Platelet-Rich Plasma for Arthroscopic Rotator Cuff Repair: A 3-Arm Randomized Controlled Trial

Abstract

Background:

Although there has been some amount of research into the use of platelet-rich plasma (PRP) after arthroscopic rotator cuff repair, most studies have not fully demonstrated its benefits. In addition, PRP formulations containing different concentrations of leukocytes have not been directly compared for rotator cuff repair.

Purpose/Hypothesis:

The purpose of this article was to determine whether arthroscopic rotator cuff repair combined with PRP injection, either leukocyte-rich PRP (LR-PRP) or leukocyte-poor PRP (LP-PRP), is superior to the control. The null hypothesis was that the addition of any PRP formulation would not result in outcomes superior to the control group.

Study Design:

Randomized controlled trial; Level of evidence, 1.

Methods:

Patients with full-thickness rotator cuff tears who underwent arthroscopic repair were assessed for eligibility. The included patients were randomized to 3 treatment groups: the LR-PRP, LP-PRP, and standard-care control groups. After the rotator cuff suture was fixed firmly, different groups of liquid PRP preparations prepared by centrifugation were injected into the tendon-to-bone interface. The functional outcomes were assessed using the University of California, Los Angeles (UCLA) score, the Constant score, the American Shoulder and Elbow Surgeons (ASES) score, the visual analog scale for pain during sleep and activity, and active range of motion at 3, 6, and 12 months after surgery. In addition, the visual analog scale score was obtained at weeks 2 and 6. Postoperative structural integrity was assessed by magnetic resonance imaging at 12 months using the Sugaya classification. Type III was considered partial retear, and types IV and V were considered complete retears. The safety of surgery was compared by the incidence of complications. The main analyses were performed in accordance with the intention-to-treat principle.

Results:

Of 150 patients initially randomized, the functional outcomes in 142 (46 LR-PRP, 47 LP-PRP, 49 control) and the structural integrity in 133 (40 LR-PRP, 46 LP-PRP, 47 control) were analyzed. There was no significant difference in the primary outcome of the UCLA score among the 3 groups (P = .169). The trends in functional outcomes and range of motion were similar for the 3 groups, with no significant differences among the groups at 12 months. However, within 6 months after surgery, the ASES score was better in the LR-PRP group than in the control group (3 months: 85.8 ± 4.1 vs 81.6 ± 8.7; P = .011; 6 months: 90.0 ± 5.4 vs 86.2 ± 6.8; P = .003). At 12 months after surgery, the overall retear rate, including partial and complete retears, was 8%. There were no significant differences in the rates of overall retear (P = .755) or complete retear (P = .633) among the 3 groups. The only surgical complication was postoperative stiffness, which occurred in 3% of patients, and the incidence did not significantly differ among the groups (P = .790).

Conclusion:

The study did not reveal that shoulders treated with the LR-PRP or LP-PRP formulations had any superior functional or structural outcomes at 12 months compared with those of the control group. However, LR-PRP may offer better ASES scores than the control group up to 6 months after surgery, and its clinical benefit remains to be proven.

Registration:

ChiCTR2100045039 (Chinese Clinical Trial Register).

Keywords

rotator cuff repair arthroscopic surgery platelet-rich plasma tendon healing

Rotator cuff tears are a prevalent cause of shoulder pain and dysfunction, and the incidence of this disorder is increasing as the population ages.³ Arthroscopic surgery for symptomatic full-thickness rotator cuff tears that do not respond to nonoperative treatment is considered appropriate treatment, with >450,000 surgeries performed annually in the United States.⁴² Advances in technology have led to fewer surgery-related complications and faster postoperative recovery. However, rotator cuff retears continue to plague surgeons, with incidence rates ranging between 9% and 94%.^6,18,29 In addition to advancements in surgical fixation techniques and suture anchor materials for rotator cuff repair, biological augmentation techniques have been considered another effective way to improve the healing rate of rotator cuffs in recent decades.^1,3

