Evaluation of bone regeneration in implants composed of hollow HA microspheres loaded with transforming growth factor β1 in a rat calvarial defect model

Implants that serve simultaneously as an osteoconductive matrix and as a device for local growth factor delivery may be required for optimal bone regeneration in some applications. In the present study, hollow hydroxyapatite (HA) microspheres (106-150 μm) in the form of three-dimensional (3-D) scaffolds or individual (loose) microspheres were created using a glass conversion process. The capacity of the implants, with or without transforming growth factor β1 (TGF-β1), to regenerate bone in a rat calvarial defect model was compared. The 3-D scaffolds supported the proliferation and alkaline phosphatase activity of osteogenic MLO-A5 cells in vitro, showing their cytocompatibility. Release of TGF-β1 from the 3-D scaffolds into phosphate-buffered saline ceased after 2-3 days when ∼30% of the growth factor was released. Bone regeneration in the 3-D scaffolds and the individual microspheres increased with time from 6 to 12 weeks, but it was significantly higher (23%) in the individual microspheres than in the 3-D scaffolds (15%) after 12 weeks. Loading with TGF-β1 (5 μg per defect) enhanced bone regeneration in the 3-D scaffolds and individual microspheres after 6 weeks, but had little effect after 12 weeks. 3-D scaffolds and individual microspheres with larger HA diameter (150-250 μm) showed better ability to regenerate bone. Based on these results, implants composed of hollow HA microspheres show promising potential as an osteoconductive matrix for local growth factor delivery in bone regeneration.