Biological systems interact with nanostructured materials on a sub–cellular level. These interactions may govern cell behaviour and the precise control of a nanomaterial's structure and surface chemistry allow for a high degree of tunability to be achieved. Cells are surrounded by an extra–cellular matrix with nano–topographical properties. Diamond based materials, and specifically nanostructured diamond has attracted much attention due to its extreme electrical and mechanical properties, chemical inertness and biocompatibility. Here the interaction of nanodiamond monolayers with human Neural Stem Cells (hNSCs) has been investigated. The effect of altering surface functionalisation of nanodiamonds on hNSC adhesion and proliferation has shown that confluent cellular attachment occurs on oxygen terminated nanodiamonds (O–NDs), but not on hydrogen terminated nanodiamonds (H–NDs). Analysis of H and O–NDs by Atomic Force Microscopy, contact angle measurements and protein adsorption suggests that differences in topography, wettability, surface charge and protein adsorption of these surfaces may underlie the difference in cellular adhesion of hNSCs reported here.

The potential use of stem cells in regenerative medicine requires the ability to be able to control stem cell fate as cellular networks are developed. Here, nanodiamonds (~10nm) are supported on glass and shown to be an excellent host for the attachment and proliferation of human neural stem cells. Moreover, it is shown that spontaneous differentiation into neurons occurs on nanodiamonds. The use of variously oxygen terminated and hydrogen terminated nanodiamonds has been explored. It is shown that O-ND monolayers promote the differentiation of hNSCs into neurons with increased total neurite length, degree of branching and density of neurites when compared with H-NDs or the glass control. The total number of neurites and total neurite length expressing MAP2, a protein enriched in dendrites, was over 5 times higher for spontaneously differentiated neurones on the O-NDs compared to the control. The fact that inexpensive nanodiamonds can be attached through simple sonication from water on 2D and 3D shapes indicates significant promise for their potential as biomaterials in which neuro-regenerative diseases can be studied.

Background: Bio-electrospray (BES) is a jet-based delivery system driven by an electric field that has the ability to form micro to nano-sized droplets. It holds great potential as a tissue engineering tool as it can be used to place cells into specific patterns. As the human central nervous system (CNS) cannot be studied in vivo at the cellular and molecular level, in vitro CNS models are needed. Human neural stem cells (hNSCs) are the CNS building block as they can generate both neurones and glial cells. Methods: Here we assessed for the first time how hNSCs respond to BES. To this purpose, different hNSC lines were sprayed at 10 kV and their ability to survive, grow and differentiate was assessed at different time points. Results: BES induced only a small and transient decrease in hNSC metabolic activity, from which the cells recovered by day 6, and no significant increase in cell death was observed, as assessed by flow cytometry. Furthermore, bio-electrosprayed hNSCs differentiated as efficiently as controls into neurones, astrocytes and oligodendrocytes, as shown by morphological, protein and gene expression analysis. Conclusions: This study highlights the robustness of hNSCs and identifies BES as a suitable technology that could be developed for the direct deposition of these cells in specific locations and configurations.