Theoretical Analysis of Remodelling Processes in Bony Tissue Engineered Implants

In order to design adequate and performing artificial tissue implants, porous biocompatible and biodegradable substrates have to be cells seeded. Moreover they have to be submitted to perfusion inside a bioreactor, during few weeks, with a nutritive fluid carrying solute ingredients necessary for the active cells to grow, proliferate, differentiate and produce extra-cellular matrices. From the understanding and control of the processes leading to the substrate degradation and extra cellular matrix remodelling taking place during the in vitro culture phase, depends widely the success in the realization of new orthopaedic biomaterials. Within this context, the analysis of the interactions between convective phenomena of hydrodynamic origin and chemical reaction of biological order which are associated to these processes is a fundamental challenge in the framework of the bone tissue engineering. In order to better account for the different intricate processes taking place in such a sample and to design a relevant experimental protocol leading to the definition of an optimal tissue implant, we proposed a theoretical model based on transport phenomena in porous active media. For these “opened” systems in state of permanent imbalance created by the local convection induced in the medium, the analysis of such complex interactions remains relatively coarse. The adopted approach is based on a formulation similar to that of the active porous media in which all the biochemical processes related to the cellular metabolism are described in terms of the physicochemical processes taking place at the fluid-solid interface, leading to the degradation and remodelling of the solid matrix. The model includes the effects of the complex microscopic architecture of the substrate and the specificity of the biological processes such as extra cellular matrix production and resorption. This leads to a numerical solution of the coupled fluid dynamics, transport equations and biochemical reaction inside the porous medium. The fundamental parameters on which depends the evolution of the structure of the medium are thus put in evidence and evaluated in the framework of bone tissue engineering. One of the revealed outcomes is the fact that local and minor interaction can lead to long-range imbalance and substantial changes in the initial architecture of the substrate even to engender phenomena of chaotic instability..