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The mechanical induction of specific cell phenotypes can only be properly controlled if the local stimuli applied to the cells are known as a function of the external applied loads. Finite element analysis of the cell carriers would be one method to calculate these local conditions. Furthermore, the constitutive model of the construct material should be able to describe mechanical events known to be responsible for cell stimulation, such as interstitial fluid flow. The aim of this study was to define a biphasic constitutive model for fibrin, a natural hydrogel often used for tissue engineering but not yet thoroughly characterized. Large strain poroelastic and poroviscoelastic constitutive equations were implemented into a finite element model of a fibrin gel. The parameter values for both formulations were found by either analytically solving equivalent low strain equations, or by optimizing directly the large strain equations based on experimental stress relaxation data. No poroelastic parameters that satisfactorily described the fibrin carrier behaviour could be found, suggesting that network viscoelasticity and fluid-flow time-dependent behaviour must be separately accounted for. It was demonstrated that fibrin can be described as a poroviscoelastic material, but a large strain characterization of the parameter values was necessary. The analytical resolution of the low strain poroviscoelastic equations was, however, accurate enough to serve as a reliable initial condition for further optimization of the parameter values with the large strain formulation.

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.

A repeated sampling bone chamber methodology was developed for the study of the influence of the mechanical environment on skeletal tissue differentiation and bone adaptation around titanium implants. Via perforations, bone grows into the implanted outer bone chamber, containing an inner bone chamber with a central test implant. An actuator--easily mounted on the outer bone chamber--allows a controlled mechanical stimulation of the test implant. After each experiment, the inner bone chamber--with its content--can be harvested and analysed. A new inner bone chamber with a central implant can be inserted consecutively in the outer bone chamber and a new experiment can start. Pilot studies led to a reliable surgical protocol and showed the applicability of the methodology, offering the possibility to study skeletal tissue differentiation and adaptation around implants under well-controlled mechanical conditions, and this protected from external loading. Repeated sampling of the bone chamber allows conducting several experiments within the same animal at the same site, thereby excluding subject- and site-dependent variability and reducing the amount of experimental animals.

The application of a bone chamber provides a controlled environment for the study of tissue differentiation and bone adaptation. The influence of different mechanical and biological factors on the processes can be measured experimentally. The goal of the present work is to numerically model the process of peri-implant tissue differentiation inside a bone chamber, placed in a rabbit tibia. 2D and 3D models were created of the tissue inside the chamber. A number of loading conditions, corresponding to those applied in the rabbit experiments, were simulated. Fluid velocity and maximal distortional strain were considered as the stimuli that guide the differentiation process of mesenchymal cells into fibroblasts, chondrocytes and osteoblasts. Mesenchymal cells migrate through the chamber from the perforations in the chamber wall. This process is modelled by the diffusion equation. The predicted tissue phenotypes as well as the process of tissue ingrowth into the chamber show a qualitative agreement with the results of the rabbit experiments. Due to the limited number of animal experiments (four) and the observed inter-animal differences, no quantitative comparison could be made. These results however are a strong indication of the feasibility of the implemented theory to predict the mechano-regulation of the differentiation process inside the bone chamber.