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.

Acrylic Bone Cement Incorporated with Low Chitosan Loadings

“…CS-based materials are ideal bioactive materials due to their biocompatibility, wound-healing ability, non-toxicity, antibacterial properties, anti-fungal properties, hydrophilicity, biodegradability, and ability to stimulate adherence, proliferation, and viability of cells [ 7 , 9 , 10 ]. Several reports exist on the addition of CS to ABC, resulting in improvement of various properties of ABC, such as increased setting time ( t set ) [ 11 ], reduced maximum exotherm temperature ( T max ) [ 6 ], increased porosity, higher antibacterial action [ 12 ], and increased bioactivity [ 2 , 5 , 13 , 14 , 15 ]. However, high CS loading generates considerable detriment to the mechanical properties of cements, restricting clinical uses to non-load-bearing applications.…”

Microfluidic-based screening of resveratrol and drug-loading PLA/Gelatine nano-scaffold for the repair of cartilage defect

“…With the help of CGG, solutions 1 and 2 were mixed and different concentration gradients were generated. According to Reynolds effect and the previous work and equation described by Jeon [25], when the liquid flowed through the micro-channels with a lower speed, it would exhibit laminar flow. In our microfluidic device, with the fluid speed of 0.1 ll/min, different laminar flow concentration gradients would be generated by means of campulitropal micro-channel design (Figure 1(A)).…”

Comprehensive evaluation and advanced modification of polymethylmethacrylate cement in bone tumor treatment

“…192 The anchoring effect of PMMA with bone will be enhanced if sufficient bone tissue is generated at the edge of PMMA and aseptic loosening will be prevented. 193 Achieving this effect is indispensable for porogens, which are mostly composed of volatile or soluble substances, 194 such as polyethylene glycol (PEG), 164 poly(lactic- co -glycolic acid) (PLGA), 165 carboxymethylcellulose (CMC), 170 carboxymethyl chitosan (CMCS), 166 and gelatin, 167 etc. However, porogens or large amounts of drugs could have deleterious effects on the mechanical properties of cement.…”