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1 | Treatment | Publication title | Level of Evidence | Publication | Authors | Indication | Study | Outcome | ||||||||||||||||||
2 | OA | PRP combined with Hyaluronic Acid | The Synergistic Effects of Hyaluronic Acid and Platelet-Rich Plasma for Patellar Chondropathy | Literature review | Biomedicines, 2024 | Costa et al. | Patellar Chondropathy | Various study reviews | While both of these orthobiologic tools have their own fair share of advantages and drawbacks, they still promote similar positive effects in degenerative joint conditions like patellar chondropathy. Success rates may be higher in the early stages of disease, where the pathological alterations are moderate | |||||||||||||||||
3 | High-Dose PRP | High-Dose Neutrophil-Depleted Platelet-Rich Plasma Therapy for Knee Osteoarthritis: A Retrospective Study | Retrospective | Journal of Clinical Medicine, 2024 | De Matthaeis et al | Knee Osteoarthritis | 212 patients, early - moderate OA (Kellgren-Lawrence grades 1 - 3) | Injection: 3 injections in 15 days intervals, lateral suprapatellar approach, into the suprapatellar bursa with a 21-gauge needle inserted above and lateral to the superior lateral aspect of the patella, angled 45 degrees beneath the patella PRP Preparation: 11 mL of whole blood into 2 x 11mL Vacutainer with separator gel and a buffered pH 7.2 dextrose solution anticoagulant (Tropocells). A total of 22 mL of whole blood was drawn, and 2 mL of PRP was obtained from each tube. Leukocyte-poor. Total platelet count: 4 mL of PRP containing 4 × 109 platelets Control group: - Limitation: the absence of a control group, lack of randomization and the presence of potential biases and confounders Results: High-dose neutrophil- and RBC-depleted PRP, containing peripheral blood mononuclear cell (PBMNC) at physiological levels, injected without prior activation is an effective treatment for KL1-KL3 KOA, showing an overall responder rate of 70%. It provides symptomatic relief, has the potential to reduce disease progression, and has sustained effects for up to 12 months. Key Findings: This study supports evidence of a clinically effective dose PRP of 4 billion platelets, suggesting that the dose is the most critical parameter for sustained therapeutic effect. | ||||||||||||||||||
4 | Superdose PRP | Comparison of Conventional Dose Versus Superdose Platelet-Rich Plasma for Knee Osteoarthritis | Prospective, triple-blind, RCT | The Orthopaedic Journal of Sports Medicine, 2024 | Patel et al. | Knee Osteoarthritis | Sample size: 89 knees; early – moderate OA (Kellgren-Lawrence grades 2 or 3); 40 knees received 4mL PRP, 49 knees received 8mL PRP Follow up: 6 months | Injection: single dose in both knees, 18-gauge needle, into the suprapatellar pouch through a superolateral approach PRP Preparation: 50- 60mL blood, Citrate phosphate dextrose adenine (CPDA-1), Leukocyte-poor Total platelet count:Group A: 4-mL PRP,2.82 ± 0.0012 billion, Group B: 8- mL PRP, 5.65 ± 0.0022 billion Control group: Group A / 40 knees Limitation: short follow-up time and small sample size; did not offer patients any postinjection imaging Results: All patient-reported outcome scores improved significantly in both groups from the baseline to the final follow-up (P<.001), with overall trends and results significantly better in group B than in group A (P<.001). Patient satisfaction at the 6-month follow-up was also better in group B (96%) compared with group A (68%). Short (2 to 7 days) self-limiting complications, such as pain and stiffness, occurred more often in group B (P<.001). Outcome measures: • Western Ontario and McMaster Universities Arthritis Index (WOMAC), • WOMAC-Pain subscale, • VAS for pain, • Knee injury and Osteoarthritis Outcome Score (KOOS). All measures taken before injection (baseline) and at 6 weeks, 3 months, and 6 months after injection. Key Findings: Higher volume (8mL) PRP injections with a greater absolute platelet count resulted in significantly better outcomes and higher patient satisfaction compared to lower volume (4mL) injections. | ||||||||||||||||||
5 | Platelet-rich plasma injections for the management of knee osteoarthritis: The ESSKA-ICRS consensus. Recommendations using the RAND/UCLA appropriateness method for different clinical scenarios | Level I | Knee Surgery, Sports Traumatology, Arthroscopy, 2024 | Kon et al. | Knee Osteoarthritis | Aim of the study: To establish recommendations on the appropriateness or inappropriateness of PRP injections for the treatment of knee OA, providing a useful reference for clinical practice. Conclusion: PRP injections are considered appropriate in patients aged ≤80 years with knee KL 0–III OA grade after failed conservative non-injective or injective treatments, while they are not considered appropriate as first treatment nor in KL IV OA grade. https://esskajournals.onlinelibrary.wiley.com/doi/full/10.1002/ksa.12320 | ||||||||||||||||||||
