A biologic solution to the problem of tendon-to-bone healing in the rotator cuff remains elusive. The repair site may lack the cellular and/or molecular signals necessary to induce appropriate differentiation of transplanted cells. Further studies are needed to determine if cell-based strategies need to be combined with growth and differentiation factors to be effective.

Biologic augmentation of acutely injured rotator cuffs with Scx-transduced MSCs may improve rotator cuff tendon healing and reduce the incidence of re-tears. However, further studies are needed to determine if this remains safe and effective in larger models.

A histologically normal insertion site does not regenerate following rotator cuff tendon-to-bone repair, which is likely due to abnormal or insufficient gene expression and/or cell differentiation at the repair site. Techniques to manipulate the biologic events following tendon repair may improve healing. We used a sheep infraspinatus repair model to evaluate the effect of osteoinductive growth factors and BMP-12 on tendon-to-bone healing. Magnetic resonance imaging and histology showed increased formation of new bone and fibrocartilage at the healing tendon attachment site in the treated animals, and biomechanical testing showed improved load-to-failure. Other techniques with potential to augment repair site biology include use of platelets isolated from autologous blood to deliver growth factors to a tendon repair site. Modalities that improve local vascularity, such as pulsed ultrasound, have the potential to augment rotator cuff healing. Important information about the biology of tendon healing can also be gained from studies of substances that inhibit healing, such as nicotine and antiinflammatory medications. Future approaches may include the use of stem cells and transcription factors to induce formation of the native tendon-bone insertion site after rotator cuff repair surgery.

Modulation of MMP-13 activity after rotator cuff repair may offer a novel biological pathway to augment tendon-to-bone healing.

Biologic augmentation of repaired rotator cuffs with MT1-MMP-transduced MSCs may reduce the incidence of retears. However, further studies are needed to determine if this remains safe and effective in larger models.