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Several mechanoregulatory tissue differentiation models have been proposed over the last decade. Corroboration of these models by comparison with experimental data is necessary to determine their predictive power. So far, models have been applied with various success rates to different experimental set-ups investigating mainly secondary fracture healing. In this study, the mechanoregulatory models are applied to simulate the implant osseointegration process in a repeated sampling in vivo bone chamber, placed in a rabbit tibia. This bone chamber provides a mechanically isolated environment to study tissue differentiation around titanium implants loaded in a controlled manner. For the purpose of this study, bone formation around loaded cylindrical and screw-shaped implants was investigated. Histologically, no differences were found between the two implant geometries for the global amount of bone formation in the entire chamber. However, a significantly larger amount of bone-to-implant contact was observed for the screw-shaped implant compared to the cylindrical implant. In the simulations, a larger amount of bone was also predicted to be in contact with the screw-shaped implant. However, other experimental observations could not be predicted. The simulation results showed a distribution of cartilage, fibrous tissue and (im)mature bone, depending on the mechanoregulatory model that was applied. In reality, no cartilage was observed. Adaptations to the differentiation models did not lead to a better correlation between experimentally observed and numerically predicted tissue distribution patterns. The hypothesis that the existing mechanoregulatory models were able to predict the patterns of tissue formation in the in vivo bone chamber could not be fully sustained.

Objectives: The local mechanical environment influences early peri-implant tissue formation. It is still unclear whether immediate loading limits or promotes peri-implant osteogenesis and which mechanical parameters are important herein. The present study evaluated the influence of well-controlled mechanical stimuli on the tissue response around immediately loaded cylindrical turned titanium implants at two different observation periods., Material and Methods: A repeated sampling bone chamber, consisting of dual-structure perforated hollow cylinders with a cylindrical implant, was installed in the tibia of 14 rabbits and used to conduct three displacement-controlled immediate loading experiments: (i) 30 microm - 400 cycles/day - 1 Hz frequency - 2 x/week - 6 weeks; (ii) 30 microm - 400 cycles/day - 1 Hz - 2 x/week - 6 weeks, followed by another 6 weeks with a 50 microm - 800 cycles/day - 1 Hz - 2 x/week loading protocol; and (iii) 0 microm implant displacement for 12 weeks. A linear mixed model and logistic mixed model with alpha=5% were conducted on the data set., Results: The tissue area fraction was significantly the highest after 12 weeks of loading. The bone area fraction was significantly different between all three loading conditions, with the highest values for the 12-week loading experiment. Twelve-week stimulation resulted in a significantly higher mineralized bone fraction than 6 weeks. Loading did have a significantly positive effect on the mineralized bone fraction. The incidence of osteoid-to-implant and bone-to-implant contact increased significantly when loading the implant for 12 weeks., Conclusion: Immediate loading had a positive effect on the tissue differentiation and bone formation around cylindrical turned titanium implants. Controlled implant micro-motion up to 50 microm had a positive effect on the bone formation at its interface.

Aim: Tissue formation at the implant interface is known to be sensitive to mechanical stimuli. The aim of the study was to compare the bone formation around immediately loaded versus unloaded implants in two different implant macro-designs., Material and Methods: A repeated sampling bone chamber with a central implant was installed in the tibia of 10 rabbits. Highly controlled loading experiments were designed for a cylindrical (CL) and screw-shaped (SL) implant, while the unloaded screw-shaped (SU) implant served as a control. An F-statistic model with alpha=5% determined statistical significance., Results: A significantly higher bone area fraction was observed for SL compared with SU (p<0.0001). The mineralized bone fraction was the highest for SL and significantly different from SU (p<0.0001). The chance that osteoid- and bone-to-implant contact occurred was the highest for SL and significantly different from SU (p<0.0001), but not from CL. When bone-to-implant contact was observed, a loading (SL versus SU: p=0.0049) as well as an implant geometry effect (SL versus CL: p=0.01) was found, in favour of the SL condition., Conclusions: Well-controlled immediate implant loading accelerates tissue mineralization at the interface. Adequate bone stimulation via mechanical coupling may account for the larger bone response around the screw-type implant compared with the cylindrical implant.

Initial osteogenesis at the implant interface is, to a great extent, determined by the implant surface characteristics and the interfacial loading conditions. The present study investigated the effect of various degrees of relative movement on the tissue differentiation around a roughened screw-shaped immediately loaded implant. Repeated-sampling bone chambers were installed in the tibia of 10 rabbits. In each of the chambers, three experiments were performed by inducing 0 (control), 30, and 90 microm implant displacement for 9 wk. A linear mixed model and a logistic mixed model with alpha = 5% determined statistical significance. Tissue filling of the bone chamber was similar for the three test conditions. The bone area fraction was significantly higher for 90 microm implant displacement compared with no displacement. A significantly higher fraction of bone trabeculae was found for 30 and 90 microm implant displacement compared with the unloaded situation. The incidence of osteoid-to-implant and bone-to-implant contact was significantly higher for 90 microm implant displacement compared with 30 and 0 microm implant displacement. Significantly more osteoid in contact with the implant was found for the loaded conditions compared with no loading. Well-controlled micro-motion positively influenced bone formation at the interface of a roughened implant. An improved bone reaction was detected with increasing micro-motion.

The combined use of experimental and mathematical models can lead to a better understanding of fracture healing. In this study, a mathematical model, which was originally established by Bailón-Plaza and van der Meulen (J Theor Biol 212:191-209, 2001), was applied to an experimental model of a semi-stabilized murine tibial fracture. The mathematical model was implemented in a custom finite volumes code, specialized in dealing with the model's requirements of mass conservation and non-negativity of the variables. A qualitative agreement between the experimentally measured and numerically simulated evolution in the cartilage and bone content was observed. Additionally, an extensive parametric study was conducted to assess the influence of the model parameters on the simulation outcome. Finally, a case of pathological fracture healing and its treatment by administration of growth factors was modeled to demonstrate the potential therapeutic value of this mathematical model.