Platelet-rich plasma (PRP) has been defined as the processed liquid of autologous blood with concentrations of platelets above baseline values¹⁵ and has gained popularity among sports medicine surgeons since its introduction in the 1990s. PRP contains >1000 bioactive proteins and is rich in growth factors and cytokines that contribute to tendon-to-bone healing, such as platelet-derived growth factors, transformation growth factor–β, and insulin-like growth factor.³² Since the 2010s, the application of PRP for rotator cuff repair enhancement has been widely studied, but the available evidence does not seem to fully support its application.^4,7,27,33,43 The heterogeneity of these results may be attributed to differences in PRP formulations used in different studies. Depending on the centrifugation protocol, PRP preparations with different leukocyte concentrations may result—namely, leukocyte-rich PRP (LR-PRP) and leukocyte-poor PRP (LP-PRP) preparations.¹ Laboratory studies have confirmed that the 2 PRP formulations differ in terms of local bioaugmentation. Dragoo et al¹² demonstrated that the inclusion of white blood cells in PRP may increase the release of growth factors but may also lead to a greater short-term inflammatory and fibrotic response than LP-PRP does, which may lead to a delayed healing response. Lin et al²⁵ also found that the growth factor content in the LR-PRP group was 1.2 to 1.8 times greater than that in the LP-PRP group and that compared with LP-PRP, LR-PRP significantly promoted the proliferation of rotator cuff tenocytes. However, evidence from clinical studies supporting the use of LR-PRP or LP-PRP remains controversial.^20,24,37 A network meta-analysis of 13 studies by Hurley et al²⁰ found that LP-PRP reduced the rate of retears and/or incomplete healing compared with controls while improving patient-reported outcomes (PROs), which is consistent with the findings of Li et al.²⁴ Hurley et al²⁰ compared LR-PRP with LP-PRP by post hoc analysis and did not find any differences in any category. According to the consensus of the International Olympic Committee medical and scientific commission, even though PRP is unlikely to be harmful, its clinical efficacy should be established through robust clinical practice.¹³

To date, a large number of studies have compared the differences between LR-PRP or LP-PRP and a control group, but none has directly compared the differences among LR-PRP, LP-RPP, and a control group. Therefore, the objective of this study was to determine whether arthroscopic rotator cuff repair combined with PRP injection, either LR-PRP or LP-PRP, is superior to a control with no additional injection. The null hypothesis was that the addition of any PRP formulation would not be superior to the control group.

Methods

Study Design

We conducted a single-center, prospective, 3-arm, parallel randomized, double-blind, controlled trial in which both participants and examiners were blinded. The study was conducted in accordance with the 2013 version of the Declaration of Helsinki and approved by the local ethics committee with registration at the Chinese Clinical Trial Register (www.chictr.org.cn; ChiCTR2100045039). During the course of this study, 1 study protocol amendment was made. The surgeons selected single-row or double-row repair techniques for the included patients according to the tear size and shape during the operation.

Patients

During the study period (from August 2021 to August 2022), patients with symptomatic full-thickness rotator cuff tears were eligible. The inclusion criteria were (1) age >18 and <75 years, (2) clinical and magnetic resonance imaging (MRI) diagnosis of full-thickness isolated supraspinatus tear, and (3) failure of >3 months of nonoperative treatment. The exclusion criteria were (1) massive rotator cuff tear; (2) open reconstruction or revision surgery; (3) concomitant shoulder stiffness, glenohumeral arthritis, glenohumeral instability, calcific tendinitis, local infection, and so forth; (4) smoking status; (5) thrombocytopenia or blood dyscrasia; (6) uncontrolled diseases such as immunopathy, cancer, or infection; or (7) unwillingness to participate. Eligible patients were enrolled in the study after providing signed informed consent.

Randomization

A random numbers table was used for randomization in this study. We selected 150 sequential random numbers starting with an arbitrary point in the table. The first 50 numbers were assigned to the LR-PRP group, the next 50 numbers were assigned to the LP-PRP group, and the last 50 numbers were assigned to the control group. These 150 numbers were then arranged in ascending order to produce a random sequence of treatment assignments. The treatment assignments were encapsulated in opaque, continuously labeled envelopes by an independent operator. After diagnostic arthroscopy to confirm the presence of a full-thickness rotator cuff tear, the same independent operator who did not participate in the surgery opened the envelopes in sequence to determine the treatment assignments.

