Platelet-Rich Plasma in Acute Muscle Injuries: An Umbrella Review and Meta-analysis of Return to Sport and Reinjury Outcomes

Abstract

Background:

Platelet-rich plasma (PRP) is frequently used in sports medicine to treat muscle injuries; however, the clinical evidence remains inconsistent and fragmented.

Purpose:

To assess whether PRP therapy improves clinical outcomes, particularly return to sport (RTS) and reinjury rate, compared with conventional treatments for acute muscle injuries.

Study Design:

Systematic review and meta-analysis; Level of evidence, 2.

Methods:

Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, a systematic search of PubMed, Embase, BVS, and Scopus was conducted through April 2025 for systematic reviews, with or without meta-analysis, to evaluate PRP for acute muscle injuries in athletes. A total of 1464 manuscripts were identified through the initial search. Main outcomes included RTS, reinjury rate, pain, and complications. Methodological quality was assessed using the Risk of Bias in Systematic Reviews (ROBIS) tool, and the certainty of the evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach. Meta-analyses were performed using random-effects models with Hartung-Knapp-Sidik-Jonkman adjustments.

Results:

Eight systematic reviews were included. PRP significantly reduced reinjury risk compared with controls (risk ratio, 0.84 [95% CI, 0.76 to 0.92]; I² = 0%), with high-certainty evidence. A reduction in RTS time favored PRP (mean difference, –4.43 days [95% CI, –9.28 to 0.42); however, it did not reach statistical significance (low-certainty evidence). Narrative synthesis suggested inconsistent short-term pain relief and low complication rates, but evidence certainty was rated very low to low due to methodological and reporting limitations.

Conclusion:

Our review study demonstrated that PRP may reduce muscular reinjury rates and potentially accelerate RTS, although benefits on pain and safety remain uncertain. Current evidence supports the selective use of PRP in sports settings; however, standardization in protocols and outcomes is needed. These findings may assist clinicians in individualizing treatment strategies involving PRP for acute muscle injuries, particularly in high-performance athletes at risk of recurrence.

Registration: CRD42021279300.

Acute muscle injuries are among the most common causes of time loss in competitive and recreational athletes,^5,4 accounting for up to 30% of all time-loss injuries in professional sports. ⁸ Despite advancements in rehabilitation strategies, recurrence rates remain high, particularly in hamstring and adductor injuries. ²⁰ In this context, platelet-rich plasma (PRP) has gained widespread attention as a potential adjunct to accelerate muscle healing, reduce pain, and shorten return to sport (RTS) time. ²⁹ PRP is frequently used in clinical and elite sports settings, yet its efficacy remains a subject of ongoing debate.

PRP is defined as a volume of the plasma fraction of autologous blood that has a platelet concentration above baseline (200,000 platelets/ul). ²³ Centrifugation is the most crucial step in the process, since it enables achieving a high platelet concentration within a small volume of plasma. ¹⁷ In addition to their role in hemostasis at sites of vascular injury, platelets also contain abundant growth factors and cytokines that are important for soft-tissue healing and bone mineralization. ⁴

In addition to PRP, the residual plasma fraction with low platelet concentration, known as platelet-poor plasma (PPP), has recently gained attention as a potential adjunct in muscle repair. Preliminary experimental data suggest that while PRP primarily promotes myoblast proliferation, PPP may facilitate the differentiation of native muscle cells, potentially supporting a more physiologic regeneration process. ²⁴ In a recent prospective cohort of collegiate athletes with acute hamstring strains, PPP injections were associated with faster pain reduction and a mean RTS time of 29 days, without recurrence at 12-month follow-up. ¹⁵ However, direct comparisons between PRP, PPP, and control groups remain limited, and the heterogeneity of existing studies precludes definitive conclusions.

Since 2009, PRP injection has grown in popularity due to public awareness secondary to the use of PRP in the treatment of high-profile athletes. ¹⁹ Numerous studies have investigated the role of PRP in the treatment of muscular lesions.^2,16,17 In animal model studies, PRP treatment decreased fibrogenesis and increased angiogenesis in muscle-contusion models, ²⁸ while other studies have reported its efficacy in enhancing the healing of tendons, cartilage, ligaments, and skeletal muscle in human models.^2,17

Although multiple randomized controlled trials and systematic reviews have evaluated PRP for muscle injuries, the findings have been inconsistent, with considerable variability in study design, PRP preparation protocols, and outcome measures. These discrepancies have led to uncertainty among clinicians about the true benefit of PRP in the management of muscle injuries. According to the International Olympic Committee consensus statement, the available evidence does not yet support the routine use of PRP for muscle injuries in elite athletes, mainly due to methodological limitations and heterogeneity across trials. ⁹ Existing systematic reviews are often limited by small sample sizes, methodological variability, and a lack of comprehensive synthesis. An umbrella review with meta-analysis is warranted to provide a high-level synthesis of current evidence and guide clinical decision-making. Therefore, this umbrella review aimed to comprehensively synthesize and critically appraise the current evidence on the efficacy of PRP for acute muscle injuries, with particular focus on RTS and reinjury outcomes. We hypothesized that PRP would reduce reinjury rates and shorten the time to RTS compared with conventional rehabilitation approaches.

