Hollow hydroxyapatite microspheres: A novel bioactive and osteoconductive carrier for controlled release of bone morphogenetic protein-2 in bone regeneration

• Published in: Acta biomaterialia Vol. 9; no. 9; pp. 8374 - 8383
• Main Authors: Xiao, Wei, Fu, Hailuo, Rahaman, Mohamed N., Liu, Yonxing, Bal, B. Sonny
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.09.2013
• Subjects: Animals; Biomedical materials; Bone Morphogenetic Protein 2 - administration & dosage; Bone Morphogenetic Protein 2 - chemistry; Bone morphogenetic protein-2; Bone regeneration; Bone Regeneration - drug effects; Bone Regeneration - physiology; Bone Substitutes - administration & dosage; Bone Substitutes - chemistry; Bones; Capsules - administration & dosage; Capsules - chemistry; Carriers; Defects; Delayed-Action Preparations - administration & dosage; Delayed-Action Preparations - chemistry; Diffusion; Equipment Design; Equipment Failure Analysis; Hollow hydroxyapatite microspheres; Hydroxyapatite; Hydroxyapatites - administration & dosage; Hydroxyapatites - chemistry; Materials Testing; Microspheres; Porosity; Rat calvarial defect model; Rats; Regeneration; Skull Fractures - pathology; Skull Fractures - physiopathology; Skull Fractures - therapy; Surgical implants; Tissue Scaffolds; Treatment Outcome; Rat calvarial defect model; Bone morphogenetic protein-2; Bone regeneration; Hollow hydroxyapatite microspheres
• ISSN: 1742-7061; 1878-7568
• DOI: 10.1016/j.actbio.2013.05.029

The regeneration of large bone defects is a common and significant clinical problem. Limitations associated with existing treatments such as autologous bone grafts and allografts have increased the need for synthetic bone graft substitutes. The objective of this study was to evaluate the capacity of novel hollow hydroxyapatite (HA) microspheres to serve as a carrier for controlled release of bone morphogenetic-2 (BMP2) in bone regeneration. Hollow HA microspheres (106–150μm) with a high surface area (>100m2g−1) and a mesoporous shell wall (pore size 10–20nm) were created using a glass conversion technique. The release of BMP2 from the microspheres into a medium composed of diluted fetal bovine serum in vitro was slow, but it occurred continuously for over 2weeks. When implanted in rat calvarial defects for 3 or 6weeks, the microspheres loaded with BMP2 (1μg per defect) showed a significantly better capacity to regenerate bone than those without BMP2. The amount of new bone in the defects implanted with the BMP2-loaded microspheres was 40% and 43%, respectively, at 3 and 6weeks, compared to 13% and 17%, respectively, for the microspheres without BMP2. Coating the BMP2-loaded microspheres with a biodegradable polymer, poly(lactic-co-glycolic acid), reduced the amount of BMP2 released in vitro and, above a certain coating thickness, significantly reduced bone regeneration in vivo. The results indicate that these hollow HA microspheres could provide a bioactive and osteoconductive carrier for growth factors in bone regeneration.