Delivery of bone morphogenetic protein-2 and substance P using graphene oxide for bone regeneration

Shin

et al. 2015

Sci Rep

224

113

Recently, graphene-based nanomaterials, in the form of two dimensional substrates or three dimensional foams, have attracted considerable attention as bioactive scaffolds to promote the differentiation of various stem cells towards specific lineages. On the other hand, the potential advantages of using graphene-based hybrid composites directly as factors inducing cellular differentiation as well as tissue regeneration are unclear. This study examined whether nanocomposites of reduced graphene oxide (rGO) and hydroxyapatite (HAp) (rGO/HAp NCs) could enhance the osteogenesis of MC3T3-E1 preosteoblasts and promote new bone formation. When combined with HAp, rGO synergistically promoted the spontaneous osteodifferentiation of MC3T3-E1 cells without hindering their proliferation. This enhanced osteogenesis was corroborated from determination of alkaline phosphatase activity as early stage markers of osteodifferentiation and mineralization of calcium and phosphate as late stage markers. Immunoblot analysis showed that rGO/HAp NCs increase the expression levels of osteopontin and osteocalcin significantly. Furthermore, rGO/HAp grafts were found to significantly enhance new bone formation in full-thickness calvarial defects without inflammatory responses. These results suggest that rGO/HAp NCs can be exploited to craft a range of strategies for the development of novel dental and orthopedic bone grafts to accelerate bone regeneration because these graphene-based composite materials have potentials to stimulate osteogenesis.

Section: Resultsmentioning

confidence: 99%

Enhanced Osteogenesis by Reduced Graphene Oxide/Hydroxyapatite Nanocomposites

Shin

et al. 2015

Sci Rep

224

113

“…The positive effects of chitosan on bone healing have been demonstrated in several in vitro and in vivo studies 33 , while graphene oxide has been used to enhance bone healing and to accelerate the regeneration and osteointegration of biomaterials, such as hydroxyapatite 34 , ß-tricalcium phosphate 20 , titanium implants 35 . However, to the best of our knowledge, the combined effect of chitosan and graphene oxide on bone defects has not been explored in vivo before.…”

Section: Discussionmentioning

confidence: 99%

Chitosan-Graphene Oxide 3D scaffolds as Promising Tools for Bone Regeneration in Critical-Size Mouse Calvarial Defects

Hermenean

Codreanu

Herman

et al. 2017

Sci Rep

102

Limited self-regenerating capacity of human skeleton makes the reconstruction of critical size bone defect a significant challenge for clinical practice. Aimed for regenerating bone tissues, this study was designed to investigate osteogenic differentiation, along with bone repair capacity of 3D chitosan (CHT) scaffolds enriched with graphene oxide (GO) in critical-sized mouse calvarial defect. Histopathological/histomorphometry and scanning electron microscopy(SEM) analysis of the implants revealed larger amount of new bone in the CHT/GO-filled defects compared with CHT alone (p < 0.001). When combined with GO, CHT scaffolds synergistically promoted the increase of alkaline phosphatase activity both in vitro and in vivo experiments. This enhanced osteogenesis was corroborated with increased expression of bone morphogenetic protein (BMP) and Runx-2 up to week 4 post-implantation, which showed that GO facilitates the differentiation of osteoprogenitor cells. Meanwhile, osteogenesis was promoted by GO at the late stage as well, as indicated by the up-regulation of osteopontin and osteocalcin at week 8 and overexpressed at week 18, for both markers. Our data suggest that CHT/GO biomaterial could represent a promising tool for the reconstruction of large bone defects, without using exogenous living cells or growth factors.

Advanced Drug Delivery Reviews

“…As a result, cellular attachment, proliferation and bone-mineralization related activities were enhanced in cells grown on the MrGO. In addition, based on the protein adsorption capability, GO can be utilized for the delivery of bone morphogenetic protein-2 (BMP-2) and substance P (SP) through electrostatic interaction between the ionized groups of GO and proteins and hydrophobic π-π stacking [171]. …”

Section: Applications In Tissue Engineering and Regenerative Medicinementioning

confidence: 99%

Graphene-based materials for tissue engineering

Shin

Jang

et al. 2016

580

418

Graphene and its chemical derivatives have been a pivotal new class of nanomaterials and a model system for quantum behavior. The material's excellent electrical conductivity, biocompatibility, surface area and thermal properties are of much interest to the scientific community. Two dimensional graphene materials have been widely used in various biomedical research areas such as bioelectronics, imaging, drug delivery, and tissue engineering. In this review we will highlight the recent applications of graphene-based materials in tissue engineering and regenerative medicine. In particular, we will discuss the application of graphene-based materials in cardiac, neural, bone, cartilage, skeletal muscle, and skin/adipose tissue engineering. We also discuss the potential risk factors of graphene-based materials in tissue engineering. In addition, we will outline the opportunities in the usage of graphene-based materials for clinical applications.