gms | German Medical Science

German Congress of Orthopedic and Trauma Surgery (DKOU 2017)

24.10. - 27.10.2017, Berlin

PARP-1 inhibition improves healing in a rat model of acute rotator cuff repair

Meeting Abstract

  • presenting/speaker Michael Künzler - Inselspital Bern, Departement für Orthopädie & Traumatologie, Bern, Switzerland
  • Matthias Zumstein - Inselspital Bern, Department of Orthopaedics and Traumatology, Bern, Switzerland
  • Michelle McGarry - University of California, Irvine, Orthopaedics Biomechanics Laboratory, Long Beach, United States
  • Masaki Akeda - University of California, Irvine, Orthopaedics Biomechanics Laboratory, Long Beach, United States
  • Hansel Ihn - University of California, Irvine, Orthopaedics Biomechanics Laboratory, Long Beach, United States
  • Brigitte von Rechenberg - University of Zurich, Musculoskeletal Research Unit, Zürich, Switzerland
  • Thay Q. Lee - University of California, Irvine, Orthopaedics Biomechanics Laboratory, Long Beach, United States

Deutscher Kongress für Orthopädie und Unfallchirurgie (DKOU 2017). Berlin, 24.-27.10.2017. Düsseldorf: German Medical Science GMS Publishing House; 2017. DocGR20-255

doi: 10.3205/17dkou552, urn:nbn:de:0183-17dkou5524

Published: October 23, 2017

© 2017 Künzler et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at http://creativecommons.org/licenses/by/4.0/.


Outline

Text

Objectives: 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 and Conclusion: 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.

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.