Biomechanical Aspects of Osteogenesis in Load-Bearing Tissue Engineering Scaffolds

There is increasing evidence that mechanical stimulation affects the fate of tissue engineering scaffolds. In clinical situations, it is critical to accelerate bone formation inside the scaffold to reduce the recovery time and increase the chance of success of the bone substitute. Mechanical stimulation is already employed in bone fractures to enhance healing process and similarly it can be used to accelerate bone formation inside the scaffold. The goal of this thesis is to quantify, through in silico and in vivo methods, how mechanical stimulation enhances bone formation in scaffold and translate the obtained results into clinical applications. In this thesis, a novel mathematical model is proposed to predict the course of bone formation in a scaffold. The mathematical model is identified and further validated using in vivo data. Using rat distal femur as an animal model, a short period of cyclic loading is found to induce long-term effects on bone formation inside scaffold. Mechanical stimulation is shown to increase the stiffness of the bone-scaffold over time. Furthermore, the effect of mechanical stimulation on dynamic of bone formation and resorption is investigated. The surgical preparation of bone-scaffold interface is also shown to be a key parameter in the fate of bone tissue engineering scaffold. Finally, all these findings are translated into a particular clinical situation, revision knee arthroplasty, using the developed mathematical model. The thesis is presented in the form of an introduction, five chapters in article format, a conclusion, and an appendix. In chapter 1, it is shown that bone formation inside scaffold follows a diffusion phenomenon. An analytical formulation for bone formation is developed, which has only three parameters: C, the final bone volume fraction, α, the so-called scaffold osteoconduction coefficient, and h, the so-called peri-scaffold osteoinduction coefficient. The three parameters are estimated by identifying the model with in vivo data of polymeric scaffolds implanted in the femoral condyle of rats. in vivo data are obtained by longitudinal micro-CT scanning of the animals. Having identified the three parameters, the model is validated by predicting the course of bone formation in two previously published in vivo studies. We find the predicted values to be consistent with the experimental values. This model allows us to spatially and temporally predict the bone formation in scaffolds with only three physically relevant parameters. In chapter 2, whether the preparation of implantation site has an impact on bone formation inside scaffolds is investigated. For this purpose, two different drilling techniques are used to create a hole in distal femur of rats: a wood drill bit and a metal drill bit. The bone volume, bone mineral density, and callus formation are assessed non-invasively using micro-CT scanning at several time points after implantation. It is found that when a wood drill bit is used, the bone