation promoting effect, and the activation of the voltage-gated calcium channels through surface potential and the promotion of the adsorption of osteogenic growth factors could be the reason. This work given a new insight of the modification for Ti implant with a light-induced surface potential, and shows potential application for bone regeneration on the clinical practice through light stimulation.


Assuntos
Grafite , Células-Tronco Mesenquimais , Diferenciação Celular , Osteogênese , Titânio
6.
J Biomed Mater Res B Appl Biomater ; 109(12): 2227-2236, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34080765

RESUMO

Electrical stimulation has been proved to be critical to regulate cell behavior. But, cell behavior is also susceptible to multiple parameters of the adverse interferences such as surface current, electrochemical reaction products, and non-uniform compositions, which often occur during direct electric stimulation. To effectively prevent the adverse interferences, a novel piezoelectric poly(vinylidene fluoride-trfluoroethylene)(P(VDF-TrFE)) layer was designed to coat onto the indium tin oxide (ITO) planar microelectrode. We found the electrical stimulation was able to regulate the osteogenic differentiation of mesenchymal stem cells (MSCs) through calcium-mediated PKC signaling pathway. Meanwhile, the surface charge of the designed P(VDF-TrFE) coating layer could be easily controlled by the pre-polarization process, which was demonstrated to trigger integrin-mediated FAK signaling pathway, finally up-regulating the osteogenic differentiation of MSCs. Strikingly, the crosstalk in the downstream of the two signaling cascades further strengthened the ERK pathway activation for osteogenic differentiation of MSCs. This P(VDF-TrFE) layer coated electrical stimulation microelectrodes therefore provide a distinct strategy to manipulate multiple-elements of biomaterial surface to regulate stem cell fate commitment.


Assuntos
Células-Tronco Mesenquimais , Osteogênese , Diferenciação Celular , Microeletrodos , Polivinil/química
7.
Biomater Sci ; 9(3): 874-881, 2021 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-33236731

RESUMO

The immune response of bone implants is closely related to the interaction between macrophages and biomaterial surfaces. In this work, the polarization behavior of mouse bone marrow-derived macrophages (BMDMs), including their morphology and expression of phenotypic markers, genes and cytokines, on charged surfaces with different potential intensities was systematically explored. We found that the charged surface could effectively promote BMDM polarization, and a higher potential intensity was conducive to the upregulation of the polarization of BMDMs into the M2 phenotype. Based on the analysis of the signaling pathways involved in integrins (αMß2 and α5ß1) and the potassium ion channel (Kv1.3), a possible underlying mechanism revealed that the integrin originated signaling pathways could more dominantly regulate macrophage polarization to the M2 phenotype. The present work therefore demonstrates that the surface charge, as a physicochemical property of material surfaces, could effectively regulate macrophage polarizations, which may provide an immunoregulation view for the surface design of biomaterials.


Assuntos
Ativação de Macrófagos , Macrófagos , Animais , Citocinas/genética , Camundongos , Fenótipo , Transdução de Sinais
8.
ACS Appl Mater Interfaces ; 12(28): 31793-31803, 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32485098

RESUMO

Titanium dioxide (TiO2) photofunctionalization has been demonstrated as an effective surface modification method for the osseointegration of implants. However, the insufficient understanding of the mechanism underlying photofunctionalization limits its clinical applications. Here, we report an ultraviolet (UV) radiant energy-dependent functionalization on TiO2 nanodots (TN) surfaces. We found the cell adhesion, proliferation, and osteogenic differentiation gradually increased with the accumulation of UV radiant energy (URE). The optimal functionalizing treatment energy was found to be 2000 mJ/cm2, which could regulate cell-specific behaviors on TN surfaces. The enhanced cell behaviors were regulated by the adsorption and functional site exposure of the extracellular matrix (ECM) proteins, which were the result of the surface physicochemical changes induced by the URE. The correlation between the URE and the reconstruction of surface hydroxyl groups was considered as an alternative mechanism of this energy-dependent functionalization. We also demonstrated the synergistic effects of FAK-RHOA and ERK1/2 signaling pathways on mediating the URE-dependent cell behaviors. Overall, this study provides a novel insight into the mechanisms of photofunctionalization, guiding the design of implants and the clinical practice of photofunctionalization.


