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Background: While platelet-rich plasma (PRP) has been widely studied for musculoskeletal disorders, few studies to date have reported its use for adhesive capsulitis (AC). Fully characterized and standardized allogenic PRP may provide clues to solve the underlying mechanism of PRP with respect to synovial inflammation and thus may clarify its clinical indications. Purpose: To clinically evaluate the safety and efficacy of a fully characterized pure PRP injection in patients with AC and to assess the effects of pure PRP on synoviocytes with or without inflammation in vitro. Study Design: Controlled laboratory study and cohort study; Level of evidence, 3. Methods: For the clinical analysis, a total of 15 patients with AC received an ultrasonography-guided intra-articular PRP injection and were observed for 6 months. Pain, range of motion (ROM), muscle strength, shoulder function, and overall satisfaction in the patients were evaluated using questionnaires at 1 week as well as at 1, 3, and 6 months after the PRP injection and results were compared with the results of a propensity score−matched control group that received a corticosteroid injection (40 mg triamcinolone acetonide). For the in vitro analysis, synoviocytes were cultured with or without interleukin-1β (IL-1β) and PRP. The gene expression of proinflammatory and anti-inflammatory cytokines as well as matrix enzymes and their inhibitors was evaluated. Results: At 6-month follow-up, pure PRP significantly decreased pain and improved ROM, muscle strength, and shoulder function to levels comparable with those after a corticosteroid injection. All pain values, strength measurements, and functional scores significantly improved up to 6 months in the PRP group, but these measures improved up to 3 months and then were decreased at 6 months in the corticosteroid group. ROM was significantly improved in the 2 groups at 6 months compared with baseline. Allogenic PRP did not cause adverse events. For the in vitro findings, PRP induced inflammation but significantly improved the IL 1β−induced synovial inflammatory condition by decreasing proinflammatory cytokines such as IL-1β, tumor necrosis factor−α, IL-6, cyclooxygenase-2, and microsomal prostaglandin E synthase−1 and decreased matrix enzymes (matrix metalloproteinase−1, −3, and −13 as well as a disintegrin and metalloproteinase with thrombospondin motifs−4 and −5) and further increasing anti-inflammatory cytokines such as vasoactive intestinal peptide. Conclusion: This study showed that PRP decreased pain and improved shoulder ROM and function to an extent comparable with that of a corticosteroid in patients with AC. Allogenic pure PRP acted in a pleiotropic manner and decreased proinflammatory cytokines only in the inflammatory condition. Clinical Relevance: Allogenic PRP could be a treatment option for the inflammatory stage of AC.

Background: Although platelet-rich plasma (PRP) is a popular option for rotator cuff disease, the underlying mechanism of PRP and its clinical indications are unclear. Further, some kinds of PRP might be detrimental to patients. Allogenic PRP prepared through a standardized process and fully characterized could eliminate variations in PRP as well as uncertainties regarding its use in each patient, which could provide clues about its mechanism of action and indications for its use. Purpose: To assess the effects of pure PRP on tenocytes with or without inflammation in an in vitro study and to evaluate the safety and efficacy of a fully characterized pure PRP injection in patients with rotator cuff disease in a clinical study. Study Design: Controlled laboratory study and cohort study; Level of evidence, 3. Methods: For the in vitro study, tenocytes were enzymatically isolated and cultured from patients with rotator cuff tear and treated with or without interleukin 1β (IL-1β) and PRP. Gene expression and protein synthesis of pro- and anti-inflammatory cytokines, enzymes and their inhibitors, matrix synthesis, and cell viability were evaluated. For the clinical study, a total of 17 patients with rotator cuff disease received ultrasonography-guided subacromial PRP injection and were followed for 6 months. Pain, range of motion, muscle strength, shoulder function, and overall satisfaction in patients were compared with the results in a propensity score–matched control group who received corticosteroid (triamcinolone acetonide 40 mg). Results: PRP induced inflammation in the absence of inflammation and ameliorated inflammation in IL-1β-induced tendinopathic conditions by regulation of cytokines such as IL-1β, cyclooxygenase 2, microsomal prostaglandin E synthase 1, vasoactive intestinal peptide, and downstream matrix metalloproteinases. No general or local adverse events were noted with regard to allogenic PRP injection. Whereas steroid injection showed earlier improvement in some kinds of pain and functional scores, PRP generally showed comparable effects with steroid injection in all clinical outcomes at 6 months. Conclusion: This study showed that allogenic pure PRP had pleiotropic effects on tenocytes depending on inflammation and that it did not cause adverse events but rather decreased pain and improved shoulder function to a degree comparable with steroid injection in patients with rotator cuff disease. Clinical Relevance: Allogenic PRP could be a treatment option for rotator cuff disease.

