A Midterm Evaluation of Postoperative Platelet-Rich Plasma Injections on Arthroscopic Supraspinatus Repair: A Randomized Controlled Trial

Abstract

Background:

Platelet-rich plasma (PRP) has been applied as an adjunct to rotator cuff repair to improve tendon-bone healing and potentially reduce the incidence of subsequent tendon retears.

Purpose:

To investigate whether the midterm clinical and radiographic outcomes of arthroscopic supraspinatus repair are enhanced after repeated postoperative applications of PRP.

Study Design:

Randomized controlled trial; Level of evidence, 1.

Methods:

A total of 60 patients (30 control; 30 PRP) were initially randomized to receive 2 ultrasound-guided injections of PRP to the tendon repair site at 7 and 14 days after double-row arthroscopic supraspinatus repair or not. A total of 55 patients (91.7%) underwent a clinical review and magnetic resonance imaging (MRI) at a mean of 3.5 years after surgery (range, 36-51 months). Patient-reported outcome measures (PROMs) included the Constant score, Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH) questionnaire, Oxford Shoulder Score (OSS), and visual analog scale (VAS) for pain. Global rating of change (GRC) scale and patient satisfaction scores were evaluated. Structural integrity of the surgical repair was assessed via MRI using the Sugaya classification system.

Results:

At the midterm review, there was no difference between the groups for any of the PROMs. No differences between the groups were demonstrated for the subjective and range of motion subscales of the Constant score, although a significantly higher Constant strength subscale score was observed in the PRP group (3.3 points; 95% CI, 1.0-5.7; P = .006). There was no evidence for any group differences in MRI scores or retear rates, with 66.7% of PRP patients and 64.3% of control patients rated as Sugaya grade 1. Two control patients had symptomatic retears (both full thickness) within the first 16 weeks after surgery compared with 2 PRP patients, who suffered symptomatic retears (both partial thickness) between 16 weeks and a mean 3.5-year follow-up.

Conclusion:

Significant postoperative clinical improvements and high levels of patient satisfaction were observed in patients at the midterm review after supraspinatus repair. While pain-free, maximal abduction strength was greater in the midterm after PRP treatment, repeated applications of PRP delivered at 7 and 14 days after surgery provided no additional benefit to tendon integrity.

Keywords

platelet-rich plasma rotator cuff repair arthroscopic surgery tendon healing clinical outcomes magnetic resonance imaging

After rotator cuff repair, tendon retear rates of 25% to 94% have been reported.^15,19,27,30 It has also been reported that rotator cuff tears can be observed in otherwise asymptomatic shoulders,^59,61 and postoperative surgical failure may still result in clinical outcomes that remain significantly better than preoperative states.⁴⁵ Nevertheless, the underlying rationale of rotator cuff repair is to restore structural integrity, and functional outcomes have been correlated with postoperative integrity of the rotator cuff.⁷ Surgical failure may be influenced by a range of factors including patient age, body mass, other systemic diseases, smoking and physical activity history, tear size, tear type, tear location and surgical technique employed, tendon quality, fatty infiltration, degree of tendon retraction and chronicity of the tear, previous and/or concomitant surgery, and postoperative rehabilitation.^# Tendon retears may occur early because of incomplete or failed initial healing after surgery or later because of a specific reinjury of the repaired rotator cuff tendon.^7,9 A number of adjunctive biological therapies have been employed to improve the quality of early tendon healing and potentially to also reduce the incidence of late tendon retears.

Platelet-rich plasma (PRP), which delivers a concentrated dose of growth factors, has now been studied extensively for its potential benefit on rotator cuff repair. While the cascade of physiological events that occurs as a result of PRP has been well reported,^41,52,65 the underlying aim is to enhance the quality of the repair at the tendon-bone interface. A number of systematic reviews and meta-analyses have suggested that PRP applied at the time of rotator cuff repair does not significantly improve clinical outcomes^{8,11,57,63,66,71} but may improve structural healing in small to moderately sized tears.^8,57,63 To date, clinical studies on PRP and rotator cuff repair have generally reported short-term outcomes. Apart from one study that followed patients to a mean of 31 months³ and several following patients to 24 months,^{2,12,25,37,49,52,53} the remaining studies only reported a short-term follow-up of ≤12 months.** Should a benefit exist in creating a more robust repair and therefore creating a tendon that is more resistant to future reinjuries, then randomized controlled trials (RCTs) with a longer term follow-up are essential to evaluate the full potential benefit of PRP.

