The Effect of Platelet Proteins Released in Response to Titanium Implant Surfaces on Macrophage Pro-Inflammatory Cytokine Gene Expression

Background and Purpose: Platelets are one of the earliest cell types to interact with surgically inserted titanium implants. This in vitro study investigated the effect of titanium surface-induced platelet releasate on macrophage cytokine gene expression. Materials and Methods: To mimic the in vivo temporal sequence of platelet arrival and protein production at the implant surface and the subsequent effect of these proteins on mediators of the immune response, the levels of platelet attachment and activation in response to culture on smooth polished, sandblasted and acid-etched (SLA), and hydrophilic-modified SLA (modSLA) titanium surfaces were first determined by microscopy and protein assay. The subsequent effect of the platelet-released proteins on human THP-1 macrophage cytokine gene expression was determined by polymerase chain reaction array after 1 and 3 days of macrophage culture on the titanium surfaces in platelet-releasate conditioned media. Results: Platelet attachment was surface dependent with decreased attachment observed on the hydrophilic (modSLA) surface. The platelet releasate, when considered independently of the surface effect, elicited an overall pro-inflammatory response in macrophage cytokine gene expression, that is, the expression of typical pro-inflammatory cytokine genes such as TNF, IL1a, IL1b, and CCL1 was significantly up-regulated whereas the expression of anti-inflammatory cytokine genes such as IL10, CxCL12, and CxCL13 was significantly down-regulated. However, following platelet exposure to different surface modifications, the platelet releasate significantly attenuated the macrophage pro-inflammatory response to microrough (SLA) titanium and hastened an anti-inflammatory response to hydrophilic (modSLA) titanium. Conclusions: Theses results demonstrate that titanium surface topography and chemistry are able to influence the proteomic profile released by platelets, which can subsequently influence macrophage pro-inflammatory cytokine expression. This immunomodulation may be an important mechanism via which titanium surface modification influences osseointegration.