Short summary

This is a prospective, randomized parallel armed, superiority study evaluating the effect of rotator cuff tear surgery of the supraspinatus tendon combined with injection of micro-fragmented tissue into the supraspinatus muscle (cell treatment group) compared to rotator cuff tear surgery only (standard care) . The primary endpoint is the change in the patient reported shoulder function twelve month after surgery assessed by the Oxford Shoulder Score.

Rationale

Rotator cuff tear (RCT) is a common shoulder disorder. The prevalence of RCTs among all age groups is around 34% according to data from the Danish National Patient Register. The tears lead to weakness, pain and reduced motility. The patients experience markedly reduced quality of life and they also pose a significant burden on the healthcare system. Premature withdrawal from the labour marked or exclusion from the workforce is imminent in these cases. The cause of rotator cuff tear is multifactorial. Acute trauma as well as chronic stress play a part in combination with inherent factors. In line with this, an age-associated risk is seen, as RCT is known to increase markedly after 50 years of age with a likelihood of 50% for people after the age of 60. Shoulder complaints are also associated with several types of occupational exposures. Thus work with the arms in a highly elevated position is associated with increased risk of ruptures of the rotator cuff tendons and shoulder symptoms is over-represented in house painters. When there is a total rupture of a tendon, it will not heal unless it is repaired surgically. However, surgery often fails to restore optimal function. Several studies indicate that degenerative changes in the damaged tendons and muscle could play a part in the suboptimal results of surgery. Initial non-surgical treatment may provide temporary pain relief but as mentioned no healing of the lesioned tendon occurs. A recent randomized study tested conventional primary tendon repair and physiotherapy in patients with small and medium-sized rotator cuff tears. The authors reported significant better results for primary tendon repair compared to conservative treatment. Normal function was not regained in any of the conservatively treated patients and in this group, tear size increased over the years. Besides, patients who crossed to secondary surgery due to failed conservative treatment experienced significantly inferior results compared to primary surgery. A strategy that includes primary tendon surgery is therefore meaningful, but with a need for additional treatment, that restores the function of the damaged rotator cuff muscle. Supraspinatus muscle biopsies from 33 patients treated at our hospital and undergoing rotator cuff repair demonstrated presence of myogenic stem cells. We also found significant variations in stem cell activation which seemed hampered according to patient age and also age of the tendon lesion (publication in press). Adipose derived mesenchymal cells are shown to support regeneration in many tissues and animal studies including our own indicates that injection of cultured adipose cells stimulates myogenesis by activating satellite cells in the torn supraspinatus muscle. Implantation of autologous micro-fragmented adipose tissue could therefore be a means for stimulation of myogenesis thereby improving the results of surgical treatment of rotator cuff lesions. The aim of the project is to examine if treatment of shoulder muscle with implantation of micro-fragmented adipose tissue can improve the results of the standard surgical treatment of rotator cuff lesions.

Description of the cohort

Patients referred to the orthopaedic department of Hospital Sønderjylland with clinical signs of a traumatic rotator cuff tear, a clinical MRI scan showing a rotator cuff tear and who fulfil all the inclusions criteria will be informed about the study. Written as well as oral information about the study will be provided by the surgeon responsible for the study in the outpatient clinic. INCLUSION CRITERIA -Age 40-69 years of age -Clinical signs and symptoms compatible with a traumatic RCT -MR verified supraspinatus tear -Reparable lesion with tendon retraction < 2 cm. -Fatty infiltration level 0-2 (out of 5) according to Fuchs et al (ref 25) and based on Goutalliers classification28 -No history of inflammatory disease -ASA score < 3 (patients in good health) -Signed consent to the study (including use of relevant data from the patient's electronic health records) EXCLUSION CRITERIA -No MRI of the shoulder -Former surgery in the affected shoulder -Signs of infection -Immunosuppression (due to clinical condition or medical therapy) -Malignancy within 5 years -Previous radiotherapy to the shoulder -BMI under 18 -BMI above 35 -Coagulopathy -Non-Danish speaking patients

Data and biological material

-Oxford Shoulder Score questionnaire -EQ5D questionnaire including the VAS-scale -Clinical healing defined as pain-free movement above shoulder level will be reported - Radiological healing 6 and 12 month post-surgery (muscle atrophy and fatty infiltration) defined as closure of the gap between the tendon and the greater tuberosity that serves as the attachment for rotator cuff muscles assessed by MRI. - A functioning supraspinatus muscle with improved muscle strain recorded be speckle tracking ultrasonography Biobank: During the study period acquired biological materials from participating patients, will be registered and stored in the research biobank at the Department of Clinical Pathology, OUH, according to current legislations and requirements. The material include aliquots of freshly isolated micro fragmented adipose tissue products and processed products hereof to enable analyses and comparisons with clinical efficacy. After the study is completed stored materials is transferred to a biobank for future research.

Collaborating researchers and departments

Orthopaedic Research Unit. Dept. of Regional health Research and Institute of Molecular Medicine, University of Southern Denmark

• Postdoc Eva Kildall Hejbøl
• Professor Henrik Daa Schrøder

OUH-CELL-BENCH, Clinical Biochemistry, Odense University Hospital OUH.

• Professor Ditte Caroline Andersen