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The fabrication of electrically conductive hydrogels is challenging as the introduction of an electrically conductive filler often changes mechanical hydrogel matrix properties. Here, we present an approach for the preparation of hydrogel composites with outstanding electrical conductivity at extremely low filler loadings (0.34 S m-1, 0.16 vol %). Exfoliated graphene and polyacrylamide are microengineered to 3D composites such that conductive graphene pathways pervade the hydrogel matrix similar to an artificial nervous system. This makes it possible to combine both the exceptional conductivity of exfoliated graphene and the adaptable mechanical properties of polyacrylamide. The demonstrated approach is highly versatile regarding porosity, filler material, as well as hydrogel system. The important difference to other approaches is that we keep the original properties of the matrix, while ensuring conductivity through graphene-coated microchannels. This novel approach of generating conductive hydrogels is very promising, with particular applications in the fields of bioelectronics and biohybrid robotics.
Assuntos
Grafite , Hidrogéis , Condutividade Elétrica , PorosidadeRESUMO
Graphene oxide (GO) is a promising material for bone tissue engineering, but the validation of its molecular biological effects, especially in the context of clinically applied materials, is still limited. In this study, we compare the effects of graphene oxide framework structures (F-GO) and reduced graphene oxide-based framework structures (F-rGO) as scaffold material with a special focus on vascularization associated processes and mechanisms in the bone. Highly porous networks of zinc oxide tetrapods serving as sacrificial templates were used to create F-GO and F-rGO with porosities >99% consisting of hollow interconnected microtubes. Framework materials were seeded with human mesenchymal stem cells (MSC), and the cell response was evaluated by confocal laser scanning microscopy (CLSM), deoxyribonucleic acid (DNA) quantification, real-time polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and alkaline phosphatase activity (ALP) to define their impact on cellular adhesion, osteogenic differentiation, and secretion of vascular growth factors. F-GO based scaffolds improved adhesion and growth of MSC as indicated by CLSM and DNA quantification. Further, F-GO showed a better vascular endothelial growth factor (VEGF) binding capacity and improved cell growth as well as the formation of microvascular capillary-like structures in co-cultures with outgrowth endothelial cells (OEC). These results clearly favored non-reduced graphene oxide in the form of F-GO for bone regeneration applications. To study GO in the context of a clinically used implant material, we coated a commercially available xenograft (Bio-Oss® block) with GO and compared the growth of MSC in monoculture and in coculture with OEC to the native scaffold. We observed a significantly improved growth of MSC and formation of prevascular structures on coated Bio-Oss®, again associated with a higher VEGF binding capacity. We conclude that graphene oxide coating of this clinically used, but highly debiologized bone graft improves MSC cell adhesion and vascularization.
Assuntos
Grafite , Células-Tronco Mesenquimais , Adesão Celular , Diferenciação Celular , DNA/metabolismo , Células Endoteliais , Grafite/química , Humanos , Células-Tronco Mesenquimais/metabolismo , Osteogênese , Engenharia Tecidual/métodos , Alicerces Teciduais/química , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Cells adapt and move due to chemical, physical, and mechanical cues from their microenvironment. It is therefore important to create materials that mimic human tissue physiology by surface chemistry, architecture, and dimensionality to control cells in biomedical settings. The impact of the environmental architecture is particularly relevant in the context of cancer cell metastasis, where cells migrate through small constrictions in their microenvironment to invade surrounding tissues. Here, a synthetic hydrogel scaffold with an interconnected, random, 3D microchannel network is presented that is functionalized with collagen to promote cell adhesion. It is shown that cancer cells can invade such scaffolds within days, and both the microarchitecture and stiffness of the hydrogel modulate cell invasion and nuclear dynamics of the cells. Specifically, it is found that cell migration through the microchannels is a function of hydrogel stiffness. In addition to this, it is shown that the hydrogel stiffness and confinement, influence the occurrence of nuclear envelope ruptures of cells. The tunable hydrogel microarchitecture and stiffness thus provide a novel tool to investigate cancer cell invasion as a function of the 3D microenvironment. Furthermore, the material provides a promising strategy to control cell positioning, migration, and cellular function in biological applications, such as tissue engineering.
Assuntos
Hidrogéis , Engenharia Tecidual , Animais , Adesão Celular , Movimento Celular , Colágeno , Humanos , Alicerces TeciduaisRESUMO
A new type of photocatalyst is proposed on the basis of aero-ß-Ga2O3, which is a material constructed from a network of interconnected tetrapods with arms in the form of microtubes with nanometric walls. The aero-Ga2O3 material is obtained by annealing of aero-GaN fabricated by epitaxial growth on ZnO microtetrapods. The hybrid structures composed of aero-Ga2O3 functionalized with Au or Pt nanodots were tested for the photocatalytic degradation of methylene blue dye under UV or visible light illumination. The functionalization of aero-Ga2O3 with noble metals results in the enhancement of the photocatalytic performances of bare material, reaching the performances inherent to ZnO while gaining the advantage of the increased chemical stability. The mechanisms of enhancement of the photocatalytic properties by activating aero-Ga2O3 with noble metals are discussed to elucidate their potential for environmental applications.
