Effects of Selective Paralysis of the Supraspinatus Muscle Using Botulinum Neurotoxin A in Rotator Cuff Healing in Rats Andreas Ficklscherer, 1 Tessa-Katharina Hartl, 1 Markus Scharf, 1 Birte Sievers, 1 Christian Schro ¨ der, 1 Stefan Milz, 2 Thomas Niethammer, 1 Matthias F. Pietschmann, 1 Peter E. Mu ¨ ller 1 1 Department of Orthopaedic Surgery, University Hospital of Munich (LMU)—Campus Grosshadern, Marchioninistr. 15, 81377 Munich, Germany, 2 Department of Anatomy, Ludwig-Maximilians-University of Munich, Munich, Germany Received 18 April 2012; accepted 11 October 2012 Published online 13 December 2012 in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/jor.22260 ABSTRACT: We hypothesized that a temporary rotator cuff paralysis using botulinum-neurotoxin A (BoNtA) would lead to an im- proved tendon-to-bone healing after repair of supraspinatus lesions. One hundred sixty Sprague–Dawley rats were randomly assigned to either the BoNtA or the control (saline) group. BoNtA/saline-solution was injected into the supraspinatus muscle 1 week prior to surgery. A supraspinatus defect was made; we distinguished between a lesion with normal and increased repair load. Furthermore, one subgroup had the operated shoulder immobilized in a cast. Histologic analysis and biomechanical testing followed. Specimens from the BoNtA-group, which were treated with an increased repair load, showed less cellularity and more organization in the interface tissue compared to the saline control group. In addition, we found that the collagen 1–3 quotient in the BoNtA specimen was significantly (p ¼ 0.0051) higher than in the control group. Ultimate load at failure between the groups was not significantly different (p > 0.05). We did not observe any significant differences between the mobilized and immobilized specimen (p ¼ 0.2079). The study shows that tendon-to-bone healing after rotator cuff repair can be altered positively using BoNtA pre-operatively. Tears with increased repair load seem to benefit the most—at least histologically. ß 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31:716–723, 2013 Keywords: rotator cuff tear; tendon-healing; biologic tendon repair; bioprotection; botulinum neurotoxin A Rotator cuff tears are one of the most common degen- erative diseases of the upper extremity and are seen in up to 30% of the population aged older than 65 years. 1,2 One can assume that the number of rotator cuff tears will continue to increase as the population grows older. Along with conservative treatment options, surgical procedures, ranging from open repair to arthroscopic rotator cuff repair techniques focused on increasing strength at the repair site in order to prevent re-rup- ture, have been further developed and evolved over the two decades. 3,4 These techniques demonstrate good short-term results in pain reduction and functional outcome. 5,6 However, several studies show that a high percentage of rotator cuff tears do not heal. 5–11 Because the healing process is influenced by a num- ber of factors, which to date have been reduced to the biomechanics of suture techniques, research now puts more attention on the biological aspects of tendon heal- ing to find ways of biologic augmentation to improve tendon-to-bone healing after rotator cuff repair. 2,12,13 Some recent studies suggest that one reason for the long-term failure of rotator cuff repair might be the preload of the tendon-bone-interface which is particu- larly increased in old and/or large tears. 14–16 Gimbel et al. 17 demonstrated in a chronic rotator cuff model in rats that the tension needed to reattach the supraspinatus tendon to the footprint increases with time after detachment and is positively correlated with failure. Davidson 14 concluded, after evaluating repair tension in 67 patients, that high-tension repairs are associated with poor subjective and objective out- comes. Lowering repair tension surgically however is limited in releasing adhesions and is subject to restrictions. Botulinum neurotoxin A (BoNtA), one of seven neu- rotoxin subtypes produced by the bacteria Clostridium botulinum, acts by binding presynaptically to high- affinity recognition sites on the cholinergic nerve ter- minals. It thereby decreases the release of acetylcho- line causing inhibition of neurotransmission resulting in muscle paralysis. BoNtA has the potential to tempo- rarily paralyze the rotator cuff muscle decreasing mus- cle tension and therefore lowering the tension at the tendon-to-bone healing site. To our knowledge, Tuzu- ner et al. 18 were the first to introduce BoNta as a neo- adjuvant in surgery as they induced forearm flexor paralysis in children less than 6 years old with zone 2 flexor tendon repairs. Tuzuner concluded that, due to a reduction in spontaneous activity of the fingers, a better rehabilitation was possible. Ma et al. 19 tried to protect a sutured Achilles tendon in an rat model with the use of BoNtA and found significantly better results in terms of rupture force 3 weeks after surgery in the BoNtA-groups. A study published by Galatz et al. 20 also showed an increase of mechanical properties in tendon healing after paralyzing the supraspinatus muscle. However, histologically the BoNtA-groups had inferior properties compared to the non-BoNtA control groups. In contrast, Hettrich et al. 21 found no differ- ence in mechanical properties but an increase in colla- gen fiber organization. Additional supporting information may be found in the online version of this article. None of the authors had professional or financial affiliations that biased the presentation. Grant sponsor: Association for Orthopaedic Research. Correspondence to: Andreas Ficklscherer (T: 0049-89-7095-0; F: 0049-89-7095-8881, E-mail: andreas.ficklscherer@med.uni-muenchen.de) ß 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. 716 JOURNAL OF ORTHOPAEDIC RESEARCH MAY 2013