Osteoconductive and Osteoinductive Implants Composed of Hollow Hydroxyapatite Microspheres

The repair of bone defects resulting from trauma, periodontal disease and congenital diseases is a common clinical problem. Autogenous bone grafts are the gold standard for treatment and allografts are alternatives but they suffer from limitations. Synthetic bone graft substitutes are typically osteoconductive but they lack the osteogenic cells and osteoinductive growths factors present in autologous bone. Consequently, they commonly require the addition of cells or growth factors to enhance bone regeneration. However, concerns have been expressed about the supraphysiological doses of bone morphogenetic proteins (such as BMP2) required for bone regeneration at a clinically acceptable rate. We have been developing hollow hydroxyapatite (HA) microspheres as a bioactive and osteoconductive carrier for BMP2 in bone regeneration. The microspheres have a customizable diameter, surface area, hollow core and mesoporous shell wall. When loaded with BMP2, the HA microspheres showed a significant capacity to induce bone growth in rat calvarial defects within 3 to 6 weeks. Removing a segment of the shell from the hollow HA microspheres resulted in the creation of "open" microspheres that showed the interior concave surface of the shell wall. The open HA microspheres showed osteoinductive-like properties based on the microconcave geometry of the interior surface of me shell wall. In this article, the characteristics of the hollow HA micro-spheres, their ability to serve as a carrier for BMP2 and their capacity to regenerate bone in a standard osseous defect model are reviewed. These hollow HA microspheres, closed or open, are promising osteoconductive and osteoinductive implants for regenerating bone in periodontal, craniofacial and non-loaded musculoskeletal defects.