Method: Large grit sandblasted and acid-etched microrough (SLA) or hydrophilic-modified SLA (modSLA) Ti surfaces were used in this study. Critical-sized calvarial defects were created in streptozotocin (STZ) induced type I diabetic Sprague-Dawley rats. The intracranial aspect of each defect was covered with an PTFE membrane while a titanium disc covered the extra-cranial defect. The titanium discs were secured with titanium pins to prevent lateral movement during the healing process. The defect was allowed to heal for a period of up to 28 days. Samples of the exudate within the calvarial defect and beneath the titanium discs was collected 1, 4 and 7 days post-surgery for inflammatory cytokine profiles, which were then analysed by using ELISA. The macrophage phenotypes on the Ti disc surfaces were determined by CD11c (M1) and CD163 (M2) immuno-fluorescent staining. Samples of the healing defects were also prepared for histomorphometric analysis.
Result: In the diabetic group, at day 1, immuno-fluorescent results demonstrated the dominant macrophage phenotype was M1 on both Ti surfaces. By day 7, more M1 macrophage phenotype driven inflammation remained on SLA surface compared to modSLA. This is in contrast to the healthy animals where there was minimal remaining inflammatory reaction on modSLA, while on SLA, although there was still significant inflammatory reaction, it was shown to be predominantly a M2 (i.e. reparative) macrophage phenotype driven inflammation by day 7. These changes of macrophage phenotype correlated with the levels of pro-inflammatory and pro-regenerative cytokines in the exudates.
Conclusion: The present study demonstrates in a systemically compromised condition the Ti surface modification modulates the early inflammatory reaction with respect to the macrophage phenotype expression.