In a previous study, we demonstrated that early tendon-bone healing and functional recovery after double-row arthroscopic supraspinatus tendon repair were not enhanced by repeated PRP injections administered at 7 and 14 days after surgery.⁶⁵ However, given that PRP may condition the rotator cuff to create a more robust healing process, thereby protecting against longer term tendon retears, further research is warranted. The present study reports the midterm clinical and radiographic outcomes of this RCT. We hypothesized that clinical outcomes would not differ between the PRP and control groups at midterm follow-up, although the incidence of tendon retears would be significantly less in the PRP group evaluated via magnetic resonance imaging (MRI).

Methods

Patients

A randomized study design was initially employed to allocate 60 patients to either double-row arthroscopic supraspinatus repair alone or repair followed by 2 ultrasound-guided PRP injections at the tendon repair site at days 7 and 14 after surgery (Figure 1).⁶⁵ Preoperatively, all patients had a symptomatic full-thickness tear of the supraspinatus confirmed on MRI, while plain films were obtained to evaluate arthritic changes. As previously reported, patients were excluded from study participation if they had undergone prior rotator cuff surgery or had glenohumeral joint osteoarthritis; contralateral shoulder symptoms; known rheumatological, neuromuscular, or autoimmune diseases; cervical disc herniation; or ongoing workers’ compensation claims. Furthermore, patients were excluded if labral, subscapularis, and/or infraspinatus tears were identified on preoperative MRI or at the time of arthroscopic surgical repair. Initially, an a priori power calculation was performed, demonstrating that 56 participants (28 in each group) were required to reveal differences at the 5% significance level, with 80% power and employing a moderate effect size (0.769), based on the ability to detect a significant difference of 1 Sugaya grade between the groups on MRI. Randomization was undertaken at 5 days after surgery via a computer block permutation method.⁶⁵ Ethics approval was obtained by St John of God Health Care (Ref: 848).

Surgical Management

The double-row arthroscopic supraspinatus tendon repair procedure, performed by the senior author (A.W.), has been previously described.⁶⁵ Briefly, surgery was performed in the lateral decubitus position under general anesthesia and an interscalene nerve block. With the arm in 30° of shoulder flexion and abduction and under 4 kg of traction, glenohumeral arthroscopic surgery was initially performed to investigate the joint and confirm the presence and type of full-thickness supraspinatus tearing, which was measured using a calibrated probe. Tears >20 mm in the anteroposterior dimension were excluded, as were partial tears and concomitant subscapularis and/or infraspinatus tears (Figure 1). After acromioplasty, the greater tuberosity was decorticated, and double-row suture-bridge supraspinatus repair with bioabsorbable anchors was performed (5.5-mm Bio-Corkscrew FT and 3.5-mm BioComposite PushLock; Arthrex) in all cases.⁶⁵ As previously reported, concomitant surgery included arthroscopic excision for acromioclavicular joint arthropathy (PRP group: n = 4; control group: n = 5) and tenotomy for long head of the biceps tendinopathy (PRP group: n = 3; control group: n = 5). Postoperatively, all patients were immobilized in a sling (UltraSling III; DonJoy) for 6 weeks and underwent a standard rehabilitation program consisting of passive range of motion exercises (initial 6 weeks), active assisted range of motion exercises (6-10 weeks), and a progressive strengthening program (10-16 weeks).

PRP Preparation and Delivery Protocol

The PRP protocol has also been previously described.⁶⁵ For those randomized to the PRP group, platelet concentrate was obtained using the Autologous Conditioned Plasma (ACP) System (Arthrex). Ten mL of autologous peripheral blood, combined with 1 mL of Anticoagulant Citrate Dextrose Solution (ACD-A), was spun in a centrifuge (ROTOFIX 32 A; Hettich) at 1500 rpm for 5 minutes. The PRP supernatant (approximately 2-4 mL) was then removed and stored in a separate sterile syringe, activated with 2 mL of CaCl₂, and injected via ultrasound guidance to the tendon repair site by an experienced musculoskeletal radiologist. Needle placement was aided by the identification of echogenic sutures at the tendon repair site, easily identified via the suture anchors and knots prominent in the double-row surgical technique. The ACP System produces a platelet concentration of approximately 470,000 platelets/mL (2.13 greater than the level in whole blood), with an estimated concentration of growth factors reported as 5 to 25 times that of normal physiological levels. It is free of both residual erythrocytes and leukocytes, which may impair local growth factor activity by free radical activation.^42,58 For the PRP group, the aforementioned guided PRP tendon injection was delivered at 7 and 14 days after surgery.

