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Graphene oxide shows great promise as a material for biomedical applications, e.g., as a multi-drug delivery platform. With this in view, reports of studies on the interaction between nanosized graphene oxide flakes and biological cells are beginning to emerge. However, the number of studies remains limited, and most used labeled graphene oxide samples to track the material upon endocytosis. Unfortunately, the labeling process alters the surface functionality of the graphene oxide, and this additional functionalization has been shown to alter the cellular response. Hence, in this work we used label-free graphene oxide. We carefully tracked the uptake of three different nanoscale graphene oxide flake size distributions using scanning/transmission electron microscopy. Uptake was investigated in undifferentiated human monocyte cells (THP-1) and differentiated macrophage cells. The data show clear size dependence for uptake, such that larger graphene oxide flakes (and clusters) are more easily taken up by the cells compared to smaller flakes. Moreover, uptake is shown to occur very rapidly, within two min of incubation with THP-1 cells. The data highlights a crucial need for cellular incubation studies with nanoparticles, to be conducted for short incubation periods as certain dependencies (e.g., size and concentration) are lost with longer incubation periods.

Artificial microvasculature, particularly as part of the blood-brain barrier, has a high benefit for pharmacological drug discovery and uptake regulation. We demonstrate the fabrication of tubular structures with patterns of holes, which are capable of mimicking microvasculatures. By using photolithography, the dimensions of the cylindrical scaffolds can be precisely tuned as well as the alignment and size of holes. Overlapping holes can be tailored to create diverse three-dimensional configurations, for example, periodic nanoscaled apertures. The porous tubes, which can be made from diverse materials for differential functionalization, are biocompatible and can be modified to be biodegradable in the culture medium. As a proof of concept, endothelial cells (ECs) as well as astrocytes were cultured on these scaffolds. They form monolayers along the scaffolds, are guided by the array of holes and express tight junctions. Nanoscaled filaments of cells on these scaffolds were visualized by scanning electron microscopy (SEM). This work provides the basic concept mainly for an in vitro model of microvasculature which could also be possibly implanted in vivo due to its biodegradability.

Self-folding films are a unique kind of thin film. They are able to deform in response to a change in environmental conditions or internal stress and form complex 3D structures. They are very promising candidates for the design of bioscaffolds, which resemble different kinds of biological tissues. In this paper, a very simple and cheap approach for the fabrication of fully biodegradable and biocompatible self-rolled tubes is reported. The tubes' folding can be triggered by temperature. A bilayer approach is used, where one component is active and another one is passive. The passive one can be any biocompatible, biodegradable, hydrophobic polymer. Gelatin is used as an active component: it allows the design of (i) self-folding polymer films, which fold at room temperature (22 °C) and irreversibly unfold at 37 °C, and (ii) films, which are unfolded at room temperature (22 °C), but irreversibly fold at 37 °C. The possibilities of encapsulation of neural stem cells are also demonstrated using self-folded tubes.

Novel approaches to develop naturally-induced drug delivery in tumor environments in a deterministic and controlled manner have become of growing interest in recent years. Different polymeric-based microstructures and other biocompatible substances have been studied taking advantage of lactic acidosis phenomena in tumor cells, which decrease the tumor extracellular pH down to 6.8. Micromotors have recently demonstrated a high performance in living systems, revealing autonomous movement in the acidic environment of the stomach or moving inside living cells by using acoustic waves, opening the doors for implementation of such smart microengines into living entities. The need to develop biocompatible motors which are driven by natural fuel sources inherently created in biological systems has thus become of crucial importance. As a proof of principle, we here demonstrate calcium carbonate Janus particles moving in extremely light acidic environments (pH 6.5), whose motion is induced in conditioned acidic medium generated by HeLa cells in situ. Our system not only obviates the need for an external fuel, but also presents a selective activation of the micromotors which promotes their motion and consequent dissolution in presence of a quickly propagating cell source (i.e. tumor cells), therefore inspiring new micromotor configurations for potential drug delivery systems.

Smart biomimetics, a unique class of devices combining the mechanical adaptivity of soft actuators with the imperceptibility of microelectronics, is introduced. Due to their inherent ability to self-assemble, biomimetic microelectronics can firmly yet gently attach to an inorganic or biological tissue enabling enclosure of, for example, nervous fibers, or guide the growth of neuronal cells during regeneration.

We employ glass microtube structures fabricated by rolled-up nanotechnology to infer the influence of scaffold dimensionality and cell confinement on neural stem cell (NSC) migration. Thereby, we observe a pronounced morphology change that marks a reversible mesenchymal to amoeboid migration mode transition. Space restrictions preset by the diameter of nanomembrane topography modify the cell shape toward characteristics found in living tissue. We demonstrate the importance of substrate dimensionality for the migration mode of NSCs and thereby define rolled-up nanomembranes as the ultimate tool for single-cell migration studies.