IADR Abstract Archives
Titanium surface-induced immunomodulation promotes osseous healing in Type II diabetes.
Objectives: To investigate the effects of titanium surface modification on macrophage phenotype and osseous healing in Type II diabetes.
Methods: In Vitro: Bone marrow derived polarised macrophages (M1, M2) from healthy and Type II diabetic rats were cultured on micro-rough (SLA) or hydrophilic-modified SLA (modSLA) titanium discs. The effects of surface-modification on macrophage phenotype and cytokine secretion were assessed. Osteoblast gene expression in response to conditioned macrophage media (indirect co-culture) was evaluated at days 1, 4 and 7.
In Vivo: The effect of titanium surface-induced immunomodulation on macrophage phenotype, cytokine secretion and osseous healing in type II diabetes was investigated in a critical-sized calvarial defect model.
Results: In vitro, immunofluorescent staining showed M1 macrophage phenotype markers to be more frequently expressed when cultured on the SLA surface compared with the modSLA surface at days 4 and 7 for both healthy and diabetic groups. These results correlated with the cytokine secretion analysis, demonstrating higher levels of pro-inflammatory cytokines on the SLA than the modSLA surface. Gradual decreases in the pro-inflammatory cytokine levels on the SLA surface were observed at days 1 and 4 in the healthy group, but were delayed in the diabetic group (day 7). Macrophage conditioned media showed that M2 macrophage released cytokines stimulated osteoblast bone marker gene expression in the healthy group. This was further enhanced by the modSLA surface. Similar modSLA surface effects were observed in the diabetic groups, however the pro-osteogenic effect was lower and delayed.
In vivo, histomorphometric analysis showed significantly more new bone formation under the modSLA surface at days 14 and 28 in the diabetic group. Immunofluorescent staining showed that the ratio of M1 to M2 markers in adherent cells was significantly lower on the modSLA surface at days 4 and 7 in the diabetic animals.
Conclusions: Titanium surface modification associated with the modSLA surface modulates the early pro-inflammatory macrophage response, attenuating inflammatory cytokine secretion and promoting a reparative M2 phenotype. These immunomodulatory effects promote osseous healing even in a systemically compromised condition such as Type II diabetes.
Methods: In Vitro: Bone marrow derived polarised macrophages (M1, M2) from healthy and Type II diabetic rats were cultured on micro-rough (SLA) or hydrophilic-modified SLA (modSLA) titanium discs. The effects of surface-modification on macrophage phenotype and cytokine secretion were assessed. Osteoblast gene expression in response to conditioned macrophage media (indirect co-culture) was evaluated at days 1, 4 and 7.
In Vivo: The effect of titanium surface-induced immunomodulation on macrophage phenotype, cytokine secretion and osseous healing in type II diabetes was investigated in a critical-sized calvarial defect model.
Results: In vitro, immunofluorescent staining showed M1 macrophage phenotype markers to be more frequently expressed when cultured on the SLA surface compared with the modSLA surface at days 4 and 7 for both healthy and diabetic groups. These results correlated with the cytokine secretion analysis, demonstrating higher levels of pro-inflammatory cytokines on the SLA than the modSLA surface. Gradual decreases in the pro-inflammatory cytokine levels on the SLA surface were observed at days 1 and 4 in the healthy group, but were delayed in the diabetic group (day 7). Macrophage conditioned media showed that M2 macrophage released cytokines stimulated osteoblast bone marker gene expression in the healthy group. This was further enhanced by the modSLA surface. Similar modSLA surface effects were observed in the diabetic groups, however the pro-osteogenic effect was lower and delayed.
In vivo, histomorphometric analysis showed significantly more new bone formation under the modSLA surface at days 14 and 28 in the diabetic group. Immunofluorescent staining showed that the ratio of M1 to M2 markers in adherent cells was significantly lower on the modSLA surface at days 4 and 7 in the diabetic animals.
Conclusions: Titanium surface modification associated with the modSLA surface modulates the early pro-inflammatory macrophage response, attenuating inflammatory cytokine secretion and promoting a reparative M2 phenotype. These immunomodulatory effects promote osseous healing even in a systemically compromised condition such as Type II diabetes.