Blinding

The study was double-blind, and randomization remained concealed to all patients and outcome assessors. In addition, the physical therapists and imaging evaluators were also blinded to the patient assignments. However, the control group was not injected with PRP, which means the surgeon became unblinded, although surgeons did not know the patient assignment at the start of the operation. The surgical procedure was therefore consistent across all patients, which reduces potential bias.

PRP Preparation

After randomization was determined during surgery, the PRP was prepared under sterile conditions intraoperatively. For patients randomized to the LR-PRP group, platelet concentrate was obtained using a PRP preparation kit (WEGO). A total of 45 mL of autologous peripheral blood combined with 5 mL of anticoagulant was first centrifuged at 697g for 10.5 min, and the red blood cell layer at the bottom was removed. The remaining upper layer liquid was collected and centrifuged at 963g for 10.5 min. After the second centrifugation, the upper plasma was removed to obtain 5 to 8 mL of LR-PRP, which was stored in a separate sterile syringe (Figure 1A). For patients randomized to the LP-PRP group, platelet concentrate and leukoreduction were obtained using the autologous conditioned plasma system (Arthrex). Autologous peripheral blood (14 mL) combined with 1.5 mL of anticoagulant was centrifuged at 1500 rpm for 5 min. The LP-PRP supernatant (approximately 5-7 mL) was then removed and stored in a separate sterile syringe (Figure 1B).

The 2 commercial PRP preparation devices used in this study have been reported to be effective at increasing platelet counts by 2 to 5 times. Simultaneously, it has been verified that leukocyte counts could be increased roughly 3-fold in the LR-PRP group^39,45 and decreased to <0.1-fold in the LP-PRP group.^17,41

Surgical Technique

Standard arthroscopic repair techniques were used to repair the rotator cuff tendon by 1 senior shoulder surgeon (X.T.) with assistants. All procedures were performed with patients in the lateral decubitus position under general anesthesia. First, the posterior and anterior portals were established. Then, thorough exploration of the glenohumeral joint was performed, and any identified lesions were treated as needed. The arthroscope was subsequently removed and redirected to the subacromial space, and a lateral working portal and a posterolateral viewing portal were established. Debridement of the bursal tissue and the subacromial area was performed. The type of acromion was assessed intraoperatively, and the required acromioplasty was carried out. The quality of the long head of the biceps was assessed, and necessary debridement, tenodesis, or tenotomy were performed. After removing the frayed tendons, the rotator cuff tear size was carefully evaluated and documented based on the method of DeOrio and Cofield.¹¹ For retracted tendons with inadequate coverage of the greater tuberosity, the necessary tendon mobilization procedure was performed. The footprint of the greater tuberosity was minimally debrided. Rotator cuff repair was performed using single-row repair or double-row repair (suture bridge technique) based on the tear size and shape. Single-row suture technique was used for patients with small or longitudinal tears. The general suture principle was to ensure complete coverage of the footprint and reduce PRP fluid injection leakage. After repair and reexamination, excess lavage saline was suctioned out, and all the portals were closed. For patients in the control group, no placebo injection was given. For patients in the PRP group, an 18-gauge intravenous cannula needle was introduced percutaneously and placed between the repaired cuff and bone bed under arthroscopic vision for the delivery of PRP to the tendon-to-bone interface (Figure 1C). PRP was injected slowly to the tendon-to-bone interface through the previously placed needle after the portals were closed.

Postoperative Rehabilitation

All patients underwent standardized postoperative rehabilitation conducted by a physical therapist. The patient was discharged the day after surgery and attended follow-up appointments at the surgeon's clinic at 2 and 6 weeks, then 3, 6, and 12 months postoperatively and annually thereafter. Immediately after surgery, the affected arm was immobilized in an abduction pillow at 30° with extorsion at 0° for 6 to 8 weeks, depending on the tear size. During this period, patients were permitted to perform passive range-of-motion exercises for their hand, elbow, and wrist. Two weeks after surgery, patients began passive forward flexion and abduction exercises with guidance at the surgeon's clinic. The patients were allowed to perform internal and external rotation exercises after an additional 2 to 4 weeks. Upon removal of the pillow, patients progressed to active assisted and active shoulder movements and were able to resume normal daily activities. It should be noted that no strengthening or resistance exercises were allowed until ≥3 months postoperatively. After a 24-week outpatient evaluation of the individual's functional recovery, patients could fully return to daily activities.