Methods

Protocol and Registration

This systematic review and meta-analysis was conducted and reported in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and registered on the International Prospective Register for Systematic Reviews (PROSPERO; CRD42025638629).

Study Identification and Selection

MEDLINE via PubMed, Scopus, BVS, and Embase were searched in April 2025. There were no restrictions on publication dates or article languages. See complete search strategies in Table 1. The selection of the studies was conducted on an Excel (Microsoft Corporation) spreadsheet. An independent reviewer (E.N.K.) initially accessed and selected potential studies for inclusion based on title and abstract evaluation. A second independent reviewer (J.W.C.S.) then evaluated and judged the selection of the studies. When necessary, a third reviewer (P.B.J.) was consulted to solve the discordances. Full texts of selected articles were collected and evaluated in the same manner.

Table 1.

Search Strategies ^a

Databases	PubMed	Scopus	Embase	BVS
Search strategy	(“platelet rich plasma”[MeSH Terms] OR (“platelet rich”[All Fields] AND “plasma”[All Fields]) OR “platelet rich plasma”[All Fields] OR (“platelet”[All Fields] AND “rich”[All Fields] AND “plasma”[All Fields]) OR “platelet rich plasma”[All Fields]) AND (“injurie”[All Fields] OR “injuried”[All Fields] OR “injuries”[MeSH Subheading] OR “injuries”[All Fields] OR “wounds and injuries”[MeSH Terms] OR (“wounds”[All Fields] AND “injuries”[All Fields]) OR “wounds and injuries”[All Fields] OR “injurious”[All Fields] OR “injury s”[All Fields] OR “injuryed”[All Fields] OR “injurys”[All Fields] OR “injury”[All Fields]) AND (“systematic review”[Publication Type] OR “systematic reviews as topic”[MeSH Terms] OR “systematic review”[All Fields])	TITLE-ABS-KEY (platelet-rich AND plasma AND injuries AND systematic AND review)	(‘platelet-rich plasma’/exp OR ‘platelet-rich plasma’ OR (‘platelet rich’ AND (‘plasma’/exp OR plasma))) AND (‘injuries’/exp OR injuries) AND (‘systematic review’/exp OR ‘systematic review’ OR (systematic AND (‘review’/exp OR review)))	platelet-rich plasma AND injuries AND systematic review AND instance: “regional”
N	255	297	746	166

^aSearch strategies were used for the literature search across 4 databases (PubMed, Scopus, Embase, and BVS). The table shows search terms, filters, and total records retrieved from each source.

Only systematic reviews were selected. The inclusion criteria were as follows:

• Population: healthy adults aged between 18 and 70 years old who had muscle injuries.

• Intervention: PRP therapy for muscle injury treatment.

• Comparator/control: conservative treatment, without PRP.

• Outcomes: main outcomes—RTS (days); reinjury rate (%); complications (n). Additional outcomes—pain, imaging, and strength.

No strict minimum follow-up duration was defined. However, only studies reporting at least 1 follow-up assessment within the first 12 weeks after intervention were included, consistent with the expected timeframe for clinical recovery in acute muscle injuries.

Data Extraction

One investigator (E.N.K.) performed the data extraction from the selected articles. For each study, the sample size, patient’s age, patient’s characteristics, muscle group injured, PRP volume, platelet count, activating agents, the number of injection sites, centrifugation, separation system, ultrasound guidance, type of studies included, the number of studies included, control condition compared, the mean time after injury and the outcomes variables—including RTS (days), reinjury rate (%), complications (n), pain, strength, and imaging—were extracted. Authors of the included articles were contacted to request missing data when necessary.

Risk of Bias Assessment

Two independent reviewers (E.N.K. and J.W.C.S.) assessed the risk of bias for all included articles. When necessary, a third reviewer was consulted to resolve the discrepancies (P.B.J.). To evaluate the methodological quality and risk of bias of the included systematic reviews, we used the Risk of Bias in Systematic Reviews (ROBIS) tool. ³⁰ The ROBIS tool is a validated instrument specifically designed for assessing the risk of bias in systematic reviews. It comprises 3 phases: (1) assessing relevance (optional); (2) identifying concerns with the review process across 4 domains (eg, study eligibility criteria, identification and selection of studies, data collection, and study appraisal, synthesis, and findings); and (3) judging the overall risk of bias. Each domain is evaluated for potential concerns, and an overall risk of bias is assessed as low, high, or unclear.

Certainty of Evidence Assessment

The certainty of evidence for each primary outcome was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. ¹² The assessment considered risk of bias, inconsistency, indirectness, imprecision, and potential publication bias across the body of evidence. The overall certainty was rated as high, moderate, low, or very low. Two independent reviewers (E.N.K. and J.W.C.S.) conducted the GRADE assessment, with disagreements resolved by consensus or consultation with a third reviewer (P.B.J.).

