Morphologically Different Hydroxyapatite Nanoparticles as Osteogenic Drug Delivery Devices for the Treatment of Osteomyelitis

Osteomyelitis is an infection of bone commonly caused by Staphylococcus aureus. The current treatment involves long-course antibiotic therapy and invasive procedures, such as surgical debridement of infected tissues in order to prevent chronic infection and bone deformity. Hydroxyapatite (HAP), naturally present in bone, is the preferred implanted material to stimulate bone regeneration. Previous research has shown HAP to possibly be an effective drug delivery device. We investigated the effect of morphology of a HAP-based antibiotic delivery device on: (1) sustained drug release profiles; (2) the bacterial growth inhibition; and (3) osteogenic performance in vitro. We precipitated four different HAP nanopowders with planar, block, needle, and spherical particle morphologies. The nanopowders were loaded with the antibiotic, clindamycin phosphate (CL), or fluorescein, a model drug used to assess drug release. Testing HAP-CL nanopowders for bacterial growth inhibition showed their satisfying antibacterial performance both in broths and on agar plates. All four HAP-fluorescein nanopowders exhibited sustained drug release, in both agitation and static experiments, over two weeks. The HAP sample with the highest specific surface area and the smallest particle size was the most effective in both drug loading and release, consequently having the highest antibacterial efficiency. We also investigated the osteogenic performance in vitro on osteoblastic MC3T3-E1 cells. Our results suggest that HAP nanoparticles of different morphologies may be effective osteogenic drug delivery devices and could be considered in place of the current invasive therapies. Funded through NIH K99-DE021416.