Understanding the impact of divalent cation substitution on hydroxyapatite: An in vitro multiparametric study on biocompatibility

Ingrid Russoni De Lima, Gutemberg Gomes Alves, Carlos Alberto Soriano, Ana Paula Campaneli, Thais Helena Gasparoto, Erivan Schnaider Ramos, Lídia Ágata De Sena, Alexandre Malta Rossi, José Mauro Granjeiro

Research output: Contribution to journalArticlepeer-review

71 Scopus citations


Hydroxyapatite (HA), a stable and biocompatible material for bone tissue therapy, may present a variable stoichiometry and accept a large number of cationic substitutions. Such substitutions may modify the chemical activity of HA surface, with possible impact on biocompatibility. In this work, we assessed the effects of calcium substitution with diverse divalent cations (Pb 2+, Sr2+, Co2+, Zn2+, Fe 2+, Cu2+, or Mg2+) on the biological behavior of HA. Physicochemical analyses revealed that apatite characteristics related to crystallinity and calcium dissolution/uptake rates are very sensitive to the nature of cationic substitution. Cytocompatibility was evaluated by mitochondrial activity, membrane integrity, cell density, proapoptotic potential, and adhesion tests. With the exception of Zn-HA, all the substituted HAs induced some level of apoptosis. The highest apoptosis levels were observed for Mg-HA and Co-HA. Cu-HA was the only material to impair simultaneously mitochondrial activity, membrane integrity, and cell density. The highest relative cell densities after exposure to the modified HAs were observed for Mg-HA and Zn-HA, while Co-HA significantly improved cell adhesion onto HA surface. These results show that changes on surface dissolution caused by cationic substitution, as well as the increase of metal species released to biological media, were the main responsible factors related to alterations on HA biocompatibility.

Original languageEnglish (US)
Pages (from-to)351-358
Number of pages8
JournalJournal of Biomedical Materials Research - Part A
Volume98 A
Issue number3
StatePublished - Sep 1 2011
Externally publishedYes


  • apoptosis
  • biocompatibility
  • cytotoxicity
  • hydroxyapatite
  • metal ion release

ASJC Scopus subject areas

  • Ceramics and Composites
  • Biomaterials
  • Biomedical Engineering
  • Metals and Alloys


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