Clinical Evaluation

Patient-reported outcome measures (PROMs) were conducted before surgery and at 6, 12, and 16 weeks after surgery.⁶⁵ These included the (1) Oxford Shoulder Score (OSS), (2) Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH) questionnaire, and (3) visual analog scale (VAS) for pain. The OSS is a 12-item questionnaire evaluating pain and function, which has demonstrated good reliability in evaluating shoulder surgery outcomes.^17,18,51 An improvement of 6.0 points on the OSS has been reported as the minimal detectable change (MDC).⁶² The QuickDASH is an 11-item questionnaire evaluating pain, symptoms, and physical function in patients with upper-limb musculoskeletal disorders⁵ and has also demonstrated good reliability, validity, and responsiveness.^5,36 The MDC for the QuickDASH has been reported as 17.1 points.⁶² The VAS required patients to rate their pain intensity on a 0- to 10-cm sliding scale (0 = no pain; 10 = worst pain imaginable) in the preceding 24 hours. In addition to these PROMs, at the midterm review (mean, 3.5 years), the VAS was used to evaluate both the frequency (VAS-F) and severity (VAS-S) of pain, while the global rating of change (GRC) scale⁴⁶ was employed to evaluate the patient’s perceived current status compared with before surgery. Finally, a patient satisfaction questionnaire was used to evaluate patients’ level of satisfaction with the rotator cuff repair overall as well as their satisfaction with the surgery to relieve their shoulder pain, improve their ability to perform normal daily and work activities, improve their ability to return to recreational activities (eg, swimming, golf), and improve their ability to participate in sporting activities (eg, tennis, squash). A categorical tool was employed: 1 = very satisfied; 2 = somewhat satisfied; 3 = somewhat dissatisfied; and 4 = very dissatisfied.

At the midterm review, the Constant score was obtained from all patients.^13,14 The subjective component of the Constant score is allotted a total of 35 points and evaluates patient-reported pain (15 points) as well as how the patients’ shoulder condition affects their ability to undertake occupational, leisure, and other daily activities (20 points). Active range of motion is allotted 40 points, consisting of forward flexion (10 points), abduction (10 points), external rotation (10 points), and internal rotation (10 points). Maximal, pain-free isometric abduction strength in 90° of shoulder abduction in the scapular plane is allotted 25 points. Finally, a total Constant score was also calculated (0-100) by summing the 3 individual subscales. The MDC for the Constant score has been reported as 18 points for rotator cuff tears.³⁹ All clinical assessments were performed by an independent assessor (J.R.E.), although this clinician was not blinded to group allocation.

Radiographic Evaluation

High-resolution MRI was undertaken in the patients at the midterm review using a 3-T scanner (Achieva 3.0T [Philips] and Discovery MR750 3.0T [GE Healthcare]) with 80 mT/m and 50 mT/m gradient power, respectively. Multiple scans were obtained in oblique coronal and oblique sagittal planes with both proton density–weighted and T2-weighted fat-suppressed turbo spin echo sequences. Proton density–weighted fat-suppressed scans were also obtained in the axial plane.

All midterm MRI scans were scored by the Sugaya classification system.⁶⁰ The status of the repair was graded as follows: grade 1 = no tear (sufficient tendon thickness with homogeneously low intensity); grade 2 = sufficient tendon thickness but with partial high intensity; grade 3 = insufficient thickness but no tendon discontinuity; grade 4 = small full-thickness retear (presence of minor discontinuity); and grade 5 = large full-thickness retear (presence of major discontinuity). The MRI assessment was performed by a fellowship-trained musculoskeletal radiologist with over 20 years of experience. Furthermore, this assessor had not performed the PRP injections and was blinded to group allocation. Interrater reliability was evaluated by having a second (experienced and blinded) musculoskeletal radiologist score all of the MRI scans, and excellent reliability was observed for the Sugaya grades (kappa = 0.88).

