Development of an injectable polymer-calcium phosphate cement composites for bone substitution

Since the discovery of injectable calcium phosphate (CaP) cements, they are widely used to fill irregularly shaped bone defects. This created an alternative to more invasive methods such as use of autografts, allografts, xenografts and synthetic pre- shaped scaffolds. Hence, this thesis aimed to design an alternative injectable bone substitute (IBS) that can better accommodate CaP additives while preserving bone- like rheological properties and performance. In this thesis, an IBS was prepared by using methylcellulose (MC), gelatin and bioceramic powder mixture. Initially, three different powder to liquid (P/L) formulations were adjusted to investigate the chemical structure, rheological characteristics, handling, mechanical and in vitro degradation properties. Then, the effect of graphene oxide (GO) incorporation investigated by analyzing their physicochemical properties and in vitro responses. Results showed that the elastic modulus was increased up to 6.89 ± 2.25 MPa from 1.72 ± 0.76 MPa with the addition of 2 wt% GO on day 14. The extracted solution of the GO reinforced IBS was found to be biocompatible with bone marrow mesenchymal stem cells (BMMSCs). Finally, zoledronic acid (ZOL) was incorporated into IBS samples. Results showed that the presence of ZOL prolonged the setting time of the IBS samples. The mechanical properties decreased with ZOL addition and increased with the incorporation of GO which was found as 25.73 MPa. In in vitro cell studies, both the inhibitory effect of ZOL and GO loaded IBS on MCF-7 cells and proliferative effect on osteoblast cells were observed. In conclusion, the outcomes of this thesis indicated that prepared IBS may be promising candidates to fill bone defects and assist bone recovery for non-load bearing applications.