title: Understanding the impact of divalent cation substitution on hydroxyapatite: an in vitro multiparametric study on biocompatibility.
abstract: 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+), Sr(2+), Co(2+), Zn(2+), Fe(2+), Cu(2+), or Mg(2+)) 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.
authors.affiliation: Clinical Research Unit, Antônio Pedro Hospital, Fluminense Federal University, Niterói, Brazil.
authors.forename: Ingrid Russoni
authors.initials: IR
authors.lastname: de Lima
authors.forename: Gutemberg Gomes
authors.initials: GG
authors.lastname: Alves
authors.forename: Carlos Alberto
authors.initials: CA
authors.lastname: Soriano
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Campaneli
authors.forename: Thais Helena
authors.initials: TH
authors.lastname: Gasparoto
authors.forename: Erivan Schnaider
authors.initials: ES
authors.lastname: Ramos
authors.forename: Lídia Ágata
authors.initials: LÁ
authors.lastname: de Sena
authors.forename: Alexandre Malta
authors.initials: AM
authors.lastname: Rossi
authors.forename: José Mauro
authors.initials: JM
authors.lastname: Granjeiro
mesh_terms: D000818:Animals; D017209:Apoptosis; D041702:BALB 3T3 Cells; D002413:Cations, Divalent / Q000737:chemistry / Q000378:metabolism*; D002448:Cell Adhesion; D002478:Cells, Cultured; D020099:Coated Materials, Biocompatible / Q000737:chemistry / Q000378:metabolism*; D017886:Durapatite / Q000737:chemistry / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology; D006801:Humans; D008422:Materials Testing; D051379:Mice; D010006:Osteoblasts / Q000166:cytology
chemical_list: D002413:Cations, Divalent; D020099:Coated Materials, Biocompatible; D017886:Durapatite