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Mater Sci Eng C Mater Biol Appl. 2016 Aug 1;65:70-9. doi: 10.1016/j.msec.2016.03.105. Epub 2016 Apr 7.

"False" cytotoxicity of ions-adsorbing hydroxyapatite - Corrected method of cytotoxicity evaluation for ceramics of high specific surface area.

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Chair and Department of Biochemistry and Biotechnology, Medical University of Lublin, Chodzki 1, 20-093 Lublin, Poland.
Institute of Low Temperature and Structure Research, PAS, Okólna 2, 50-422 Wrocław, Poland.
Research and Development Centre Novasome sp. z o.o., Olsztyńska 5, 51-423 Wrocław, Poland.


An assessment of biomaterial cytotoxicity is a prerequisite for evaluation of its clinical potential. A material is considered toxic while the cell viability decreases under 70% of the control. However, extracts of certain materials are likely to reduce the cell viability due to the intense ions adsorption from culture medium (e.g. highly bioactive ceramics of high surface area). Thus, the standard ISO 10993-5 procedure is inappropriate for cytotoxicity evaluation of ceramics of high specific surface area because biomaterial extract obtained in this method (ions-depleted medium) is not optimal for cell cultures per se. Therefore, a simple test was designed as an alternative to ISO 10993-5 standard for cytotoxicity evaluation of the biomaterials of high surface area and high ions absorption capacity. The method, presented in this paper, included the evaluation of ceramics extract prepared according to corrected procedure. The corrected extract was found not cytotoxic (cell viability above 70%), suggesting that modified method for cytotoxicity evaluation of ions-adsorbing ceramics is more appropriate than ISO 10993-5 standard. For such biomaterials, the term "false" cytotoxicity is more suitable. Moreover, it was noted that NRU assay and microscopic observations should be recommended for cytotoxicity evaluation of ceramics of high surface area.


Calcium phosphate; Cytotoxicity; High specific surface area; Ions supplementation; Ions uptake

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