Studying the Effect of Mechanical Stimulation in Endochondral in Vitro Models

Bone healing occurs through two distinct pathways: direct (primary) and endochondral ossification, with the mechanical environment at the fracture site being crucial in determining the respective pathway. Absolute stability promotes direct (primary or Haversian) bone healing via the migration and direct osteogenic differentiation of mesenchymal stromal cells across the fracture line. On the other hand, it is widely accepted that secondary fracture healing is triggered by a certain level of mechanical stimulation that initiates and promotes a cascade of events towards the formation of an intermediate cartilaginous callus matrix, that will eventually remodel into bone. In his strain theory, back in 1980, Prof Perren proposed that the bone healing process is regulated by the displacement applied at the fracture site relative to the size of a fracture gap (strain). Since, many in vivo studies have further investigated the affect of mechanical stimulus on the bone healing outcome, by applying different regiments or loading types. Though, optimal stimulation parameters to enhance fracture healing have not yet been entirely defined. There are still uncertainties concerning the magnitude of the deformation, its frequency, timing and duration. In addition, the influence of those parameters on the cellular process of hypertrophic cartilage formation and remodeling - critical for bone healing - is still not fully understood. In this context, our latest research focused on understanding the influence of mechanical parameters on the differentiation fate of naïve mesenchymal stem cells, using a custom-designed bioreactor for precise manipulation of strain conditions and loading protocols. A better understanding of the effect of strain on the cellular response and mechanism involved during hypertrophic chondrocyte differentiation and callus formation is crucial knowledge for the development of biomechanically optimized implants, as well as for the establishment of superior rehabilitation protocols.