Role of Platelet-Rich Plasma Injection in Anterior Cruciate Ligament Reconstruction: A Meta-Analysis of Randomized Controlled Trials
Abstract
1. Introduction
2. Methods
2.1. Literature Search
2.2. Study Eligibility
2.3. Inclusion Criteria
2.4. Exclusion Criteria
2.5. Data Extraction
2.6. Quality Assessment
2.7. Statistical Analysis
3. Results
3.1. Literature Selection
3.2. Basic Characteristics of the Literature
3.3. Quality Assessment
3.4. VAS Score
3.5. IKDC Score
3.6. Lysholm Score
3.7. Tegner Score
3.8. Anterior Knee Laxity
3.9. Physical Examinations and Other Outcomes
3.10. Radiological Outcomes
3.11. Data Synthesis of PRP Parameters
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
| ACL | Anterior Cruciate Ligament |
| PRP | Platelet-Rich Plasma |
| PRISMA | Preferred Reporting Items for Systematic Reviews and Meta-Analyses |
| IKDC | International Knee Documentation Committee |
| MD | Mean Difference |
| CI | Confidence Interval |
| RCTs | Randomized Controlled Trials |
| KOOS | Knee Injury and Osteoarthritis Outcome Score |
| VAS | Visual Analogue Scale |
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| First Author-Year | Study Design-LOE | Sample Size | Age (Years) | Sex (Male /Female) | Follow-Up (Months) | Drop Out | ||||
|---|---|---|---|---|---|---|---|---|---|---|
| PRP | No PRP | PRP | No PRP | PRP | No PRP | PRP | No PRP | |||
| Ventura-2005 | RCT-I | 10 | 10 | 36.6 ± 9.3 | 30.2 ± 5.3 | 9/1 | 9/1 | 6 | 0 | 0 |
| Orrego-2008 | RCT-II | 29 | 29 | 30 (15–57) | 85% | 6 | 3 | 2 | ||
| Nin-2009 | RCT-I | 50 | 50 | 26.1 (14–57) | 26.6 (15–59) | 40/10 | 38/12 | 6 | 0 | 0 |
| Silva-2009 | RCT-II | 30 | 10 | 26.8 ± 5.3 | 38/2 | 3 | 0 | 0 | ||
| Vogrin-2010 | RCT-I | 25 | 25 | 37.2 ± 8.4 | 32.6 ± 12.3 | 15/10 | 16/9 | 3 | 4 | 5 |
| Vogrin-2010 | RCT-I | 25 | 25 | 35.4 ± 10.0 | 33.0 ± 12.5 | 15/10 | 16/9 | 6 | 3 | 2 |
| Cervellin-2012 | RCT-I | 20 | 20 | 22.9 ± 4.3 | 22.7 ± 3.5 | 20/0 | 20/0 | 12 | 2 | 3 |
| de Almeida-2012 | RCT-I | 12 | 15 | 25.8 (18–44) | 23.1 (15–34) | 10/2 | 14/1 | 6 | 2 | 2 |
| Mirzatolooei-2013 | RCT-I | 25 | 25 | 26.4 (18–40) | 26.9 (18–40) | 20/3 | 22/1 | 3 | 4 | 5 |
| Rupreht-2013 | RCT-I | 25 | 25 | 37.2 ± 8.4 | 32.6 ± 12.3 | 15/10 | 16/9 | 6 | 4 | 5 |
| Rupreht-2013 | RCT-I | 25 | 25 | 37.2 ± 8.4 | 32.6 ± 12.3 | 15/10 | 16/9 | 6 | 2 | 2 |
| Seijas-2013 | RCT-I | 50 | 50 | NA | NA | NA | NA | 12 | 1 | 1 |
| Vadalà-2013 | RCT-II | 20 | 20 | 34.5 (18–48) | 20/0 | 20/0 | 14.7 | 0 | 0 | |
| Starantzis-2014 | RCT-I | 30 | 30 | 29.4 ± 7.3 | 31.3 ± 8.0 | 38/13 | 12 | 5 | 4 | |
| Seijas-2015 | RCT-I | 23 | 21 | NA | NA | 20/3 | 17/3 | 12 | 0 | 1 |
| Seijas-2016 | RCT-I | 23 | 21 | NA | NA | 20/3 | 17/3 | 24 | 0 | 1 |
| Walters-2018 | RCT-II | 30 | 29 | 30 ± 12 | 10/17 | 12/11 | 24 | 7 | 8 | |
| Mahdi-2019 | RCT-I | 14 | 13 | 25.77 | 25.77 | 14/0 | 13/0 | 3 | 0 | 0 |
| Gong-2022 | RCT-I | 30 | 30 | 33.5 ± 8.97 | 34.9 ± 9.68 | 18/12 | 21/9 | 12 | 3 | 4 |
| Kumar-2022 | RCT-I | 35 | 35 | 28.34 ± 4.32 | 29.71 ± 2.99 | 22/13 | 23/12 | 3 | 0 | 0 |
| Munde-2023 | RCT-I | 44 | 43 | 28.37 ± 2.8 | 27.4 ± 7.0 | 36/4 | 38/2 | 6 | 4 | 3 |
| Lin-2024 | RCT-I | 10 | 10 | 28.4 ± 7.8 | 29.7 ± 9.9 | 6/2 | 6/4 | 12 | 2 | 0 |
| Ye-2024 | RCT-I | 60 | 60 | 28.0 ± 7.9 | 30.0 ± 8.0 | 43/17 | 41/19 | 12 | 3 | 3 |
| Author-Year | Graft Source | Graft Type | Fixation Method | Rehabilitation Protocol |
