Surface charge-dependent osteogenic behaviors of edge-functionalized graphene quantum dots

Understanding the relationship between stem cell’ osteogenic capacity and physicochemical properties of nanomaterials is essential for designing new tissue engineering materials capable of regulating stem cell fate. It has reported that the surface potential of nanomaterials affects cell behavior, however, the underlying mechanism is still controversial and surface charge was not the only variable in the studies performed. In this work, graphene quantum dots (GQDs) were used as a simplified model for single-factor study for the effect of surface charge on osteogenic differentiation, by changing the surface charge of GQD only while keeping all other variables constant. Notably, it was found that the positively charged GQD⁺ exerted no impact on osteogenic differentiation, while the negatively charged GQD‾ could significantly enhance osteogenic differentiation of human mesenchymal stem cells (hMSCs) by activating the BMP/Smad signaling pathway. The negatively charged GQD‾ was then encapsulated in gelatin methacrylamide (GelMA) hydrogel via a UV light-activated photopolymerization in the presence of photoinitiator, obtaining an 3D injectable GQD‾/GelMA hydrogel scaffold. A significantly accelerated bone regeneration induced by GQD‾/GelMA hydrogel scaffolds was observed in the mouse calvarial defect model. The systematic study of the effects of surface charge on the stem cell behavior could provide much inspiration for the tissue engineering application of nanomaterials. © 2020 Elsevier B.V.