Outcome Measures

The primary outcome was the difference in change from baseline to 12 months in the University of California, Los Angeles (UCLA) shoulder rating scale among the 3 groups. The secondary outcomes included PRO measures (PROMs) according to the Constant score and the American Shoulder and Elbow Surgeons (ASES) score; pain, as measured by a visual analog scale (VAS) during sleep and activity; active range of motion (ROM), including flexion, abduction, external rotation, and internal rotation; and structural integrity, as assessed by 12-month MRI. All of the clinical assessments were performed before surgery and 3, 6, and 12 months after surgery. In addition, the VAS score for pain was obtained at weeks 2 and 6. Complications were also recorded and assessed. The criteria for postoperative shoulder stiffness were set as passive flexion of <120° or external rotation at side of <30° at 3 months according to the definition of Oh et al.³⁰

The UCLA score is a PROM of shoulder disease severity that captures pain and shoulder functions, with a maximum score of 35 representing the best. The Constant score and ASES score are the other 2 PROMs that assess shoulder pain and function, both with scores of 100 representing the best condition. The VAS for pain requires patients to rate their pain intensity on a 0- to 10-cm scale, with higher scores representing more pain. All PROMs and VASs were independently scored by the patients. Active ROM was measured by a blinded assessor with a goniometer. External rotation and internal rotation were measured with the arm at the side. Structural integrity was assessed with MRI at 12 months postoperatively. The imaging results were assessed by a radiologist and a surgeon (X.T.), neither of whom knew the patient group at the time of the assessment. Postoperative rotator cuff integrity was assessed using the Sugaya classification,⁴⁰ where types I and II were considered healed rotator cuff, type III was considered partial retear, and types IV and V were considered complete retear. Partial retears and complete retears were classified as overall retears.

Sample Size

The sample size was calculated for an analysis of our primary outcome, the result of the UCLA score after 12 months. We found that 41 patients were needed in each treatment group to detect a minimal mean difference between groups of 2.3 points with an SD of 4,²⁶ a power of 80%, and a 2-side significance level of .05. To compensate for an expected 20% dropout rate, we predefined our required sample size as 150 participants in total.

Statistical Analysis

The main analyses were performed in accordance with the intention-to-treat principle. A descriptive analysis was performed in which continuous variables were described by the mean and standard deviation and categorical variables were defined by counts and percentages. The demographic data were analyzed using analysis of variance for continuous variables or chi-square tests for categorical variables. PROMs and active ROMs were compared using a general linear mixed model for repeated measures, considering the treatment group and time as fixed factors. If a significant time-treatment group interaction term was found, pairwise comparisons among the treatment groups at each time point were conducted. If not significant, the treatment main effect was tested next. The proportions of patients who experienced retears were compared using chi-square tests, and stratified analysis was carried out according to tear size and repair technique. The analyses were conducted using SPSS Statistics (Version 26; IBM), with checks for normality. P values <.05 were considered significant.

Results

Participants

A CONSORT (Consolidated Standards of Reporting Trials) flowchart was used to identify and assess patients for inclusion (Figure 2). Between August 1, 2021, and August 30, 2022, 307 consecutive patients with radiographic findings of rotator cuff tear were assessed for eligibility. Of these, 150 patients who fulfilled the study's inclusion and exclusion criteria were included in the trial and were randomly assigned to the 3 groups. The mean age of the overall cohort was 55.6 ± 9.5 years, and the majority were female (n = 96; 64%).

The baseline characteristics and operative variables of the 150 patients who received the allocated interventions were balanced among the 3 groups (Table 1).