|---|---|---|---|---|
| Ventura-2005 | Autograft | Quadrupled hamstring tendon | Transcondylic fixation (femoral side) and interference screw (tibial side) | Immediate post-operative mobilization without a knee brace, protected weight bearing for 3 weeks, and return to sporting activities at 6 months. |
| Orrego-2008 | Autograft | Quadrupled hamstring tendon | Biodegradable transfixing pin (femoral side) and biodegradable interference screw (tibial side) | NA |
| Nin-2009 | Allograft | Patellar tendon | 2 biodegradable cross pins (femoral side) and biodegradable interference screw (tibial side) | Immediate post-operative immobilized with a knee brace, whole range of movement after 10 days, Cycling at 2 to 3 months, straight-line running, at 4 months, and sports at 6 months. |
| Silva-2009 | Autograft | Double-bundle hamstring tendon | EndoButton CL devices (femoral side) and bioabsorbable interference screw (tibial side) | Immobilization of the knee with a brace in full extension for a week after surgery, after which mobilization is started, below 90 of flexion until the fourth week and then, increasing the flexion of the knee 15 every week. Protection from weight bearing is used for 5 weeks after surgery. |
| Vogrin-2010 | Autograft | Double-looped hamstring tendon | 2 bioabsorbable cross pins (femoral side) and bioabsorbable interference screw (tibial side) | No rehabilitation brace was used postoperatively. Running at 12 weeks and contact sports at 6 months provided that the patient had no knee joint effusion, achieved a full range of motion and obtained muscle strength of at least 90% compared to the contralateral leg. |
| Vogrin-2010 | Autograft | Double-looped hamstring tendon | 2 bioabsorbable cross pins (femoral side) and bioabsorbable interference screw (tibial side) | No rehabilitation brace was used postoperatively. Running was allowed at 12 weeks and contact sports at 6 months in cases with no knee-joint effusion, full range of motion and obtained muscle strength of 90% compared with the contralateral leg. |
| Cervellin-2012 | Autograft | Bone-patellar tendon-bone | NA | Weight bearing with the knee extended for the first 15 days, followed by partial weight bearing for the next 15 days. walking without the aid of crutches during the second months. During the third and fourth months, closed kinetic chain exercises and gradual return to sports activity were allowed. |
| de Almeida-2012 | Autograft | Bone-patellar tendon-bone | A transverse double pin absorbable system (femoral side) and an absorbable interference screw (tibial side). | Early range of motion and progressive weight-bearing with crutches for 3 weeks. |
| Mirzatolooei-2013 | Autograft | Quadrupled hamstring tendon | A cross-pin (femoral side) and bio-absorbable interference screw (tibial side) | Wore a knee immobilizer in full extension for two weeks. |
| Rupreht-2013 | Autograft | Double-looped hamstring tendon | 2 bioabsorbable cross pins (femoral side) and one bioabsorbable interference screw (tibial side) | NA |
| Rupreht-2013 | Autograft | Double-looped hamstring tendon | 2 bioabsorbable cross pins (femoral side) and one bioabsorbable interference screw (tibial side) | NA |
