Co-injection of human adipose stromal cells and rhBMP-2/fibrin gel enhances tendon graft osteointegration in a rabbit anterior cruciate ligament-reconstruction model

The objective of this study was to investigate whether the co-injection of human adipose stromal cells (hASCs) and rhBMP-2/fibrin gel into the bone tunnels of anterior cruciate-ligament reconstructions can effectively enhance tendon graft osteointegration. We performed bilateral reconstructions using autologous semitendinosus tendons in 45 New Zealand rabbits, which we divided into three groups. We injected the bone tunnels with fibrin gel for group 1, rhBMP-2 (1 mu g/ml)/fibrin gel for group 2, and hASCs wrapped in rhBMP-2 (1 mu g/ml)/fibrin gel for group 3. We sacrificed five rabbits (two for histological assessment and three for biomechanical tests) from each group at 2, 4, and 8 weeks post surgery. At 2 and 4 weeks post surgery, histological analysis showed that fibro-cartilage had appeared in the tendon-bone interface in group 2. At 4 weeks post surgery, mature bone cells could be seen in group 3. There was new bone formed between the host bone and the graft in groups 2 and 3 at 8 weeks post surgery. Biomechanical testing showed that at 4 and 8 weeks post surgery, the ultimate failure loads in group 3 were significantly higher than those in groups 1 and 2 (both P=0.01). The tendon stiffness in group 3 was significantly higher than that in the other groups at 4 weeks post surgery (P=0.01). Our results indicate that co-injection of hASCs and rhBMP-2/fibrin gel has the potential to promote tendon-bone healing after anterior cruciate-ligament reconstruction.