Degree of biological apatite c-axis orientation rather than bone mineral density controls mechanical function in bone regenerated using recombinant bone morphogenetic protein-2

The aim of the present study was to assess the bone regeneration process in defects introduced into rabbit long bones, which were regenerated with controlled release of recombinant bone morphogenetic protein-2 (rBMP-2). The orientation of the biological apatite (BAp) c-axis and bone mineral density (BMD) were compared as predictors of bone mechanical function. A 20-mm-long defect was introduced in rabbit ulnas, and 17 µg of rBMP-2 was controlled-released into the defect using a biodegradable gelatin hydrogel as the carrier. In the bone regeneration process, two characteristic phases may have been governed by different factors. First, new bone formation actively occurred, filling the bone defect with newly formed bone tissue and increasing the BMD. This process was regulated by the strong osteoinductive capacity of rBMP-2. Second, after filling of the defect and moderate BMD restoration, preferential BAp c-axis orientation began to increase, coincident with initiation of remodeling. In addition, the BAp c-axis orientation, rather than BMD, was strongly correlated with Young's modulus, an important index of bone mechanical function, particularly in the later stage of bone regeneration. Thus, preferential BAp c-axis orientation is a strong determinant and predictor of the mechanical function of tissue-engineered bone. Therefore, analysis of BAp preferential c-axis orientation in addition to measurement of BMD is crucial in assessment of bone mechanical function.