Inflammatory potential of in vivo aged basic calcium phosphate (BCP) crystals

摘要

The aim of this study was to compare the inflammatory potential of synthetic native versus in vivo aged BCP crystals. Three synthetic BCP crystals were tested: stoechiometric hydroxyapatite (HAY), Carbonated Apatite (CA) containing 3.2percent of carbonate and Octacalcium phosphate (OCP). Crystal aging was achieved by introducing BCPs in a diffusion chamber (DC) then implanted intraperitoneally in a rat for a period of time ranging from 6h to 2 weeks. Aged and native BCPs were tested using the conventional air pouch model. Aging and air pouch testing were performed in the same animal. All 3 tested crystals underwent surface modifications as revealed by FTIR analysis, consisting of protein adsorption and carbonate enrichment, through material-dependent processes: HAY adsorbed significantly less proteins and demonstrated a low carbonate enrichment onto the surface through a maturation process. Native CA crystals, grew through secondary nucleation. In the mean time, CA adsorbed significantly less proteins than OCP (p<0.02). OCP experienced much more surface modifications. As revealed by TEM, new crystals made of carbonated apatite grew through heterogeneous nucleation, while proteins were extensively adsorbed. These different aging processes induced variable inflammatory properties: native CA induced acute inflammation which was inhibited after aging, while native and aged HAY were not phlogistic, and native and aged OCP were responsible for acute inflammatory responses. Competition between protein adsorption (acting as a passivation process) and new CA deposition (responsible for a continuous inflammatory activation) was responsible for the differences in biological responses. This study suggests that aging of BCPs should be taken into account when considering their long term in-vivo tolerance.