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.

Cationic and Anionic Substitutions in Hydroxyapatite

“…Comparing the effects of various cationic substitutions of HAp in in vitro tests, Mg-HAp showed the highest ion release into the culture medium and the highest relative cell density, together with Zn-HAp, even if the most cell apoptosis was also recorded on Mg-HAp, despite the good cell viability [73].…”

A Solid-State NMR Study of Selenium Substitution into Nanocrystalline Hydroxyapatite

“…Calcium cations may be partially replaced by several cationic substituents, i.e. , Mg 2+ , Mn 2+ , Zn 2+ , Sr 2+ , Ag + or Cr 3+ [10,11]. The structural hydroxyl groups are located in columns ··· OH OH OH ···, where oxygen atoms are too distant (3.44 Å) to form hydrogen bonds [9].…”

Insights on the properties of levofloxacin-adsorbed Sr- and Mg-doped calcium phosphate powders

“…HA deserved a particular attention because of its chemical and structural & Catarina F. Marques acmarques@ua.pt similarities with the inorganic phase of human bone and its biocompatibility, osteoconductive and osteophilic nature [17,18]. Moreover, the crystalline lattice of HA is able to easily incorporate foreign substituting ions that enhance osteointegration and mechanical properties of the grafts [19][20][21][22][23]. Magnesium (Mg 2? )…”