6 | The use of injectable orthobiologics for knee osteoarthritis: A European ESSKA-ORBIT consensus. Part 1—Blood-derived products (platelet-rich plasma) | Level II | Level I | Laver et al. | Knee Osteoarthritis | Aim of the study: The aim of this European Society of Sports Traumatology, Knee Surgery and Arthroscopy (ESSKA) consensus is to provide recommendations based on evidence and expert opinion to improve indications, decisionmaking and administration‐related aspects when using blood‐derived orthobiologics (for simplicity indicated as PRP—platelet‐rich plasma—with PRP being the most common product) for the management of knee osteoarthritis (OA). Conclusion: The consensus group reached a high level of agreement on all the questions/statements despite the lack of clear evidence for some questions. According to the results from this consensus group, given the large body of existing literature and expert opinions, PRP was regarded as a valid treatment option for knee OA and as a possible first-line injectable treatment option for nonoperative management of knee OA, mainly for KL grades 1–3. https://esskajournals.onlinelibrary.wiley.com/doi/10.1002/ksa.12077 | ||||||||||||||||||||
7 | PRP combined with Hyaluronic Acid | Is the Combination of Platelet-Rich Plasma and Hyaluronic Acid the Best Injective Treatment for Grade II-III Knee Osteoarthritis? A Prospective Study | RCT | Advances in Orthopedics, 2023 | Ciapini et al. | Grade II-III Knee Osteoarthritis | 60 patients, groups | Our study suggests that the combination of platelet-rich plasma and hyaluronic acid represents an innovative and valuable alternative to the administration of its two components alone. Being capable of reducing both pain and functional impairment within the 6 months that follow its administration, this treatment represents a promising frontier for the nonsurgical approach for patients who sufer from mild-to-moderate knee osteoarthritis.Our study suggests that the combination of platelet-rich plasma and hyaluronic acid represents an innovative and valuable alternative to the administration of its two components alone. Being capable of reducing both pain and functional impairment within the 6 months that follow its administration, this treatment represents a promising frontier for the nonsurgical approach for patients who sufer from mild-to-moderate knee osteoarthritis. | ||||||||||||||||||
8 | Bone Marrow Stem Cell | Human bone marrow mesenchymal stem cell injection in subchondral lesions of knee osteoarthritis: a prospective randomized study versus contralateral arthroplasty at a mean fifteen year follow-up | Randomized study | International Orthopaedics, 2020 | P. Hernigou et al. | Knee Osteoarthritis, Total Joint Replacement | 140 patients, They received TKA on one side and a subchondral injection of MSCs (from iliac bone marrow concentrate) on the contralateral knee during the same anaesthetic. The bone marrow graft of 20 cm3 volume (10 cc in the tibia and 10 cc in the femur) contained average 7800MSCs/mL (range 3120 to 11,560). | Results After treatment with MSCs injection in bone marrow lesions of the subchondral bone, medial femorotibial compartment BML volume experienced regression over 24 months (mean regression 1.5 cm3, range 0.8 to 3.2 cm3). At the most recent follow up (average of 15 years, range 10 to 20 years), a total of 25 (18%) of the 140 patients underwent total knee arthroplasty performed at a mean of ten years (range, 5 to 15 years) after the date of the cell therapy. The overall incidence of knee arthroplasty after cell therapy was 1.19% per person-year which was equivalent to the risk of a revision for a primary TKA in the contralateral knees of the same patient population (21 revisions, corresponding to 1.00% revision per person-year; p = 0.34). After adjusting for confounders, persistent BMLs larger than 3 cm3 after cell therapy was a strong independent risk factor for total knee arthroplasty (hazard ratio HR = 4.42 [95% CI = 2.34 to 7.21]; p < 0.001), regardless of OA grade, with higher risks demonstrated for larger BMLs. Incidence rates of arthroplasty were also higher for young patients and for knees presenting severe malalignment. Conclusions This study showed that subchondral bone marrow concentrate (as compared with TKA) had a sufficient effect on pain to postpone or avoid the TKA in the contra lateral joint of patients with bilateral osteoarthritis. Bone marrow lesions were predictive factors for future knee arthroplasty in the knee with subchondral cell therapy at ten years follow-up. | ||||||||||||||||||
