Locally Delivered Nonsteroidal Antiinflammatory Drug: A Potential Option for Heterotopic Ossification Prevention

Oral nonsteroidal antiinflammatory drugs (NSAIDs) are prescribed for heterotopic ossification prophylaxis following at-risk injuries and procedures. We hypothesized that NSAIDs may be delivered locally in a wound for heterotopic ossification prophylaxis. In in vitro work, we cultured osteoblasts with three commercially available NSAIDs and then measured cell viability and DNA content. Indomethacin caused a 50% decrease in DNA at the lowest dose (0.0001 mM) and the most potent decrease in cell viability (<10% of control at 0.0005 mM). Ketorolac and ibuprofen required 10 times the dose to achieve a comparable decrease (<20% of control at 0.005 mM). In an animal study, 20 rats per treatment group received a full-thickness wound dressed with either saline-moistened gauze, saline-moistened chitosan sponge, or chitosan sponge loaded with indomethacin. After 28 days, we examined the tissue for healing. Wounds exposed to indomethacin loaded sponges demonstrated fewer inflammatory cells. All 20 rats in the indomethacin group had complete epithelial coverage at 28 days. Eighteen (90%) wounds in the saline-chitosan group and 11 (55%) wounds in the saline-gauze group were healed. Locally delivered NSAIDs may be useful for heterotopic ossification prophylaxis due to effects on osteoblast viability and lack of negative effects on wound healing.