| Seijas-2013 | Autograft | Bone-patellar tendon-bone | Hydroxylapatite screws (both femoral and tibia sides) | Postoperatively, the knee was immobilized with 2 plaster splints. At week 4, progressive weight-bearing ambulation was allowed as pain tolerated. Pool exercises were started at week 6, outdoor cycling at month 3, progressive running at month 4, and return to unrestricted sporting activities at month 6. |
| Vadalà-2013 | Autograft | Hamstring tendon | Swing-Bridge device (femoral side) and the Evolgate (tibial side) | Post-operatively, all patients started weight-bearing with the use of crutches the day after the operation. Within the first 6 weeks, patients started progressive isotonic and isokinetic exercises. Patients involved in sports activities were allowed to return to practice their sport 6 months after surgery, and patients involved in noncontact sports after 4 months. |
| Starantzis-2014 | Autograft | Quadrupled hamstring tendon | Crosspin or Endobutton (femoral side) and biodegradable interference screw + bone bridge suture anchoring (tibial side) | NA |
| Seijas-2015 | Autograft | Bone-patellar tendon-bone | NA | NA |
| Seijas-2016 | Autograft | Bone-patellar tendon-bone | NA | NA |
| Walters-2018 | Autograft | Bone-patellar tendon-bone | Two titanium cannulated interference screws (both femoral and tibial side) | NA |
| Mahdi-2019 | Autograft | Quadrupled-strand hamstring tendon | “Suspensory” fixation mechanism (Endobutton) in both sides. | NA |
| Gong-2022 | Autograft | Quadrupled-strand hamstring tendon | Endobutton (femoral side) and Intrafx Device (tibial side) | Partial weight-bearing was permitted with the brace locked in full extension within 4 weeks after operation. Full weight-bearing with the brace was permitted at the seventh week after operation; full weight-bearing without the brace was permitted at the third month after operation. Walking, running and contact sports were permitted after 3, 6 and 9 months, respectively. |
| Kumar-2022 | Autograft | Hamstring tendon | Endobutton (femoral side) and biodegradable interference screw (tibial side) | Standard ACL rehabilitation protocol which included gaining a range of motion, muscle strength and returning to preinjury status in phasic manner. |
| Munde-2022 | Autograft | Quadrupled hamstring tendon | Adjustable loop button (femoral side) and biodegradable interference screw (tibial side) | In the first phase (up to 2 weeks) all patients were started on full weight-bearing walking with crutches, isometric quadriceps exercises, etc. In the second phase (2–4 weeks), quadricep strengthening exercises, knee ROM exercises, and balance exercises started. In the third and fourth phase (1–6 months), resistance band quadriceps, hamstring strengthening exercises, jogging, controlled single-leg jumping, plyometric exercises, etc. were done. |
| Lin-2024 | Autograft | Fourth or fifth-strand hamstring tendon | Interference screws (femoral side) and Interference screws + cancellous post-screw (tibial side) | Every subject underwent the program at 1, 3, 5, 7, and 9 weeks post-surgery. |
| Ye-2024 | Autograft | Quadrupled-strand hamstring tendon | Cortical buttons (femoral side) and biodegradable interference screw + cortical button with an adjustable loop (tibial side) | Standardized rehabilitation education from a physical therapist through verbal instruction, printed brochures, and online videos before discharge. |