Assuntos
Nanoestruturas/química , Titânio/química , Raios Ultravioleta , Animais , Carbono/química , Humanos , Nanopartículas/química , Osteogênese/efeitos da radiação , Transdução de Sinais/efeitos dos fármacos
9.
Biomater Sci ; 8(13): 3685-3696, 2020 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-32478763

RESUMO

Gene delivery based on bioactive coatings on collagen has great potential for applications in bone repair. Meanwhile, controlled gene delivery at specific times/regions is essential for an efficient and complete bone reconstruction process. However, spatio-temporal regulation of gene release and delivery remains a great challenge. In this paper, we used visible light illumination to effectively regulate gene release and subsequent delivery into biological cells. A visible light responsive and bioactive nanocomposite coating (based on collagen/gold nanoparticles, e.g., Col/AuNPs) was prepared through hydrothermal and sol-gel processes and was used as a loading platform for complexes of enhanced green fluorescent protein and Lipofectamine2000 (LF/GFP). The results showed that the amount of immobilized LF/GFP was increased on Col/AuNPs and the release of pre-adsorbed LF/GFP was significantly enhanced in a spatio-temporal and controlled manner under visible light illumination. Moreover, the cellular intake of the released genes was improved, thus enhancing the gene expression efficiency of the cells. The mechanism of enhanced controlled gene delivery was attributed to the changes in collagen structures and rearrangement of cytoskeletal structures induced by the photothermal effect. The developed Col/AuNP composite coating is effective for both controlled surface-mediated gene delivery and gene-mediated bone repair.


Assuntos
Materiais Revestidos Biocompatíveis/química , Luz , Nanocompostos/química , Células 3T3 , Animais , Diferenciação Celular , Células Cultivadas , Colágeno/química , Ouro/química , Camundongos , Osteogênese , Tamanho da Partícula , Propriedades de Superfície
10.
Mater Sci Eng C Mater Biol Appl ; 113: 110970, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32487388

RESUMO

High performance of biomaterial surfaces provides a sound basis to mediate cellular growth behavior. In this work, we attempted to incorporate both positive and negative magnetostriction particles of CoFe2O4 (CFO) and TbxDy1-xFe2 alloy (TD) into piezoelectric poly(vinylidene fluoride-trifluoroethylene) (P(VDF-TrFE)) for forming high magnetoelectric effect films, on which osteogenic differentiation could be dynamically mediated by a magnetic-field-induced surface potential (φME).The negatively poled film with TD/CFO volume ratio of 1:4 (1T4C) showed a highest magnetoelectric effect with φME of -171 mV at 2800 Oe. Compared with CFO/P(VDF-TrFE) and TD/P(VDF-TrFE) films, the φME increased about 213% and 173%, respectively. This could result from that P(VDF-TrFE) dipole domains receive a larger off-axial stress caused by the distribution characteristic of CFO and TD in P(VDF-TrFE), consequently to facilitate P(VDF-TrFE) dipole domain rearrangement. When MSCs were cultured on 1T4C film for 7 or 14 days, the magnetic actuation was setup to begin at the 4th or 8th day after the culture. The 7-day osteogenic differentiation was hardly affected for magnetic actuation at 4th day, moreover, the 14-day differentiation was significantly enhanced for magnetic actuation at 8th day. The enhancement appears just at a relatively late period of the cell growth, probably because the cells need a steady change in cell membrane potential to disassociate pairs of ß-catenin and E-cadherin and activate osteogenic-related signaling pathway. This work could provide an alternative way to promote performance for magnetoelectric materials, and get insight into understanding of interactions of surface potential with cells.


Assuntos
Materiais Biocompatíveis/química , Diferenciação Celular , Magnetismo , Osteogênese , Ligas/química , Animais , Materiais Biocompatíveis/farmacologia , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Cobalto/química , Compostos Férricos/química , Potenciais da Membrana/efeitos dos fármacos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Nanopartículas/química , Osteogênese/efeitos dos fármacos , Polímeros/química , Ratos , Ratos Sprague-Dawley , Titânio/química
11.
ACS Appl Mater Interfaces ; 12(15): 17290-17301, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32208666

RESUMO

Surface-mediated gene delivery has attracted more and more attentions in biomedical research and applications because of its characteristics of low toxicity and localized delivery. Herein, a novel visible-light-regulated, surface-mediated gene-delivery platform is exhibited, arising from the photoinduced surface-charge accumulation on silicon. Silicon with a pn junction is used and tested subsequently for the behavior of surface-mediated gene delivery under visible-light illumination. It is found that positive-charge accumulation under light illumination changes the surface potential and then facilitates the delivery of gene-loaded carriers. As a result, the gene-expression efficiency shows a significant improvement from 6% to 28% under a 10 min visible-light illumination. Such improvement is ascribed to the increase in surface potential caused by light illumination, which promotes both the release of gene-loaded carriers and the cellular uptake. This work suggests that silicon with photovoltaic effect could offer a new strategy for surface-mediated, gene-delivery-related biomedical research and applications.