Data analysis

RevMan Web (Cochrane Collaboration) software was used to conduct the meta-analysis. We performed 2 separate meta-meta-analyses: one for the outcome RTS (days) and another for the reinjury rate (no. of events). For both outcomes, we employed random-effects models using the Restricted Maximum Likelihood (REML) estimator and the Hartung-Knapp-Sidik-Jonkman (HKSJ) adjustment to account for heterogeneity across the included meta-analyses.

For the RTS (days) outcome, which was reported as a continuous variable using mean differences (MDs), with corresponding 95% CIs and standard errors, we used the Generic Inverse Variance (GIV) method implemented in RevMan Web to pool effect estimates. This method allows for the weighting of each meta-analysis based on the precision of its estimate.

For the reinjury rate (no. of events) outcome, reported using binary effect measures such as risk ratios (RRs), odds ratios, or risk differences, we first transformed all measures into a common metric, namely log risk ratios. The GIV method in RevMan Web was then used to pool the log-transformed RRs.

To enhance the robustness of our findings, we performed additional sensitivity analyses using alternative random-effects estimators in R (via the meta and metafor packages) (R Foundation for Statistical Computing). These analyses were intended to confirm the consistency of the results under different model specifications, particularly given the small number of included studies and anticipated heterogeneity.

Heterogeneity was quantified using the I² statistic and tau-squared (τ²). Because of the small number of included meta-analyses, we did not assess publication bias.

All statistical procedures were conducted independently by 2 researchers (E.N.K. and J.W.C.S.). Any discrepancies in analysis or interpretation were resolved through discussion and consensus.

Results

Flow of Studies Through the Review

The research in PubMed, Scopus, Lilacs, and BVS identified 1464 articles. After title and abstract screening, 1388 articles were excluded, along with 44 duplicate articles. A total of 32 articles were selected for full review. However, 24 articles were excluded for the following reasons: animal studies (n = 2); did not analyze muscle injuries (n = 6); did not provide sufficient data on the assessment of muscle injuries (n = 6); did not synthesize the results in the selected outcomes (n = 6); did not present sufficient dataon the evaluation of muscle injuries with the use of PRP (n = 2); were not a systematic review (n = 1); or were systematic reviews already included in this study, and thus excluded to avoid duplication of results (n = 1). Thus, 8 articles were included in this systematic review.^{1,11,13,18,22,25-27} A flow diagram of the full selection process is presented in Figure 1.

Figure 1.

PRISMA flow diagram.

A PRISMA 2020 flow diagram summarizing the selection process of systematic reviews included in the umbrella review. PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

Characteristics of Included Studies

Characteristics of the selected systematic reviews are shown in Table 2. Participants across the studies included both recreational and professional athletes, with reported ages ranging from approximately 20 to 45 years. Six of the 8 reviews^{1,13,18,22,25,26} focused primarily on hamstring injuries, whereas 3 reviews^11,18,27 additionally analyzed quadriceps, gastrocnemius, or adductor lesions.

Table 2.

Characteristics of the Included Systematic Reviews ^a

Author	Afonso etal 1	Grassi etal 11	Hamid etal 13	Molina etal 18	Pas etal 22	Rudisill etal 25	Seow etal 26	Sheth etal 27
DOI	10.1007/s40279-022-01783-z	10.1007/s40279-018- 0860-1	10.1371/journal.pone.0090538	biblio-1125541	10.1136/bjsports-2015-094879	10.1177/23259671211053833	10.1177/0363546520916729	10.1016/j.arthro.2017.06.039
Patients’ characteristics	n = 210; age: 20-38 y; sports players	n = 374; mean age, 30 y; professional male athletes	n = 27; mean age, not reported; professional sportsmen	n = 394; age, 21-45.6 y; characteristics not reported	n = 526; age, 20-32 y; characteristics not reported	n = 161; mean age, 26.2 ± 6.5; characteristics not reported	n = 207; mean age, not reported; characteristics not reported	n = 268; mean age, 25.1 y; characteristics not reported
Muscle group injured	Hamstring	Hamstring, rectus femoris, quadriceps, gastrocnemius,thigh, foot and ankle, and shoulder	Hamstring and adductor muscle group	Hamstring, gastrocnemius, quadriceps	Hamstring	Hamstring	Hamstring	Hamstring, quadriceps, gastrocnemius,thigh, foot and ankle, and shoulder
PRP volume	3-8 mL single application	3-8 mL	2.5 mL	2-3 mL	3 mL	1-8 mL	2.5-6 mL	3-5 mL
Platelet count	Not reported	433 ± 128*109/L to 1381 ± 430*109/L	Not reported	232*109/L to 289*109/L	433 ± 128*109/L to 1297*109/L	Not reported	433*109/L to 1297*109/L	433 ± 128*109/L to 1297*109/L
Activating agents	Not reported	Calcium chloride and no activating agent	Not reported	Calcium chloride and no activating agent	Not reported	Not reported	Calcium gluconate and no activating agent	Not reported
No. of injection sites	1-3 locations	1-2 locations	Not reported	Not reported	Not reported	Not reported	1-3 locations	1-2 locations
Centrifugation	Not reported	Not reported	Not reported	1400 - 4800 rpm	Not reported	Not reported	Not reported	Not reported
Separation system	Not reported	MCS+, Haemonetics, Braintree; ACP, Arthrex; GPS III, Biomet	Not reported	MCS+, Haemonetics; Ortho. Pras 20 Kit; Biomet Recover, GPS III Platelet separation system; Arthrex Medizinische Instrumente GmbH	Biomet; Arthrex	Not reported	GPS III, Biomet; Arthrex Medizinische Instrumente GmbH; RegenKit BCT-3 (Regenlab); Angel Whole Blood Separation System (Cytomedix Inc); Smart PReP (Harvest Technologies)	GPS III, Biomet; Arthrex Medizinische Instrumente GmbH
Ultrasound guidance	No	Yes	No	Yes	Yes	Not reported	Yes	Yes
Outcomes	RTS, day; reinjury rate	RTS, days; reinjury rate (%); complications (n); pain; strength; flexibility/ROM; functional scores; imaging	RTS, days	RTS, days; reinjury rate; pain	RTS, days; risk of reinjury (n); HR	RTS, days; reinjury rate	RTS, days; reinjury rate (%); complications (n)	RTS, days; reinjury rate (%)
Types of studies included	12 parallel randomized control trials; 2 non-randomized control trials	6 randomized control trials	1 randomized control trial; 3 in vivo laboratory studies	6 randomized control trials	10 randomized control trials	11 randomized control trials	10 control trials	5 randomized control trials
No. of studies included	14	6	4	7	10	11	10	5
Control	0.9% NaCl isotonic saline solution; Platelet-poor plasma	Conventional physical therapy, physical therapy and hematoma aspiration, physical therapy and isotonic saline injection	No intervention	Conventional physical therapy; platelet-poor plasma	Conventional physical therapy; platelet-poor plasma	0.9% NaCl isotonic saline solution; No intervention	Conventional physical therapy	0.9% NaCl isotonic saline solution; conventional physical therapy
Mean time after injury	Not reported	2.3 to 14.2 days	Not reported	Not reported	5 to 7 days	2 to 8 days	Not reported	3 to 4.6 days

