Purpose: The deleterious effects of blocking movement of normal joints has been demonstrated by numerous animal experiments and clinical observations. Conversely, mobilisation of the joints leads to metabolic and trophic effects commonly attributed to changes in the nutritional status of the cartilage. In vitro experiments and mechanobiological studies have however suggested that more fundamental mechanisms are operating, demonstrating the impact of physical factors on biological cell regulation and tissue organisation. The purpose of our experimentation was to study the biological effects of movement on a model of skeletal regeneration from mesenchymatous tissue. The tested hypothesis was that movement crossing a living tissue causes the emission of specific signals which contribute to its anatomic and functional organisation.

Material and methods: We used 27 immature rabbits for the model. We transferred a vascularised periosteal flap to the knee region in order to initiate a process of skeletal tissue regeneration. The regenerated tissue was submitted to joint movements caused by the animal’s spontaneous movements. In the first group of animals, the knee was left intact. In the second group, 25 mm of the distal femur was removed, including the condyles. Tissue regeneration was compared with that obtained without joint movement.

Results: Qualitative changes in regenerated tissue were found to be influenced by movement. The differentiation of the mesenchymatous precursors was oriented towards production of cartilage and fibrocartilage. In the group with a sectioned femur, a mobile cartilage joint space was obtained at the interface between the regenerated femur and the tibia. A functional neo-joint was formed.

Discussion: This model of tissue regeneration, similar to that observed in experimental nonunion, demonstrated the contribution of multipotent stem cells of diverse origins. Joint mobility and its mechanical consequences produced information which were perceived as a modification of the environment. They regulated the differentiation of pluripotent cell elements and thus guided the spatial and temporal organisation of in vivo tissue repair processes.

Conclusion: Our results confirm the major influence of mechanical constraints on the organisation of skeletal tissue. The effect is expressed by the remodelling of mature tissues, but is also observed in immature tissues implicated in morphogenesis and skeletal regeneration processes. The transduction mechanisms remain to be described. However, the results obtained for cartilage regeneration demonstrate the practical interest of periosteal arthroplasty. Further improvement of the model to optimise continuous passive movement would open new perspectives for in vivo joint regeneration.

Purpose: Regeneration of skeletal tissue for fracture repair or during morphogenesis involves common phases of cell proliferation and differentiation. Mesenchymatous precursor cells have multiple origins. These cells can be identified in the bone marrow, in the deep layer of the periosteum and in the endosteum. More recently, the presence of circulating multipotent stem cells has been demonstrated in the general circulation. Their contribution to skeletal regeneration processes is suspected. The experiments we report allow visualisation of the multidirectional differentiation phenomena involving mesenchymatous precursor cells in an animal model of skeletal tissue regeneration.

Material and methods: An experimental surgical protocol was developed to study the regeneration of skeletal tissue in New Zealand rabbits. Eighteen animals were used. A vascularised periosteum flap was transferred onto the medial aspect of the knee. The flap was fixed in order to be exposed to flexion and extension stress during spontaneous ambulation. The joint was not damaged in any way and the adjacent bone segments were left intact. The animal was allowed to move freely postoperatively. The animal was sacrificed two days to eight weeks later to study standard histological slices taken from the regenerate region and the recipient knee joint.

Results: The zone of influence of the flap was recognised early in the environment where it was apposed. This zone involved the marrow of the metaphyseal regions, the neighbouring muscles, the joint cavity, and the menisci. Cell proliferation was noted in each of these sites. It was associated with differentiation of the precursor elements in multiple directions of the mesenchymatous lines. This led to production of cartilaginous, bony, fibrous, and even muscle tissue in the medullary cavity, in the menisci, and in the open joint space. Immunohistochemistry demonstrated the contribution of the mesenchymatous stem cells whose circulating pool was visualised.

Discussion: This work is in agreement with the recent demonstration of the contribution of stem cells to general healing phenomena, and the physiological turnover of healthy tissue.

Conclusion: The strong potential of multipotent stem cells for tissue reparation and regeneration processes opens important perspectives for cell therapy and tissue engineering. The demonstration of physiological processes operating in vivo which involve participation of the endogenous cell pool is of importance for all fields of medicine and surgery for the treatment of the musculoskeletal system.