| Author-Year | Processing Machine | Whole Blood Volume (mL) | Anticoagulants | Spin Speed (rpm) | Spin Time (min) | Platelet Concentration (mm3) | Activation | Form | Leukocyte | Location | Time Point | Volume (mL) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Ventura-2005 | GPS Biomet Merck technique (Biomet Inc., Warsaw, IN, USA) | 54 | Citric acid | 3200 | 12 | NA | Autologous thrombin | gel | rich | Femoral and tibial tunnels | Intraoperative | NA |
| Orrego-2008 | Biomet GPS II kit (Biomet, Warsaw, IN, USA) | 57 | NA | 200 | 15 | NA | Autologous thrombin with CaCl2 | gel + liqiud | rich | Between the strands of the graft and femoral tunnel | Intraoperative | 6 |
| Nin-2009 | Beckman J-6B, Beckman Coulter Spain, Madrid, Spain | 40 | Citric acid | 1st: 3000 2nd: 1000 | 1st: 8 2nd: 6 | 837,000 | CaCl2 | gel | poor | Graft was covered with gel and inside the tibial tunnel | Intraoperative | 4 |
| Silva-2009 | Mini GPS III Kit (Biomet) | 27 | Citric acid | 3200 | 15 | NA | Autologous thrombin | gel + liqiud | rich | Between the strands of the graft and inside the femoral tunnel | Intraoperative | 3 |
| Vogrin-2010 | Magellan (Medtronic Biologic Therapeutics and Diagnostics, Minneapolis, MN, USA) autologous platelet separator | 50 | 10% calcium citrate | NA | NA | 978 × 109/L (range 552 to 1326 × 109/L) | Autologous thrombin | gel | rich | Between the strands of the graft and inside the femoral and tibial tunnels. | Intraoperative | 6 |
| Vogrin-2010 | Magellan autologous platelet separator (Medtronic Biologic Therapeutics and Diagnostics, Minneapolis, MN, USA) | 50 | 10% calcium citrate | NA | NA | 962 (552–1326) G/L | Autologous thrombin | gel | rich | Between the strands of the graft and inside the femoral and tibial tunnels. | Intraoperative | 6 |
| Cervellin-2012 | Gravitational Platelet Separation II (GPS) system (Biomet Biologics, Inc., Warsaw, IN, USA) | 54 | ACD-A | 3200 | 15 | NA | Autologous thrombin with CaCl2 | gel | rich | Patellar and tendon bone plug harvest site | Intraoperative | NA |
| de Almeida-2012 | A Haemonetics MCS1 9000 cell separator with a specific kit for platelet apheresis 995-E (Haemonetics Corp., Braintree, MA, USA) | 450 | 10% citrate | NA | NA | 1,185,166 ± 404,472 | Autologous thrombin with CaCl2 | gel | poor | Patellar tendon defect | NA | 20–40 |
| Mirzatolooei-2013 | Double syringe system (Arthrex, Naples, FL, USA) | 10 | NA | 1500 | 5 | NA | CaCl2 | liquid | poor | Between the strands of the graft and inside the femoral and tibial tunnels. | Intraoperative | 3.5 |
| Rupreht-2013 | Magellan autologous platelet separator (Medtronic Biologic Therapeutics and Diagnostics) | 50 | NA | NA | NA | NA | Autologous thrombin | gel | rich | Between the strands of the graft and inside the femoral and tibial tunnels. | Intraoperative | 6 |
| Rupreht-2013 | Magellan autologous platelet separator (Medtronic Biologic Therapeutics and Diagnostics) | 50 | NA | NA | NA | 978 × 109/L (range 552 to 1326 × 109/L) | Autologous thrombin | gel | rich | Between the strands of the graft and inside the femoral and tibial tunnels. | Intraoperative | 6 |
| Seijas-2013 | PRGF technique (BTI Systems Vitoria, Spain) | NA | NA | NA | NA | NA | No activation | liquid | NA | Suprapatellar joint after portal suture | Intraoperative | 8 |
