The cytotoxic effect of methotrexate loaded bone cement on osteosarcoma cell lines

Kim, H S; Park, Y B; Oh, Jedo; Yoo, Kwang Hyun; Lee, S H

doi:10.1007/s002640100293

Cited by 23 publications

(10 citation statements)

References 14 publications

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“…Hernigou et al [1] reported for the first time that cement implants containing MTX were able to release the drug for a period of months. Subsequent detailed in vitro works evaluated elution kinetics of MTX from the cement pellets [2,4,5]. All authors reported the greatest elution during the first day for all concentrations, with rapid decrease during the following days, and stabilisation to a constant rate of release after two weeks of incubation.…”

Section: Discussionmentioning

confidence: 99%

“…Kim at al. [5] showed that the mean amount of MTX eluted from pellet over a 28-day period ranged from 7.2% to 11.7%. Our data were similar and suggested that the majority of the MTX remained in the bone cement.…”

Section: Discussionmentioning

confidence: 99%

“…The next question was the MTX formulation. Although most authors are using the powdered MTX [1,3,5], for potential use in clinical practice where the bone cement must be prepared under sterile conditions, the sterile form of MTX must be also available. Routinely, MTX is available in hospitals as a sterile infusion solution for anticancer therapy.…”

Section: Discussionmentioning

confidence: 99%

“…The hardened pellets were processed as described previously [5], i.e. washed in sterile saline solution for one minute, sterilised with 70% ethanol for 20 min, and again washed twice for one minute.…”

Section: Mtx Elution From Mtx-loaded Cement Pelletsmentioning

confidence: 99%

“…The combination retains useful mechanical properties of polymethylmethacrylate alone and offers the advantage of local cytostatic influence of MTX on remaining tumour cells in surrounding tissue [3,4], as has been shown during a series of in vitro toxicity testing on various cell lines including those from osteosarcoma [1,3,[5][6][7]. In addition, in vivo experiments in rats with osteosarcoma demonstrated that implantation of MTXloaded cement to the centre of a tumour temporally slows tumour growth, attenuates bone destruction, and prolongs survival of animals [1,4].…”

Section: Introductionmentioning

confidence: 99%

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Methotrexate released in vitro from bone cement inhibits human stem cell proliferation in S/G2 phase

Procházka

Soukup

Hroch

et al. 2009

International Orthopaedics (SICOT)

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Methotrexate (MTX) released from bone cement showed a useful local effect in animal models of bone tumours. However, local toxic reactions such as impaired wound healing were observed in areas surrounding the MTX-loaded implant. Therefore, we hypothesised that MTX released from bone cement would have harmful effects on human mesenchymal stem cells (MSC)-one of the basic components of bone marrow and tissue reparatory processes. Moreover, elution of MTX was calculated from implants prepared either with liquid or powdered MTX. During the 28-day incubation, the cement compounded with liquid MTX showed the highest elution rate of the drug. MTX released from pellets produced a significant decrease in proliferation of MSC as a consequence of a blockade of their cell cycle in the S/G2 phase. These findings indicate impairment of stem cell function in marginal areas surrounding the MTX-loaded cement and may help to explain problems with regeneration of tissues in these locations.Résumé Le Methotrexate (MTX) libéré par le ciment acrylique a un effet certain sur les tumeurs osseuses développées sur un modèle animal. Cependant, des réac-tions toxiques locales telles que défauts de cicatrisation ont été observées à proximité de l'implantation de ce ciment. Nous faisons donc l'hypothèse que le Methotrexate MTX libéré par le ciment a un effet nocif néfaste sur les cellules mésenchyméteuses humaines MSC qui sont l'un des composants de base de la moelle osseuse et des phénom-ènes de la réparation tissulaire. De plus, la dynamique de pénétration du méthotrexate a été analysée à partir d'implants préparés avec du liquide ou de la poudre de méthotrexate. Au cours des 28 jours d'incubation, le ciment préparé avec du méthotrexate liquide montre un taux important de pénétration de la drogue. Le méthotrexate libéré des billes de ciment entraîne une diminution significative de la prolifération des cellules mésenchymé-teuses avec un bloquage cellulaire à la phase S/G2. Ces travaux montrent que la fonction cellulaire est altérée au voisInage du méthotrexate pouvant expliquer les problèmes de régénétration tissulaire.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Mtx Elution From Mtx-loaded Cement Pelletsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Methotrexate released in vitro from bone cement inhibits human stem cell proliferation in S/G2 phase

Procházka

Soukup

Hroch

et al. 2009

International Orthopaedics (SICOT)

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Mechanical and cytotoxicity testing of acrylic bone cement embedded with microencapsulated 2‐octyl cyanoacrylate

2013

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The water-reactive tissue adhesive 2-octyl cyanoacrylate (OCA) was microencapsulated in polyurethane shells and incorporated into Palacos R bone cement. The tensile and compressive properties of the composite material were investigated in accordance with commercial standards, and fracture toughness of the capsule-embedded bone cement was measured using the tapered double-cantilever beam geometry. Viability and proliferation of MG63 human osteosarcoma cells after culture with extracts from Palacos R bone cement, capsule-embedded Palacos R bone cement, and OCA were also analyzed. Incorporating up to 5 wt % capsules had little effect on the compressive and tensile properties of the composite, but greater than 5 wt % capsules reduced these values below commercial standards. Fracture toughness was increased by 13% through the incorporation of 3 wt % capsules and eventually decreased below the toughness of the capsule-free controls at capsule contents of 15 wt % and higher. The effect on cell proliferation and viability in response to extracts prepared from capsule-embedded and commercial bone cements were not significantly different from each other, whereas extracts from OCA were moderately toxic to cells. Overall, the addition of lower wt % of OCA-containing microcapsules to commercial bone cement was found to moderately increase static mechanical properties without increasing the toxicity of the material.

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The effectiveness and mechanical properties of chemotherapy‐impregnated cement in Ewing sarcoma

Goldin

Healey

2023

Journal Orthopaedic Research

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Bone cement is often used in the surgical treatment of Ewing sarcoma (ES). Chemotherapy‐impregnated cement (CIC) has never been tested in slowing ES growth. The purpose of the study is to determine if CIC can decrease cell proliferation, and to assess changes in the mechanical qualities of the cement. Chemotherapeutic agents including doxorubicin, cisplatin, etoposide, and SF2523 were mixed with bone cement. ES cells were plated and exposed to cell growth media that had contained CIC or regular bone cement (RBC) as a control, and cell proliferation assays were performed daily for 3 days. Mechanical testing on RBC and CIC was also performed. There was a significant decrease (p < 0.001) in cell proliferation among all cells treated with CIC compared to cells treated with RBC by 48 h postexposure. Additionally, there was a synergistic effectiveness of the CIC noted when multiple antineoplastic agents were combined. Three‐point bending tests did not reveal substantial reductions in tolerated maximum bending load and maximal displacement at maximal bending load between CIC and RBC. Statement of Clinical Significance: CIC does appear to be effective at decreasing cell growth and does not appear to substantially alter the mechanical properties of the cement.

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The cytotoxic effect of methotrexate loaded bone cement on osteosarcoma cell lines

Cited by 23 publications

References 14 publications

Methotrexate released in vitro from bone cement inhibits human stem cell proliferation in S/G2 phase

Methotrexate released in vitro from bone cement inhibits human stem cell proliferation in S/G2 phase

Mechanical and cytotoxicity testing of acrylic bone cement embedded with microencapsulated 2‐octyl cyanoacrylate

The effectiveness and mechanical properties of chemotherapy‐impregnated cement in Ewing sarcoma

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