Table 1

Patient Characteristics and Surgical Variables^a

	LR-PRP n = 50	LP-PRP n = 50	Control n = 50
Age, y	54.4 ± 10.2	56.4 ± 10.1	56.0 ± 8.2
Sex
Female	31 (62)	30 (60)	35 (70)
Male	19 (38)	20 (40)	15 (30)
Body mass index	23.9 ± 3.0	24.8 ± 3.0	24.7 ± 3.2
Affected side
Left	13 (26)	14 (28)	12 (24)
Right	37 (74)	36 (72)	38 (76)
Symptom duration, mo	22.0 ± 26.6	24.2 ± 39.7	22.4 ± 31.4
Dominant arm, n	31 (62)	34 (68)	33 (66)
Diabetes, n	6 (12)	9 (18)	7 (14)
Tear size
Small	5 (10)	3 (6)	8 (16)
Medium	33 (66)	32 (64)	32 (64)
Large	12 (24)	15 (30)	10 (20)
Repair technique
Single row	9 (18)	6 (12)	14 (28)
Double row	41 (82)	44 (88)	36 (72)
Anchors, n	2.7 ± 1.2	2.8 ± 1.0	2.6 ± 1.2
Biceps tenotomy/tenodesis	13 (26)	20 (40)	15 (30)
Acromioplasty	50 (100)	47 (94)	49 (98)

Data are presented as mean ± SD or n (%). LP-PRP, leukocyte-poor platelet-rich plasma; LR-PRP, leukocyte-rich platelet-rich plasma.

Clinical Assessment

The data completeness rate was 99% (148/150) at 6 months and 95% (142/150) at 12 months, with no difference among the 3 groups (P = .535). The primary outcome, the UCLA score, significantly improved in the 3 groups at 12 months (time effect P < .001) (Table 2). The 3 groups experienced similar changes in the UCLA score over time, with no significant difference at the 12-month follow-up (treatment effect P = .169).

Table 2

Comparison of Clinical Outcomes Among 3 Groups to 12 Months^a

	LR-PRP	LP-PRP	Control	Time Effect P	Treatment Effect P	Time × Treatment Effect P
UCLA				<.001	.169	.204
Baseline	21.1 ± 4.5	19.1 ± 5.9	20.3 ± 4.7
3 months	24.7 ± 3.1	24.1 ± 4.5	23.4 ± 4.4
6 months	29.3 ± 2.8	29.2 ± 3.2	28.5 ± 2.9
12 months	32.3 ± 3.5	32.3 ± 2.7	32.1 ± 2.6
Constant				<.001	.180	.340
Baseline	75.1 ± 12.7	71.7 ± 15.3	74.4 ± 12.7
3 months	70.0 ± 9.7	68.2 ± 11.6	66.0 ± 12.0
6 months	84.7 ± 8.0	83.9 ± 8.3	82.3 ± 7.5
12 months	92.2 ± 7.5	92.1 ± 6.0	91.9 ± 6.4
ASES				<.001	.212	.040
Baseline	78.7 ± 10.0	78.1 ± 9.1	79.3 ± 8.5
3 months	85.8 ± 4.1	84.7 ± 6.7	81.6 ± 8.7
6 months	90.0 ± 5.4	88.9 ± 5.9	86.2 ± 6.8
12 months	91.2 ± 8.5	91.0 ± 7.6	92.0 ± 8.1
VAS during sleep				<.001	.907	.469
Baseline	5.2 ± 1.3	5.5 ± 1.3	5.1 ± 1.5
2 weeks	3.0 ± 1.7	3.0 ± 1.6	2.9 ± 1.7
6 weeks	2.2 ± 1.5	1.9 ± 1.3	2.2 ± 1.4
3 months	1.3 ± 1.2	1.6 ± 1.4	1.6 ± 1.4
6 months	0.8 ± 1.0	0.8 ± 1.1	0.9 ± 1.0
12 months	0.5 ±0.9	0.5 ± 0.8	0.5 ± 0.8
VAS during activity				<.001	.571	.261
Baseline	4.6 ± 1.5	5.0 ± 1.9	4.6 ± 1.5
2 weeks	1.9 ± 0.8	1.8 ± 0.9	1.9 ± 1.0
6 weeks	1.6 ± 1.0	1.4 ± 0.8	1.5 ± 1.0
3 months	1.4 ± 0.8	1.5 ± 1.0	1.4 ± 0.9
6 months	0.8 ± 0.8	0.8 ± 0.8	1.0 ± 0.8
12 months	0.6 ± 0.7	0.7 ± 0.7	0.7 ± 0.7
Flexion				<.001	.038	.104
Baseline	159.3 ± 27.2	146.6 ± 34.1	150.4 ± 28.8
3 months	154.3 ± 22.4	148.5 ± 28.1	142.8 ± 31.2
6 months	168.7 ± 11.8	170.5 ± 11.1	168.4 ± 12.0
12 months	177.4 ± 6.1	177.7 ± 5.2	177.6 ± 6.0
Abduction				<.001	.058	.259
Baseline	154.2 ± 33.6	142.0 ± 36.9	145.5 ± 35.4
3 months	149.2 ± 27.6	144.2 ± 32.6	135.5 ± 33.0
6 months	168.1 ± 13.1	170.1 ± 11.3	166.6 ± 13.8
12 months	177.4 ± 6.1	178.1 ± 4.5	176.3 ± 8.3
External rotation				<.001	.080	.079
Baseline	58.1 ± 15.2	52.5 ± 16.9	58.2 ± 15.6
3 months	38.6 ± 10.8	39.0 ± 11.1	37.1 ± 10.1
6 months	55.4 ± 11.6	54.1 ± 12.6	51.2 ± 11.6
12 months	66.5 ± 6.4	65.5 ± 8.0	64.1 ± 7.6
Internal rotation				<.001	.106	.499
Baseline	76.4 ± 18.7	74.4 ± 20.6	75.8 ± 19.7
3 months	46.3 ± 14.6	43.2 ± 15.6	38.4 ± 12.6
6 months	61.6 ± 13.1	60.2 ± 13.7	58.2 ± 13.2
12 months	78.7 ± 12.6	77.2 ± 10.8	76.9 ± 11.8

