The possibility to control bone formation would be favorable in many areas of medicine, where bone defects is still a major challenge. Insulin has been suggested to exert both systemic and local anabolic effects in bone tissues. This raised the question whether locally administrated insulin could provide new therapeutic strategies for patients with local bone defects and impaired bone healing. The aim of this study was to evaluate bone formation in non-diabetic rats when local insulin is administered. This study differs from previous reports in two aspects: the use of non-diabetic animals and locally administered insulin. Twenty-four implants were inserted into 12 rats-one insulin-coated and one control-in each tibia for four weeks. Interferometry and histomorphometry were used to evaluate the surface topography and bone formation, respectively. Results demonstrated no significant changes in surface topography after insulin immobilization. Histomorphometry revealed significantly more bone around the insulin-coated implants (BA) (p = 0.005) and a similar amount of bone at the implant surface (BIC) (p = 0.117) compared with the controls. It was concluded that locally administered insulin from a titanium implant surface has the potential to increase bone formation not only in diabetic subjects but also in non-diabetic subjects.

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We aimed to investigate the influence of titanium surface characteristics on epigenetic mechanisms and DNA damage/repair pathways. Osteoblast-like cells (MG63) were incubated on glass, smooth titanium, and minimally rough titanium discs, respectively, for 0, 1, 6, and 24 hr. The presence of double-stranded DNA damage (γH2AX), DNA repair (Chk2), and epigenetic markers (AcH3 & DNMT1) were investigated using immunofluorescence. There were no Chk2-positive cells on the minimally rough titanium surfaces at all-time points, in comparison to glass and smooth titanium. Total γH2AX-positive cells on minimally rough titanium gradually decreased as incubation time increased, on the contrary to smooth titanium. Minimally rough titanium surfaces induced cytoplasmic staining of DNMT1 up to 99% at 24 hr. For epigenetic markers related to the DNA damage/repair pathway, minimally rough titanium surfaces showed the lower percentage of AcH3-positive cells compared to glass and smooth titanium surface. The findings in the current study show that titanium surface characteristics indeed influence DNA damage and the DNA repair pathway, including epigenetic factors.