BMP-2 Incorporation into 3D Printed Porous Hydroxyapatite by Rapid Biomimetic Co-Precipitation Technique Using Accelerated Calcium Phosphate Solution

Abstract

Bone morphogenetic protein (BMP-2) is multi-functional growth factor and widely used osteoinductive cell mediator which was loaded into the osteoconductive bone graft to accelerate bone healing and osteointegration of the graft. Rapid biomimetic co-precipitation technique by using newly developed accelerated calcium phosphate solution was investigated as a mean to enhance the incorporation of BMP-2 on three dimensionally printed porous hydroxyapatite (3DP HA) and its release characteristic compared to typical direct adsorption. Two initial BMP-2 concentrations of 1 and 10 μg/mL were employed in this study. After loading, new octacalcium phosphate leaf-like crystals were observed to form on the surface of BMP-2 loaded 3DP HA by using biomimetic co-precipitation technique at both concentrations while none was seen in the direct adsorption technique. Biomimetic co-precipitation technique yielded two times greater in total BMP-2 loading content, but displayed lower releasing rate than those of the direct adsorption technique. Cell differentiation of pre-osteoblast MC3T3-E1 on the BMP-2 loaded 3DP HA by using biomimetic co-precipitation was also greater enhanced compared to non-loaded or direct adsorbed samples. The increase in content and decrease in releasing rate of BMP-2 by using biomimetic co-precipitation technique could be related to the formation of new octacalcium phosphate crystals on the 3DP HA which incorporated BMP-2 into their structures and retarded its release.