^aThis table summarizes key characteristics of the included systematic reviews, including authors, study design, PRP protocols, comparators, and reported outcomes. ACP, autologous conditioned plasma; BCT-3, RegenKit BCT-3 (Regenlab); GPS III, Gravitational Platelet Separation System III (Biomet); HR, hazard ratio; MCS+, Multi-Component System Plus; MD, mean difference; n, number of studies or participants; PPP, platelet-poor plasma; PRP, platelet-rich plasma; RCT, randomized controlled trial; ROM, range of motion; RR, risk ratio; rpm, revolutions per minute; RTS, return to sport.

The time between injury and PRP administration, when reported, ranged from 2.3 to 14.2 days after injury.^11,22,25,26 Five reviews^{11,18,22,26,27} included only randomized controlled trials, while 2 reviews^1,14 also included nonrandomized or observational studies. Injection protocols varied across studies, but all reviews reporting injection frequency described single-dose PRP applications.^{1,11,13,18,22,25-27} Reported outcomes consistently included RTS time (all 8 reviews), reinjury rate,^{11,18,22,25-27} pain,^12,18 and complications.^11,26

Overall Critical Appraisal of Included Reviews

Across the 8 systematic reviews,^{1,11,12,18,22,25-27} substantial heterogeneity was identified in study scope, methodological rigor, and reporting detail. The earliest reviews, such as those by Hamid etal ¹³ and Pas etal, ²² established the foundation for PRP research in acute muscle injuries but included small randomized cohorts and limited protocol standardization. Subsequent reviews, including Grassi etal, ¹¹ and Seow etal, ²⁶ applied more rigorous inclusion criteria and quantitative synthesis, improving statistical precision but still reporting inconsistent effects on RTS outcomes.

Afonso etal ¹ uniquely adopted a living review design, updating evidence in real time and integrating multiple conservative interventions; however, PRP-specific data were diluted by broader rehabilitation content. In contrast, Molina etal ¹⁸ and Rudisill etal ²⁵ emphasized clinical applicability in elite athletes, providing detailed procedural variables (eg, injection volume, ultrasound guidance) that facilitate cross-trial comparison. Sheth etal ²⁷ represented one of the few analyses incorporating meta-analytic subgroup assessment by muscle group and injury grade.

Despite these methodological advances, key limitations persisted across reviews: incomplete reporting of platelet concentration and activation methods,^11,18,22,25 short follow-up durations (<12 weeks in all), and inconsistent definitions of reinjury. Only 3 reviews^11,22,24 explicitly discussed risk-of-bias assessment tools, and 2 reviews^1,25 combined randomized and nonrandomized evidence, reducing overall certainty.

Collectively, these reviews highlight the need for standardized PRP protocols and consistent reporting of outcomes.

Risk of Bias Assessment

The risk of bias assessment using the ROBIS tool revealed that, among the 8 systematic reviews included in this umbrella review, 6 reviews^{1,11,13,22,25,27} were classified as having a low overall risk of bias, indicating high methodological reliability. In contrast, 1 review ¹⁸ was rated as having a high risk of bias, primarily due to concerns regarding the selection of studies and the methods used for data synthesis. One additional review ²⁶ was judged to have an unclear risk of bias due to insufficient reporting across key methodological domains, precluding a definitive judgment.

