|Beitragstitel||PARP-1 Inhibition Improves Healing in a Rat Model of Acute Rotator Cuff Repair|
Introduction: Repair of rotator cuff tears (RCT) have a high retear rate due to the formation of mechanical inferior scar tissue during the healing period and so far there is no way to improve it therapeutically. We hypothesized that PARP-1 inhibition improves biomechanical and histological properties of the repair in a rat model of acute rotator cuff repair.
Methods: 24 Sprague Dawley rats were randomly allocated into an Inhibitor and Control group (n = 12 each). In all rats the tendon of the supraspinatus muscle was sharply detached from its insertion at the humeral head and immediately repaired with a single transosseous suture. Starting one day prior to surgery the rats of the Inhibitor group received 12.5mg/kg/d Veliparib in their drinking water (ABT-888, APExBio, TX, USA), which continued during the recovery period. The water uptake was monitored to assure accurate uptake of the inhibitor. The animals were sacrificed 8 weeks after surgery and analyzed utilizing macroscopic, biomechanical and histological methods.
Results: Macroscopically the SSP muscles of the Inhibitor group had a significantly higher cross sectional area at their midsubstance (p=0.034). In total the Inhibitor group had a significantly better histological grading of the longitudinal joint sections than the Control group (p=0.022) with less scar tissue formation and a tendency to better formation of the neo-entheses, less vascularity of the tendon and better tendon organization. Muscle fiber diameter in the quadrant with high mechanical demand was significantly higher in the Inhibitor group (p=0.0004). During biomechanical testing most of the specimens in the Inhibitor group failed in the tendon midsubstance (n=4/6), whereas most of the Controls failed at the entheses (n=4/6). The differences in yield load, stiffness, energy absorbed to failure and ultimate load did not reach statistical significance.
Conclusion: Inhibition of PARP-1 activity leads to a better histological healing of the RCT repair, which leads to failure at the tendon midsection during biomechanical testing; in addition, it leads to both higher histological muscle fiber cross-section and higher macroscopical muscle diameter. Although biomechanical properties were not significantly different between the groups due to being underpowered, the PARP-1 inhibitor group showed a general trend of improvement. Taken together we conclude that PARP-1 inhibition is beneficial for the healing after acute rotator cuff repair.