Relaxin enhances bone regeneration with BMP‐2‐loaded hydroxyapatite microspheres

Abstract Our aims were to 1) evaluate the capacity of hollow hydroxyapatite (HA) microspheres (212–250 μm) to serve as a delivery system for controlled release of BMP‐2 in vitro and 2) examine relaxin as an enhancer of BMP‐2 for bone regeneration. Hollow HA microspheres were converted from borate glass microspheres and characterized using X‐ray diffraction, Fourier‐transform infrared spectroscopy, scanning electron microscopy, and the Brunauer–Emmett–Teller method. The microspheres loaded with BMP‐2 and relaxin were implanted for 6 weeks in Sprague Dawley rats with calvarial defects. BMP‐2 alone in the range up to 1 μg per defect exhibited dose‐dependent bone regeneration while relaxin alone in the range up to 0.25 μg per defect did not promote bone regeneration. When compared with BMP‐2 alone (1 μg per defect), a 50% reduction in the BMP‐2 dose was achieved with the addition of 0.05, 0.1, or 0.25 μg of relaxin per defect. These results show that loading HA microspheres with a combination of relaxin and BMP‐2 can significantly reduce the BMP‐2 dose required to regenerate an equivalent amount of bone.