Assuntos
Técnicas de Transferência de Genes , Luz , Animais , Linhagem Celular , Proteínas de Fluorescência Verde/genética , Camundongos , RNA Interferente Pequeno/química , RNA Interferente Pequeno/metabolismo , Ratos , Silício/química , Propriedades de Superfície
12.
Stem Cells ; 38(3): 395-409, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31721356

RESUMO

Mesenchymal stem cells (MSCs), which are undifferentiated stem cells with the property of stemness and the potential to differentiate into multiple lineages, including osteoblasts, have attracted a great deal of attention in bone tissue engineering. Consistent with the heterogeneity of MSCs, various surface markers have been used. However, it is still unclear which markers of MSCs are best for cell amplification in vitro and later bone regeneration in vivo. Krüppel-like Factor 2 (KLF2) is an important indicator of the stemness of human MSCs (hMSCs) and as early vascularization is also critical for bone regeneration, we used KLF2 as a novel in vitro marker for MSCs and investigated the angiogenesis and osteogenesis between KLF2+ MSCs and endothelial cells (ECs). We found a synergistic interaction between hMSCs and human umbilical vein ECs (HUVECs) in that KLF2+ stemness-maintained hMSCs initially promoted the angiogenesis of HUVECs, which in turn more efficiently stimulated the osteogenesis of hMSCs. In fact, KLF2+ hMSCs secreted angiogenic factors initially, with some of the cells then differentiating into pericytes through the PDGF-BB/PDGFR-ß signaling pathway, which improved blood vessel formation. The matured HUVECs in turn synergistically enhanced the osteogenesis of KLF2+ hMSCs through upregulated vascular endothelial growth factor. A three-dimensional coculture model using cell-laden gelatin methacrylate (GelMA) hydrogel further confirmed these results. This study provides insight into the stemness-directed synergistic interaction between hMSCs and HUVECs, and our results will have a profound impact on further strategies involving the application of KLF2+ hMSC/HUVEC-laden GelMA hydrogel in vascular network bioengineering and bone regeneration.


Assuntos
Regeneração Óssea/fisiologia , Fatores de Transcrição Kruppel-Like/metabolismo , Células-Tronco Mesenquimais/metabolismo , Humanos
13.
ACS Biomater Sci Eng ; 6(4): 2020-2028, 2020 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-33455350

RESUMO

Light-induced cell harvest shows much potential in in vitro cell culture. In this work, a light-responsive monolayer graphene (Gr)/titanium dioxide nanodot (TN) film is designed and used for light-induced cell harvest. It is found that after 20 min of 365 nm UV or 450 nm visible light illumination, different types of cells could be detached from the surface effectively. The highest cell detachment ratio reaches about 95%. The mechanism of such a cell detachment is contributed to light illumination generates charge accumulation, which, in turn, changes the conformation of the extracellular matrix protein molecules adsorbed to a more disordered state, and eventually leads to the cells detachment. Such UV and visible light responsive Gr/TiO2 film could be a good candidate for a surface with light-induced cell detachment property.


Assuntos
Grafite , Técnicas de Cultura de Células , Luz , Titânio
14.
ACS Appl Mater Interfaces ; 11(47): 43857-43864, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31692325

RESUMO

Graphene (Gr) presents promising applications in regulating the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Light illumination is regarded as a spatiotemporally controllable, easily applicable, and noninvasive mean to modulate material responses. Herein, Gr-transferred silicon (Gr/Si) with a Schottky junction is utilized to evaluate the visible-light-promoted osteogenic differentiation of BMSCs. Under light illumination, light-induced charges, owing to the formation of the Schottky junction at the interface of Gr and Si, accumulated on the surface and then changed the surface potential of Gr/Si. The Schottky junction and surface potential at the interface of Gr and Si was measured by photovoltaic test and scanning Kelvin probe microscopy. Alkaline phosphatase (ALP) activity and quantitative real-time polymerase chain reaction (PCR) measurement showed that such variations of surface improved the osteogenic differentiation of BMSCs, and the activation of the voltage-gated calcium channels through surface potential and accumulation of cytosolic Ca2+ could be the reason. Moreover, X-ray photoelectron spectroscopy characterization showed that surface charge could also affect BMSCs differentiation through the promotion or inhibition of the adsorption of osteogenic growth factors. Such light-promoted osteogenic differentiation of BMSCs on Gr/Si may have huge potential for biomedical materials or devices for bone regeneration application.


