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

• Published in: Osteoarthritis and cartilage open 2022-06, Vol.4 (2), p.100257, Article 100257
• Main Authors: Nagelli, Christopher V., De La Vega, Rodolfo E., Coenen, Michael, De Padilla, Consuelo Lopez, Panos, Joseph A., Tovar, Alejandro, Müller, Sebastian A., Evans, Christopher H.
• Format: Article
• Language: English
• Subjects: Cartilage repair; Gene delivery; Knee; Long-term; Osteochondral defects; Rabbit
• ISSN: 2665-9131; 2665-9131
• DOI: 10.1016/j.ocarto.2022.100257

To evaluate a single-step, gene-based procedure for repairing osteochondral lesions. Osteochondral 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-β1 (Ad.TGF-β1) 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-β1 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-β1 was evaluated. At 2 weeks, GFP expression was seen at variable levels within the cartilaginous lesion. At 3 months, there was no statistically significant improvement (p ​> ​0.05) in healing of lesions receiving Ad.TGF-β1 and variability was high. At 12 months, there were still no significant difference (p ​> ​0.05) between the empty defects and those receiving Ad.TGF-β1 in the overall, cartilage, and bone scores. Variability was still high. In vitro experiments suggested that variability reflected variable transduction efficiency and chondrogenic activity of the marrow clots; using fibrin gels instead of marrow may address this issue but more research is needed. This approach to improving the repair of osteochondral lesions needs further refinement to reduce variability and provide a more robust outcome.