Data are presented as mean ± SD. ASES, American Shoulder and Elbow Surgeons; LP-PRP, leukocyte-poor platelet-rich plasma; LR-PRP, leukocyte-rich platelet-rich plasma; UCLA, University of California, Los Angeles; VAS, visual analog scale.

At 12 months postoperatively, each group achieved significant improvements in PROMs, pain scores, and active ROM (time effect P < .001) (Table 2). A significant time × treatment interaction was observed for the ASES score (time × treatment effect P = .040) (Table 2), with a higher score within 6 months postoperatively for patients in the LR-PRP group than for those in the control group (3 months: 85.8 ± 4.1 vs 81.6 ± 8.7; P = .011; 6 months: 90.0 ± 5.4 vs 86.2 ± 6.8; P = .003) (Table 2), which indicated that LR-PRP may accelerate the recovery process. However, the maximal difference of 4.2 points between the LR-PRP and the control groups did not exceed the minimal clinically important difference (MCID) for ASES scores reported in previous literature.²⁸ The interaction effects of the Constant score, VAS scores, and ROM showed no significance (Table 2). The main effect analysis was then performed. Overall, there were no significant differences in the Constant score (P = .180), VAS score for pain during sleep (P = .907), VAS score for pain during activity (P = .571), abduction (P = .058), external rotation (P = .080), or internal rotation (P = .106) among the 3 groups over time (Table 2). A significant difference in flexion was found (treatment effect P = .038) (Table 2); however, further analysis found no differences between the groups.

Structural Integrity

A total of 133 patients completed MRI evaluation at 12 months: 40 of 50 (82%) in the LR-PRP group, 46 of 50 (92%) in the LP-PRP group, and 47 of 50 (94%) in the control group. No difference in the proportion of patients among the 3 groups was found (P = .103). Of these 133 patients, 1 in the control group had a complete retear (Sugaya IV), and 9 had a partial retear (Sugaya III), including 2 in the LR-PRP group, 4 in the LP-PRP group, and 3 in the control group. There were no significant differences in the rates of overall retears (LR-PRP vs LP-PRP vs control: 5% vs 9% vs 9%; P = .755) or complete retears (LR-PRP vs LP-PRP vs control: 0% vs 0% vs 2%; P = .633) among the 3 groups. Stratified analysis also found no effect of preoperative tear size or repair technique on postoperative retear.

