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Are recombinant human bone morphogenetic protein-7 and tobramycin compatible? An experiment in rats
Alan T Kawaguchi1, A Hari Reddi, Steven A Olson
1Alpine Orthopaedic Medical Group Inc., 333 East Alpine Avenue, Stockton, CA 95204, USA.
Objectives:
To evaluate the effects of local antibiotics on bone morphogenetic protein-induced new bone formation in vivo.
Design:
In the research laboratory, inactive collagenous bone matrix was reconstituted with 1 microg of recombinant human bone morphogenetic protein-7 and implanted subcutaneously in the thorax bilaterally in 30 male Long-Evans rats.
Intervention:
In group A (n = 2), the inactive collagenous bone matrix alone was implanted, bilaterally, and one of these pellets treated with either 500 microg tobramycin in aqueous solution or 3 tobramycin-impregnated polymethyl methacrylate beads. In group B (n = 4), the reconstituted pellets were not treated with tobramycin. In group C (n = 8), 1 reconstituted pellet in each rat was treated with 500 microg tobramycin in aqueous solution. In group D (n = 8), 3 tobramycin beads were placed in contact with 1 of the 2 reconstituted pellets in each rat. In group E (n = 8), 3 tobramycin beads were placed on the dorsal surface of 4 of the rats. All rats were killed on day 11.
Main Outcome Measurement:
Bone formation was evaluated by alkaline phosphatase assay and histology. Tobramycin elution from the beads after day 11 was measured by placing the explanted beads into a phosphate buffer solution to incubate for 24 hours.
Results:
There was no difference in the alkaline phosphatase activity between the tobramycin treated and untreated implants. Histologic evaluation of the implants revealed areas of robust new bone formation in both the tobramycin treated and untreated implants.
Conclusions:
The results by both alkaline phosphatase assay and histologic evaluation in this rat model indicate that there is no inhibition of recombinant human bone morphogenetic protein-7-induced new bone formation by locally applied tobramycin. Recombinant human bone morphogenetic protein-7 is osteoinductive in the presence of locally applied tobramycin. A composite osteogenic device containing both tobramycin and recombinant human bone morphogenetic protein-7 may be developed that can simultaneously induce bone healing and decrease the risk for infection.