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Research

SYNTHESIS AND CHARACTERIZATION OF INJECTABLE BONE SUBSTITUTES FOR NON-LOAD BEARING ANATOMIC REGIONS

The European Orthopaedic Research Society (EORS) 25th Annual and Anniversary Meeting, Munich, Germany, September 2017. Part 2 of 2.



Abstract

The combination of natural polymers with calcium phosphate cements (CPCs) by mimicking the highly mineralized collagen-based matrix of native bone is crucial in order to obtain mechanically compatible injectable bone substitute (IBS) formulations. This combination overcomes the drawbacks of CPCs like high resorbability, poor mechanical properties, and degradability. In this study, methylcellulose (MC) was combined with CPCs because of MC's thermoresponsive behavior which makes MC suitable for IBS application. In addition, gelatin (GEL) was also incorporated to adjust the gelation temperature and to enhance cell adhesion. These polymers combination makes the liquid (L) phase. The powder (P) phase comprised of tetra calcium phosphate (TTCP), dicalcium phosphate dehydrates (DCPD), and calcium sulfate dehydrates (CSD). TTCP and DCPD are commonly studied for the development of bone cements and they lead to high-density products. CSD was added to the powder phase to increase the porosity as well as to enhance mechanical properties of the IBS. TTCP was synthesized using a solid state method. Test tube inversion method was used to adjust the gelation temperature. GEL concentration was kept constant at 5 wt% and MC concentration varied between 1.5 and 12 wt%. The weight fraction of P/L phase was used as 1.8:1 (wt/wt). Synthesized IBS was characterized by using X-Ray Diffraction (XRD), Fourier Transform Infrared Analysis (FTIR), Zeta Particle Size Analysis, rheometry, and thermogravimetric analysis. XRD and FTIR analysis proved that TTCP was successfully synthesized with a particle size of 430.1 nm. The particle size of P phase mixture was measured as 581.1 nm. Based on the test tube inversion tests, weight fraction of MC was chosen as 10 and 12 while the weight fraction of GEL was fixed as 5. FTIR spectra of the liquid phase was showed that there was a hydrophilic interaction between MC and GEL since both Amide I at 1633 cm−1 and β-gylcosides bonds among saccharide units at 900–1230 cm−1 were clearly seen. MC10GEL5/P and MC12GEL5/P were analyzed by the XRD. According to this analysis, only the peaks of TTCP, DCPD, and CSD were observed. From the rheological data obtained from the rheometer, it is evident that all the prepared formulations exhibited Newtonian flow. The measured viscosity of all the investigated formula remained constant with the applied force over time. The MC12GEL5/P had the highest viscosity value due to its high concentration of MC (12% w/v). Results of TG of the synthesized IBS showed two main decomposition steps for the L phase because of the hydrophilic interaction between MC and GEL. The synthesized self-crosslinkable IBS represent promising platforms for future studies in bone tissue engineering. Overall, the presented study identified a novel IBS with suitable viscoelastic properties for non-invasive treatment of bone defects which may ultimately be a substitute for surgery for a wide variety of therapeutic applications.


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