Hydroxyapatite as a Carrier for Bone Morphogenetic Protein
Bone morphogenetic proteins (BMPs) can induce the formation of new bone in numerous orthopedic and dental applications in which loss of bone is the main issue. The combination of BMP with a biomaterial that can carry and deliver proteins has been demonstrated to maximize the therapeutic effects of BMPs. However, no ideal candidate with optimal characteristics as a carrier has emerged for clinical use of BMPs. Hydroxyapatite (HA) is a potential BMP carrier with its osteoconductive properties and desirable characteristics as a bone graft biomaterial. In this study, 3 different methods to load BMP into HA materials were characterized and compared based on the BMP uptake and release profile. BMP was loaded into HA in 3 ways: (1) incorporation of BMP during HA precipitation, (2) HA immersion in BMP solution, and (3) BMP incorporation during dicalcium phosphate dihydrate (DCPD) conversion to HA. The size of HA crystals decreased when BMP was loaded during HA precipitation and HA immersion in BMP solution; however, it did not change when BMP was loaded during DCPD-to-HA conversion. The highest BMP uptake was achieved using the immersion method followed by HA precipitation, and the lowest via DCPD conversion. It is interesting to note that BMP loading during HA precipitation resulted in sustained and prolonged BMP release compared with the 2 other BMP loading methods. In conclusion, BMP incorporation during HA precipitation revealed itself to be the best loading method.

The X-ray diffraction (XRD) spectra of (A) hydroxyapatite (HA) precipitates at pH 8 and 37°C; (B) dicalcium phosphate dihydrate (DCPD) precipitates at pH 5 and room temperature; and (C) DCPD converted to HA at pH 13 and 70°C.

The X-ray diffraction (XRD) pattern of crystals after bone morphogenetic protein (BMP) uptake via (A) incorporation during hydroxyapatite (HA) precipitation; (B) HA immersion in BMP solution; and (C) incorporation during BMP dicalcium phosphate dihydrate (DCPD)-to-HA conversion.

Scanning electron micrograph (SEM) images of (A) hydroxyapatite (HA) precipitates at pH 8 and 37°C; (B) dicalcium phosphate dihydrate (DCPD) precipitates at pH 5 and at room temperature; (C) DCPD converted to HA at pH 13 and 70°C; (D) HA crystals after bone morphogenetic protein (BMP) incorporation during HA precipitation; (E) HA crystals after immersion in a BMP solution; (F) Figure 3E boxed area magnified (HA crystals); and (G) HA crystals after BMP incorporation during DCPD-to-HA conversion.

Release profile of bone morphogenetic protein (BMP) from hydroxyapatite (HA) powders prepared using 3 BMP loading methods.

Percentage of bone morphogenetic protein (BMP) released from hydroxyapatite (HA) powders, based on the extent of BMP uptake for each respective BMP loading method.
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