ROS Scavenging Graphene-Based Hydrogel Enhances Type H Vessel Formation and Vascularized Bone Regeneration Via ZEB1/Notch1 Mediation.

The regeneration strategy for bone defects is greatly limited by the bone microenvironment, and excessive reactive oxygen species (ROS) seriously hinder the formation of new bone. Reduced graphene oxide (rGO) is expected to meet the requirements because of its ability to promote bone defect repair and to scavenge free radicals through electron transfer. We have developed antioxidant hydrogels based on gelatine methacrylate (GM), acrylyl-β-cyclodextrin (Ac-CD), and rGO functionalized with β-cyclodextrin (β-CD) for skull defect regeneration, but the mechanism of how rGO-based hydrogels enhance bone repair remains unclear. In this work, we confirmed that the GM/Ac-CD/rGO hydrogel had good antioxidant capacity, and promoted osteogenic differentiation of BMSCs and angiogenesis of HUVECs. The RNA-seq data suggested that the hydrogel containing rGO promoted the expression of ZEB1/Notch1, indicating that the GM/Ac-CD/rGO hydrogel affected ZEB1/Notch1 to promote bone repair. Furthermore, we used two-photon laser scanning microscopy to observe the ROS in a skull defect in vivo. The GM/Ac-CD/rGO hydrogel promoted type H vessel formation in a rat skull defect model. In conclusion, the hydrogel neutralizes ROS in the vicinity of a skull defect and stimulates ZEB1/Notch1 to promote the coupling of osteogenesis and angiogenesis, which may be a possible approach for bone regeneration. This article is protected by copyright. All rights reserved.