Graphene-augmented nanofiber scaffolds demonstrate new features in cells behaviour

Abstract

Three-dimensional (3D) customized scaffolds capable to mimic a native extracellular matrix open new frontiers in cells manipulation and advanced therapy. The major challenge is in a proper substrate for in vitro models on engineered scaffolds, capable to modulate cells differentiation. Here for the first time we demonstrate novel design and functionality of the 3D porous scaffolds of aligned, self-assembled ceramic nanofibers of ultra-high anisotropy ratio (~107), augmented into graphene shells. This unique hybrid nano-network allows an exceptional combination of selective guidance stimuli of stem cells differentiation, immune reactions variations, and local immobilization of cancer cells, which was not available before. The scaffolds were shown to be able to direct human mesenchymal stem cells (important for stimulation of neuronal and muscle cells) preferential orientation, to suppress major inflammatory factors, and to localize cancer cells; all without additions of specific culture media. The selective downregulation of specific cytokines is anticipated as a new tool for understanding of human immune system and ways of treatment of associated diseases. The effects observed are self-regulated by cells only, without side effects, usually arising from use of external factors. New scaffolds may open new horizons for stem cells fate control such as towards axons and neurites regeneration (Alzheimer’s disease) as well as cancer therapy development.

<p>The effects of graphene and mesenchymal stem cells in cutaneous wound healing and their putative action mechanism</p>

“…138 The stiffness, elasticity, porosity and reactivity of the material may potentially affect cellular behavior through the forces applied, the activation of various molecules during the cell adhesion process and interactions with the scaffold. [152][153][154] Thus, the creation of an effective physical platform will allow for the control of various processes such as the attachment, proliferation and differentiation of MSCs. Moreover, it may also assist in the development of a specific required biological effect via the direction of the behavior of the cell.…”

“…Kalbacova et al 70 were the first to demonstrate that graphene in the monolayer form is non-toxic for MSCs and, moreover, stimulates the growth thereof. Kazantseva et al 152 showed that grapheneaugmented inorganic nanofiber scaffolds do not impede the normal growth of adipose-derived hMSC; moreover, they are able to both direct the preferential orientation and alter the morphology of MSCs. Shine et al 122 showed that hMSCs are capable of uniformly covering calcium silicate/graphene composites and that composites with a higher content of graphene (1%) enhance cell proliferation.…”

Hybrid graphene–ceramic nanofibre network for spontaneous neural differentiation of stem cells

“…Recently, we have demonstrated novel, grapheneaugmented inorganic nanofibre (GAIN) scaffolds capable of mimicking ECM providing highly anisotropic environment combined with oriented porosity [29][30][31], guiding cells to line up along the longitudinal axis of the fibres with a spindle-like shape and more than usually elongated cytoplasmic lamellipodia extensions. These GAIN scaffolds do not impede the normal growth of MSCs, whose oriented morphology indicates cell polarization for the preference of a specific differentiation [29]. Here, for the first time, we demonstrate that MSCs seeded on the 'graphenized', highly anisotropic ceramic nanofibre scaffolds undergo a spontaneous differentiation into neural lineage without any external stimuli.…”

“…The unique self-assembled metal oxide fibre network with an average single fibre diameter of approximately 40 nm and length of 2-10 cm with 85 -95% oriented porosity was produced using a bottom-up approach of controlled liquidphase oxidation [30,31]. These substrates were used for graphene shell growth in a single-step process of novel catalyst-free chemical vapour deposition (CVD) at 10008C at ambient pressure in a mixture of N 2 þ CH 4 gases (figure 1) [29,30]. In contrast to many other studies, graphene on the nanofibres (estimated thickness of order of approximately 1 nm, figure 1) was not functionalized in any way and became augmented to the underlying oxide fibre surface during the manufacturing process.…”

Graphene-Augmented Nanofiber Scaffolds Trigger Gene Expression Switching of Four Cancer Cell Types

“…We recently demonstrated a method and the properties of such self-aligned nanofiber scaffolds made of aluminum oxide capable of guiding various cells reactions. 30 , 33 Ceramics have substantially higher stiffness than any of known polymers or hydrogels and are not commonly considered to be a material mimicking cells natural environment (perhaps with the exception of bone tissue). Bare ceramics substrates however do not possess high versatility in nanotopology due to presence of covalent bonding and more rigid crystal lattice, even in the case of amorphous materials.…”