Abstract
Purpose
Platelet-derived growth factor-BB (PDGF-BB) is a well characterized wound healing protein known to be chemotactic and mitogenic for cells of mesenchymal origin, including osteoblasts and chondrocytes. Biocompatible scaffolds, combined with growth factors such as PDGF-BB, have potential to stimulate regeneration and repair of osseous and cartilaginous tissues. The purpose of this study was to determine the efficacy and safety of recombinant human PDGF-BB (rhPDGF-BB) combined with a collagen implant to augment healing of osteochondral defects.
Method
A single osteochondral defect (8mm x 8mm) was created in the medial femoral condyle of 32 adult goats. Collagen implants(8.5mm x 8mm) hydrated with four doses of rhPDGF-BB (0g, 15g, 75g, 500g) were press-fit into the defect. Defects in four animals were left untreated. All goats were sacrificed 12 weeks postoperatively. Macroscopic evaluation and quantitative CT analyses were performed. Histologic sections were stained with Safranin O/Fast Green and assessed with a modified ODriscoll scoring scale for cartilage and bone repair. Significance was determined by One-Way ANOVA or nonparametric Kruskal-Wallis.
Results
Macroscopic evaluation indicated significant improvement of the gross cartilage repair score for the rhPDGF-BB treatment groups compared to the 0g rhPDGF-BB control (500g;0g) and empty defect groups (500,75,15g; Empty). MicroCT analysis indicated a significant increase in trabecular number for the 500g group compared to 0g control, 75g, and Empty groups(p=0.004). Average bone volume reconstitution for the 500g group was increased (58.8%) compared to the 0g control. The total cartilage repair score was significantly improved (p=0.048) in the 500g treatment group (14.30.3) compared to the 0g control group (12.10.4). All rhPDGF-BB treatment groups exhibited increased Safranin-O staining of the matrix compared to the 0g control group, and a significantly decreased incidence(p=0.01) of subchondral cyst formation compared to the empty defect group.
Conclusion
The results of this study indicate that rhPDGF-BB, combined with a collagen implant, is safe and improves repair of large osteochondral defects located in a high-load bearing region in a caprine model. Increases in gross scoring and histopathologic cartilage repair score for the rhPDGF-BB treatment groups, in addition to the presence of bony bridging, especially for the 500g rhPDGF-BB treatment group, indicate enhanced reconstitution of the subchondral bone and overlying repair tissue. The cartilage repair score was increased, on average, in the empty defect group relative to the 0g rhPDGF-BB group, however this score may be partially inflated due to collapse of the surrounding native tissue into the defect. Combined with a significant decrease in cyst formation in all rhPDGF-BB treatment groups, these results suggest that rhPDGF-BB, combined with a collagen implant, may have promise as a therapeutic agent for osteochondral defect repair.
