Biologic augmentation of rotator cuff tendon-healing with use of a mixture of osteoinductive growth factors

Background: Clinical studies have demonstrated a high rate of incomplete healing of rotator cuff tendon repair. Since healing of such a repair is dependent on bone ingrowth into the repaired tendon, we hypothesized that osteoinductive growth factors would improve rotator cuff tendon-healing. Methods: Seventy-two skeletally mature sheep underwent detachment of the infraspinatus tendon followed by immediate repair. The animals received one of three treatments at the tendon-bone interface: (1) an osteoinductive bone protein extract on a Type-I collagen sponge carrier, (2) the collagen sponge carrier alone, and (3) no implant. The animals were killed at six and twelve weeks, and the repaired rotator cuff was evaluated with use of magnetic resonance imaging, plain radiographs, histologic analysis, and biomechanical testing. Results: A gap consistently formed between the end of the repaired tendon and bone in this model, with reparative scar tissue and new bone spanning the gap. Magnetic resonance imaging showed that the volume of newly formed bone (p < 0.05) and soft tissue (p < 0.05) in the tendon-bone gap were greater in the growth factor-treated animals compared with the collagen sponge control group at both time-points. Histologic analysis showed a fibrovascular tissue in the interface between tendon and bone, with a more robust fibrocartilage zone between the bone and the tendon in the growth factor-treated animals. The repairs that were treated with the osteoinductive growth factors had significantly greater failure loads at six weeks and twelve weeks (p < 0.05); however, when the data were normalized by tissue volume, there were no differences between the groups, suggesting that the treatment with growth factor results in the formation of poor-quality scar tissue rather than true tissue regeneration. The repairs that were treated with the collagen sponge carrier alone had significantly greater stiffness than the growth factor-treated group at twelve weeks (p = 0.005). Conclusions: This model tests the effects of growth factors on scar tissue formation in a gap between tendon and bone. The administration of osteoinductive growth factors resulted in greater formation of new bone, fibrocartilage, and soft tissue, with a concomitant increase in tendon attachment strength but less stiffness than repairs treated with the collagen sponge carrier alone. Clinical Relevance: This study is the first, as far as we know, to demonstrate the possibility of increasing tissue formation in a tendon-bone gap with use of a biologic agent. It shows the importance of the use of magnetic resonance imaging to evaluate the repaired tendon, since the findings on gross observation and even histologic examination could easily be interpreted as representing an intact repair. Further studies with use of more clinically relevant models of tendon-bone repair may support the use of growth factors to improve clinical outcomes.