title: The influence of titanium surface characteristics on macrophage phenotype polarization during osseous healing in type I diabetic rats: a pilot study.
abstract: OBJECTIVE
  This study assessed the effect of titanium surface modification on macrophage phenotype polarization and osseous healing under diabetic conditions.
  
  
  METHODS
  Critical-sized calvarial defects were created in healthy and streptozotocin-induced type I diabetic Sprague-Dawley rats. Titanium (Ti) discs with either large-grit sandblasted and acid-etched micro-rough (SLA) or hydrophilic-modified SLA (modSLA) surfaces were used to cover the healing defect for a period of up to 28 days. Samples of the exudate within the calvarial defect and beneath the titanium discs were collected 1, 4 and 7 days post-surgery for inflammatory cytokine analysis using an ELISA. The macrophage phenotype(s) on the Ti disc surfaces were determined by CD11c+ (M1) and CD163+ (M2) immunofluorescent staining. Samples of the healing defects at days 14 and 28 were also prepared for histomorphometric analysis.
  
  
  RESULTS
  Cytokine levels in the diabetic animals were higher than those of the healthy group throughout the observation period. The modSLA surface significantly reduced MIP-2 levels at day 1 in both diabetic and healthy animals, and MCP-1 levels at day 4 in the diabetic animals. Immuno-fluorescent staining showed that an M2-like macrophage phenotype was more frequently found on the modSLA surface at day 1 in healthy and day 4 in both healthy and diabetic animals. Histomorphometric analysis showed more new bone formation on the modSLA surface at days 14 and 28 in both groups, although statistically significant differences were only found in the healthy group.
  
  
  CONCLUSIONS
  Diabetic conditions greatly increased the expression of proinflammatory cytokines during osseous healing. The modSLA surface was shown to promote an M2-like macrophage phenotypic response in titanium adherent macrophages despite the significantly elevated inflammatory environment induced by uncontrolled type I diabetes. Modulation of the macrophage phenotype by the modSLA surface in the early healing period was associated with osseous healing under both healthy and uncontrolled diabetic conditions.
authors.affiliation: School of Dentistry and Oral Health, Centre for Medicine and Oral Health, Griffith Health Institute, Griffith University (Gold Coast Campus), Southport, QLD, Australia.|Menzies Health Institute Queensland, Griffith University, Gold Coast, QLD, Australia.
authors.forename: Ryan S B
authors.initials: RSB
authors.lastname: Lee
authors.affiliation: School of Dentistry and Oral Health, Centre for Medicine and Oral Health, Griffith Health Institute, Griffith University (Gold Coast Campus), Southport, QLD, Australia.|Menzies Health Institute Queensland, Griffith University, Gold Coast, QLD, Australia.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Hamlet
authors.affiliation: School of Dentistry and Oral Health, Centre for Medicine and Oral Health, Griffith Health Institute, Griffith University (Gold Coast Campus), Southport, QLD, Australia.|Menzies Health Institute Queensland, Griffith University, Gold Coast, QLD, Australia.
authors.forename: Saso
authors.initials: S
authors.lastname: Ivanovski
mesh_terms: D000818:Animals; D000069343:Bone-Implant Interface; D003921:Diabetes Mellitus, Experimental / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology; D005260:Female; D008264:Macrophages / Q000502:physiology*; D010641:Phenotype; D010865:Pilot Projects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013499:Surface Properties; D014025:Titanium
chemical_list: D014025:Titanium
keywords: GBR; Inflammation; bone-implant interactions; cytokines; diabetes; surface chemistry/hydrophilicity