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Combining osteoinductive and antimicrobial and antimicrobial therapies to improve healing of contaminated/infected segmental long bone defects

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University of Southern California Los Angeles United States

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BMP2-coupled Nanosilver-PLGA composite grafts have been shown to successfully repair grossly infected segmental defects.However, BMP2regenerated bones are known to have cyst-like bone voids and extensive amounts of fatty tissue. In this study, we hypothesize that addition of the osteoinductive growth factor Nell-1 to the BMP2-coupled Nanosilver-PLGA composite grafts will achieve higher quality bone and faster rates of fusion. Nell-1 BMP2 were added to Nanosilver PLGA scaffolds and implanted into 6 mm rat femoral defects contaminated with 108 S. aureus Mu50. High resolution faxitron images were obtained at 2, 4, 6, 8, 10, and 12 weeks. Femurs were harvested at 12 weeks post-operation. MicroCT analysis, histology, and immunohistochemistry were performed. Nell-1 BMP2 showed faster healing of femoral defects by 8 weeks post-operation compared to 12 weeks in the previous study with BMP2 alone. Progressive mineralization was seen starting at4 weeks, with 100 fusion achieved by 8 weeks. MicroCT 3D reconstructions showed robust bone formation with no cyst formation. Histology showed densely packed woven and lamellar bone. Nell-1 BMP2 appear to have synergistic effects. The combination of BMP2 Nell-1 improved bone formation over either cytokine alone, and is a promising combination therapy for faster healing of contaminated bone loss.

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Technical Report,15 Dec 2008,14 Dec 2012



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