NET CHANGE IN PERIOSTEAL STRAIN DURING STANCE SHIFT LOADING AFTER SURGERY CORRELATES TO RAPID DE NOVO BONE GENERATION IN CRITICAL SIZED DEFECTS

摘要

In an ovine femur model, proliferative woven bone fills critical sized defects enveloped by periosteum within two weeks of treatment with the one stage bone transport surgery. We hypothesize that mechanical loading modulates this process. Using high-definition optical strain measurements we determined prevailing periosteal strains for normal and surgically treated ovine femora subjected ex vivo to compressive loads simulating in vivo stance shifting (n=3 per group, normal versus treated). We determined spatial distribution of calcein green, a label for bone apposition in first the two weeks after surgery, in 15°, 30°, and 45° sectors of histological cross sections through the middle of the defect zone (n=6 bones, 3–4 sections/bone). Finally, we correlated early bone formation to either the maximal periosteal strain or the net change in maximal periosteal strain. We found that treatment with the one stage bone transport surgery profoundly changes the mechanical environment of cells within the periosteum during stance shift loading. The pattern of early bone formation is repeatable within and between animals and relates significantly to the actual strain magnitude prevailing in the periosteum during stance shift loading. Interestingly, early bone apposition after the surgery correlates more to the maximal net change in strain (above circa 2000–3000 µε, in tension or compression) rather than strain magnitude per se, providing further evidence that changes in cell shape may drive mechanoadaptation by progenitor cells. These important insights regarding mechanobiologic factors that enhance rapid bone generation in critical sized defects can be translated to the tissue and organ scale, providing a basis for the development of best practices for clinical implementation and the definition of movement protocols to enhance the regenerative effect.