Improved titanium and steel implants : Studies on bisphosphonate, strontium and surface treatments

• Purpose: The general aim of this thesis was to increase the understanding of biomaterial surface modifications and local delivery of osteoporosis drugs for bone integration. We therefore (i) characterised and investigated model surface coatings for controlled drug delivery in a rat tibia screw model (ii) elucidated the effect of surface treatment for activation of complement system in vitro.Materials and methods: Bisphosphonate was immobilised directly to implant surfaces by two methods. In the first method, bisphosphonate was bound via a crosslinked fibrinogen layer to titanium surfaces. In the second method, stainless steel screws were first dip coated in a TiO2 solgel, and thereafter incubated in simulated body fluid (SBF). The so prepared thin calcium phosphate layer on titania bound then bisphosphonate directly with high affinity. The drug release kinetics was determined in vitro by 14C marked alendronate that was quantified with scintillation techniques. The screws were inserted in the metaphysis of rat tibia and the mechanical fixation monitored by screw pullout measurements after 2 or 4 weeks of implantation. In order to compare two different osteoporosis drugs, bisphosphonate and strontium ranelate, stainless steel and PMMA screws were inserted in the tibial metaphysis of rat for 4 and 8 weeks. Bisphosphonate was then delivered subcutaneously and strontium ranelate orally during the whole implantation period. The mechanical fixation was analysed by pullout force measurements, and bone architecture studied by micro-computed tomography (μCT). The immune complement activation on sol-gel- and smooth titanium surfaces was analysed in human blood plasma before and after annealing of titanium at 100-500ºC or upon UVO-treatment for up to 96 hours.Results: Bisphosphonate coated screws enhanced the screw pull out force after 2 weeks of implantation by more than 30% (fibrinogen coating) and by 93% after 4 weeks (sol-gel derived TiO2 coating). Systemically administered bisphosphonate enhanced the mechanical screw fixation after 4 weeks by more than 96% and after 8 weeks by more than 55% as compared to strontium ranelate treated animals (p = 0.00). Strontium ranelate treatment did not show significant improvement of screw pullout force after 4 and 8 weeks, compared to control. The immune complement surface deposition from blood plasma vanished irreversibly after Ti heat treatment at 250-300 ºC during 30 minutes or after UVO exposure for 24 hours or longer. Tentatively, changes in surface water/hydroxyl binding upon heat- and UVO treatments were observed by XPS and infrared spectroscopy.Conclusions: The results show that fixation at short implantation time (weeks) of orthopaedic implant can be enhanced by immobilised bisphosphonate on stainless steel or titanium implants. Systemic delivery of strontium ranelate showed no significant effect on implant fixation in rat tibia, and we hypothesise therefore that strontium ranelate will not become a power tool to increase the early implant fixation, but may be beneficial at longer times. Heat annealing or UVO-treatment of titanium surfaces change the surface hydroxylation, leading to decreased immune complement deposition from blood plasma.

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