Preparation of resorbable carbonate-substituted hollow hydroxyapatite microspheres and their evaluation in osseous defects in vivo

Hollow hydroxyapatite (HA) microspheres, with a high-surface-area mesoporous shell, can provide a unique bioactive and osteoconductive carrier for proteins to stimulate bone regeneration.However, synthetic HA has a slow resorption rate and a limited ability to remodel into bone. In the present study, hollow HA microspheres with controllable amounts of carbonate substitution (0-12 wt.%) were created using a novel glass conversion route and evaluated in vitro and in vivo. Hollow HA microspheres with-12 wt.% of carbonate (designated CHAl2) showed a higher surface area (236 m(2) g(-1)) than conventional hollow HA microspheres (179 m(2) g(-1)) and a faster degradation rate in a potassium acetate buffer solution. When implanted for 12 weeks in rat calvarial defects, the CHAl2 and HA microspheres showed a limited capacity to regenerate bone but the CHAl2 microspheres re sorbed faster than the HA microspheres. Loading the microspheres with bone morphogenetic protein-2 (BMP2) (1 mu g per defect) stimulated bone regeneration and accelerated resorption of the CHAl2 microspheres. At 12 weeks, the amount of new bone in the defects implanted with the CHAl2 microspheres (73 +/- 8%) was significantly higher than the HA microspheres (59 +/- 2%) while the amount of residual CHAl2 microspheres (7 2% of the total defect area) was significantly lower than the HA microspheres (21 +/- 3%). The combination of these carbonate-substituted HA microspheres with clinically safe doses of BMP2 could provide promising implants for healing non-loaded bone defects. (C) 2015 Elsevier B.V. All rights reserved.