Interlaboratory studies on in vitro test methods for estimating in vivo resorption of calcium phosphate ceramics

Atsuo Ito, Yu Sogo, Atsushi Yamazaki, Mamoru Aizawa, Akiyoshi Osaka, Satoshi Hayakawa, Masanori Kikuchi, Kimihiro Yamashita, Yumi Tanaka, Mika Tadokoro, Lídia Ágata De Sena, Fraser Buchanan, Hajime Ohgushi, Marc Bohner

Research output: Contribution to journalArticle

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Abstract

A potential standard method for measuring the relative dissolution rate to estimate the resorbability of calcium-phosphate-based ceramics is proposed. Tricalcium phosphate (TCP), magnesium-substituted TCP (MgTCP) and zinc-substituted TCP (ZnTCP) were dissolved in a buffer solution free of calcium and phosphate ions at pH 4.0, 5.5 or 7.3 at nine research centers. Relative values of the initial dissolution rate (relative dissolution rates) were in good agreement among the centers. The relative dissolution rate coincided with the relative volume of resorption pits of ZnTCP in vitro. The relative dissolution rate coincided with the relative resorbed volume in vivo in the case of comparison between microporous MgTCPs with different Mg contents and similar porosity. However, the relative dissolution rate was in poor agreement with the relative resorbed volume in vivo in the case of comparison between microporous TCP and MgTCP due to the superimposition of the Mg-mediated decrease in TCP solubility on the Mg-mediated increase in the amount of resorption. An unambiguous conclusion could not be made as to whether the relative dissolution rate is predictive of the relative resorbed volume in vivo in the case of comparison between TCPs with different porosity. The relative dissolution rate may be useful for predicting the relative amount of resorption for calcium-phosphate-based ceramics having different solubility under the condition that the differences in the materials compared have little impact on the resorption process such as the number and activity of resorbing cells. Statement of significance The evaluation and subsequent optimization of the resorbability of calcium phosphate are crucial in the use of resorbable calcium phosphates. Although the resorbability of calcium phosphates has usually been evaluated in vivo, establishment of a standard in vitro method that can predict in vivo resorption is beneficial for accelerating development and commercialization of new resorbable calcium phosphate materials as well as reducing use of animals. However, there are only a few studies to propose such an in vitro method within which direct comparison was carried out between in vitro and in vivo resorption. We propose here an in vitro method based on measuring dissolution rate. The efficacy and limitations of the method were evaluated by international round-robin tests as well as comparison with in vivo resorption studies for future standardization. This study was carried out as one of Versailles Projects on Advanced Materials and Standards (VAMAS).

Original languageEnglish
Pages (from-to)347-355
Number of pages9
JournalActa Biomaterialia
Volume25
DOIs
Publication statusPublished - Oct 1 2015

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Calcium phosphate
Ceramics
Dissolution
Calcium Phosphates
Phosphates
Porosity
Solubility
Magnesium
Zinc
Songbirds
Buffers
calcium phosphate
tricalcium phosphate
In Vitro Techniques
Ions
Standardization
Research
Calcium
Animals
Cells

Keywords

  • Calcium phosphate
  • Dissolution
  • Resorption
  • Round-robin test

ASJC Scopus subject areas

  • Biomaterials
  • Biomedical Engineering
  • Biotechnology
  • Biochemistry
  • Molecular Biology

Cite this

Interlaboratory studies on in vitro test methods for estimating in vivo resorption of calcium phosphate ceramics. / Ito, Atsuo; Sogo, Yu; Yamazaki, Atsushi; Aizawa, Mamoru; Osaka, Akiyoshi; Hayakawa, Satoshi; Kikuchi, Masanori; Yamashita, Kimihiro; Tanaka, Yumi; Tadokoro, Mika; De Sena, Lídia Ágata; Buchanan, Fraser; Ohgushi, Hajime; Bohner, Marc.

In: Acta Biomaterialia, Vol. 25, 01.10.2015, p. 347-355.

Research output: Contribution to journalArticle

Ito, A, Sogo, Y, Yamazaki, A, Aizawa, M, Osaka, A, Hayakawa, S, Kikuchi, M, Yamashita, K, Tanaka, Y, Tadokoro, M, De Sena, LÁ, Buchanan, F, Ohgushi, H & Bohner, M 2015, 'Interlaboratory studies on in vitro test methods for estimating in vivo resorption of calcium phosphate ceramics', Acta Biomaterialia, vol. 25, pp. 347-355. https://doi.org/10.1016/j.actbio.2015.07.040
Ito, Atsuo ; Sogo, Yu ; Yamazaki, Atsushi ; Aizawa, Mamoru ; Osaka, Akiyoshi ; Hayakawa, Satoshi ; Kikuchi, Masanori ; Yamashita, Kimihiro ; Tanaka, Yumi ; Tadokoro, Mika ; De Sena, Lídia Ágata ; Buchanan, Fraser ; Ohgushi, Hajime ; Bohner, Marc. / Interlaboratory studies on in vitro test methods for estimating in vivo resorption of calcium phosphate ceramics. In: Acta Biomaterialia. 2015 ; Vol. 25. pp. 347-355.
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AU - Osaka, Akiyoshi

AU - Hayakawa, Satoshi

AU - Kikuchi, Masanori

AU - Yamashita, Kimihiro

AU - Tanaka, Yumi

AU - Tadokoro, Mika

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N2 - A potential standard method for measuring the relative dissolution rate to estimate the resorbability of calcium-phosphate-based ceramics is proposed. Tricalcium phosphate (TCP), magnesium-substituted TCP (MgTCP) and zinc-substituted TCP (ZnTCP) were dissolved in a buffer solution free of calcium and phosphate ions at pH 4.0, 5.5 or 7.3 at nine research centers. Relative values of the initial dissolution rate (relative dissolution rates) were in good agreement among the centers. The relative dissolution rate coincided with the relative volume of resorption pits of ZnTCP in vitro. The relative dissolution rate coincided with the relative resorbed volume in vivo in the case of comparison between microporous MgTCPs with different Mg contents and similar porosity. However, the relative dissolution rate was in poor agreement with the relative resorbed volume in vivo in the case of comparison between microporous TCP and MgTCP due to the superimposition of the Mg-mediated decrease in TCP solubility on the Mg-mediated increase in the amount of resorption. An unambiguous conclusion could not be made as to whether the relative dissolution rate is predictive of the relative resorbed volume in vivo in the case of comparison between TCPs with different porosity. The relative dissolution rate may be useful for predicting the relative amount of resorption for calcium-phosphate-based ceramics having different solubility under the condition that the differences in the materials compared have little impact on the resorption process such as the number and activity of resorbing cells. Statement of significance The evaluation and subsequent optimization of the resorbability of calcium phosphate are crucial in the use of resorbable calcium phosphates. Although the resorbability of calcium phosphates has usually been evaluated in vivo, establishment of a standard in vitro method that can predict in vivo resorption is beneficial for accelerating development and commercialization of new resorbable calcium phosphate materials as well as reducing use of animals. However, there are only a few studies to propose such an in vitro method within which direct comparison was carried out between in vitro and in vivo resorption. We propose here an in vitro method based on measuring dissolution rate. The efficacy and limitations of the method were evaluated by international round-robin tests as well as comparison with in vivo resorption studies for future standardization. This study was carried out as one of Versailles Projects on Advanced Materials and Standards (VAMAS).

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