Data and Statistical Analyses

Descriptive statistics for baseline demographics and PROMs, tear size, and follow-up time were calculated for each group for those participants providing data at the midterm review (mean, 3.5 years). The groups were compared on these factors using chi-square or independent t tests for variables to identify potential confounders of the treatment effect due to differential dropout. For the QuickDASH and OSS scores, which were also collected before surgery and at 6, 12, and 16 weeks after surgery⁶⁵ as well as at the midterm review, random-effects Tobit models using all 60 cases were employed to obtain the best unbiased estimate of the mean (and 95% CI) difference between the control and PRP groups. A Tobit model rather than a general linear model was used, as the scores displayed significant floor (QuickDASH) or ceiling (OSS) effects. For those outcomes that were only measured at a mean 3.5-year follow-up (Constant, VAS-F, VAS-S, GRC, patient satisfaction, and MRI scores), the difference between the control and PRP groups was estimated as follows: (1) Constant subjective and Constant range of motion subscale scores using Tobit regression, (2) Constant strength subscale and Constant total scores using linear regression, and (3) ordinal variables (VAS-F, VAS-S, GRC, satisfaction, and MRI scores) using the nonparametric Mann-Whitney test. Sensitivity analyses were performed for parametric models by adjusting for sex and baseline OSS or QuickDASH scores. Statistical analysis was performed using Stata/IC 14.1 for Windows (StataCorp).

Results

The mean follow-up time was 42.1 ± 4.3 months (range, 36-51 months), and a total of 55 of 60 patients (91.7%) provided data at this time (PRP: n = 27; control: n = 28). Of the 5 patients who were not evaluated, 2 patients from the control group suffered retears within the first 16 weeks after surgery and underwent reoperations. This included 1 control patient who had symptoms at 12 weeks after surgery after a traumatic event, demonstrating a full-thickness retear on MRI and later undergoing revision double-row rotator cuff repair at 11 months after her primary repair. The second control patient demonstrated a full-thickness retear on MRI at the 16-week radiographic review, with pain and weakness that persisted until revision double-row rotator cuff repair was undertaken 9 months after his primary repair. Furthermore, 2 patients from the PRP group suffered retears and underwent subsequent reoperations between 16 weeks and final follow-up. This included 1 PRP patient who had symptoms after 4 months for no apparent reason, later confirmed on MRI as a partial-thickness retear, and subsequently underwent revision double-row rotator cuff repair at 8 months after her primary repair. The second PRP patient had symptoms after an aggressive exercise session, later confirmed on MRI as a partial-thickness retear, and subsequently underwent revision double-row rotator cuff repair at 10 months after his primary repair. One patient (PRP group) was lost to follow-up (see Figure 1). Table 1 displays the demographics, tear size, preoperative scores, and follow-up time for each group for those providing midterm follow-up data. Patients remaining in the trial were comparable on all factors, although there was a slightly lower proportion of male patients in the PRP group (40.7% vs 60.7%, respectively; P = .139) and a slightly poorer OSS score in the PRP group (P = .066) before surgery versus the control group.

Table 1

Preoperative Demographics, Tear Size, PROM Scores, and Follow-up Time for Participants With Midterm Follow-up Data^a

Variable	Control (n = 28)	PRP (n = 27)	P Value
Male sex, n (%)	17 (60.7)	11 (40.7)	.139^b
Surgery on dominant limb, n (%)	19 (67.9)	16 (59.3)	.508^b
Age, y	59.7 ± 11.4 (38-81)	59.5 ± 11.0 (29-74)	.958^c
Tear size, cm
Anteroposterior	1.5 ± 0.4 (1.0-2.0)	1.4 ± 0.4 (1.0-2.0)	.851^c
Mediolateral	1.1 ± 0.2 (1.0-1.7)	1.3 ± 0.3 (1.0-2.0)	.273^c
QuickDASH	36.4 ± 21.0 (9.1-81.8)	42.8 ± 16.0 (18.2-77.3)	.209^c
Oxford Shoulder Score	31.3 ± 7.5 (11-42)	27.8 ± 6.2 (12-38)	.066^c
Follow-up time, mo	42.7 ± 4.0 (36-49)	41.5 ± 4.7 (36-51)	.296^c

Data are presented as mean ± SD (range) unless otherwise specified. PROM, patient-reported outcome measure; PRP, platelet-rich plasma; QuickDASH, Quick Disabilities of the Arm, Shoulder and Hand.

