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. 2008 Oct 21;131(2):121-7.
doi: 10.1016/j.jconrel.2008.07.022. Epub 2008 Jul 20.

Treatment of osteomyelitis in rats by injection of degradable polymer releasing gentamicin

Yaron S Brin  1 , Jacob Golenser, Boaz Mizrahi, Guy Maoz, Abraham J Domb, Shyamal Peddada, Shmuel Tuvia, Abraham Nyska, Meir Nyska
Affiliations

Treatment of osteomyelitis in rats by injection of degradable polymer releasing gentamicin

Yaron S Brin et al. J Control Release. .

Abstract

We evaluated the potential of an injectable degradable polymer-poly(sebacic-co-ricinoleic-ester-anhydride) containing gentamicin for the treatment of osteomyelitis. Osteomyelitis of both tibiae was induced in 13 female Fischer rats by injecting a suspension containing approximately 105 (CFU)/ml of S. aureus into the tibial medullar canal. Three weeks later both tibiae were X-rayed, drilled down the medullar canal, washed with 50 microl gentamicin solution (80 mg/2 ml) and then injected with 50 microl P(SA-RA)+gentamycin 20% w/v to the right tibia and 50 microl P(SA-RA) without gentamicin to the left tibia. After an additional 3 weeks, the rats were sacrificed, and radiographs of the tibiae were taken. Histopathological evaluation of the tibiae was done in a blinded manner. X-ray radiographs showed that all tibiae developed changes compatible with osteomyelitis in 3 weeks. Histological evaluation revealed significant differences between right and left tibiae in 10 rats. In the left tibia moderate intramedullary abscess formation occurred. In most treated tibiae typical changes included the absence (or minimal grade only) of abscesses. The treated group developed significantly less intramedullary abscesses; the p value was 0.028. Locally injected degradable polymer releasing gentamicin proved to be efficient histologically in the treatment of osteomyelitis.

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Figures

Figure 1
Figure 1
the structure of the polymer:
Figure 2
Figure 2
Rats number 3 and 4. The x-ray was taken 42 days after inoculation. Drilling was done in the tibia between the two red arrows. Entry site between tibial plateau and tuberosity. A KW of 0.8 mm was used to drill down the tibial canal for 1cm. The rt. tibiae were treated with polymer and gentamicin and the lt. tibiae were treated with polymer only. Note the periosteal reaction in the lt. tibia of rat number 4, and the bone lucency of the lt. tibia of rat number 3 (arrows).
Figure 3
Figure 3

  1. Note: all photos were taken from animal # 2, left and right legs

  2. B. Right tibia - diaphyseal region – The leg was injected with a polymer loaded with gentamicin. Note: The absence of intramedullary abscesses, which were replaced by stromal tissue having multiple cavities from where the test compound was washed out during the histological processing (arrows). Hematoxylin and Eosin, X 10.

  3. C. Left tibia - diaphyseal region – The leg was injected with plain polymer. Note: presence of multiple intramedullary abscesses with bluish granules, representing the Gram positive stained, Staphylococcus aureus (arrows). Gram staining, X 10.

  4. D. Right tibia - intramedullary stromal tissue within the diaphyseal region – The leg was injected with a polymer loaded with gentamicin. Note: There is no Gram positive stained, Staphylococcus aureus bacteria (arrows). Gram staining, X 10.

  5. E. Left tibia - diaphyseal region – The leg was injected with plain polymer. Note: presence of multiple intramedullary abscesses with bluish granules, representing the Gram positive stained, Staphylococcus aureus bacteria (arrows). Gram staining, X 40.

  6. F. Right tibia - intramedullary stromal tissue within the diaphyseal region – The leg was injected with a polymer loaded with gentamicin. Note: There is no Gram positive stained, Staphylococcus aureus bacteria (arrows). Gram staining, X 40.

  1. level of evidence

  2. Shyamal

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