The goal of this clinical trial is to learn whether platelet-rich plasma (PRP) injection, made from a participant's own blood, can help heal the tendon and improve shoulder symptoms in people with partial tears of the supraspinatus tendon.

The main questions it aims to answer are:

• Does PRP help the tendon heal?
• Does PRP improve pain, shoulder movement, daily function, and shoulder magnetic resonance imaging (MRI) findings?

Researchers will compare PRP plus standard of care (physical therapy) to standard of care alone to see if PRP leads to better healing and better clinical results. Researchers will also study if differences in specific biomolecules in PRP are associated with differences in treatment response.

Participants will:

• receive standard of care treatment, with or without PRP injection depending on the study group
• have blood collected for PRP preparation
• have their pain, shoulder movement, and shoulder function assessed
• undergo shoulder MRI scans
• be followed over time to measure healing and symptom improvement

Purpose and rationale:

Rotator cuff injuries are common musculoskeletal injuries and among the most frequent causes of shoulder pain and disability. The mechanisms underlying tendon repair are complex and are promoted by local cell activation, cell migration and proliferation, pro- and anti-inflammatory cytokines and growth factors, extracellular matrix production and reorganization. Growth factors are a key element of tissue regeneration and healing, and several growth factors/cytokines have been applied in osteoarticular conditions, in both animal and human studies. Platelet-rich plasma (PRP) is a platelet concentrate produced from autologous blood sample manipulation that is abundant in growth factors and cytokines with potential regenerative capabilities. The role of PRP in several osteoarticular conditions has been established, but controversy remains in shoulder applications, with recent evidence of benefits in shoulder augmentation surgery for rotator cuff repair. Our study evaluates the performance of autologous PRP injection in partial rotator cuff tears for tendon regeneration as an adjuvant to the standard of care treatments, the relationship of PRP growth factor/cytokine content with clinical efficacy and imaging findings that may predict clinical decision-making, prognostication and treatment response.

Hypothesis and objectives The study hypothesis is that PRP promotes tendon regeneration and clinical improvement in participants with partial supraspinatus tears when added to standard rehabilitation care.

The primary objective is to evaluate the impact of PRP on tendon regeneration and clinical improvement in participants with partial supraspinatus tears, in addition to standard rehabilitation care.

Secondary objectives are:

1. Evaluate the clinical outcome and imaging changes in patients with partial supraspinatus tears after PRP administration compared to rehabilitation therapy alone;
2. Evaluate imaging biomarkers for clinical decision-making in patients with partial supraspinatus tears, as well as prognostic and treatment response;
3. Study the role of different cytokines, growth factors, platelet and leucocyte concentrations in rotator cuff tendon regeneration and clinical outcome after PRP administration;
4. Study the concentration and patient-to-patient variability of different cytokines and growth factors as well as platelet and leucocyte concentration in PRP formulations.

Study design This is a prospective randomized clinical study with two main pathways and one laboratory component. Participants with clinically and radiologically confirmed partial supraspinatus tendon tears will be recruited after diagnostic evaluation and informed consent. Randomization will be performed after confirmation of eligibility using a computerized minimization algorithm to ensure balance between study groups by sex. Allocation will be implemented by an independent investigator using a secure centralized system.

All participants will receive a standard home-based exercise programme within a rehabilitation protocol. Clinical follow-up will be performed at baseline, 1 month, 3 months, 6 months, 12 months, and 24 months after inclusion, or PRP injection as applicable. Magnetic resonance imaging (MRI) will be performed at baseline during diagnosis and at 3 and 12 months after inclusion.

Task 1: Standard rehabilitation care In Task 1, participants with partial rotator cuff tears will undergo conservative management with physical therapy. The aim of this pathway is to evaluate the clinical course and imaging evolution of participants treated with standard rehabilitation care alone.

Conservative management rehabilitation protocol

A specific rehabilitation protocol is employed by the Sports Medicine team, and is as follows:

In-person session frequency: 2x/week (1st month), 1x/week (2nd month), 2 sessions (3rd month) Total number of sessions: 14 Total duration: 12 weeks Progression criteria: tolerable pain (≤3/10 during exercise, with no worsening lasting >24 h)

In-person sessions:

Each session ~45-60 minutes Warm-up (5-10 min mobility exercises + light resistance band) Main strengthening exercises (20-30 min) Final stretching exercises Patient education and load progression

Rehabilitation Exercise Protocol: MOON Shoulder Group

Outcome measures for this task include clinical and imaging evaluation of the target shoulder, including symptoms, pain duration, traumatic etiology, sleep disturbance, pain intensity measured by the Visual Analog Scale (VAS), pain intensity in the non-target shoulder, Subjective Shoulder Value (SSV), Constant-Murley (CM) score, ultrasound findings, MRI findings, and standard-of-care treatment received.