At the domain level, most reviews adequately addressed the definition of eligibility criteria and conducted systematic and reproducible search strategies. However, isolated deficiencies were identified in some reviews, particularly in the transparency of selection procedures, the use of standardized critical appraisal tools, and the description of synthesis methods. The high-risk review presented methodological limitations that may have compromised the internal validity of its conclusions, while the unclear-risk review lacked sufficient detail to assess its methodological rigor.

Detailed assessments of ROBIS phases 2 and 3 are provided in Tables 3 and 4, while a summary of the overall risk of bias is presented in Table 5.

Table 3.

Phase 2: Identifying Concerns With the Review Process ^a

Study	Afonso etal 1	Grassi etal 11	Hamid etal 13	Molina etal 18	Pas etal 22	Rudisill etal 25	Seow etal 26	Sheth etal 27
1.1	Y	PY	PY	Y	Y	Y	PY	PY
1.2	Y	Y	Y	Y	Y	Y	Y	Y
1.3	Y	Y	Y	Y	Y	Y	Y	Y
1.4	Y	Y	Y	Y	Y	Y	Y	Y
1.5	Y	Y	Y	Y	Y	Y	Y	Y
1. Concerns regarding specification of study eligibility criteria. Rationale for concern:	Low	Low	Low	Low	Low	Low	Low	Low
2.1	Y	Y	Y	N	N	N	N	N
2.2	Y	Y	Y	Y	Y	Y	NI	PY
2.3	Y	Y	Y	Y	Y	Y	Y	Y
2.4	Y	Y	Y	Y	Y	Y	Y	Y
2.5	Y	Y	Y	Y	Y	Y	Y	Y
2. Concerns regarding methods used to identify and/or select studies. Rationale for concern:	Low	Low	Low	Low	Low	Low	Unclear. The literature search was limited to published articles, and it was not indicated whether additional research was conducted to identify relevant publications.	Low
3.1	Y	Y	Y	Y	Y	Y	Y	Y
3.2	Y	Y	Y	Y	Y	Y	Y	Y
3.3	Y	Y	Y	Y	Y	Y	Y	Y
3.4	Y	Y	Y	N	Y	Y	Y	Y
3.5	Y	Y	Y	N	Y	Y	Y	Y
3. Concerns regarding methods used to collect data and appraise studies. Rationale for concern:	Low	Low	Low	Unclear. The study did not provide an evaluation of the risk of bias.	Low	Low	Low	Low
4.1	Y	Y	Y	Y	Y	Y	Y	Y
4.2	Y	PY	PY	Y	PY	PY	PY	PY
4.3	Y	Y	Y	Y	Y	Y	Y	Y
4.4	Y	Y	Y	Y	Y	Y	Y	Y
4.5	PN	PN	PN	PN	PN	PN	PN	PN
4.6	Y	Y	Y	Y	Y	Y	Y	Y
4. Concerns regarding the synthesis and findings. Rationale for concern:	Unclear. There was a high heterogeneity in the methods from the primary studies.	Unclear. There was a high heterogeneity in the methods from the primary studies.	Unclear. There was a high heterogeneity in the methods from the primary studies.	High. There was a high heterogeneity in the methods and results from the primary studies.	Unclear. There was a high heterogeneity in the methods from the primary studies.	Unclear. There was a high heterogeneity in the methods from the primary studies.	Unclear. There was a high heterogeneity in the methods from the primary studies.	Unclear. There was a high heterogeneity in the methods from the primary studies.

^aDetailed assessment of phase 2 of the ROBIS tool: identification of concerns in the review process. Each domain includes signaling questions and final concern judgments. N, no; NI, no information; PN, probably no; PY, probably yes; ROBIS, Risk of Bias in Systematic Reviews; Y, yes.

Table 4.

Phase 3: Judging the Overall Risk of Bias ^a

Study	Afonso etal 1	Grassi etal 11	Hamid etal 13	Molina etal 18	Pas etal 22	Rudisill etal 25	Seow etal 26	Sheth etal 27
A	Y	Y	Y	PY	Y	Y	Y	Y
B	Y	Y	Y	Y	Y	Y	Y	Y
C	Y	Y	Y	PY	Y	Y	Y	Y
Risk of bias in the review	Low	Low	Low	High	Low	Low	Unclear	Low

^aFinal Risk of ROBIS judgments (phase 3) for the overall risk of bias of each included review, based on synthesis of all domains. N, no; NI, no information; PN, probably no; PY, probably yes; ROBIS, Risk of Bias in Systematic Reviews; Y, yes.

Table 5.

