Effects of Incorporating Carboxymethyl Chitosan into PMMA Bone Cement Containing MethotrexateReport as inadecuate




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Treatment of bone metastases usually includes surgical resection with local filling of methotrexate MTX in polymethyl methacrylate PMMA cement. We investigated whether incorporating carboxymethyl chitosan CMCS in MTX-PMMA cement might overcome disadvantages associated with MTX. To determine the optimal CMCS+MTX concentration to suppress the viability of cancer cells, an integrated microfluidic chip culturing highly metastatic lung cancer cells H460 was employed. The mechanical properties, microstructure, and MTX release of CMCS+MTX-PMMA cement were evaluated respectively by universal mechanical testing machine, scanning electron microscopy SEM, and incubation in simulated body fluid with subsequent HPLC-MS. Implants of MTX-PMMA and CMCS+MTX-PMMA cement were evaluated in vivo in guinea pig femurs over time using spiral computed tomography with three-dimensional image reconstruction, and SEM at 6 months. Viability of H460 cells was significantly lowest after treatment with 57 μg-mL CMCS + 21 μg-mL MTX, which was thus used in subsequent experiments. Incorporation of 1.6% w-w CMCS to MTX-PMMA significantly increased the bending modulus, bending strength, and compressive strength by 5, 2.8, and 5.2%, respectively, confirmed by improved microstructural homogeneity. Incorporation of CMCS delayed the time-to-plateau of MTX release by 2 days, but increased the fraction released at the plateau from 3.24% MTX-PMMA to 5.34%. Relative to the controls, the CMCS+MTX-PMMA implants integrated better with the host bone. SEM revealed pores in the cement of the CMCS+MTX-PMMA implants that were not obvious in the controls. In conclusion, incorporation of CMCS in MTX-PMMA appears a feasible and effective modification for improving the anti-tumor properties of MTX-PMMA cement.



Author: Bo-Ming Liu, Ming Li, Bao-Sheng Yin, Ji-Yang Zou, Wei-Guo Zhang , Shou-Yu Wang

Source: http://plos.srce.hr/



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