Failed Healing of Rotator Cuff Repair Correlates with Altered Collagenase and Gelatinase in Supraspinatus and Subscapularis Tendons
Robertson C, Chen CC, Shindle MK, Cordasco FA, Rodeo SA, Warren RF. Am J Sports Med 2012 Sep;40(9):1993-2001. Epub 2012 Aug 15.
Rotator cuff tears are a common cause of shoulder pain and disability. Surgical repair is often recommended in an attempt to reduce pain and restore function. Unfortunately, recurrent defects often persist (20-94% of cases) due to failure of the rotator cuff to heal. Several biologic and environmental factors have been implicated as important to tendon healing and remodeling; therefore, their presence (or lack thereof) may be critical when repairing torn rotator cuff tendons. The objective of this study was to identify histological characteristics and biologic factors present in the torn rotator cuff prior to repair and determine their relationship to tissue healing following repair. Thirty five patients with rotator cuff disease (>35 years of age, tear isolated to supraspinatus, no chronic oral anti-inflammatory use, no corticosteroid injection within 3 months, no prior surgery) underwent a biopsy of four locations: torn supraspinatus edge (most diseased portion), subacromial bursa, synovium (area of rotator interval), and intact subscapularis tendon (control). These tissues were extracted and collagen organization, cellularity, vascularity, and the expression of pro-inflammatory, remodeling, and angiogenic factors were evaluated. Post-operative ultrasound was used to evaluate healing of the rotator cuff. A linear model (designed to predict tendon healing) was applied to determine if the tendon biology relates to tendon healing. Seven patients (23%) had failed healing of the rotator cuff (defect group). Both groups (healed and defect) showed improvement in the American Shoulder and ElbowSurgeons (ASES) shoulder score (collected at baseline and follow-up) with no difference between groups. Results showed an increase in degradation factors (MMP-1 and MMP-9) and a decrease in the proteoglycan, biglycan, and altered expression of collagen I and III (both indicative of increased tissue remodeling), in the supraspinatus tendon of the defect group compared to the healed group. No differences in pro-inflammatory or angiogenic factors were identified. Interestingly, increased degradation factors were also found in the uninjured subscapularis tendon of the defect group compared to the healed group. Bursal tissue showed an increase in COX-2 (an enzyme associated with inflammation and pain) and the synovium showed increased pro-inflammatory cells, vascularity, and synovial thickening in the defect group. Additionally, there was a strong relationship between increased expression of degradation factors and failed healing of the rotator cuff.
This study demonstrates that degradation factors (MMP-1 and MMP-9) were increased in rotator cuff tendons that failed to heal compared to those that healed. These factors were also strong predictors of failed healing of the rotator cuff. MMP-1, a collagenase, is effective in degrading collagen, a primary component of tendons and important in remodeling and repair, while MMP-9, a gelatinase, is effective in degrading collagen fragments. Overexpression of these genes at the time of surgery may increase the likelihood of repair failure. Interestingly, degradation factors were also increased in the adjacent subscapularis tendon and degenerative changes were observed in the bursa and synovium in the defect group, suggesting the presence of a “global degenerative process” in the joint. The entire synovial environment may be compromised (in addition to the torn cuff tendon) which may place the joint at a higher risk for injury. Therefore, interventions targeting the shoulder joint as a whole, in addition to the torn tendon, may be warranted. Previous studies have shown that degradation factors can be controlled by mechanical stresses (i.e. activity level). It is possible that pre-surgical conservative treatment strategies targeting specific stretching and mobilization protocols may be useful in preventing further degeneration of the torn tendon and overall joint; however, future research is necessary in order to identify optimal loading regimens before definitive recommendations could be made. How might our understanding of the joint’s biologic environment improve treatment strategies for patients? Does anyone do pre-surgical rehabilitation prior to rotator cuff repair to improve tendon healing?
Written by: Katherine Reuther
Reviewed by: Stephen Thomas