title: Interlaboratory studies on in vitro test methods for estimating in vivo resorption of calcium phosphate ceramics.
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.
  
  
  CONCLUSIONS
  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).
authors.affiliation: National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki 305-8566, Japan. Electronic address: atsuo-ito@aist.go.jp.
authors.forename: Atsuo
authors.initials: A
authors.lastname: Ito
authors.affiliation: National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki 305-8566, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Sogo
authors.affiliation: Department of Resources and Environmental Engineering, Waseda University, Shinjuku-ku, Tokyo 169-8555, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yamazaki
authors.affiliation: Department of Applied Chemistry, School of Science and Technology, Meiji University, Tama-ku, Kawasaki, Kanagawa 214-8571, Japan.
authors.forename: Mamoru
authors.initials: M
authors.lastname: Aizawa
authors.affiliation: Department of Medical and Bioengineering Science, Graduate School of Natural Science and Technology, Okayama University, Tsushima, Okayama, Okayama 700-8530, Japan.
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Osaka
authors.affiliation: Department of Medical and Bioengineering Science, Graduate School of Natural Science and Technology, Okayama University, Tsushima, Okayama, Okayama 700-8530, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hayakawa
authors.affiliation: National Institute for Materials Science, Tsukuba, Ibaraki 305-0044, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Kikuchi
authors.affiliation: Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Chiyoda-ku, Tokyo 101-0062, Japan.
authors.forename: Kimihiro
authors.initials: K
authors.lastname: Yamashita
authors.affiliation: Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Chiyoda-ku, Tokyo 101-0062, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: National Institute of Advanced Industrial Science and Technology (AIST), Amagasaki, Hyogo 661-0974, Japan.
authors.forename: Mika
authors.initials: M
authors.lastname: Tadokoro
authors.affiliation: Instituto Nacional de Metrologia, Qualidade e Tecnologia - Inmetro, Diretoria de Metrologia Científica e Industrial - Dimci, Divisão de Metrologia de Materiais - Dimat, CEP 25250-020 Xerém - Duque de Caxias, RJ, Brazil.
authors.forename: Lídia Ágata
authors.initials: LÁ
authors.lastname: de Sena
authors.affiliation: Queen's University, School of Mechanical and Aerospace Engineering, Ashby Building, Stranmillis Road, Belfast BT9 5AH, UK.
authors.forename: Fraser
authors.initials: F
authors.lastname: Buchanan
authors.affiliation: National Institute of Advanced Industrial Science and Technology (AIST), Amagasaki, Hyogo 661-0974, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Ohgushi
authors.affiliation: RMS Foundation, Bischmattstr. 12, CH-2544 Bettlach, Switzerland.
authors.forename: Marc
authors.initials: M
authors.lastname: Bohner
mesh_terms: D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D001862:Bone Resorption / Q000473:pathology*; D002130:Calcium Phosphates / Q000494:pharmacology*; D002516:Ceramics / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D007527:Isoenzymes / Q000378:metabolism; D008422:Materials Testing / Q000379:methods*; D016062:Porosity; D011817:Rabbits; D000071681:Tartrate-Resistant Acid Phosphatase
chemical_list: D002130:Calcium Phosphates; D007527:Isoenzymes; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase; C018392:tricalcium phosphate
keywords: Calcium phosphate; Dissolution; Resorption; Round-robin test