Assuntos
Grafite/química , Células-Tronco Mesenquimais/citologia , Osteogênese , Silicones/química , Engenharia Tecidual/instrumentação , Fosfatase Alcalina/genética , Fosfatase Alcalina/metabolismo , Animais , Canais de Cálcio/genética , Canais de Cálcio/metabolismo , Diferenciação Celular , Células Cultivadas , Luz , Masculino , Células-Tronco Mesenquimais/metabolismo , Ratos , Ratos Sprague-Dawley
15.
ACS Omega ; 4(21): 19350-19357, 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31763559

RESUMO

Naringin, a Chinese herbal medicine, has been demonstrated to concentration-dependently promote osteogenic differentiation of mesenchymal stem cells (MSCs). However, it remains a challenge to load naringin on coatings for osteogenesis and further control the release kinetics. Here, we demonstrated that the release behavior of naringin on rutile nanorod films could be controlled by either mixing naringin with gelatin methacryloyl (GelMA) before spinning onto the films or soaking the obtained GelMA-incorporated films with the naringin solution to achieve the distinct degradation-type release and diffusion-type release, respectively. We further revealed that the naringin-loaded coatings facilitated adhesion, proliferation and late differentiation, and mineralization of MSCs. Our findings provided a novel strategy to engineer the coatings with controlled release of naringin and emphasized the bioactivity of naringin for the osteogenic differentiation of MSCs.

16.
J Nanobiotechnology ; 17(1): 102, 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31581945

RESUMO

Natural extracellular matrices (ECMs) are three-dimensional (3D) and multi-scale hierarchical structure. However, coatings used as ECM-mimicking structures for osteogenesis are typically two-dimensional or single-scaled. Here, we design a distinct quasi-three-dimensional hierarchical topography integrated of density-controlled titania nanodots and nanorods. We find cellular pseudopods preferred to anchor deeply across the distinct 3D topography, dependently of the relative density of nanorods, which promote the osteogenic differentiation of osteoblast but not the viability of fibroblast. The in vivo experimental results further indicate that the new bone formation, the relative bone-implant contact as well as the push-put strength, are significantly enhanced on the 3D hierarchical topography. We also show that the exposures of HFN7.1 and mAb1937 critical functional motifs of fibronectin for cellular anchorage are up-regulated on the 3D hierarchical topography, which might synergistically promote the osteogenesis. Our findings suggest the multi-dimensions and multi-scales as vital characteristic of cell-ECM interactions and as an important design parameter for bone implant coatings.


Assuntos
Substitutos Ósseos/química , Nanotubos/química , Osteogênese , Titânio/química , Animais , Diferenciação Celular , Linhagem Celular , Sobrevivência Celular , Fibroblastos/citologia , Masculino , Camundongos , Nanotubos/ultraestrutura , Osteoblastos/citologia , Próteses e Implantes , Coelhos
17.
Biomaterials ; 222: 119456, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31476662

RESUMO

Geometry sensing of cells inevitably involves cytoskeletal remodeling and the activation of biochemical signaling, which control multiple aspects of cell behaviors, such as proliferation, differentiation and migration. A variety of size-, shape- and geometry-dependent cell behaviors have been revealed, but the role of geometric chirality in regulating cellular behaviors and the underlying biophysical mechanisms remain elusive. Here, we report an intriguing mechanotransduction of stem cells on chiral geometries that human mesenchymal stem cells (hMSCs) prefer to migrate towards dextral geometry with nearly 30% relative advantage in migration speed, referred to as "chirotaxis". We also found that cell adhesion, proliferation, and differentiation of hMSCs are greatly enhanced for cells cultured on dextral geometry than those on sinistral geometry, by triggering transcription factor AP-1 complex through p38/MAPK signaling that regulates hMSCs fate and activity. We demonstrated that the cytoskeletal network consisting of transverse and radial stress fibers exhibits a strengthening/offsetting effect on dextral/sinistral geometry through focal adhesion sites, and consequently, cell's cytoskeletal contractility on the dextral geometry is nearly 80% higher. These findings highlight the importance of geometric chirality as an extracellular cue in regulating stem cell's behaviors through cell-material interactions.