Complications

Postoperative shoulder stiffness was observed in 4 patients: 1 from the LR-PRP group, 1 from the LP-PRP group, and 2 from the control group. All 4 patients regained ROM with extended rehabilitation exercises and avoided a second surgical procedure at 6 months. No other complications were recorded. This variable did not significantly differ between the groups (P = .790).

Discussion

Our study did not reveal that the LR-PRP or LP-PRP formulations had any effect on producing superior PROMs or active ROM at 12 months compared with those of the control group. A significantly greater ASES score, without achieving the MCID, was detected in the LR-PRP group than in the control group within 6 months after surgery. MRI assessments at 12 months after surgery also did not provide evidence that PRP use resulted in better structural integrity. The addition of PRP after surgery did not cause any adverse events. To our knowledge, this is the first randomized controlled trial to directly compare the outcomes of using LR-PRP, LP-PRP, or no PRP augmentation after arthroscopic rotator cuff tear repair using both clinical and imaging criteria.

Although laboratory studies have confirmed the feasibility of PRP for the treatment of tendinopathy, evidence on its clinical feasibility remains controversial.^{4,19,27,32,35} With the publication of a large number of level 1 and 2 studies, meta-analyses on the use of PRP after rotator cuff repair with different designs have been published.^{5,16,20,24,37} A previous meta-analysis found that PRP does not seem to improve PROMs.⁵ However, several subsequent meta-analyses revealed that compared with control, LP-PRP improved PROMs, but no advantages of LR-PRP were found.^20,37 However, the lack of studies directly comparing the effects of LR-PRP and LP-PRP limits the direct generalization of these conclusions. Our study directly compared LR-PRP, LP-PRP, and a control group, but we did not find that PRP provided superior PROMs 12 months after surgery, which is consistent with what has been reported in the vast majority of original articles.^2,26,33 During a shorter follow-up period (3 months and 6 months postoperatively), we observed that the LR-PRP group had higher ASES scores than did the control group. This finding is consistent with many studies suggesting that PRP may provide a faster recovery process early on,^26,33 but there is also the opposite conclusion that PRP may delay recovery.^22,35 Notably, the difference in our study did not reach the MCID reported in the previous literature²⁸; thus, the realistic benefit of this difference for patients needs to be carefully evaluated. Unlike most previous studies that did not report the ROM,^2,35,40 we found that the application of PRP may help patients recover ROM at an early stage. Our study found that patients in both the LR-PRP and the LP-PRP groups had slightly greater ROM than did those in the control group at both 3 and 6 months, although the difference was not significant.

Many studies have reported that PRP may provide more pain relief benefits than the control group.^20,24,37 Our study did not find any improvement effect of PRP on pain at any time point, during either sleep or daily activity. Interestingly, Randelli et al³³ found that within 1 month, pain scores were significantly lower in the PRP group than in the control group, but these differences disappeared at 3, 6, and 12 months of follow-up. At the 24-month follow-up, a difference in the VAS score was found between the 2 groups, but no differences in the PROMs were found. At the same time, 10 years of follow-up confirmed that the difference in the VAS score between the 2 groups at 24 months disappeared once again.³⁴ This suggests that we should be more cautious about the clinical significance of differences in VAS scores.

There is no consensus on the improvement in structural integrity after rotator cuff repair with PRP applications. Studies by Bergeson et al⁴ and Rodeo et al³⁵ reported negative results for PRP application, as confirmed by MRI and ultrasound, respectively. Most scholars have reported that PRP use may have positive or neutral results.²⁶ Hurley et al²⁰ suggested that LP-PRP may not be superior to LR-PRP in terms of structural integrity. However, these results were obtained through network meta-analysis, and we are the first clinical study to directly compare the effects of the 2 PRP formulations on structural integrity, finding no superior outcomes at 1 year for either LR-PRP or LP-PRP compared with the control group. At the same time, the rates of complete retear (1%) and overall retear (8%) in our study were also lower than those reported in the literature. This may be due to the lower mean age of our cohort and the exclusion of patients with massive tears, as previous studies have confirmed advanced age and tear size as risk factors for retearing after surgery.^14,23 The use of double-row suture bridge fixation in >80% of patients may also reduce the risk of retearing.¹⁹ We observed that most of the patients in our cohort typically performed low-intensity activities, which might have also lowered their risk of retearing after surgery.⁸ The vast majority of retears occur within 1 year of surgery; as time passes after surgery, retears continue to occur, and patients with retears have worse PROMs than those with intact rotator cuffs.^9,34 Considering that only 2 studies reported follow-up beyond 5 years,^27,34 studies examining the use of PRP over a longer follow-up period are warranted.

