Local administration of aspirin improves osseointegration of hydroxyapatite-coated titanium implants in ovariectomized rats through activation of the Notch signaling pathway

Osteoporosis-induced impaired bone regeneration would result in compromised osseointegration of hydroxyapatite-coated titanium and high rate of implant failure. Local administration of aspirin promotes osteoblast proliferation and inhibits osteoclast proliferation, and positively affects bone regeneration in osteoporotic condition. We hypothesized that reduced osteogenesis may account for poor osseointegration of hydroxyapatite-coated titanium which could be ameliorated by using local aspirin. The aim of this study was to confirm the effect of the local incorporation of aspirin into hydroxyapatite-coated titanium implants in the osteoporotic and normal condition. Twelve-week-old female Sprague–Dawley rats were used for this study. Twelve weeks after bilateral ovariectomy, all animals were randomly divided into three groups: group Sham, group OVX and group OVX + ASP, and the rats from OVX and Sham received hydroxyapatite-coated implants and animals belong to group OVX + ASP received aspirin-hydroxyapatite-coated implants until death at 12 weeks, respectively. After 12-week healing period, local treatment with aspirin revealed improved osseointegration compared to OVX, with significant improvement of the bone area ratio and bone-to-implant contact in histomorphometry, the bone mass and trabecular architecture in micro-CT evaluation, and the maximal push-out force in push out test. Moreover, group OVX + ASP presented the strongest effect on Jagged1, Notch1, and Hes-1(P