Task 2: PRP plus standard rehabilitation care In Task 2, participants will undergo percutaneous PRP administration in addition to physical therapy. Autologous PRP will be prepared from peripheral blood collected on the day of injection. A defined volume of freshly prepared PRP (2mL) will be injected at or near the supraspinatus tendon tear within seconds after preparation, and a remaining aliquot will be reserved for cellular and molecular analysis. After injection, the patient will remain for a 30-minute observation period to exclude potential immediate complications, such as fever, chills, pruritus or vaso-vagal reaction. The patient is advised to rest for the first 48h after injection, and use of NSAIDs is prohibited. Participants will be advised to apply an ice pack during the first week after injection. Rescue analgesia with paracetamol 500 mg or paracetamol 375 mg plus tramadol 125 mg up to three times daily will be allowed when needed. Analgesic and anti-inflammatory medication use, including frequency and amount, will be recorded during the first 3 weeks after intervention. Participants will also complete a dedicated 3-month physical rehabilitation programme. Adverse events will be recorded throughout follow-up.

Outcome measures for this task include PRP preparation and administration parameters, including time to injection, extracted and injected dose, injection site, operator, discharge status, complications, time to analysis, cell count, growth factor and cytokine concentrations, pH, and fibrinogen levels. Clinical and imaging evaluation of the target shoulder will also be performed, including symptoms, pain duration, traumatic etiology, sleep disturbance, pain intensity assessed by VAS in both the target and non-target shoulder, SSV, CM score, ultrasound findings, MRI findings, and standard-of-care treatment received.

Task 3: PRP composition and biomarker analysis Task 3 is intended to evaluate the relationship between PRP composition and tendon regeneration or clinical improvement, through detection of interindividual variability in PRP products. After PRP preparation, a small aliquot of each sample will be stored for analysis of cellular composition, pH, fibrinogen, growth factors, and cytokines. These laboratory results will be compared with clinical and imaging outcomes. Samples for cellular quantification will be analysed within 4 hours of preparation. Cell counts and leukocyte subset characterization will be performed by flow cytometry. For molecular analysis, aliquots will be stored at -80°C until batch analysis using bead-based flow assay kits for simultaneous quantification of multiple analytes in a single sample.

Cellular outcomes will include platelet count, white blood cell count, lymphocyte count, monocyte count, neutrophil count, pH, and fibrinogen. Molecular outcomes will include concentrations of vascular endothelial growth factor (VEGF), platelet-derived growth factor AA (PDGF-AA), platelet-derived growth factor BB (PDGF-BB), transforming growth factor beta 1 (TGF-β1), epidermal growth factor (EGF), and fibroblast growth factor (FGF), as well as interleukin-1 receptor antagonist (IL-1Ra), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), interleukin-10 (IL-10), and interferon gamma (IFN-γ).

Clinical management and contingency plan Participants allocated to conservative treatment will complete a 3-month rehabilitation period, after which treatment response will be reassessed. Treatment failure will be defined as less than a 2-point reduction in VAS pain score and/or less than a 12-point improvement in CM score. In cases of unsuccessful conservative treatment, alternative therapeutic options will be proposed according to best clinical practice.

Inclusion Criteria:

• Eligible patients are at least 18 years old, and have clinical (VAS pain score ≥4, loss of >25% in ROM, positive in at least one clinical test such as Jobe, Neer, Drop arm, Hawins-Kennedy, Patte) and imaging findings compatible with partial supraspinatus tear, within 3 months of diagnosis.
• Patients may have undergone conservative treatments, including lifestyle modification, oral analgesics, or physical therapy, with the exception of shoulder injections.
• Must be willing to provide consent.

Exclusion Criteria:

• Patients less than 18 years old
• Patients with other or concomitant rotator cuff or shoulder muscle/tendon tear(s), complete tears, SLAP tears ≥ grade 2
• Patients with auto-immune based joint diseases, osteoarthritis (KL grade ≥ 2), adhesive capsulitis, infection, nerve-related conditions, immunocompromised conditions, malignancy, coagulopathy
• Patients on antiplatelet, anticoagulant, antitumor or immunosuppressive drugs
• Uncontrolled diabetes, other systemic disorders (hepatitis, rheumatoid arthritis)
• Pregnancy
• Shoulder instability
• Previous shoulder injection or surgery
• Unwillingness to provide informed consent

Physical therapists, radiologists and data collecting personnel will be blinded