| Vadalà-2013 | PRP Fast Biotech kit (MyCells PPT-Platelet Preparation Tube) | 10 | NA | NA | NA | NA | Autologous thrombin with Ca-gluconate | liquid + gel | NA | Between the strands of the graft and inside the femoral and tibial tunnels. | Intraoperative | 15 |
| Starantzis-2014 | Biomet GPS III kit (Biomet, Warsaw, IN, USA) | 55 | ACD-A | 3200 | 15 | NA | CaCl2. | liquid + gel | rich | Between the strands of the graft and inside the femoral tunnel. | Intraoperative | 6 |
| Seijas-2015 | NA | 20cc | NA | NA | NA | NA | NA | NA | NA | Patellar bone gap, tibial bone gap, and the center of harvest gap. | Intraoperative | 4 |
| Seijas-2016 | NA | 34cc | Sodium citrate | 1800 | 8 | NA | CaCl2 | gel | NA | Patellar bone gap, tibial bone gap, and the center of harvest gap. | Intraoperative | 4 |
| Walters-2018 | A PRP separation kit and centrifuge system (ACP PRP; Arthrex) | 10 | ACD-A | 1500 | 5 | NA | CaCl2 | gel | poor | Patellar donor site | NA | 3–5 |
| Mahdi-2019 | Trima Accel Automated Blood Collection system | 100–150 | NA | NA | NA | 5–7 × 107 | No activation | liquid | NA | Inside femoral tunnel and intra-articularly | Intraoperative | 6 |
| Gong-2022 | Platelet Rich Plasma Preparation Kits (WEGO; Beijing, China) and a centrifuge (WEGO; Beijing, China) | 36 | ACD-A | NA | NA | NA | No activation | liquid | NA | Inside the bone tunnels and graft | Intraoperative | 4 |
| Kumar-2022 | NA | NA | NA | NA | NA | NA | No activation | liquid | NA | Between the strands of the graft and inside the femoral and tibial tunnels. | Intraoperative | NA |
| Munde-2023 | Remi R8 C fixed angle microcentrifuge | 17 | ACD-A | 1st: 1500 2nd: 2500 | 1st: 15 2nd: 10 | NA | platelet agitator | gel | NA | Inside the femoral tunnel | Intraoperative | 3–4 |
| Lin-2024 | NA | 30 | NA | 3200 | 6 | NA | NA | gel | NA | At each end of the graft (bone tunnel side) and into the knee joint. | Intraoperative | NA |
| Ye-2024 | commercially used system (Platelet-Rich Plasma Preparation Kit; WEGO Ltd.) | 45 | ACD-A | NA | 1st: 10 2nd: 15 | 678 ± 173 × 109/L | No activation | liquid | poor | Intra-articular injection | 4 weeks, 8 weeks and 3 months postoperatively | 5 |
| Author-Year | Selection Bias | Performance Bias | Detection Bias | Attrition Bias | Reporting Bias | Other Bias | |
|---|---|---|---|---|---|---|---|
| Random Sequence Generation | Allocation Concealment | Blinding of Participants and Personnel | Blinding of Outcome Assessment | Incomplete Outcome Data | Selective Reporting | ||
| Ventura-2005 | high | high | high | high | high | low | high |
| Orrego-2008 | low | unclear | low | low | low | low | low |
| Nin-2009 | low | low | low | low | low | low | unclear |
| Silva-2009 | unclear | unclear | low | unclear | low | low | unclear |
| Vogrin-2010 | low | low | low | low | low | low | unclear |
| Cervellin-2012 | low | low | low | low | low | low | low |
| de Almeida-2012 | low | low | low | low | low | low | unclear |
| Mirzatolooei-2013 | low | low | unclear | unclear | low | low | unclear |
| Rupreht-2013 | unclear | unclear | low | low | low | low | unclear |
| Rupreht-2013 | low | low | low | low | low | low | unclear |
| Seijas-2013 | unclear | unclear | unclear | low | low | low | unclear |
| Vadalà-2013 | unclear | unclear | unclear | low | low | low | unclear |
| Starantzis-2014 | low | unclear | low | low | low | low | low |
| Seijas-2015 | low | low | low | low | low | low | unclear |
| Seijas-2016 | low | low | low | low | low | low | unclear |
