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bioRxiv · 10.1101/2021.09.22.461300

Expedited gene delivery for osteochondral defect repair in a rabbit knee model: a one-year investigation

Nagelli, C. V.·De La Vega, R. E.·Coenen, M.·Padilla de Lopez, C.·Panos, J. A.·Tovar, A.·Mueller, S. A.·Evans, C. H.
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Abstract

ObjectiveTo evaluate a single-step, gene-based procedure for repairing osteochondral lesions. DesignOsteochondral lesions were created in the patellar groove of skeletally mature rabbits. Autologous bone marrow aspirates were mixed with adenovirus vectors carrying cDNA encoding green fluorescent protein (Ad.GFP) or transforming growth factor-{beta}1 (Ad.TGF-{beta}1) and allowed to clot. The clotted marrow was press-fit into the defects. Animals receiving Ad.GFP were euthanized at 2 weeks and intra-articular expression of GFP examined by fluorescence microscopy. Animals receiving Ad.TGF-{beta}1 were euthanized at 3 months and 12 months; repair was compared to empty defects using histology and immunohistochemistry. Complementary in vitro experiments assessed transgene expression and chondrogenesis in marrow clots and fibrin gels. In a subsequent pilot study, repair at 3 months using a fibrin gel to encapsulate Ad.TGF-{beta}1 was evaluated. ResultsAt 2 weeks, GFP expression was seen at variable levels within the cartilaginous lesion. At 3 months, there was a statistically significant improvement in healing of lesions receiving Ad.TGF-{beta}1, although variability was high. At 12 months, there was no difference between the empty defects and those receiving Ad.TGF-{beta}1 in overall score and cartilage score, but the bone healing score remained higher. Variability was again high. In vitro experiments suggested that variability reflected variable transduction efficiency and chondrogenic activity of the marrow clots; using fibrin gels instead of marrow provided more uniformity in healing. ConclusionsThis approach to improving the repair of osteochondral lesions holds promise but needs further refinement to reduce variability and provide a more robust outcome.

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Nagelli, C. V., De La Vega, R. E., Coenen, M., Padilla de Lopez, C., Panos, J. A., Tovar, A., Mueller, S. A., Evans, C. H.. 2021-09-24. Expedited gene delivery for osteochondral defect repair in a rabbit knee model: a one-year investigation. https://doi.org/10.1101/2021.09.22.461300

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