TY - UNPB

T1 - Bioactive Diamond Scaffolds Support Survival and Axonal Regeneration of hESC-Derived Injured Interneurons

AU - Sørensen, Roar Jakob Fleng

AU - Bertram, Nicolas

AU - Dubonyte, Ugne

AU - Han, Anpan

AU - Kirkeby, Agnete

AU - Berg, Rune W.

AU - Kaur, Jaspreet

PY - 2024/8/5

Y1 - 2024/8/5

N2 - 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.

AB - 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.

KW - Faculty of Health and Medical Sciences

M3 - Preprint

SP - 1

EP - 32

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

PB - Social Science Research Network (SSRN)

ER -