Bioactive Diamond Scaffolds Support Survival and Axonal Regeneration of Hesc-Derived Injured Interneurons

Abstract

Injury to the central nervous system (CNS) can have devastating consequences for the individual, and strategies to promote endogenous axonal regeneration may be a promising future therapeutic avenue. In case of spinal cord injury, one approach is to generate a scaffold-bridge across the injury site onto which the neuronal axons can grow and reconnect. Inspired by various properties of diamond, including its chemical inertness, we propose here a strategy of coating synthetic diamond scaffolds with proteins of beneficial properties to promote biocompatibility of the scaffolds towards neurons. Here, we show that bare, non-coated diamond scaffolds, when terminated with either oxygen or hydrogen, were unable to adhere human embryonic stem cell-derived interneurons in culture. In contrast, oxygen terminated protein-coated scaffolds (i.e. bioactive diamond scaffold) efficiently enabled neuronal attachment and also supported the survival, migration, and neurite elongation across an induced injury gap in culture. Hydrogen terminated bioactive scaffolds were similarly shown to exhibit cell adhesion, migration, and neurite elongation upon injury, but not as efficiently as oxygen-terminated bioactive scaffolds. This data suggests that bioactive synthetic diamond scaffolds could provide a valuable tool for future therapeutic strategies in the context of CNS injuries.

Note:
Funding Declaration: This study received funding from the Lundbeck Foundation: R273-2018-169, R366-2021-233, R336-2020-963, and the Novo Nordisk Foundation: NNF21CC0073729.

Conflict of Interests: None.

Keywords: Diamond scaffolds, hESCs, central nervous system injury, regenerative strategy