Background: A corticosteroid injection is commonly used to treat tendinopathy, but it has been associated with negative effects on tendon homeostasis. Platelet-rich plasma (PRP) is known to have proliferative and anabolic effects as well as cytoprotective effects against corticosteroids on tenocytes. However, the combined effects of a corticosteroid and PRP on the anti-inflammatory, matrix synthesis, and cytoprotective potential of tenocytes in conditions simulating tendinopathy have not been investigated. Purpose: To assess the effects of PRP on tenocytes from degenerative rotator cuff tears with the concomitant use of a corticosteroid in interleukin 1β (IL-1β)–induced tendinopathic conditions. Study Design: Controlled laboratory study. Methods: Tenocytes were enzymatically isolated and cultured from patients with degenerative rotator cuff tears. PRP was prepared using a plateletpheresis system, and growth factor concentrations were measured. To evaluate the gene expression of proinflammatory and anti-inflammatory cytokines, enzymes and their inhibitors, and matrix molecules, cells were cultured with 1 ng/mL IL-1β, 1 μM dexamethasone, and 10% (vol/vol) platelet-poor plasma (PPP) and PRP of 200, 1000, and 4000 × 103/μL; quantitative real-time reverse transcriptase polymerase chain reaction was also performed. Western blotting was performed to investigate the protein synthesis of degradative enzymes and their inhibitors. Cell viability, apoptosis, and senescence assays were also conducted. Results: PRP did not interfere with the anti-inflammatory effects of dexamethasone on tenocytes pretreated with IL-1β, but it increased the synthesis of tissue inhibitor of metalloproteinase (TIMP)–1 and -3. Meanwhile, PRP did not induce anti-inflammatory cytokines that had been suppressed with a corticosteroid. It did increase the type I/III collagen ratio mainly through the suppression of type III collagen expression. PRP reversed the decreased viability, increased apoptosis, and induced senescence with IL-1β and a corticosteroid. Conclusion: This study shows that the addition of PRP does not interfere with the anti-inflammatory effects of a corticosteroid on IL-1β–treated tenocytes from degenerative rotator cuff tears but that it does avoid the deleterious side effects of a corticosteroid. Clinical Relevance: PRP can be clinically useful with a corticosteroid as a treatment for tendinopathy.

Platelet-rich plasma (PRP) is expected to have a biological augmentation potential in the healing of various diseases and injuries, including rotator cuff tears. However, few evaluations have been performed specifically for large to massive tears.To assess the efficacy of PRP augmentation in patients undergoing arthroscopic repair for large to massive rotator cuff tears.Randomized controlled trial; Level of evidence, 1.A total of 48 patients scheduled for arthroscopic repair of large to massive rotator cuff tears were randomly assigned to receive either PRP-augmented (PRP group) or conventional treatment (conventional group). In the PRP group, 3 PRP gels (3 × 3 mL) were applied to each patient between the torn end and the greater tuberosity. The primary outcome measure was the retear rate assessed by magnetic resonance imaging (MRI) or computed tomographic arthrography (CTA) at a minimum of 9 months after surgery. Secondary outcome measures included pain, range of motion, muscle strength, overall satisfaction, functional scores, and the change in cross-sectional area (CSA) of the supraspinatus.The retear rate of the PRP group (20.0%) was significantly lower than that of the conventional group (55.6%) (P = .023). Clinical outcomes showed no statistical difference between the 2 groups (all P.05) except for the overall function (P = .043). The change in 1-year postoperative and immediately postoperative CSA was significantly different between the 2 groups: -15.54 ± 94.34 mm² in the PRP group versus -85.62 ± 103.57 mm² in the conventional group (P = .047).The application of PRP for large to massive rotator cuff repairs significantly improved structural outcomes, as evidenced by a decreased retear rate and increased CSA of the supraspinatus compared with repairs without PRP augmentation. While there was no significant difference in clinical outcomes except the overall shoulder function after 1-year follow-up, better structural outcomes in the PRP group might suggest improved clinical outcomes at longer term follow-up.

