Effects of Incorporating Carboxymethyl Chitosan into PMMA Bone Cement Containing Methotrexate

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 th...

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Bibliographic Details
Published in:PloS one 2015-12, Vol.10 (12), p.e0144407-e0144407
Main Authors: Liu, Bo-Ming, Li, Ming, Yin, Bao-Sheng, Zou, Ji-Yang, Zhang, Wei-Guo, Wang, Shou-Yu
Format: Article
Language:English
Subjects:
Animals
Anticancer properties
Bend strength
Bending modulus
Biocompatibility
Biocompatible Materials - chemistry
Biomedical materials
Body fluids
Bone cements
Bone Cements - chemistry
Bone implants
Bone Neoplasms - drug therapy
Bone Neoplasms - secondary
Bone Neoplasms - surgery
Calcium phosphates
Cancer
Cell culture
Cell Line, Tumor
Cement
Chitosan
Chitosan - analogs & derivatives
Chitosan - chemistry
Compressive Strength
Computed tomography
Computer simulation
Electron microscopy
Femur - diagnostic imaging
Femur - pathology
Femur - surgery
Growth factors
Guinea Pigs
High-performance liquid chromatography
Homogeneity
Humans
Hydroxyapatite
Image processing
Image reconstruction
Imaging, Three-Dimensional
In vitro methods and tests
In vivo methods and tests
Lab-On-A-Chip Devices
Liquid chromatography
Lung cancer
Lung diseases
Materials Testing
Mechanical properties
Mechanical tests
Metastases
Metastasis
Methotrexate
Methotrexate - chemistry
Methotrexate - therapeutic use
Microfluidics
Microscopy, Electron, Scanning
Microstructure
Orthopedics
Polymethyl methacrylate
Polymethyl Methacrylate - chemistry
Polymethylmethacrylate
Scanning electron microscopy
Studies
Surgery
Surgical implants
Tomography, Spiral Computed
Transplants & implants
Viability
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0144407