771 BMP2 Reverses Anti-inflammatory Environment Created by SLActive In Vitro

Friday, March 23, 2012: 2 p.m. - 3:15 p.m.
Presentation Type: Poster Discussion Session
S.L. HYZY1, R. OLIVARES-NAVARRETE2, C. TAN1, B.D. BOYAN3, and Z. SCHWARTZ4, 1Biomedical Engineering, Gerogia Institute of Technology, Atlanta, GA, 2Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA, 3Institute of Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, 4Georgia Institute of Technology, Atlanta, GA
Objective: High-energy microtextured titanium (Ti) surfaces promote faster healing and osseointegration. Interleukins (IL) and cytokines form a complex regulatory network that determines overall inflammatory response, regulating early osseointegration. Clinically, BMP2 is used alone or in combination with biomaterials to increase peri-implant bone formation. However, the effect of material surface properties and BMP2 on inflammation is unclear. Here we examined how surface microstructure affects osteoblast interleukin production, whether BMP2 treatment alters this response, and the BMP signaling pathway regulating this effect.

Method: MG63 osteoblast-like cells were cultured on tissue culture polystyrene (TCPS) or Ti [PT, Ra<0.4μm; sandblasted/acid-etched (SLA), Ra=3.2μm; hydrophilic-SLA (SLActive)]. At confluence, cells were incubated with media±40ng/ml BMP2. Interleukin expression was measured 12h after treatment by real-time qPCR and secreted interleukins measured 24h after treatment by ELISA. The role of exogenous BMP2 in mediating IL expression was examined in cultures incubated with specific signal transduction pathway inhibitors: dorsomorphin (Smad), (5Z)-7-Oxozeanol (TAB/TAK1), or H-8 (PKA).

Result: Interleukin expression and secretion was modulated by surface roughness and energy. Osteoblasts grown on rough surfaces decreased levels of pro-inflammatory IL6, IL8, and IL17, an effect amplified on SLActive surfaces. Production of anti-inflammatory IL10 increased on Ti surfaces compared to TCPS, with the highest levels on SLActive surfaces. BMP2 reversed the surface effects, and increasing pro-inflammatory interleukins and decreasing anti-inflammatory IL10 in a surface roughness-dependent fashion. 5Z-7-Oxozeaenol and dorsomorphin, but not H-8, blocked the effect of BMP2 on IL1A and IL6 expression. 5Z-7-Oxozeaenol and H-8 blocked the effect of BMP2 on IL10 expression. 

Conclusion: The results suggest surface roughness and energy modulate the initial inflammatory response, increasing anti-inflammatory and reducing pro-inflammatory interleukins. BMP2 reversed the surface effects via a mechanism involving the TAB/TAK1 pathway. The data may suggest that side effects of BMP2 treatment during osseointegration are mediated by its effect on the inflammatory process.

This abstract is based on research that was funded entirely or partially by an outside source: NIH

Keywords: BMP-2, Inflammation, Osteoblasts/osteoclasts and Surfaces
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