Nanoscale geometry determines mechanical biocompatibility of vertically aligned nanofibers

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A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä
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Acta Biomaterialia, Volume 146
Vertically aligned carbon nanofibers (VACNFs) are promising material candidates for neural biosensors due to their ability to detect neurotransmitters in physiological concentrations. However, the expected high rigidity of CNFs could induce mechanical mismatch with the brain tissue, eliciting formation of a glial scar around the electrode and thus loss of functionality. We have evaluated mechanical biocompatibility of VACNFs by growing nickel-catalyzed carbon nanofibers of different lengths and inter-fiber distances. Long nanofibers with large inter-fiber distance prevented maturation of focal adhesions, thus constraining cells from obtaining a highly spread morphology that is observed when astrocytes are being contacted with stiff materials commonly used in neural implants. A silicon nanopillar array with 500 nm inter-pillar distance was used to reveal that this inhibition of focal adhesion maturation occurs due to the surface nanoscale geometry, more precisely the inter-fiber distance. Live cell atomic force microscopy was used to confirm astrocytes being significantly softer on the long Ni-CNFs compared to other surfaces, including a soft gelatin hydrogel. We also observed hippocampal neurons to mature and form synaptic contacts when being cultured on both long and short carbon nanofibers, without having to use any adhesive proteins or a glial monoculture, indicating high cytocompatibility of the material also with neuronal population. In contrast, neurons cultured on a planar tetrahedral amorphous carbon sample showed immature neurites and indications of early-stage apoptosis. Our results demonstrate that mechanical biocompatibility of biomaterials is greatly affected by their nanoscale surface geometry, which provides means for controlling how the materials and their mechanical properties are perceived by the cells. Statement of significance: Our research article shows, how nanoscale surface geometry determines mechanical biocompatibility of apparently stiff materials. Specifically, astrocytes were prevented from obtaining highly spread morphology when their adhesion site maturation was inhibited, showing similar morphology on nominally stiff vertically aligned carbon fiber (VACNF) substrates as when being cultured on ultrasoft surfaces. Furthermore, hippocampal neurons matured well and formed synapses on these carbon nanofibers, indicating high biocompatibility of the materials. Interestingly, the same VACNF materials that were used in this study have earlier also been proven to be capable for electrophysiological recordings and sensing neurotransmitters at physiological concentrations with ultra-high sensitivity and selectivity, thus providing a platform for future neural probes or smart culturing surfaces with superior sensing performance and biocompatibility.
Funding Information: We wish to thank MSc Jarkko Etula for kindly providing us the ta-C containing samples, and PhD Toni Pasanen for kindly providing us the antireflective black silicon material that was used in upright fluorescence imaging. We wish to also thank PhD Christoffer Kauppinen for sharing his knowledge in lift-off processing, and PhD Ali Shah for great discussion and sharing his expertise in cryogenic etching. We acknowledge the provision of facilities by Aalto University at OtaNano - Micronova Nanofabrication Centre and we would also like to thank the Biomedicum Imaging Unit (BIU), Helsinki, for microscopy services. This work was supported by European Union's Horizon 2020 research and innovation programme H2020-FETPROACT-2018-01 (No. 824070), Academy of Finland (No. 321996 and No. 328854), and Jane and Aatos Erkko Foundation. Publisher Copyright: © 2022 The Author(s) | openaire: EC/H2020/824070/EU//CONNECT
Astrocyte, Atomic force microscopy, Carbon nanofiber, Focal adhesion, Mechanical biocompatibility
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Rantataro, S, Parkkinen, I, Pande, I, Domanskyi, A, Airavaara, M, Peltola, E & Laurila, T 2022, ' Nanoscale geometry determines mechanical biocompatibility of vertically aligned nanofibers ', Acta Biomaterialia, vol. 146, pp. 235-247 .