title: Preparation of resorbable carbonate-substituted hollow hydroxyapatite microspheres and their evaluation in osseous defects in vivo.
abstract: 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 CHA12) 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 CHA12 and HA microspheres showed a limited capacity to regenerate bone but the CHA12 microspheres resorbed faster than the HA microspheres. Loading the microspheres with bone morphogenetic protein-2 (BMP2) (1 μg per defect) stimulated bone regeneration and accelerated resorption of the CHA12 microspheres. At 12 weeks, the amount of new bone in the defects implanted with the CHA12 microspheres (73±8%) was significantly higher than the HA microspheres (59±2%) while the amount of residual CHA12 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.
authors.affiliation: Department of Materials Science and Engineering, Missouri University of Science and Technology, Rolla, MO 65409, United States.
authors.forename: Wei
authors.initials: W
authors.lastname: Xiao
authors.affiliation: Department of Orthopaedic Surgery, University of Missouri, Columbia, MO 65212, United States.
authors.forename: B
authors.initials: B
authors.lastname: Sonny Bal
authors.affiliation: Department of Materials Science and Engineering, Missouri University of Science and Technology, Rolla, MO 65409, United States. Electronic address: rahaman@mst.edu.
authors.forename: Mohamed N
authors.initials: MN
authors.lastname: Rahaman
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000737:chemistry; D001861:Bone Regeneration / Q000187:drug effects; D018786:Bone Substitutes; D002254:Carbonates / Q000737:chemistry*; D017886:Durapatite / Q000737:chemistry* / Q000627:therapeutic use; D008863:Microspheres; D010012:Osteogenesis; D051381:Rats
chemical_list: D055396:Bone Morphogenetic Protein 2; D018786:Bone Substitutes; D002254:Carbonates; D017886:Durapatite
keywords: Bone morphogenetic protein-2; Bone regeneration; Hollow hydroxyapatite microspheres; Rat calvarial defect model; Resorbable hydroxyapatite