ROBIS Summary Assessment of the Included Reviews ^a

Study	1. Study Eligibility Criteria	2. Identification and Selection of Studies	3. Data Collection and Study Appraisal	4. Synthesis and Findings	Risk of Bias in the Review
Afonso etal 1
Grassi etal 10
Hamid etal 12
Molina etal 18
Pas etal 22
Rudisill etal 25
Seow etal 26
Sheth etal 27

^aVisual summary of risk-of-bias judgments across the ROBIS domains for each included review. Green indicates low risk, red indicates high risk, and blue indicates unclear risk. ROBIS, Risk of Bias in Systematic Reviews.

Certainty of Evidence Assessment

The GRADE evaluation indicated that the certainty of evidence for the outcome reinjury rate was high, supported by consistent findings, precise effect estimates, and a low risk of bias across studies. In contrast, the certainty for RTS was rated as low, mainly due to substantial heterogeneity (I² = 80%) and confidence intervals that included the null effect. The outcomes pain and complications were rated as very low and low, respectively, reflecting serious concerns in multiple domains—including methodological limitations, inconsistency among studies, and imprecision in reported results. Complete GRADE assessment is demonstrated in Table 6.

Table 6.

GRADE Assessment of Certainty of Evidence for Each Primary Outcome ^a

Outcome	Sport, Days	Reinjury Rate, %	Pain	Complications
N of reviews (studies)	5 reviews (multiple RCTs)	4 reviews (multiple RCTs)	2 reviews (narrative)	2 reviews (narrative)
Study design	Systematic reviews of RCTs	Systematic reviews of RCTs	Systematic reviews of RCTs	Systematic reviews of RCTs
Risk of bias	Not serious	Not serious	Serious (limited reporting)	Serious (incomplete reporting)
Inconsistency	Serious (I2 = 80%)	Not serious (I2 = 0%)	Serious	Not serious
Indirectness	Not serious	Not serious	Serious (secondary outcome)	Not serious
Imprecision	Borderline (CI includes null)	Not serious	Serious	Serious (few events)
Publication bias	Undetected	Undetected	Undetected	Undetected
Overall certainty	●●○○ Low	●●●● High	●○○○ Very low	●●○○ Low

^aJudgments are based on risk of bias, inconsistency, indirectness, imprecision, and publication bias. Overall certainty was rated as high (●●●●), moderate (●●●○), low (●●○○), or very low (●○○○) according to GRADE criteria. GRADE, Grading of Recommendations Assessment, Development, and Evaluation; RCT, randomized controlled trials.

Assessment of publication bias was not performed because the number of studies per outcome was insufficient to allow meaningful funnel plot analysis or statistical tests.

Meta-analysis: RTS

A meta-analysis including 5 studies^{11,13,18,22,26} (n = 1116 participants; 548 PRP and 568 control) evaluated the effect of PRP compared with control interventions on RTS time, measured in days. The pooled MD favored PRP, with a reduction of 4.43 days on average in RTS time compared with controls (MD, –4.43 days [95% CI, –9.28 to 0.42), although this did not reach statistical significance (P = .06).

The analysis employed a random-effects model using the Hartung-Knapp-Sidik-Jonkman method to account for between-study heterogeneity. Substantial heterogeneity was observed (I² = 80%; χ² = 33.16; df = 4; P < .0001), and the estimated between-study variance (τ²) was 13.69 (95% CI, 2.77-100.54), calculated using the REML method. The forest plot graphic of this meta-analysis is shown in Figure 2.

Figure 2.

Forest plot graphic of RTS.

Meta-analysis comparing PRP versus control therapies for RTS time, measured in days. The pooled effect did not reach statistical significance. MD, mean difference; PRP, platelet-rich plasma; RTS, return to sport.

Meta-analysis: Reinjury Rate (Number of Events)

A meta-analysis of 4 studies^11,22,26,27 involving a total of 729 participants (353 in the PRP group and 376 in the control group) assessed the effect of PRP on the rate of muscle reinjury. The pooled results demonstrated a statistically significant reduction in the risk of reinjury in the PRP group compared with control interventions. The combined RR was 0.84 (95% CI, 0.76-0.92; P = .01), indicating a 16% relative reduction in the likelihood of reinjury after PRP treatment.

The analysis was conducted using a random-effects model with the HKSJ adjustment. No heterogeneity was observed among the included studies (I² = 0%; τ² = 0.00; χ² = 0.09, df = 3; P = .99), supporting the consistency of the effect across study populations and methodologies. The forest plot graphic of this meta-analysis is shown in Figure 3.

Figure 3.

Forest plot graphic of reinjury rate (number of events).

Meta-analysis comparing PRP versus control therapies for muscular reinjury rate. PRP significantly reduced the reinjury risk. PRP, platelet-rich plasma; RR, risk ratio.

Narrative Synthesis: Pain

Two of the 8 included systematic reviews^11,18 reported data on pain outcomes after PRP application in the treatment of acute muscle injuries. Molina etal ¹⁸ identified 5 primary studies that assessed pain using the visual analog scale or other validated scoring systems. Among these, 3 studies described a transient reduction in pain intensity in the PRP groups during the early rehabilitation phase. However, none of the included studies demonstrated sustained differences in pain levels between PRP and control groups at the final follow-up.Similarly, Grassi etal ¹¹ qualitatively reported short-term pain relief associated with PRP, but did not find consistent or statistically significant effects across trials. Due to variability in outcome measures, assessment time points, and incomplete reporting of data, a quantitative synthesis was not feasible.

