Introduction: The long consolidation phase of patients undergoing distraction osteogenesis (DO) causes a high risk of side effects and contributes to high costs. Thus, the development and evaluation of treatments that accelerate the bone consolidation process is of great interest. Evidence suggests that recombinant human bone morphogenetic protein 2 (rhBMP-2) increases the mechanical integrity of the callus. However, the potential benefits of rhBMP-2 on trabecular microarchitecture during DO have not been investigated up to date. In this study the regenerate microarchitecture was assessed using 3D micro-computed tomography (CT).

Methods: Mid-diaphyseal osteotomies were created in the right limb of twenty-four skeletally mature sheep, which were stabilized with an external fixator. After a latency period of 4 days, the tibiae were distracted at a rate of 1.25 mm daily over a period of 20 days. The operated limbs were randomly assigned to three treatment groups and one control group: (A) triple injection of rhBMP-2/NaCl, (B) single injection of rhBMP-2/Hydroxylapatite, and (C) single injection of buffer/Hydroxylapatit, (D) no injection. Groups A and C were injected at day 27. Group B was injected on days 3, 10 and 17. The animals were sacrificed after 74 days. The tibiae were analyzed by CT and for bone volume/total volume (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th.), trabecular separation (Tb.Sp.) and Connectivity. The BV/TV was maesured for the total volume of the distraction zone (BV/TVtotal) respectively in a subvolume with emphasize on the cortical bone region (BV/TVcortical). All other microarchitecture parameters were measured in the cortical weighted subvolume.

Results: The stereologic evaluation revealed a significant higher BV/TVcortical, Tb.N and Connectivity in the triple rhBMP-2 injected group A than in the control (D). Furthermore, the Tb.Sp. in group A was significant lower than in group D. The single injections of rhBMP-2/carrier in group B showed a significant higher BV/TVcortical, Tb.N and Connectivity than the control (D). Although the BV/TVcortical was increased in group A and B, there was no significant difference in BV/TV total between the rhBMP-2 treated groups (A, B) and the control (D).

Discussion: In this DO model a triple injection of rhBMP-2 has been demonstrated to induce significant changes in trabecular microarchitecture. RhBMP-2 does not increase the total amount of newly formed bone, but it enhances the formation of the corticalis. The microstructural changes in the cortical volume: increase of Tb.N and Connectivity, decrease of Tb.Sp., are discussed to be biomechanically highly relevant. This study suggests that rhBMP-2 optimizes the trabecular microarchitecture, which might explain the advanced mechanical integrity of newly formed bone under rhBMP-2 treatment.

Introduction: Despite advances in endoprosthesis fixation by implant surface alteration, the problem of aseptic implant loosening still exists. Especially in patients with revisions osseointegration and filling of gaps at the bone-implant interface is mandatory for implant survival. Simple BMP-2 immersion has been introduced previously to act as an osteoinductive coating for advanced osseointegration. However, because of the uncontrolled release kinetics and subsequent molecular action and activity of BMP-2, purely osteoinductive actions are hard to differentiate from osteoclastic BMP-actions leading to bone remodelling, which could counteract the implant fixation process and might be the reason for failed attempts to use BMP-2 for implant fixation. In this study we investigated the osteoinductive potency of BMP-2 bound to titanium surfaces by a highly controlled molecular coupling with specifically designed polymers, allowing a slow controlles release kinetics. We present the first results of two different polymers that were implanted in the tibia and femora of New Zealand White Rabbits.

Methods: In this study we designed cylindrical titanium-implants with an inner thread (Ti6-Alï·& #8220;4V, 3 mm hight x 3 mm diameter) and an electropolished outer surface that were coated with different polymers. The polymers were fixed to the surface using the photochemical method of grafting. The implants were implanted in the proximal tibia and distal femora of New Zealand White Rabbits. The anatomical locations of the implants were alternated to test their osseointegration in different quality of bone (cancellous vs. cortical bone). After 4 weeks the animals were sacrificed and DEXA-scans (Dual-energy X-ray absorptiometry), micro-CT and histological analysis were performed. ANOVA and t-test were used for statistic analysis.

Results: In high-resolution DEXA-scans we found a difference in bone mineral density (BMD) between PVBP and a control implant in the distal femora (PVBP 0,720 g/cm², control 0,661 g/cm²) and in the proximal tibia (PVBP 0,633 g/cm², control 0,431 g/cm²) with an increase of bone mineral density. In the histological investigation we found an increase of osteoblasts around the implants coated with PVBP and PVBP-Co-Acryloxysuccimid. Furthermore, the micro-CT scans showed an increase of BV/TV (bone volume/total volume) for both polymers.

Discussion: In this study we present the first results of the investigation of polymer-coated titanium-implants implanted in the proximal tibia and distal femora of New Zealand White Rabbits. The results of DEXA-scans, micro-CT and histological analysis showed an increase of osseointegration. We suggest that controlled release kinetics after coupling of these polymers with BMP-2 can additionally increase osseointegration. To get a closer look on the polymers, their characteristics in-vivo, and coupling with BMP-2 further investigations are conducted.