Chi-square test.

Independent t test.

Table 2 presents a comparison between the control and PRP groups for all clinical outcome measures at the mean follow-up time of 3.5 years. There was no evidence of a difference between the PRP and control groups for the QuickDASH, OSS, or total Constant scores, and most participants displayed values at, or near, the best score possible for these measures. Figures 2 and 3 display the change over the course of the study in the QuickDASH and OSS scores, respectively. Although there was no difference between the groups for the Constant subjective and range of motion subscales, there was a 3.3-point higher Constant strength subscale score observed in the PRP group compared with the control group after adjusting for sex (95% CI, 1.0-5.7; P = .006). Participants in both groups had minimal pain, very positive GRC scores, and very high satisfaction scores, and there was no evidence of any group difference in these measures.

Table 2

Comparison Between Groups for Clinical Outcome Measures at 3.5-Year Follow-up^a

Outcome Measure	Control^b (n = 28)	PRP^b (n = 27)	Unadjusted Mean Difference		Adjusted Mean Difference^c
Outcome Measure	Median (IQR)	Median (IQR)	PRP – Control (95% CI)	P Value	PRP – Control (95% CI)	P Value
QuickDASH	2.3 (0.0 to 6.8)	2.3 (0.0 to 4.5)	0.9^d (–8.3 to 10.0)	.853	−0.1^d (–10.0 to 9.2)	.976
OSS	48.0 (44.0 to 48.0)	48.0 (45.0 to 48.0)	0.1^d (–4.5 to 4.8)	.918	1.0^d (–3.0 to 5.6)	.682
Constant score
Subjective	35.0 (33.0 to 35.0)	35.0 (30.0 to 35.0)	−1.6^e (–7.0 to 3.9)	.572	−0.1^e (–5.6 to 5.4)	.970
Range of motion	40.0 (38.0 to 40.0)	40.0 (40.0 to 40.0)	4.2^e (–1.7 to 10.0)	.162	4.4^e (–1.7 to 10.5)	.155
Strength, mean ± SD	14.4 ± 6.3	15.3 ± 6.6	0.9^f (–2.6 to 4.3)	.619	3.3^f (1.0 to 5.7)	.006
Total, mean ± SD	85.2 ± 11.3	86.2 ± 11.4	1.0^f (–5.2 to 7.2)	.744	4.4^f (–1.0 to 9.8)	.109
VAS frequency	00 (0 to 1.5)	00 (0 to 1.0)	N/A	.493^g	N/A	N/A
VAS severity	00 (0 to 1)	00 (0 to 1)	N/A	.732^g	N/A	N/A
GRC (–5 to 5)	5 (4 to 5)	5 (4 to 5)	N/A	.579^g	N/A	N/A
Satisfaction (1 to 4)
Pain relief	1 (1 to 1)	1 (1 to 1)	N/A	.771^g	N/A	N/A
Activities of daily living	1 (1 to 1)	1 (1 to 1)	N/A	.771^g	N/A	N/A
Recreation^h	1 (1 to 1)	1 (1 to 1)	N/A	.626^g	N/A	N/A
Sportⁱ	1 (1 to 1)	1 (1 to 1)	N/A	.416^g	N/A	N/A
Overall	1 (1 to 1)	1 (1 to 1)	N/A	.589^g	N/A	N/A

GRC, global rating of change; IQR, interquartile range; N/A, not applicable; OSS, Oxford Shoulder Score; PRP, platelet-rich plasma; QuickDASH, Quick Disabilities of the Arm, Shoulder and Hand; VAS, visual analog scale.

Reported values are as observed (ie, using only those patients available at midterm follow-up).

Adjusted for baseline OSS scores (or baseline QuickDASH scores) and sex.

Random-effects Tobit model estimate from full sample (n = 60).

Tobit regression.

Linear regression.

Nonparametric Mann-Whitney test.

Missing 1 PRP patient.

Missing 7 patients (5 control and 2 PRP).

There was no evidence of any group difference in MRI-based outcomes using the Sugaya classification system (Table 3). The majority of participants in both groups scored well on MRI for tendon integrity at a mean 3.5-year postoperative follow-up, with 18 PRP patients (66.7%) and 18 control patients (64.3%) rated as Sugaya grade 1 and 27 PRP patients (100.0%) and 27 control patients (96.4%) rated as Sugaya grades 1 to 3 (Table 3).

