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

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Robertson CM, Chen CT, Shindle MK, Cordasco FA, Rodeo SA, & Warren RF (2012). Failed healing of rotator cuff repair correlates with altered collagenase and gelatinase in supraspinatus and subscapularis tendons. The American Journal of Sports Medicine, 40 (9), 1993-2001 PMID: 22896627