A 1-year study of osteoinduction in hydroxyapatite-derived biomaterials in an adult sheep model: part II. Bioengineering implants to optimize bone replacement in reconstruction of cranial defects.

The present study investigated hydroxyapatite biomaterials implanted in critical-size defects in the calvaria of adult sheep to determine the optimal bioengineering of hydroxyapatite composites to facilitate bone ingrowth into these materials. Five calvarial defects measuring 16.8 mm in diameter were made in each of 10 adult sheep. Three defects were filled with cement paste composites of hydroxyapatite and beta-tricalcium phosphate as follows: (1) 100 percent hydroxyapatite-cement paste, (2) 60 percent hydroxyapatite-cement paste, and (3) 20 percent hydroxyapatite-cement paste. One defect was filled with a ceramic composite containing 60 percent hydroxyapatite-ceramic, and the fifth defect remained unfilled. One year after implantation, the volume of all biomaterials was determined by computed tomography, and porosity and bone replacement were determined using backscatter electron microscopy. Computed tomography-based volumetric assessment 1 year after implantation demonstrated that none of the unfilled cranial defects closed over the 1-year period, confirming that these were critical-size defects. There was a significant increase in volume in both the cement paste and ceramic implants containing 60 percent hydroxyapatite (p < 0.01). There was no significant change in volume of the remaining cement paste biomaterials. Analysis of specimens by backscatter electron microscopy demonstrated mean bone replacement of 4.8 +/- 1.4 percent (mean +/- SEM) in 100 percent hydroxyapatite-cement paste, 11.2 +/- 2.3 percent in 60 percent hydroxyapatite-cement paste, and 28.5 +/- 4.5 percent in 20 percent hydroxyapatite-cement paste. There was an inverse correlation between the concentration of hydroxyapatite and the amount of bone replacement in the cement paste for each composite tested (p < 0.01). Bone replacement in 60 percent hydroxyapatite-ceramic composite (13.6 +/- 2.0 percent) was not significantly different from that in 60 percent hydroxyapatite-cement paste. Of note is that the ceramic composite contained macropores (200 to 300 microm) that did not change in size over the 1-year period. All cement paste composites initially contained micropores (3 to 5 nm), which remained unchanged in 100 percent hydroxyapatite-cement paste. Cement paste implants containing increased tricalcium phosphate demonstrated a corresponding increase in macropores following resorption of the tricalcium phosphate component. Bone replacement occurred within the macropores of these implants. In conclusion, there was no significant bone ingrowth into pure hydroxyapatite-cement paste (Bone Source, Stryker-Leibinger Inc., Dallas, Texas) in the present study. The introduction of macropores in a biomaterial can optimize bone ingrowth for reconstruction of critical-size defects in calvaria. This was demonstrated in both the ceramic composite of hydroxyapatite tested and the cement paste composites of hydroxyapatite by increasing the composition of a rapidly resorbing component such as beta-tricalcium phosphate.