Table 3

MRI-Based Sugaya Classification Grades at 3.5-Year Follow-up^a

Sugaya Classification	Control (n = 28)	PRP (n = 27)	P Value
Sugaya grades, median (interquartile range)	1 (1-2)	1 (1-2)	.719
Grade 1	18 (64.3)	18 (66.7)
Grade 2	5 (17.9)	6 (22.2)
Grade 3	4 (14.3)	3 (11.1)
Grade 4	1 (3.6)	00 (0.0)
Grade 5	00 (0.0)	00 (0.0)

Data are presented as n (%) unless otherwise specified. MRI, magnetic resonance imaging; PRP, platelet-rich plasma.

Discussion

Biological therapies such as PRP have been employed to enhance the quality of early tendon healing in rotator cuff repair, and some studies with a short-term follow-up have suggested a reduced failure-to-heal rate, particularly with small to moderately sized tears.^8,57,63 It is also important to evaluate longer term outcomes to ascertain whether the adjunctive postoperative application of PRP creates a more robust and stable repair, with potentially increased resistance to future reinjuries and late tendon retears. In a case-controlled study, Hernigou et al⁴⁰ reported that rotator cuff repair treated with mesenchymal stem cells at the time of surgery had not only improved tendon healing at 6 months but also had a reduced incidence of further tendon ruptures during the following 10 years after surgery. The most important finding of the current RCT was, despite significantly greater strength in patients who underwent repeated PRP injections at 7 and 14 days after arthroscopic supraspinatus repair, no other differences were observed in the clinical or MRI-based outcomes at a mean 3.5 years after surgery.

This study presents the longest follow-up of an RCT investigating rotator cuff repair and adjunctive PRP treatment. Of the initial 60 patients recruited, the early MRI-based evaluation at 16 weeks after surgery employing the Sugaya classification system demonstrated no significant between-group differences. As outlined, 2 control patients had symptomatic retears within 4 months of surgery (both full-thickness retears, 1 after a traumatic event and 1 for unknown reasons, with both undergoing revision rotator cuff repair at 11 and 9 months, respectively).⁶⁵ In the current study, between 4 months and a mean 3.5-year follow-up, 1 other control patient had a partial-thickness retear on MRI, although the patient was relatively asymptomatic and has not undergone revision surgery. However, in comparison, while there were no early retears observed in the PRP group, 2 PRP patients suffered retears and underwent subsequent reoperations between 4 months after surgery and a mean 3.5 years (1 partial-thickness tear for unknown reasons and 1 partial-thickness tear after exercise, with both undergoing revision rotator cuff repair, at 8 and 10 months, respectively). Therefore, at the midterm review, the 4 patients (2 control; 2 PRP) who suffered retears were excluded from analysis, with only 1 PRP patient lost to follow-up. As per the Sugaya classification system, the distribution of patients over the 5 grades was similar for both groups. A strength of this study was the independent assessment of MRI scans by 2 musculoskeletal radiologists, with excellent interobserver reliability observed. Despite recent reviews suggesting that PRP improves structural tendon healing of small to medium-sized tendon tears, the present study was unable to demonstrate any difference in the longer term retear rate when using PRP with the MRI assessment employed. This study is limited in power to detect differences in the rates of retears.

Despite our findings, and the clinical relevance in comparing these results to those in the published literature, it should be highlighted that PRP application protocols vary. For reasons discussed later, this study adopted delayed and repeated injections of PRP at postoperative days 7 and 14 to minimize any potential washout effect from arthroscopic administration as well as permit the delivery of the PRP product at a time suggested to be most beneficial for the tendon healing process.^16,33,69 However, other published studies often employed a single (or multiple) PRP injection at, or into, the repair site at the time of surgery.^†† Gwinner et al³⁷ employed multiple PRP injections at the repair site as well as into the subacromial bursa at the time of surgery, with a second injection at 7 days after surgery into the subacromial bursa. Hak et al³⁸ injected into the tendon intraoperatively in several positions along the repair site as well as into the subacromial bursa, with a second series of injections at the tendon-bone interface and into the subacromial bursa at 4 weeks after surgery. Other studies have created a PRP fibrin matrix or gel, employed as an augment to the repair or placed between the rotator cuff tendon and bone.^{3,10,34,43,44,55,67} Therefore, differing application systems need to be acknowledged, and the most optimal process is yet to be determined.

