Aseptic loosening of femoral implants in total hip replacement remains an unsolved orthopaedic problem. This paper investigates the potential role of bone sialoprotein (BSP) in enhancing bone-implant adherence. As BSP is osteoinductive in rat calvarial models, we investigated whether BSP is similarly osteoinductive when coated onto intramedullary femoral implants.BSP-coated titanium implants were implanted into the femur of female 'Wistar' rats (average weight 215 g) that were sacrificed at days 10, 20 and 30. Harvested femoral implants were subjected to pullout testing and then examined histologically.BSP-coated implants demonstrate osteoinduction when examined histologically. Plugging the femoral canal with BSP prior to inserting the implant neither increased implant pullout strengths nor further increased osteoblastic activity.This study has demonstrated for the first time that BSP is osteoinductive when coated onto femoral implants and inserted into bones subjected to mechanical loading. However, we found that pullout strengths are a function of implant surface topographical characteristics and are not affected by BSP coating or histological osteoinduction.
IntroductionThe increasing misuse of both prescription and illicit opioids has culminated in a national healthcare crisis in the United States. Oxycodone is among the most widely prescribed and misused opioid pain relievers and has been associated with a high risk for transition to compulsive opioid use. Here, we sought to examine potential sex differences and estrous cycle-dependent effects on the reinforcing efficacy of oxycodone, as well as on stress-induced or cue-induced oxycodone-seeking behavior, using intravenous (IV) oxycodone self-administration and reinstatement procedures.MethodsIn experiment 1, adult male and female Long-Evans rats were trained to self-administer 0.03 mg/kg/inf oxycodone according to a fixed-ratio 1 schedule of reinforcement in daily 2-h sessions, and a dose-response function was subsequently determined (0.003–0.03 mg/kg/inf). In experiment 2, a separate group of adult male and female Long-Evans rats were trained to self-administer 0.03 mg/kg/inf oxycodone for 8 sessions, followed by 0.01 mg/kg/inf oxycodone for 10 sessions. Responding was then extinguished, followed by sequential footshock-induced and cue-induced reinstatement tests.ResultsIn the dose-response experiment, oxycodone produced a typical inverted U-shape function with 0.01 mg/kg/inf representing the maximally effective dose in both sexes. No sex differences were detected in the reinforcing efficacy of oxycodone. In the second experiment, the reinforcing effects of 0.01–0.03 mg//kg/inf oxycodone were significantly attenuated in females during proestrus/estrus as compared to metestrus/diestrus phases of the estrous cycle. Neither males nor females displayed significant footshock-induced reinstatement of oxycodone seeking, but both sexes exhibited significant cue-induced reinstatement of oxycodone seeking at magnitudes that did not differ either by sex or by estrous cycle phase.DiscussionThese results confirm and extend previous work suggesting that sex does not robustly influence the primary reinforcing effects of oxycodone nor the reinstatement of oxycodone-seeking behavior. However, our findings reveal for the first time that the reinforcing efficacy of IV oxycodone varies across the estrous cycle in female rats.
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