Circadian clock regulation via biomaterials for nucleus pulposus.

Abstract

Circadian clock disorder during tissue degeneration has been considered the potential pathogenesis for various chronic diseases, such as intervertebral disc degeneration (IVDD). In this study, circadian clock-regulating biomaterials (ClockMPs) that could effectively activate the intrinsic circadian clock of nucleus pulposus cells (NPCs) in IVDD and improve the physiological function of NPCs for disc regeneration were fabricated via air-microfluidic technique and the chemical cross-linking between polyvinyl alcohol and modified-phenylboronic acid. In vitro experiments verified that ClockMPs could scavenge reactive oxygen species to maintain a stable microenvironment for the circadian clock by promoting the binding of BMAL1 and CLOCK proteins. ClockMPs could regulate the expression of core circadian clock genes by activating the PI3K-AKT pathway in NPCs to remodel the intrinsic circadian clock and promote extracellular matrix synthesis. Furthermore, in vivo experiments of IVDD treated with ClockMPs proved that ClockMPs could promote disc regeneration by regulating the circadian clock of NPCs. In conclusion, ClockMPs provided a novel and promising strategy for circadian clock regulation during tissue regeneration. This article is protected by copyright. All rights reserved.