Are recombinant human bone morphogenetic protein-7 and tobramycin compatible? An experiment in rats

Alan T. Kawaguchi, A Hari Reddi, Steven A. Olson, Kent E. Yinger, H. David Moehring

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

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 μg 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 μg tobramycin in aqueous solution or 3 to bramycin-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 μg 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.

Original languageEnglish (US)
Pages (from-to)225-232
Number of pages8
JournalJournal of Orthopaedic Trauma
Volume18
Issue number4
DOIs
StatePublished - Apr 2004
Externally publishedYes

Fingerprint

Tobramycin
Osteogenesis
Alkaline Phosphatase
Bone Matrix
human BMP7 protein
Long Evans Rats
Bone Morphogenetic Proteins
Polymethyl Methacrylate
Histology
Buffers
Research Design
Thorax
Phosphates
Anti-Bacterial Agents

Keywords

  • Antibiotic beads
  • BMP-7
  • Bone formation
  • Tobramycin

ASJC Scopus subject areas

  • Surgery
  • Orthopedics and Sports Medicine
  • Physical Therapy, Sports Therapy and Rehabilitation

Cite this

Are recombinant human bone morphogenetic protein-7 and tobramycin compatible? An experiment in rats. / Kawaguchi, Alan T.; Reddi, A Hari; Olson, Steven A.; Yinger, Kent E.; Moehring, H. David.

In: Journal of Orthopaedic Trauma, Vol. 18, No. 4, 04.2004, p. 225-232.

Research output: Contribution to journalArticle

Kawaguchi, Alan T. ; Reddi, A Hari ; Olson, Steven A. ; Yinger, Kent E. ; Moehring, H. David. / Are recombinant human bone morphogenetic protein-7 and tobramycin compatible? An experiment in rats. In: Journal of Orthopaedic Trauma. 2004 ; Vol. 18, No. 4. pp. 225-232.
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AB - 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 μg 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 μg tobramycin in aqueous solution or 3 to bramycin-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 μg 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.

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