Comparative In Vivo Study of Biocompatibility of Apatites Incorporated with 1% Zinc or Lead Ions versus Stoichiometric Hydroxyapatite

Abstract

Hydroxyapatite is the main ceramic material that has being used in bone repair, although its physico-chemical and in vivo behavior should be better understood. A method to improve the biocompatibility of HA is the substitution of calcium with divalent cations which enhance mechanic resistance and can modulate inflammatory response against implanted material. In this study we analyzed the biocompatibility of HA doped with one per cent of Zn2+ or Pb2+. The first one has being described as an inflammation modulator and the second would be a model for chronic toxicity assay. Biocompatibility of the both materials was studied in vivo following the ISO 10993-6 standard. HA cylinders (ZnHA, PbHA and stoichiometric HA as positive control) were implanted into subcutaneous tissue of 45 Balb-c mice and after 1, 3 and 9 weeks the animals were euthanized (5 for each experimental condition). Necropsies of the skin containing reactional tissue were removed, fixed in 10% formaldehyde and followed the histological processing for paraffin embedding and staining with Hematoxylin-Eosine and Picrosirius red. Microscopic analysis showed for all groups moderate inflammatory response, decreasing throughout the experimental periods, with ZnHA group showing more intense response. Similar presence of macrophages, fibrosis and angiogenesis were observed among the groups. Thereby, we can conclude that ZnHA and PbHA are biocompatible and not bioresorbable, being the ZnHA potentially indicated as bone graft. Detailed studies are required to better understand the role of PbHA as chronic model for lead toxicity.