Although PRP has the potential to improve structural integrity after rotator cuff repair, surgeons still have some safety concerns when applying PRP, such as infection, arthrofibrosis, hyperplasia, carcinogenesis, and tumor growth.^4,22 Bergeson et al⁴ reported a 12% infection rate in the PRP group but not in the control group. Our study did not find an increased risk of infection or postoperative stiffness due to PRP use. Consistent with the vast majority of studies reported,^{22,26,31,43,44} PRP should be safe when applied with strict adherence to the principles of sterile procedures. The different conclusions about the usefulness of PRP in various studies could be attributed to several factors related to the preparation and use of PRP. The leukocyte concentration is considered to be an important influencing factor, and our study focused on exploring the difference between LR-PRP and LP-PRP. A high concentration of leukocytes may cause more inflammation and growth factor release than a low concentration,¹⁹ but an excessive inflammatory response is not conducive to postoperative tendon healing. Therefore, some scholars believe that LR-PRP may cause excessive scarring and thus affect tendon quality,^10,36,41,44 whereas some clinical and basic studies favor the use of LR-PRP.^12,16,25 Our study found no difference between the 2 formulations, and the effect of leukocytes in PRP warrants further investigation.

Liquid PRP, which was accepted in our study, rather than platelet-rich fibrin may be more beneficial for tendon healing in patients with small to large tears.^21,24,37 Although PRP in the fibrin state could prolong the release of growth factors,¹ its space-occupying effect may offset this advantage.³⁵ In addition to the leukocyte concentration and PRP form, the PRP injection time may also play a role. Zhang et al⁴⁴ reported that 3 injections of PRP after surgery could reduce the rate of postoperative retearing in medium to large tears. However, given the increased time and financial costs associated with 3 injections, such a treatment should be selected with caution.

Limitations

The limitations of our study must also be noted. First, the follow-up period in our study was relatively short. Recent literature reported that functional scores at 1 year after arthroscopic rotator cuff repair are sufficiently representative of treatment outcomes in the cohort, as only very small gains with no clinical differences were observed between 1 year and 2 years.³⁸ Considering that our primary outcome was the UCLA score, we believe that the 12-month follow-up results are worth reporting. Second, our study included isolated supraspinatus tendon tears, limiting the generalization of our results to multiple rotator cuff tendon tears or massive rotator cuff tears. These types of rotator cuff tears also predict a worse prognosis, which requires further exploration and effort. Third, compared with similar rotator cuff repair studies with PRP, our sample size was relatively large. However, outcomes such as structural integrity may be underpowered, as our sample size was calculated using the UCLA score. The best solution to this problem is to carry out a multicenter study with a larger sample size. Last, we used 2 commercial PRP preparations. Previous studies have demonstrated the effectiveness of these 2 preparation methods in the regulation of platelet and leukocyte concentrations. However, in our cohort, we did not record relevant data and did not precisely control the dose of PRP injected into each patient, which should be further improved in future experimental designs.

Conclusion

Our study did not reveal that shoulders treated with LR-PRP or LP-PRP formulations had any superior functional or structural outcomes at 12 months compared with those of the control group. However, LR-PRP may offer better ASES scores than the control group ≤6 months after surgery, and its clinical benefit remains to be proven.

Footnotes

Submitted May 15, 2024; accepted August 26, 2024.

One or more of the authors has declared the following potential conflict of interest or source of funding: This study was supported in part by grants from National Natural Science Foundation of China (82072514, 82272569) and New Technique Program of West China Hospital (20HXJS011). AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto. The ethics committee of West China Hospital, Sichuan University, provided approved for this study (2020-1287).

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