Standard bone healing stages occur during delayed bone healing, albeit with a different temporal onset and spatial distribution of callus tissues

Abstract

Bone healing is considered as a recapitulation of a developmental program initiated at the time of injury. This study tested the hypothesis that in delayed bone healing the regular cascade of healing events, including remodeling of woven to lamellar bone, would be similar compared to standard healing, although the temporal onset would be delayed. A tibial osteotomy was performed in sheep and stabilized with a rotationally unstable fixator leading to delayed healing. The sheep were sacrificed at 2, 3, 6, 9 weeks and 6 months postoperatively. The temporal and spatial tissue distributions in the calluses and the bone microstructure were examined by histology. Although histological analysis demonstrated temporal and spatial callus tissue distribution differences, delayed healing exhibited the same characteristic stages as those seen during uneventful standard healing. The delayed healing process was characterized by a prolonged presence of hematoma, a different spatial distribution of new bone and delayed and prolonged endochondral bone formation. A change in the spatial distribution of callus formation was seen by week 6 leading to bone formation and resorption of the cortical bone fragments, dependent on the degree to which the cortical bone fragments were dislocated. At 6 months, only 5 out of 8 animals showed complete bony bridging with a continuous periosteum, although lamellar bone and newly formed woven bone were present in the other 3 animals. This study demonstrates that during delayed bone healing all stages of the healing cascade likely take place, even if bony consolidation does not occur. Furthermore, the healing outcome might be related to the periosteum’s regenerative capacity leading to bony union or absence of bony bridging.