Clinically, no differences were observed between the groups in any of the PROMs employed, including the QuickDASH, OSS, VAS, and Constant subjective subscale. This is consistent with previous reports on the use of PRP to enhance rotator cuff repair, which have also demonstrated no clinical benefit from the adjunctive use of PRP.^‡‡ In the current study, patients in both the PRP and control groups significantly improved over time up until the midterm clinical follow-up. Most patients displayed values at, or near, the best score possible for the PROMs employed, with a ceiling effect demonstrated. While this may suggest that the QuickDASH and OSS are not sufficiently sensitive enough to detect differences in higher functioning shoulders, it is interesting to note that despite block randomization, the PRP group had worse (not statistically significant) clinical outcomes via the OSS and QuickDASH before surgery, which were comparable with the control group at the midterm review. The postoperative improvement observed in the QuickDASH and OSS in this study appears consistent with the existing literature evaluating outcomes after rotator cuff repair in combination with PRP.²⁵ However, it must be acknowledged that a range of other PROMs have been employed in these studies, including the American Shoulder and Elbow Surgeons (ASES) questionnaire,^{3,25,41,43,52,55} the Simple Shoulder Test (SST),^{3,12,34,43,44,53,67,68} the subjective shoulder value (SSV),³⁷ the University of California, Los Angeles (UCLA) score,^{12,43,44,49,52,53,56,67} the Shoulder Pain and Disability Index (SPADI),^43,44 the Western Ontario Rotator Cuff Index (WORC),^37,41 and the L’Insalata shoulder score.⁵⁵ The use of different PROMs makes a direct comparison difficult.

We also observed no differences in the overall Constant score between the groups. Apart from one study that demonstrated significantly better Constant scores at 12 and 24 months after surgery in patients with adjunctive treatment with PRP,⁵² the majority of studies reported comparable Constant score values.^§§ Unfortunately, most studies that employed the Constant score presented the overall score and did not present the individual subscales (subjective, range of motion, and strength).^2,3,10,49,52 This makes it difficult to detect whether there is a specific between-group difference. In the current study, although we also observed no group differences in the total Constant score, or the subjective or range of motion subscales, there was a significant group difference observed for maximal, pain-free isometric abduction strength in favor of the PRP group. The findings of this study suggest that PRP treatment could improve the quality of the tendon repair and late tendon remodeling, permitting greater pain-free abduction strength. Prior studies that have reported postoperative strength outcomes have generally found no between-group differences.^{10,12,25,43,44,53,55} Further studies with a longer term follow-up may be required to confirm our findings.

It must be acknowledged that differences exist between PRP systems commercially available, and these differences may influence reported outcomes. PRP products may differ with respect to the volume of autologous blood drawn, the preparation and concentration of platelets and growth factors available, and the inclusion of leukocytes as well as the timing and delivery mechanism of the product.^8,11,48,57 For example, a recent meta-analysis showed that only leukocyte-rich PRP injections under ultrasound guidance are effective for the treatment of tendinopathy.²⁴ It has been reported that biological augmentation too early in the tendon healing cascade may prove ineffective,³³ with some growth factors including bone morphogenetic protein–13, platelet-derived growth factor–B, and transforming growth factor–B1 all expressed maximally at days 7 and 14⁶⁹ and the cytokine-mediated temporal expression of collagen types I and III increased from day 7 onward.¹⁶ Therefore, the present study adopted delayed and repeated injections of PRP, under ultrasound guidance at postoperative days 7 and 14, into the supraspinatus tendon repair site to minimize any potential washout effect from arthroscopic administration as well as to permit the delivery of the PRP product at a time suggested to be most beneficial for the tendon healing process.

