Effect of sustained release of rhBMP-2 from dried and wet hyaluronic acid hydrogel carriers compared with direct dip coating of rhBMP-2 on peri-implant osteogenesis of dental implants in canine mandibles

Hyaluronic acid (HA) hydrogel has been used as a carrier of recombinant human bone morphogenetic protein (rhBMP)-2 for sustained delivery. To enhance peri-implant osteogenesis, a dried coating of rhBMP-2 HA hydrogel (BMP-HAH) on dental implants was designed; this approach provides the advantage of omitting in situ preparation of wet HA hydrogel. Sustained release of rhBMP-2 was more efficient for dried hydrogel over wet hydrogel. For both types, the released rhBMP-2 consistently led to enhanced alkaline phosphatase activity and osterix expression in human mesenchymal stromal cells. Histomorphometric analysis 4 weeks after placement of a dental implant in canine mandibles showed that the dried coating of BMP-HAH (10 μg/ml, n = 6) resulted in a significantly greater bone area (BA) than the wet BMP-HAH (10 μg/ml, n = 6) (p = 0.006) and implants without any coating (n = 6) (p = 0.022), while simple dip coating with rhBMP-2 (10 μg/ml, n = 6) resulted in significantly greater BA than the other three groups (p < 0.0005). Bone-to-implant contact (BIC) was significantly different only between the dried and wet coating of BMP-HAH (p = 0.014). Our results suggest that a simple dip coating of rhBMP-2 is more effective for increased peri-implant osteogenesis compared to a coating of BMP-HAH with sustained release.