Narrative synthesis: Complications

Given the limited number of studies and the low incidence of complications, a meta-analysis could not be performed. Only 2 of the 8 included systematic reviews^11,26 provided extractable data on treatment-related complications. In the review by Seow etal, ²⁶ the reported complication rate associated with PRP injection was 5.2% ± 2.9%, with events ranging from post-injection discomfort and pain to transient sciatic nerve irritation. These adverse events were generally mild, with no reported infections, and in most cases, symptoms resolved spontaneously or were not associated with lasting deficits. Similarly, Grassi etal ¹² reported no statistically significant difference in complication rates between PRP and control groups across the included randomized controlled trials, noting only minor adverse effects such as injection-site discomfort or transient hematoma. No serious adverse events were described in either review.

Narrative synthesis: Other Outcomes

Only 1 of ¹¹ the 8 included systematic reviews. reported data on additional secondary outcomes beyond RTS, reinjury, pain, and complications. These outcomes included muscle strength, flexibility, range of motion, functional scores, and imaging findings, such as ultrasound or magnetic resonance imaging (MRI)-based assessments of muscle healing. The review qualitatively synthesized these outcomes, based on a limited number of primary studies with heterogeneous methodologies. While some studies suggested improvements after PRP application, the reporting was inconsistent, and standardized outcome measures were lacking. Due to the limited evidence and variability in reporting, no quantitative synthesis was performed for these domains.

Discussion

The main findings of this umbrella review indicate that PRP therapy may be beneficial in the management of acute muscle injuries in athletes. Overall, most of the included systematic reviews demonstrated high methodological quality according to the ROBIS assessment, although caution remains warranted when interpreting findings from reviews with identified or potential bias. Quantitatively, PRP significantly reduced the risk of muscular reinjury compared with conservative treatments (pooled RR, 0.84 [95% CI, 0.76-0.92]; I² = 0%; P = .01), representing an approximate 16% relative reduction in recurrence. Although the pooled analysis for RTS time favored PRP (MD, –4.43 days [95% CI, –9.28 to 0.42]; I² = 80%; P = .06), the effect did not reach statistical significance. Nevertheless, both meta-analyses consistently favored PRP over control interventions, suggesting a potential clinical benefit in selected contexts.

RTS Time

The impact of PRP on RTS time remains a matter of ongoing debate. In our umbrella review, although the pooled analysis favored PRP over control interventions, the mean reduction in RTS time did not reach statistical significance. However, the trend observed suggests a potential benefit for accelerating functional recovery. These findings are consistent with previous meta-analyses, such as the one conducted by Grassi etal, ¹¹ which also reported a significantly shorter RTS time favoring PRP (MD, –7.17 days), although results lost significance in subgroup analyses restricted to double-blind studies or hamstring-only injuries.

Several hypotheses may explain the variability in RTS outcomes. First, PRP formulations and injection protocols varied widely across studies, with heterogeneity in leukocyte content, volume, and administration timing potentially influencing therapeutic efficacy. Andia and Abate ³ emphasize that PRP products lack uniformity and that this variability likely underlies inconsistent results in muscle injury studies. Moreover, the definition and criteria for RTS were not standardized, ranging from subjective athlete-reported readiness to more objective strength and imaging criteria, thereby introducing measurement bias. ²¹ Grassi etal ¹¹ highlighted that studies with lower methodological rigor tended to favor PRP, raising concerns about the reliability of earlier positive findings.

Despite these limitations, some studies support the potential of PRP to reduce convalescence duration. For example, the pilot human trial summarized by Hamid etal ¹³ reported a significantly shorter recovery time in athletes receiving autologous conditioned serum, a PRP derivative, compared with controls (16.6 vs 22.3 days), alongside favorable MRI findings. However, the lack of blinding and small sample size reduces the generalizability of these findings. Additionally, in the living systematic review by Afonso etal, ¹ PRP did not consistently shorten RTS or reduce reinjury risk, and the certainty of evidence was graded as very low due to heterogeneity and high risk of bias across studies.

Taken together, our meta-analysis adds to the growing body of evidence suggesting that PRP might have a modest effect in shortening RTS time. However, given the lack of statistical significance in high-quality studies and the substantial methodological heterogeneity observed, the routine use of PRP for the sole purpose of accelerating RTS in muscle injuries cannot yet be recommended.

Reinjury Rate

Our meta-analysis demonstrated that PRP significantly reduced the rate of muscular reinjury in athletes compared with control interventions. These findings are clinically relevant, as muscle reinjuries often result in prolonged downtime, higher treatment costs, and greater functional impairment.^20,26,27 Clique ou toque aqui para inserir o texto. Notably, all included studies reported point estimates favoring PRP, even if none reached statistical significance individually. This consistency strengthens the overall signal toward a protective effect. Previous systematic reviews, such as those of Grassi etal ¹¹ and Seow etal, ²⁶ reported similar tendencies, although most did not perform a pooled analysis due to limited data availability.

