Enhanced Osteogenic Differentiation of Human Fetal Cartilage Rudiment Cells on Graphene Oxide-PLGA Hybrid Microparticles.

Stuart C Thickett,Per B Zetterlund,Ella Hamilton,Brooke L Farrugia,Megan S Lord,Gokulan Yogeswaran

doi:10.3390/jfb10030033

Abstract

Poly(d,l–lactide–co–glycolide) (PLGA) has been extensively explored for bone regeneration applications; however, its clinical use is limited by low osteointegration. Therefore, approaches that incorporate osteoconductive molecules are of great interest. Graphene oxide (GO) is gaining popularity for biomedical applications due to its ability to bind biological molecules and present them for enhanced bioactivity. This study reports the preparation of PLGA microparticles via Pickering emulsification using GO as the sole surfactant, which resulted in hybrid microparticles in the size range of 1.1 to 2.4 µm based on the ratio of GO to PLGA in the reaction. Furthermore, this study demonstrated that the hybrid GO-PLGA microparticles were not cytotoxic to either primary human fetal cartilage rudiment cells or the human osteoblast-like cell line, Saos-2. Additionally, the GO-PLGA microparticles promoted the osteogenic differentiation of the human fetal cartilage rudiment cells in the absence of exogenous growth factors to a greater extent than PLGA alone. These findings demonstrate that GO-PLGA microparticles are cytocompatible, osteoinductive and have potential as substrates for bone tissue engineering.

Highlights

The repair of critical size bone defects as a result of trauma, tumor resection or congenital abnormalities is an unmet clinical need for orthopedics and dentistry
Graphene oxide (GO)-PLGA particles were prepared via a Pickering emulsion using GO as the stabilizer and anisole as the solvent and were compared to a control system where PLGA particles prepared with poly(vinyl alcohol) (PVA) as the stabilizer
This study demonstrated that GO-PLGA microparticles can be synthesized via a Pickering emulsion using GO as the sole surfactant

Summary

Introduction

The repair of critical size bone defects as a result of trauma, tumor resection or congenital abnormalities is an unmet clinical need for orthopedics and dentistry. There is interest in developing off-the-shelf biomaterial strategies for rapid bone repair. Biodegradable synthetic polymers such as poly(lactide–co–glycolide) (PLGA) have been widely explored for bone tissue engineering applications due to their tunable mechanical and degradation properties, unlimited availability and approved clinical use by the US Food and Drug Administration [1,2,3]. Graphene oxide (GO) has gained attention for biomedical applications due to its cytocompatibility and capacity to bind various biological molecules via its surface carbon and oxygen functional groups, which stabilize the GO sheets in aqueous media [5,6]. The range of functional groups in GO enables it to be readily incorporated into a polymer matrix and often results in improved mechanical and biological properties compared to the neat polymer [7]. GO-PLGA microparticles alone or incorporated into silk membranes have been reported to support osteoblast growth over 28 days with the addition of exogenous growth factors [8,9,10,11]

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