Preparation of graphene oxide-reinforced calcium phosphate/calcium sulfate/methylcellulose-based injectable bone substit

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Research Letter

Preparation of graphene oxide-reinforced calcium phosphate/calcium sulfate/methylcellulose-based injectable bone substitutes Öznur Demir Oğ uz

and Duygu Ege

, Boğaziçi University, Institute of Biomedical Engineering, Istanbul 34684, Turkey

Address all correspondence to Duygu Ege at [email protected] (Received 10 June 2019; accepted 5 September 2019)

Abstract In this study, an injectable bone substitute (IBS) was produced by mixing a liquid and powder phase. The liquid phase consisted of 8 wt% methylcellulose (MC), 2.5% gelatin, and different amounts of graphene oxide (GO). The powder phase was composed of tetracalcium phosphate (TTCP), dicalcium phosphate dihydrate (DCPD), and calcium sulfate dihydrate (CSD). The results showed that 1 and 1.5 wt% GO added IBS samples showed higher stability, injectability, rheological properties, and biocompatibility than the other GO added IBS samples. GO addition significantly decreased the setting time, but it did not significantly affect the compressive strength of the samples.

Introduction Calcium phosphate cements (CPCs) are widely used to fill bone voids for fracture fixation.[1,2] In 1986, Brow and Chow introduced an injectable CPC composed of tetracalcium phosphate (TTCP) and dicalcium phosphate anhydrous. This powder mixture has the ability to set in situ when combined with an aqueous liquid and then precipitate into hydroxyapatite (HA) as the final product.[1,3–5] This precipitated HA has a more similar crystal structure to biological HA than sintered HA with finer grains.[6] Hence, they are used as injectable bone substitutes (IBS) with their unique properties such as self-setting ability, good injectability, easy moldability, high bioactivity, and feasibility.[1,7] However, the injectable CPCs have some drawbacks, including the possibility of a collapse in body fluids, poor degradability, and weak mechanical properties.[8] These physical properties should be improved to make them more applicable in practice. In literature, many methods are presented to overcome drawbacks of CPCs, such as adjusting powder-toliquid ratio, using pore-making agents like acetic acid or citric acid. The setting time was modified by sodium phosphate or calcium sulfate. The mechanical properties were improved by combining with poly(methyl methacrylate) (PMMA). Moreover, methods have been developed to enhance their bone repair ability such as adding calcium silicate, HA, zinc, magnesium, or fluoride ions.[1] To adjust the rheological properties of CPCs, the aqueous liquid could be chosen as a polymeric material.[9,10] In this study, the polymeric phase of the bone filler was prepared by using methylcellulose (MC) and gelatin. MC/gelatin mixture is a thermosensitive formulation which undergoes sol–gel transition at the body temperature. Studies state that the cellulose provides the optimal mechanical properties for orthopedic

surgeries, augments the osteoconductivity, and also leads to a longer implant lifetime by causing slow resorption of CPC.[11,12] Gelatin, which is a chemi