RESUMO
Tetrapodal zinc oxide (t-ZnO) is used to fabricate polymer composites for many different applications ranging from biomedicine to electronics. In recent times, macroscopic framework structures from t-ZnO have been used as a versatile sacrificial template for the synthesis of multi-scaled foam structures from different nanomaterials such as graphene, hexagonal boron nitride or gallium nitride. Many of these fabrication methods rely on wet-chemical coating processes using nanomaterial dispersions, leading to a strong interest in the actual coating mechanism and factors influencing it. Depending on the type of medium (e.g. solvent) used, different results regarding the homogeneity of the nanomaterial coating can be achieved. In order to understand how a medium influences the coating behavior, the evaporation process of water and ethanol is investigated in this work using in situ synchrotron radiation-based micro computed tomography (SRµCT). By employing propagation-based phase contrast imaging, both the t-ZnO network and the medium can be visualized. Thus, the evaporation process can be monitored non-destructively in three dimensions. This investigation showed that using a polar medium such as water leads to uniform evaporation and, by that, a homogeneous coating of the entire network.
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BACKGROUND: The treatment of glioblastomas (GBM) is still a clinical challenge. Current GBM therapeutic plans focus on the development of new strategies for local drug administration in the tumor cavity to realize an efficient long-term treatment with small side-effects. Here, different amounts of residual GBM cells and healthy brain cells define the microenvironment of the tumor cavity after individual surgical GBM resection (complete or incomplete). METHODS: We evaluated available in vivo data and determined the required amounts and numerical ratios of GBM and healthy brain cells for our in vitro (in)complete resection dual co-culture model. We applied a generic two-drug treatment [Temozolomide (TMZ) in combination with AT101, followed by single AT101 treatment] strategy and analyzed the results in comparison with appropriate mono-culture systems to prove the applicability of our model. RESULTS: We established a suitable GBM dual co-culture model, mimicking the complete and incomplete resection in vitro, giving stable and reliable results on drug testing. Both dual co-culture conditions protectively influenced on cell death and growth rates of primary GBMs when treated with TMZ+AT101/AT101, although the treatment strategy per se was still efficient. Cell death of astrocytes correlated with amounts of increasing GBM cell numbers in the incomplete resection model upon drug treatment, and probably GBM-released chemokine and cytokines were involved in this interplay. CONCLUSIONS: Our results suggest that this dual co-culture model provides a biologically relevant platform for the discovery and compound screening of local GBM treatment strategies.
Assuntos
Antineoplásicos Alquilantes/toxicidade , Antineoplásicos Fitogênicos/toxicidade , Astrócitos/citologia , Glioblastoma/patologia , Microglia/citologia , Análise de Variância , Astrócitos/efeitos dos fármacos , Encéfalo/citologia , Técnicas de Cocultura , Glioblastoma/tratamento farmacológico , Glioblastoma/cirurgia , Gossipol/análogos & derivados , Gossipol/toxicidade , Humanos , Microglia/efeitos dos fármacos , Temozolomida/toxicidadeRESUMO
Graphene hydrophobic coatings paved the way towards a new generation of optoelectronic and fluidic devices. Nevertheless, such hydrophobic thin films rely only on graphene non-polar surface, rather than taking advantage of its surface roughness. Furthermore, graphene is typically not self-standing. Differently, carbon aerogels have high porosity, large effective surface area due to their surface roughness, and very low mass density, which make them a promising candidate as a super-hydrophobic material for novel technological applications. However, despite a few works reporting the general super-hydrophobic and lipophilic behavior of the carbon aerogels, a detailed characterization of their wetting properties is still missing, to date. Here, the wetting properties of graphene aerogels are demonstrated in detail. Without any chemical functionalization or patterning of their surface, the samples exhibit a super-lipophilic state and a stationary super-hydrophobic state with a contact angle up to 150 ± 15° and low contact angle hysteresis ≈ 15°, owing to the fakir effect. In addition, the adhesion force of the graphene aerogels in contact with the water droplets and their surface tension are evaluated. For instance, the unique wettability and enhanced liquid absorption of the graphene aerogels can be exploited for reducing contamination from oil spills and chemical leakage accidents.
