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.
Over the past 30 years, stem cell technologies matured from an attractive option to investigate neurodegenerative diseases to a possible paradigm shift in their treatment through the development of cell-based regenerative medicine (CRM). Implantable cell replacement therapies promise to completely restore function of neural structures possibly changing how we currently perceive the onset of these conditions. One of the major clinical hurdles facing the routine implementation of stem cell therapy is the limited and inconsistent benefit observed thus far. While unclear, numerous pre-clinical and a handful of clinical cell fate imaging studies point to poor cell retention and survival. Coupling the need to better understand these mechanisms while providing scalable approaches to monitor these treatments in both pre-clinical and clinical scenarios, we show a proof of concept bioimpedance electronic platform for the Agile development of smart and mobile biomedical applications like neural implants or highly portable monitoring devices.
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