We acknowledge some study limitations. First, we evaluated tendon integrity using a validated, morphological scoring tool.⁶⁰ While the reliability assessment between 2 observers was excellent, it remains subjective and qualitative. Emerging methods of tendon imaging through T2 mapping may provide a more accurate method of quantitative tendon measurements^26,28,47 in future research, which may prove more sensitive to detect tendon structural improvement with PRP. Second, the outcomes of this study cannot be generalized across larger tears, outcomes involving multiple rotator cuff tendons, or single-row repair techniques. This study evaluated outcomes in supraspinatus tears ≤20 mm, which was selected to minimize the influence of other factors that are more likely to coexist with larger and chronic tears, also linked with an increased risk of surgical repair failure, including larger tear size, chronicity of the condition, muscle atrophy, tissue quality, fatty infiltration, and degree of tendon retraction.^29,31,32 In addition, we acknowledge that we employed a double-row technique in small rotator cuff tears that may not warrant the adjunctive use of PRP augmentation. However, given the space required to inject the construct, along with PRP containment, a single-row method is not appropriate. Furthermore, recent reviews have suggested that any trend toward a beneficial outcome on reducing retears is most likely if PRP is applied at the tendon-bone interface in double-row repair and with small and/or medium-sized tears.^57,63 These were all factors that were included in the current study, and no discernible MRI-based differences at the midterm review were noted. However, we do acknowledge other factors that we did not control for in this study which may be associated with rotator cuff tears and/or surgical failure, including obesity³⁵ and smoking.⁵⁰

Third, the patients were not blinded to their randomization because of the impracticality of giving control patients 2 placebo injections on days 7 and 14 after surgery, corresponding with the PRP injection time points. The nonblinded nature of the study could have biased PROMs, even at the midterm review. An independent assessor (J.R.E.) was recruited to collect the clinical outcomes, although he was also not blinded to patient randomization. Nevertheless, the primary outcome measure of this study was the MRI evaluation, and this was performed by 2 independent radiologists who were both blinded to group randomization. Finally, while patient satisfaction and PROMs scored very well across both groups, it is clear that a ceiling effect was demonstrated within the PROMs employed. This suggests that the QuickDASH and OSS are not sufficiently sensitive to detect differences in higher functioning shoulders, and any potential improvements occurring from the adjunctive application of PRP were not detected with these instruments. While the clinical relevance of the between-group difference observed in strength is unknown, particularly in this older patient cohort who were all satisfied with their outcomes, strength as assessed with the Constant score is less vulnerable to ceiling effects and may be more reflective of functional improvement. This study did not evaluate and/or report on the return of, or ability to undertake, sport-specific activities involving higher demand upper limb movements. While this may have been more sensitive in detecting higher level differences between patients, particularly in patients with expectations of returning to sports or younger patients, the large age range of patients and the fact that 28 of 55 patients (50.9%) were ≥60 years of age at the time of surgery, while 37 of 55 patients (67.3%) were ≥60 years at the time of the midterm review, may have confounded such an analysis.

In conclusion, this RCT presents the longest follow-up of clinical and MRI-based outcomes in patients after arthroscopic supraspinatus repair treated with, or without, postoperative PRP injections at the tendon repair site. Our first hypothesis was confirmed, with no differences observed in other clinical outcomes between the 2 groups. However, this study suggests a benefit with PRP for improving pain-free abduction strength. Our second hypothesis was not supported in which we did not observe any evidence of PRP improving MRI-based outcomes including reduced retear rates. This study does not support the rationale for PRP enabling a more robust tendon repair at midterm that was more durable and resistant to tendon reinjuries. Future research may include larger multitendon repairs, with more sophisticated functional and MRI-based outcome measures, to further evaluate the efficacy of PRP products on enhancing tendon healing and reducing late reinjury rates upon returning to daily activities, work, and sport.

Footnotes

#

References 1, 20 -23, 29, 31, 32, 35, 41, 50, .

**

References 4, 6, 10, 34, 38, 41, 43, 44, 55, 56, 64, 67, 68, .

††

References 12, 25, 41, 49, 52, 53, 56, 68, .

‡‡

References 2, 3, 10, 12, 25, 34, 37, 38, 41, 43, 44, 49, 53, 55, 56, 67, .

§§

References 2, 3, 10, 25, 34, 37, 41, 43, 44, 49, 53, 68, .

One or more of the authors has declared the following potential conflict of interest or source of funding: For the early outcomes collected as part of this study, Arthrex provided a research grant to assist with the early clinical evaluations as well as donated disposable syringes. Medivenn provided a research grant that assisted with the cost of 3- to 4-year magnetic resonance imaging scans. A.W., M.H.Z., and T.A. have shares in Orthocell.

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