title: Effects of Incorporating Carboxymethyl Chitosan into PMMA Bone Cement Containing Methotrexate.
abstract: 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.
authors.affiliation: Department of Orthopedics, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116044, China.|Dalian Medical University, Dalian, Liaoning, 116044, China.
authors.forename: Bo-Ming
authors.initials: BM
authors.lastname: Liu
authors.affiliation: Department of Orthopedics, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116044, China.|Dalian Medical University, Dalian, Liaoning, 116044, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Orthopedics, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116044, China.|Dalian Medical University, Dalian, Liaoning, 116044, China.
authors.forename: Bao-Sheng
authors.initials: BS
authors.lastname: Yin
authors.affiliation: Department of Orthopedics, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116044, China.|Dalian Medical University, Dalian, Liaoning, 116044, China.
authors.forename: Ji-Yang
authors.initials: JY
authors.lastname: Zou
authors.affiliation: Department of Orthopedics, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116044, China.|Dalian Medical University, Dalian, Liaoning, 116044, China.
authors.forename: Wei-Guo
authors.initials: WG
authors.lastname: Zhang
authors.affiliation: Department of Orthopedics, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116044, China.|Dalian Medical University, Dalian, Liaoning, 116044, China.
authors.forename: Shou-Yu
authors.initials: SY
authors.lastname: Wang
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D001843:Bone Cements / Q000737:chemistry; D001859:Bone Neoplasms / Q000188:drug therapy / Q000556:secondary / Q000601:surgery*; D045744:Cell Line, Tumor; D048271:Chitosan / Q000031:analogs & derivatives* / Q000737:chemistry; D019245:Compressive Strength; D005269:Femur / Q000000981:diagnostic imaging / Q000473:pathology / Q000601:surgery*; D006168:Guinea Pigs; D006801:Humans; D021621:Imaging, Three-Dimensional; D056656:Lab-On-A-Chip Devices; D008422:Materials Testing; D008727:Methotrexate / Q000737:chemistry / Q000627:therapeutic use*; D008855:Microscopy, Electron, Scanning; D019904:Polymethyl Methacrylate / Q000737:chemistry*; D036542:Tomography, Spiral Computed
chemical_list: D001672:Biocompatible Materials; D001843:Bone Cements; C514968:carboxymethyl-chitosan; D019904:Polymethyl Methacrylate; D048271:Chitosan; D008727:Methotrexate