Reduced graphene oxide-coated hydroxyapatite composites stimulate spontaneous osteogenic differentiation of human mesenchymal stem cells

Abstract

Human mesenchymal stem cells (hMSCs) have great potential as cell sources for bone tissue engineering and regeneration, but the control and induction of their specific differentiation into bone cells remain challenging. Graphene-based nanomaterials are considered attractive candidates for biomedical applications such as scaffolds in tissue engineering, substrates for SC differentiation and components of implantable devices, due to their biocompatible and bioactive properties. Despite the potential biomedical applications of graphene and its derivatives, only limited information is available regarding their osteogenic activity. This study concentrates upon the effects of reduced graphene oxide (rGO)-coated hydroxyapatite (HAp) composites on osteogenic differentiation of hMSCs. The average particle sizes of HAp and rGO were 1270 ± 476 nm and 438 ± 180 nm, respectively. When coated on HAp particulates, rGO synergistically enhanced spontaneous osteogenic differentiation of hMSCs, without hampering their proliferation. This result was confirmed by determining alkaline phosphatase activity and mineralization of calcium and phosphate as early and late stage markers of osteogenic differentiation. It is suggested that rGO-coated HAp composites can be effectively utilized as dental and orthopedic bone fillers since these graphene-based particulate materials have potent effects on stimulating the spontaneous differentiation of MSCs and show superior bioactivity and osteoinductive potential.

Synergistic effects of reduced graphene oxide and hydroxyapatite on osteogenic differentiation of MC3T3-E1 preosteoblasts

“…Von Kossa staining was not observed in the control cultures without any particles or composites. These results imply that the late stage marker of osteogenic differentiation was enhanced by the synergistic effect of rGO nanosheets and HAp microparticles without the addition of osteogenic factors [63,64]. Recently, it has been revealed that gelatinfunctionalized GO can be efficiently used for the biomimetic mineralization of HAp, leading to promote the osteogenic differentiation of MC3T3-E1 preosteoblasts [65].…”

Graphene and graphene oxide as nanomaterials for medicine and biology application

“…In a culture of mesenchymal cells (MSC) dispersed in a colloidal solution of HAp coated with rGO, elevated alkaline phosphates activity (ALP) and deposition of nodules of calcium than HAp or rGO alone were shown. Moreover, the cells also showed a high expression level of osteopontin and osteocalcin that play important roles in bone mineralization [124]. As osteocalcin is expressed in late stages of differentiation of osteoblasts [125], it is likely that the rGO/HAp composite promotes differentiation of these cells [124].…”

“…Moreover, the cells also showed a high expression level of osteopontin and osteocalcin that play important roles in bone mineralization [124]. As osteocalcin is expressed in late stages of differentiation of osteoblasts [125], it is likely that the rGO/HAp composite promotes differentiation of these cells [124]. Other osteoconductive bioceramics like calcium phosphate as well as β-tricalcium phosphate (β-TCP) can be mixed with graphene to improve its in vitro bioactivity.…”

Nanomaterials in dentistry – potential capabilities, applications, limitations and hazards. Review of the literature. Part 2

“…This result was confirmed by determining the alkaline phosphatase activity and mineralization of calcium and phosphate as early-and late-stage markers of osteogenic differentiation. It is suggested that RGO-coated HAP composites can be effectively utilised as dental and orthopaedic bone fillers because these graphene-based particulate materials can potently stimulate the spontaneous differentiation of MSCs and show superior bioactivity and osteoinductive potential [54].…”