Recently published data indicate that immobilized N-bisphosphonate enhances the pullout force and energy uptake of implanted stainless steel screws at 2 weeks in rat tibia. This study compares titanium screws with and without a bisphosphonate coating in the same animal model. The screws were first coated with an 100-nm thick crosslinked fibrinogen film. Pamidronate was subsequently immobilized into this film via EDC/NHS-activated carboxyl groups within the fibrinogen matrix, and finally another N-bisphosphonate, ibandronate, was physically adsorbed. The release kinetics of immobilized ¹⁴C-alendronate was measured in buffer up to 724 h and showed a 60% release within 8 h. Mechanical tests demonstrated a 32% (p = 0.04) and 48% (p = 0.02) larger pullout force and energy until failure after 2 weeks of implantation, compared to uncoated titanium screws. A control study with physically adsorbed pamidronate showed no effect on mechanical fixation, probably due to a too small adsorbed amount. We conclude that the fixation of titanium implants in bone can be improved by fibrinogen matrix-bound bisphosphonates.

A variety of surface modifications have been tested for the enhancement of screw fixation in bone, and locally delivered anti-osteoporosis drugs such as bisphosphonates (BP) are then of interest. In this in vivo study, the impact of surface immobilized BP was compared with systemic BP delivery and screws with no BP. After due in vitro characterization, differently treated stainless steel (SS) screws were divided into four groups with 10 rats each. Three of the groups received screws coated with sol gel derived TiO2 and calcium phosphate (SS+TiO2+CaP). One of these had no further treatment, one had alendronate (BP) adsorbed to calcium phosphate mineral, and one received systemic BP treatment. The fourth group received uncoated SS screws and no BP (control). The screw pullout force was measured after 4 weeks of implantation in rat tibiae. The immobilized amount and release rate of alendronate could be controlled by different immersion times. The SS+TiO2+CaP coating did not increase the pullout force compared to SS alone. Surface delivered alendronate enhanced the pullout force by 93% [p = 0.000; 95% Confidence Interval (CI): 67-118%] compared to SS, and by 39% (p = 0.044; 95% CI: 7-71%) compared to systemic alendronate delivery. Both surface immobilized and systemically delivered alendronate improved implant fixation. Also, locally delivered, that is, surface immobilized alendronate showed a better fixation than systemically delivered. Using sot gel derived TiO2 as a platform, it is possible to administer controllable amounts of a variety of BPs.

Titanium (Ti) is a well known metallic biomaterial extensively used in dental, orthopaedic-, and occasionally also in blood contacting applications. It integrates well to bone and soft tissues, and is shown upon blood plasma contact to activate the intrinsic pathway of coagulation and bind complement factor 3b. The material properties depend largely on those of the nm-thick dense layer of TiO2 that becomes rapidly formed upon contact with air and water. The spontaneously formed amorphous Ti-oxide has a pzc similar to 5-6 and its water solubility is at the order of 1-2 micromolar. It is often subjected to chemical- and heat treatments in order to increase the anatase- and ruble crystallinity, to modify the surface topography and to decrease the water solubility. In this work, we prepared sol gel derived titanium and smooth PVD titanium surfaces, and analysed their oxide and protein deposition properties in human blood plasma before and after annealing at 100-500 degrees C or upon UVO-treatment for up to 96 hours. The blood plasma results show that complement deposition vanished irreversibly after heat treatment at 250-300 degrees C for 30 minutes or after UVO exposure for 24 hours or longer. XPS and infrared spectroscopy indicated change of surface water/hydroxyl binding upon the heat- and UVO treatments, and increased Ti oxidation. XRD analysis confirmed an increased crystallinity and both control (untreated) and annealed smooth titanium displayed low XRD-signals indicating some nanocrystallinity, with predominantly anatase phase. The current results show that the behaviour of titanium dioxide in blood contact can be controlled through relatively simple means, such as mild heating and illumination in UV-light, which both likely irreversibly change the stoichiometry and structure of the outmost layers of titanium dioxide and its OH/H2O binding characteristics.

Strontium ranelate increases bone mass and is used in the treatment of osteoporosis. Its effects in metaphyseal bone repair are largely unknown. We inserted a stainless steel and a PMMA screw into each tibia of male Sprague-Dawley rats. The animals were fed with ordinary feed (n =40) or with addition of strontium ranelate (800mg/kg/day; n = 20). As a positive control, half of the animals on control feed received alendronate subcutaneously. The pullout force of the stainless steel screws was measured after 4 and 8 weeks, and μCT was used to assess bone formation around the PMMA screws. No significant effects of strontium treatment on pullout force were observed, but animals treated with bisphosphonate showed a doubled pullout force. Strontium improved the microarchitecture of the cancellous bone below the primary spongiosa at the growth plate, but no significant effects were found around the implants. Strontium is known to improve bone density, but it appears that this effect is weak in conjunction with metaphyseal bone repair and early implant fixation.