Finite element analysis of degradation, growth factor release and signaling pathway interactions in a 3D scaffold

Bone scaffolds promise a great potential to gain new treatment strategies to control bone healing and regeneration processes due to their tunable nature. Bone tissue engineering (BTE) gains enduring attention of researchers from various disciplines since it is a multidisciplinary field. This thesis provides a comprehensive examination modeling degradation of a 3D porous polymeric bone scaffold aiming to enhance bone healing with growth factor release and the effect of signaling pathway interactions. A set of reaction-diffusion equations were solved using COMSOL Multiphysics software which employs finite element method (FEM). In the first part, we performed a parametric study with the developed FEM model focusing on scaffold degradation, BMP-2 growth factor release and degradation rates. To validate our 3D model, a previous validation case was performed on a simpler geometry. Next, a signaling pathway evolving due to the released BMP-2 was also modeled deriving Ordinary Differential Equations (ODEs) based on mass action law. The ODE system was subject to Michaelis Menten approach, and a detailed mathematical derivation is presented. In the third part, two optimization algorithms were developed to find optimum values for some selected set of the previously examined parameters effecting the scaffold degradation and growth factor release kinetics. This thesis forms the groundwork for an initial FEM model to be used in analyzing 3D bone scaffolds for degradation and release kinetics in association with signaling pathway interactions. This model should be very useful for various bone scaffold design studies with integration of existing key mechanisms such as angiogenesis into the presented model.