Optimization and Modelling of a Bioreactor for the production of bone construct – OMBIOS

More than 2.2 million bone grafting procedures (autologous bone graft and banked bone) take place annually worldwide to ensure adequate bone healing in many skeletal problems. Due to its histocompatible and nonimmunogenic features, autologous bone harvested from donor sites, such as the iliac crest, is the most widely used option. Grafts of this kind are osteoconductive, osteoinductive, and osteogenic. However, autologous bone grafting adds significant morbidity to the surgical procedure, and increases operative time and costs. Most of the difficulties result from the harvest of the bone graft, and may increase hospital stay, blood loss, post-operative pain, and the risk of infection or fracture. These disadvantages have prompted an ongoing search for alternative methods that would supersede the need for an iliac crest harvest. The availability of mesenchymal stem cells (MSCs) and the potential of inducing the osteogenic phenotype are motivating the development of custom-tailored materials known as “bone constructs”. In such cases, the clinical scenario involves expansion of MSCs in monolayer and their seeding onto an individual resorbable porous scaffold prior to surgery. We have developed a perfusion bioreactor designed to automate the production of bone constructs (THERABONE 2007-2010). The proof of concept was established in a large animal model of clinical relevance. The filling of large metatarsal sheep bone defects with bone constructs prepared in the bioreactor resulted in a satisfactory bone repair.
The OMBIOS project has two objectives: (i) cognitive: to understand the impact of 3D mechanical microenvironment on hMSCs in the development, repair and bone tissue engineering and (ii) application: this knowledge is essential to develop a bioreactor in a rational way. The first step will be to study the respective roles of shear stress and hydrostatic compression on the induction of human MSCs into the osteogenic pathway and to study the forces applied into the bioreactor. A second step will be responsible for designing a bioreactor of clinical grade and evaluate the functionality of the bone construct product in vivo and in vitro. The main perspective of this project is its transfer to the clinic, therefore great attention will be paid to use our method for clinical application.