Mechanistically, PRP may reduce reinjury risk by enhancing tissue healing through growth factor-mediated fibroblast activation, angiogenesis, and modulation of inflammation.^3,8,21 However, the precise biological mechanisms remain under investigation, and it is unclear whether the observed effect is sustained in the long term. In addition, definitions of reinjury varied across studies: some relied solely on clinical criteria, while others included imaging or functional performance metrics. Despite this, the consistent trend across trials and lack of heterogeneity lend support to the potential role of PRP in reducing recurrence, especially in athletes at high risk of reinjury due to premature return to activity or high-performance demands.

Emerging Evidence on PPP

Recent investigations have proposed PPP as a potentially superior biologic therapy for acute muscle injuries. While PRP contains a high concentration of platelets and growth factors that stimulate early proliferation and angiogenesis, PPP may exert more balanced regenerative effects by promoting myogenic differentiation and limiting excessive fibroblast activation. Two recent studies reported that PPP injections led to faster functional recovery and lower recurrence rates compared with PRP in small randomized cohorts of athletes with acute thigh injuries.^15,24 The hypothesized mechanism involves reduced profibrotic signaling mediated by TGF-β, leading to improved muscle fiber organization. However, these findings remain preliminary, as sample sizes were limited and PPP preparation protocols lack standardization. Future comparative trials are warranted to clarify whether PPP provides distinct clinical advantages over PRP for muscle regeneration.

Pain

The available evidence suggests that PRP may offer transient pain relief during the early phases of rehabilitation. However, the limited and inconsistent reporting of pain as an outcome, combined with the heterogeneity of measurement tools, time points, and clinical contexts, precludes definitive conclusions. Furthermore, pain relief may be a secondary benefit of accelerated tissue repair, rather than a direct effect of PRP.^6,7 These limitations highlight the need for more targeted research using standardized pain scales and follow-up protocols to clarify whether PRP provides meaningful analgesic benefits in the context of muscle injury recovery.

Complications

PRP demonstrated a favorable safety profile for the treatment of muscle injury. No serious adverse events or infections were reported in either review. These findings are consistent with the broader PRP literature across other musculoskeletal conditions, in which autologous PRP is generally considered safe due to its nonimmunogenic and minimally invasive nature. ¹⁰ However, the low frequency of reporting and lack of standardization in adverse event definitions underscore the need for more rigorous safety monitoring in future trials.

Limitations

This umbrella review presents several limitations that should be acknowledged. First, only 8 systematic reviews met the eligibility criteria, and many included only a small number of primary studies, which may have limited the statistical power and generalizability of the pooled analyses. Second, there was substantial heterogeneity in PRP preparation and administration protocols (variations in injection volume, frequency, leukocyte content, activation methods, and timing), which precluded meaningful subgroup or dose-response analyses and may have contributed to inconsistencies in treatment effects. Third, the included reviews employed heterogeneous definitions and outcome measures for key endpoints, such as RTS, reinjury rate, and pain, and showed wide variation in follow-up duration and assessment tools. Moreover, adverse event reporting was inconsistent and often incomplete, limiting the ability to comprehensively evaluate the safety profile of PRP.

While the ROBIS assessment indicated that most reviews were at low risk of bias, the methodological quality of the underlying primary studies was variable. This was reflected in the GRADE assessment: the certainty of the evidence was rated as high only for the outcome of reinjury rate, whereas other outcomes, such as RTS, pain, and complications, were downgraded due to concerns related to inconsistency, imprecision, and risk of bias. These limitations highlight the need for more rigorous, standardized trials to strengthen the evidence based on the efficacy and safety of PRP for the treatment of muscle injuries.

Clinical Implications

Despite these limitations, the findings of this umbrella review provide relevant insights for clinical practice. The observed reduction in reinjury rates associated with PRP, along with the trend toward shorter RTS time, suggests a potential role for PRP as an adjunct in the rehabilitation of acute muscle injuries, particularly in high-performance athletes at elevated risk for recurrence. However, given the lack of standardized PRP preparation and delivery protocols, clinicians should interpret these findings with caution and avoid generalizing results across different PRP formulations. Furthermore, the evidence does not currently support the routine use of PRP for pain control or as a replacement for structured rehabilitation protocols, which remain the cornerstone of muscle injury management. Until large-scale, well-controlled trials with standardized outcome measures are available, the use of PRP should be individualized and guided by clinical judgment, patient preference, and context-specific factors.

Conclusion

Our review study demonstrated that PRP may reduce muscular reinjury rates and potentially accelerate RTS, although benefits on pain and safety remain uncertain. Current evidence supports the selective use of PRP in sports settings; however, standardization in protocols and outcomes is needed. These findings may assist clinicians in individualizing treatment strategies involving PRP for acute muscle injuries, particularly in high-performance athletes at risk of recurrence.

Data Sharing Statement

We intend to share individual deidentified participant data from the studies included in this review. Related documents will be available via the PROSPERO protocol (CRD42021279300). These data will be made available immediately following publication, for an unlimited period, to researchers who provide a methodologically sound proposal. Access will be granted upon request by contacting the corresponding author.