Background: Two main questions about the use of platelet-rich plasma (PRP) for regeneration purposes are its effect on the speed of healing and the quality of healing. Despite recent numerous studies, evidence is still lacking in this area, especially in a representative patient population with medium to large rotator cuff tears. Purpose: To assess the efficacy of PRP augmentation on the speed and quality of healing in patients undergoing arthroscopic repair for medium to large rotator cuff tears. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: A total of 74 patients scheduled for arthroscopic repair of medium to large rotator cuff tears were randomly assigned to undergo either PRP-augmented repair (PRP group) or conventional repair (conventional group). In the PRP group, 3 PRP gels (3 × 3 mL) were applied to each patient between the torn end and the greater tuberosity. The primary outcome was the Constant score at 3 months after surgery. Secondary outcome measures included the visual analog scale (VAS) for pain, range of motion (ROM), muscle strength, overall satisfaction and function, functional scores, retear rate, and change in the cross-sectional area (CSA) of the supraspinatus muscle. Results: There was no difference between the 2 groups in the Constant score at 3 months ( P > .05). The 2 groups had similar results on the VAS for pain, ROM, muscle strength, overall satisfaction and function, and other functional scores (all P > .05) except for the VAS for worst pain ( P = .043). The retear rate of the PRP group (3.0%) was significantly lower than that of the conventional group (20.0%) ( P = .032). The change in 1-year postoperative and immediately postoperative CSAs was significantly different between the 2 groups: –36.76 ± 45.31 mm2 in the PRP group versus −67.47 ± 47.26 mm2 in the conventional group ( P = .014). Conclusion: Compared with repairs without PRP augmentation, the current PRP preparation and application methods for medium to large rotator cuff repairs significantly improved the quality, as evidenced by a decreased retear rate and increased CSA of the supraspinatus, but not the speed of healing. However, further studies may be needed to investigate the effects of PRP on the speed of healing without risking the quality.

Background: Platelet-rich plasma (PRP) has been recently used to enhance and accelerate the healing of musculoskeletal injuries and diseases, but evidence is still lacking, especially on its effects after rotator cuff repair. Hypothesis: Platelet-rich plasma accelerates recovery after arthroscopic rotator cuff repair in pain relief, functional outcome, overall satisfaction, and enhanced structural integrity of repaired tendon. Study Design: Cohort study; Level of evidence, 2. Methods: Forty-two patients with full-thickness rotator cuff tears were included. Patients were informed about the use of PRP before surgery and decided themselves whether to have PRP placed at the time of surgery. Nineteen patients underwent arthroscopic rotator cuff repair with PRP and 23 without. Platelet-rich plasma was prepared via plateletpheresis and applied in the form of a gel threaded to a suture and placed at the interface between tendon and bone. Outcomes were assessed preoperatively and at 3, 6, 12, and finally at a minimum of 16 months after surgery (at an average of 19.7 ± 1.9 months) with respect to pain, range of motion, strength, and overall satisfaction, and with respect to functional scores as determined using the following scoring systems: the American Shoulder and Elbow Surgeon (ASES) system, the Constant system, the University of California at Los Angeles (UCLA) system, the Disabilities of the Arm, Shoulder and Hand (DASH) system, the Simple Shoulder Test (SST) system, and the Shoulder Pain and Disability Index (SPADI) system. At a minimum of 9 months after surgery, repaired tendon structural integrities were assessed by magnetic resonance imaging. Results: Platelet-rich plasma gel application to arthroscopic rotator cuff repairs did not accelerate recovery with respect to pain, range of motion, strength, functional scores, or overall satisfaction as compared with conventional repair at any time point. Whereas magnetic resonance imaging demonstrated a retear rate of 26.7% in the PRP group and 41.2% in the conventional group, there was no statistical significance between the groups ( P = .388). Conclusion: The results suggest that PRP application during arthroscopic rotator cuff repair did not clearly demonstrate accelerated recovery clinically or anatomically except for an improvement in internal rotation. Nevertheless, as the study may have been underpowered to detect clinically important differences in the structural integrity, additional investigations, including the optimization of PRP preparation and a larger randomized study powered for healing rate, are necessary to further determine the effect of PRP.