Repair of segmental bone defects in the rat: An experimental model of human fracture healing

Bone repair models in animals may be considered relevant to human fracture healing to the extent that the sequence of events in the repair process in the model reflect the human fracture healing sequence. In the present study , the relevance of a recently developed segmental defect model in rat fibul a to human fracture healing was investigated by evaluating temporal progres sion of rigidity of the fibula, mineral content of the repair site, and his tological changes. In this model, a surgically created 2-mm-long defect was grafted with a 5-mm-long tubular specimen of demineralized bone matrix (DB M) by inserting it over the cut ends of the fibula. The temporal increase i n rigidity of the healing fibula demonstrated a pattern similar to biomecha nical healing curves measured in human fracture healing. This pattern was c haracterized by a short phase of rapidly rising rigidity during weeks 4-7 a fter surgery, associated with a sharp increase in the mineral content of th e repair tissue. This was preceded by a phase of nearly zero rigidity and f ollowed by a phase of slow rate of increase approaching a plateau. Histolog ically, chondroblastic and osteoblastic blastema originating from extraskel etal and subperiosteal (near fibula-graft junction) regions, infiltrated th e DBM graft during the first 2 weeks. The DBM graft assumed the role of a " bridging callus." By weeks 6-8, most of the DBM was converted to new woven and trabecular bone with maximal osteoblastic activity and minimal endochon dral ossification. Medullary callus formation started with direct new bone formation adjacent to the cortical and endosteal surfaces in the defect and undifferentiated cells in the center of the defect at 3 weeks. The usual b one repair process in rodents was altered by the presence of the DBM graft to recapitulate the sequential stages of human fracture healing, including the formation of a medullary callus, union with woven and lamellar bone, an d recreation of the medullary canal. (C) 1999 by Elsevier Science Inc. All rights reserved.