Assuntos
Mecanotransdução Celular/fisiologia , Células-Tronco Mesenquimais/citologia , Células-Tronco/citologia , Western Blotting , Diferenciação Celular/fisiologia , Células Cultivadas , Simulação por Computador , Citoesqueleto/metabolismo , Imunofluorescência , Humanos , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais/fisiologia , Fator de Transcrição AP-1/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
18.
ACS Appl Mater Interfaces ; 11(28): 25457-25464, 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31282143

RESUMO

A facile strategy is needed for accurate time-space supply of suitable growth factors or drugs. Polypyrrole (PPy) was able to carry almost all kinds of negatively charged biomolecules through anodizing method, which made it an appropriate way for codeposition of multiple molecules. The difference in the conjugation between different molecules and PPy makes it possible for selective release when the redox state of PPy changes. In this work, bovine serum albumin (BSA) and heparin (Hep) were chosen to be the model molecules in view of their differences in the level of electronegativity and molecular weight. Double-layer deposition method was used to improve the biocompatibility of PPy/BSA/Hep film. It was found the content of BSA and Hep in the film can be controlled by regulating deposition current and time. BSA release was facilitated under positive voltage and then promote the proliferation of preosteoblasts, while Hep release was promoted under negative voltage and enhance cell differentiation. Our work provides a dual-molecule model in PPy for selective release and further explores the mechanism of release selectivity, this discovery has potential applications in tissue engineering and regenerative medicine.


Assuntos
Adesão Celular , Condutividade Elétrica , Heparina/química , Membranas Artificiais , Osteoblastos/metabolismo , Polímeros/química , Pirróis/química , Soroalbumina Bovina/química , Animais , Bovinos , Linhagem Celular , Camundongos , Osteoblastos/citologia
19.
ACS Appl Mater Interfaces ; 11(25): 22218-22227, 2019 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-31199127

RESUMO

The surface electric potential of biomaterials has been extensively proven to play a critical role in stem cells' fate. However, there are ambiguous reports on the relation of stem cells' osteogenic capacity to surface potential characteristics (potential polarity and intensity). To address this, we adopted a surface with a wide potential range and both positive/negative polarity in a comprehensive view to get insight into surface potential-regulating cellular osteogenic differentiation. Tb xDy1- xFe2 alloy/poly(vinylidene fluoride-trifluoroethylene) magnetoelectric films were prepared, and the film could provide controllable surface potential characteristics with positive or negative polarity and potential (ϕME) intensity variation from 0 to ±120 mV as well as keep the surface chemical composition and microstructure unchanged. Cell culture results showed that osteogenic differentiation of mesenchymal stem cells on both positive and negative potential films was obviously upregulated when the /ϕME/ intensities were set from 0-55 mV. Differently, the highest upregulated osteogenic differentiation on the positive potential films corresponded to the /ϕME/ intensity from 35-55 mV and was better than that on the negative potential films whereas the highest on the negative potential films corresponded to the /ϕME/ intensity from 0-35 mV and was better than that on the positive potential films. This fact could illustrate why previous reports appeared ambiguously; i.e., the comparative result in osteogenic differentiation between the positive and negative potential films strongly depends on the selection of surface potential intensity. On the basis of assaying of the exposed functional sites (RGD and PHSRN) of the adsorbed fibronectin (FN) and the expression of cellular integrin α5 and ß1 subunits, the difference in the behavior between the positive and negative potential films was attributed to the distinct conformation of adsorbed fibronectin (FN) and the opposite changing trend with /ϕME/ for the two films, which triggers the osteogenesis-related FAK/ERK signaling pathway to a different extent. This study could provide new cognition for the in-depth understanding of the regulation mechanism underlying surface potential characteristics in cell behaviors.


Assuntos
Fibronectinas/metabolismo , Adesão Celular/fisiologia , Proliferação de Células/fisiologia , Humanos , Integrina alfa5/metabolismo , Integrina beta1/metabolismo , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Osteogênese/fisiologia , Espectroscopia Fotoeletrônica , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X
20.
Materials (Basel) ; 12(5)2019 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-30857349

RESUMO

It is well known that three-dimensional (3D) printing is an emerging technology used to produce customized implants and surface characteristics of implants, strongly deciding their osseointegration ability. In this study, Ti alloy microspheres were printed under selected rational printing parameters in order to tailor the surface micro-characteristics of the printed implants during additive manufacturing by an in situ, controlled way. The laser path and hatching space were responsible for the appearance of the stripy structure (S), while the bulbous structure (B) and bulbous⁻stripy composite surface (BS) were determined by contour scanning. A nano-sized structure could be superposed by hydrothermal treatment. The cytocompatibility was evaluated by culturing Mouse calvaria-derived preosteoblastic cells (MC3T3-E1). The results showed that three typical microstructured surfaces, S, B, and BS, could be achieved by varying the 3D printing parameters. Moreover, the osteogenic differentiation potential of the S, B, and BS surfaces could be significantly enhanced, and the addition of nano-sized structures could be further improved. The BS surface with nano-sized structure demonstrated the optimum osteogenic differentiation potential. The present research demonstrated an in situ, controlled way to tailor and optimize the surface structures in micro-size during the 3D printing process for an implant with higher osseointegration ability.

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