Pyrolytic Carbon Nanograss Enhances Neurogenesis and Dopaminergic Differentiation of Human Midbrain Neural Stem Cells

Abstract

Advancements in research on the interaction of human neural stem cells (hNSCs) with nanotopographies and biomaterials are enhancing the ability to influence cell migration, proliferation, gene expression, and tailored differentiation toward desired phenotypes. Here, the fabrication of pyrolytic carbon nanograss (CNG) nanotopographies is reported and demonstrated that these can be employed as cell substrates boosting hNSCs differentiation into dopaminergic neurons (DAn), a long-time pursued goal in regenerative medicine based on cell replacement. In the near future, such structures can play a crucial role in the near future for stem-cell based cell replacement therapy (CRT) and bio-implants for Parkinson's disease (PD). The unique combination of randomly distributed nanograss topographies and biocompatible pyrolytic carbon material is optimized to provide suitable mechano-material cues for hNSCs adhesion, division, and DAn differentiation of midbrain hNSCs. The results show that in the presence of the biocoating poly-L-lysine (PLL), the CNG enhances hNSCs neurogenesis up to 2.3-fold and DAn differentiation up to 3.5-fold. Moreover, for the first time, consistent evidence is provided, that CNGs without any PLL coating are not only supporting cell survival but also lead to significantly enhanced neurogenesis and promote hNSCs to acquire dopaminergic phenotype compared to PLL coated topographies.

Silk scaffolding drives self-assembly of functional and mature human brain organoids

“…Scanning electron microscope (SEM) imaging of the generated scaffold and subsequent organoid formation showed that silk, templated by air bubbles, polymerizes into flat microfibers with thickness of ~1 µm and composed of defined nanofibrils (Figure 1G). Notably, nano-topography could play an important role by facilitating and enhancing cell adhesion and neuronal growth even on cell-inert substrates (Asif et al, 2020). SEM images further show that both neuronal progenitors interact directly with the silk surface and successfully attached along the length of the silk microfibers in the engineered organoids (Figure 1H) while differentiating into mature neurons with projections extending along the silk scaffold (Figure 1I, Supplementary Figure S1A,B).…”

Polystyrene Nanopillars with Inbuilt Carbon Nanotubes Enable Synaptic Modulation and Stimulation in Interfaced Neuronal Networks

“…[ 4–9 ] In this framework, conductive substrates made by, or enriched with, carbon‐based nanomaterials (as carbon nanotubes [CNT] or graphene) have proved pivotal in interfacing nerve cells and studying their behavior. [ 10–12 ]…”

“…[4][5][6][7][8][9] In this framework, conductive substrates made by, or enriched with, carbon-based nanomaterials (as carbon nanotubes [CNT] or graphene) have proved pivotal in interfacing nerve cells and studying their behavior. [10][11][12] In particular, for neuronal or progenitor cell cultures, NP patterned substrates have been designed to significantly influence proliferation and guidance, neural differentiation, outgrowth, and development. [13,14] In the field of neuroscience, vertical nanowires or NPs have been shown to support the formation of axons in hippocampal neurons, and that of functional neuronal networks.…”

Selective Direct Laser Writing of Pyrolytic Carbon Microelectrodes in Absorber-Modified SU-8

“…Several approaches for the microfabrication of biocompatible carbon microelectrodes have been investigated, such as inkjet printing [17], UV lithography [18,19], plasma etch-ing [20,21], and UV embossing [22]. Most of these strategies are based on the so-called carbon MEMS (CMEMS) process [23].…”