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Localized therapy of the highly malignant brain tumor glioblastoma multiforme (GBM) could help to drastically improve the treatment efficiency and increase the patient's median survival. Here, a macroscopic PDMS matrix composed of interconnected microchannels for tailored drug release and localized GBM therapy is introduced. Based on a simple bottom-up fabrication method using a highly versatile sacrificial template, the presented strategy solves the scaling problem associated with the previously developed microchannel-based drug delivery systems, which were limited to two dimensions due to the commonly employed top-down microfabrication methods. Additionally, tailoring of the microchannel density, the fraction of drug-releasing microchannels and the macroscopic size of the drug delivery systems enabled precise adjustment of the drug release kinetics for more than 10 days. As demonstrated in a long-term GBM in vitro model, the release kinetics of the exemplarily chosen GBM drug AT101 could be tailored by variation of the microchannel density and the initial drug concentration, leading to diffusion-controlled AT101 release. Adapting a previously developed GBM treatment plan based on a sequential stimulation with AT101, measured anti-tumorigenic effects of free versus PDMS-released AT101 were comparable in human GBM cells and demonstrated efficient biological activity of PDMS-released AT101.
Assuntos
Neoplasias Encefálicas , Glioblastoma , Neoplasias Encefálicas/tratamento farmacológico , Linhagem Celular Tumoral , Liberação Controlada de Fármacos , Glioblastoma/tratamento farmacológico , Humanos , SiliconesRESUMO
Brain implants are promising instruments for a broad variety of nervous tissue diseases with a wide range of applications, e.g. for stimulation, signal recording or local drug delivery. Recently, graphene-based scaffold materials have emerged as attractive candidates as neural interfaces, 3D scaffolds, or drug delivery systems due to their excellent properties like flexibility, high surface area, conductivity, and lightweight. To date, however, there is a lack of appropriate studies of the foreign body response, especially by glial cells, towards graphene-based materials. In this work, we investigated the effects of macroscopic, highly porous (>99.9%) graphene oxide (GO) and reduced graphene oxide (rGO) (conductivity â¼1 S m-1) scaffolds with tailorable macro- and microstructure on human astrocyte and microglial cell viability and proliferation as well as expression of neuroinflammation and astrogliosis associated genes in an indirect contact approach. In this in vitro model, as well as ex vivo in organotypic murine brain slices, we could demonstrate that both GO and rGO based 3D scaffolds exert slight effects on the glial cell populations which are the key players of glial scar formation. These effects were in most cases completely abolished by curcumin, a known anti-inflammatory and anti-fibrotic drug that could in perspective be applied to brain implants as a protectant.
Assuntos
Materiais Biocompatíveis/toxicidade , Grafite/toxicidade , Neuroglia/efeitos dos fármacos , Alicerces Teciduais/efeitos adversos , Alicerces Teciduais/química , Animais , Astrócitos/citologia , Astrócitos/efeitos dos fármacos , Materiais Biocompatíveis/química , Encéfalo/citologia , Encéfalo/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Curcumina/farmacologia , Estimulação Encefálica Profunda/efeitos adversos , Sistemas de Liberação de Medicamentos/efeitos adversos , Condutividade Elétrica , Feminino , Reação a Corpo Estranho/induzido quimicamente , Reação a Corpo Estranho/patologia , Grafite/química , Humanos , Técnicas In Vitro , Teste de Materiais , Camundongos , Camundongos Transgênicos , Neuroglia/citologia , Oxirredução , Próteses e Implantes/efeitos adversosRESUMO
Despite tremendous efforts toward fabrication of three-dimensional macrostructures of two-dimensional (2D) materials, the existing approaches still lack sufficient control over microscopic (morphology, porosity, pore size) and macroscopic (shape, size) properties of the resulting structures. In this work, a facile fabrication method for the wet-chemical assembly of carbon 2D nanomaterials into macroscopic networks of interconnected, hollow microtubes is introduced. As demonstrated for electrochemically exfoliated graphene, graphene oxide, and reduced graphene oxide, the approach allows for the preparation of highly porous (> 99.9%) and lightweight (<2 mg cm-3) aeromaterials with tailored porosity and pore size as well as tailorable shape and size. The unique tubelike morphology with high aspect ratio enables ultralow-percolation-threshold graphene composites (0.03 S m-1, 0.05 vol%) which even outperform most of the carbon nanotube-based composites, as well as highly conductive aeronetworks (8 S m-1, 4 mg cm-3). On top of that, long-term compression cycling of the aeronetworks demonstrates remarkable mechanical stability over 10â¯000 cycles, even though no chemical cross-linking is employed. The developed strategy could pave the way for fabrication of various macrostructures of 2D nanomaterials with defined shape, size, as well as micro- and nanostructure, crucial for numerous applications such as batteries, supercapacitors, and filters.