ZINC DOPED HYDROXYAPATITE AS IMMUNOMODULATORY BIOMATERIAL

International audienceObjectives: Hydroxyapatite (HA) is widely used as implant or coating biomaterial in affected bones or prosthesis metal parts. The release of HA particles mounts an inflammatory response and if uncontrolled, could result in implant loss. We have recently shown that HA particles induce the activation of human polymorphonuclear cells (PMNs) and increase secretion of their inflammatory mediators. A study by our group showed that zinc-substituted HA particles have the capacity to modulate the expression of cytokines by monocytes. The purpose of this work is to determine the effect of zinc on HA-mediated acute inflammation. Materials and Methods: PMNs (from healthy adult volunteers) were cultured in the absence or presence of HA powders, substituted or not with zinc ions. Conditioned media were used for IL-8 measurement (ELISA), gelatin zymmography and Boyden chamber chemotaxis assay. PMNs total mRNAs were extracted for IL-8 mRNA measurement (RT-PCR). Results: IL-8 concentration measurement showed a 45% decrease when PMNs were in contact with HA containing 5% Zn (HA5%) compared with HA alone. Such decrease in protein levels was associated with 47.5% decrease in IL-8 mRNAs as confirmed by RT-PCR. Gelatin zymography analysis shows that HA-activated PMNs increased MMP-9 secretion whereas HA 5%- activated cells exhibit a basal level of gelatinase B secretion. Moreover, Boyden chamber chemotaxis results show that HA5%-activated PMNs supernatants are less chemotactic than HA-activated PMNs supernatants. Conclusions: Our data show that HA5% has the capability to decrease the expression and secretion of inflammatory mediators such as IL-8 and MMP-9, leading to reduced neutrophil influx at the inflammation site. Studies are underway to investigate the underlying mechanism(s) of zinc substituted HA (e.g., signal transduction) in the processes. Data from these studies will help gain new insights into PMN's role in HA-associated inflammation surrounding prosthesis