| Walters-2018 | low | low | low | low | low | low | low |
| Mahdi-2019 | unclear | unclear | unclear | unclear | low | low | unclear |
| Gong-2022 | low | unclear | unclear | low | low | low | low |
| Kumar-2022 | low | unclear | unclear | unclear | low | low | low |
| Munde-2023 | low | low | unclear | low | low | low | low |
| Lin-2024 | low | unclear | low | low | low | low | low |
| Ye-2024 | low | low | low | low | low | low | low |
| Outcomes | Author-Year | Grade | PRP Group | Non-PRP Group | p-Value | Follow-Up |
|---|---|---|---|---|---|---|
| Anterior drawer test | Mahdai-2019 | <5/5–10/>10 | 12/2/0 | 1/10/2 | <0.0001 | 1 month |
| Ventura-2005 | negative/positive | 9/1 | 10/0 | NS | 6 months | |
| Kumar-2022 | 1/2/3 | 33/2/0 | 31/4/0 | 0.303 | 3 months | |
| Munde-2023 | negative/positive | 39/1 | 33/7 | NS | 6 months | |
| Ye-2024 | 0/1/2/3 | 54/3/0/0 | 55/2/0/0 | 0.65 | 12 months | |
| Lachman test | Mahdai-2019 | <5/6–10 | 12/2 | 6/7 | 0.033 | 1 month |
| Ventura-2005 | negative/positive | 9/1 | 9/1 | NS | 6 months | |
| Munde-2023 | negative/positive | 39/1 | 33/7 | NS | 6 months | |
| Mirzatolooei-2013 | negative/positive | 25/0 | 25/0 | NS | 3 months | |
| Vadála-2013 | negative/positive | 20/0 | 20/0 | NS | 14.7 months | |
| Kumar-2022 | 1/2/3 | 33/2/0 | 31/4/0 | 0.808 | 3 months | |
| Ye-2024 | 0/1/2/3 | 54/0/3/0 | 55/0/0/2 | 0.68 | 12 months | |
| Pivot shift test | Starantzis-2014 | negative/positive | 30/0 | 30/0 | NS | 12 months |
| Mahdai-2019 | absent/pivot glide | 12/2 | 5/8 | 0.014 | 1 month | |
| Vadála-2013 | (neg, +1)/(neg, +1) | 16/4 | 18/2 | NS | 14.7 months | |
| Ye-2024 | 0/1/2/3 | 54/2/1/0 | 55/0/1/1 | 0.68 | 12 months | |
| Objective IKDC | Nin-2009 | A/B/C/D | 35/15/0/0 | 35/13/2/0 | NS | 24.3 months |
| Orrego-2008 | (A + B)/(C + D) | 24/2 | 26/1 | NS | 6 months | |
| Vadála-2013 | A/B/C/D | 16/4/0/0 | 16/4/0/0 | NS | 14.7 months |
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Ibrahim, A.A.; Opoku, M.; Mahamat Abdramane, A.; Fang, M.; Liu, X.; Mustapha, A.; Li, Y.; Xiao, W.; Zhang, K.; Liu, S. Role of Platelet-Rich Plasma Injection in Anterior Cruciate Ligament Reconstruction: A Meta-Analysis of Randomized Controlled Trials. Bioengineering 2026, 13, 455. https://doi.org/10.3390/bioengineering13040455
Ibrahim AA, Opoku M, Mahamat Abdramane A, Fang M, Liu X, Mustapha A, Li Y, Xiao W, Zhang K, Liu S. Role of Platelet-Rich Plasma Injection in Anterior Cruciate Ligament Reconstruction: A Meta-Analysis of Randomized Controlled Trials. Bioengineering. 2026; 13(4):455. https://doi.org/10.3390/bioengineering13040455
Chicago/Turabian StyleIbrahim, Ahmed Abdirahman, Michael Opoku, Abakar Mahamat Abdramane, Mingqing Fang, Xu Liu, Abdulraheem Mustapha, Yusheng Li, Wenfeng Xiao, Kai Zhang, and Shuguang Liu. 2026. "Role of Platelet-Rich Plasma Injection in Anterior Cruciate Ligament Reconstruction: A Meta-Analysis of Randomized Controlled Trials" Bioengineering 13, no. 4: 455. https://doi.org/10.3390/bioengineering13040455
APA StyleIbrahim, A. A., Opoku, M., Mahamat Abdramane, A., Fang, M., Liu, X., Mustapha, A., Li, Y., Xiao, W., Zhang, K., & Liu, S. (2026). Role of Platelet-Rich Plasma Injection in Anterior Cruciate Ligament Reconstruction: A Meta-Analysis of Randomized Controlled Trials. Bioengineering, 13(4), 455. https://doi.org/10.3390/bioengineering13040455