9 | AAOS Clinical Practice Guideline | AAOS Clinical Practice Guideline Summary: Management of Osteoarthritis of the Knee (Nonarthroplasty), Third Edition | Systematic review | Journal of the American Academy of Orthopaedic Surgeons, May 2022 | R. H. Brophy et al. | Knee Osteoarthritis | Reviewing more than 14,400 abstracts and more than 2,400 full-text articles to develop 27 recommendations supported by 617 research articles meeting stringent inclusion criteria | injections being corticosteroid, hyaluronic acid, and platelet-rich plasma. Controversy exists over the effectiveness of each intra-articular injection. Among the options for intra-articular injections, corticosteroid had considerable evidence with 19 high-quality and six moderate-quality studies supporting the use of intra-articular corticosteroid, although the duration of benefits was often only 3 months. Platelet-rich plasma is an alternative with two high-quality studies and one moderate-quality study supporting reduced pain and improved function in patients with knee osteoarthritis; however, the evidence demonstrated inconsistency with a worse treatment response in patients with severe knee osteoarthritis. In addition, concerns have been raised for platelet-rich plasma regarding the cost and safety profile. Although intra-articular hyaluronic acid is commonly used to treat knee osteoarthritis, it was not consistently supported by the 17 high-quality and 11 moderate-quality studies. The recommendation does recognize the potential for hyaluronic acid to benefit patients as the calculated number needed to treat was 17 patients; however, the current evidence does not identify the subset of patients who benefit from hyaluronic acid to explain the observed inconsistency in the evidence. As a result, the recommendation was against the routine use of hyaluronic acid in patients with knee osteoarthritis. Read the article for the full guideline. | ||||||||||||||||||
10 | PRP | The Application of Platelet-Rich Plasma for Patients Following Total Joint Replacement: A Meta-Analysis of Randomized Controlled Trials and Systematic Review | A Meta-Analysis of Randomized Controlled Trials and Systematic Review | Frontiers in Surgery, 2022 | H. Shu et al. | Total Joint Replacement | a total of 10 origin RCTs were included in the current systematic review. | The application of platelet-rich plasma to patients following total keen arthroplasty is associated with pain relief and decreased Hb drop. In addition, available data reveal that platelet-rich plasma accelerates wound healing rates in patients undergoing total hip arthroplasty. Intra-operative PRP is active; however, more prospective and multicenter studies are warranted to confirm these results. | ||||||||||||||||||
11 | Industry funding impacts, PRP | Failure to disclose industry funding impacts outcomes in randomized controlled trials of platelet-rich plasma | Review, level of evidence: I. | Knee surgery, sports traumatology, arthroscopy: official journal of the European Society of Sports Traumatology, Knee Surgery, Arthroscopy (ESSKA), Aug 2022 | K. Chou et al. (abstract only) | Musculoskeletal disorders | 1440 records were screened with 87 trials included in the final analysis. | Results: Of the 87 studies, 61 (70%) reported a statistically significant primary outcome. The presence of industry funding was not predictive of a statistically significant primary outcome [OR = 0.36, 95% CI 0.096-1.36, (n.s.)]. Studies that did not state whether industry funding was present had a higher chance of reporting a statistically significant primary outcome (OR = 3.61, 95% CI 1.1-11.9, p = 0.035). Sample size and length of follow-up were not predictive of a statistically significant primary outcome. Conclusion: The results of the current study conclude that industry funding had no impact on the reporting of positive results for RCTs investigating PRP in musculoskeletal disorders. However, not disclosing sources of funding was associated with a higher likelihood of reporting positive results. The results of trials that fail to disclose funding sources should be interpreted with caution in the PRP literature. | ||||||||||||||||||
12 | HA vs.PRP | Role and Effectiveness of Intra-articular Injection of Hyaluronic Acid in the Treatment of Knee Osteoarthritis: A Systematic Review | Systematic Review | Cureus, Apr 2022 | S. Chavda et al. | Knee Osteoarthritis | 38 studies, 22 (57.9%) were double blind; 8 (21%) single blind, 3 (7.9%) non-blind, 4 (10%) with simple randomization and 1 (2.7%) was open labelled | IA-HA injections have a limited role in the treatment of knee osteoarthritis in those patients who do not have sufficient pain relief with topical or oral medication and physical therapy. It is safe and effective except for minor side effects such as local pain and swelling lasting for a few days. Severe allergic reactions are extremely rare. They provide adequate pain relief and functional improvement for up to six months irrespective of a number of injections and type of preparations used. The combination formulations with corticosteroids or PRP or MSCs show better results than HA alone. Combining HA with newer molecules such as peptides or diclofenac for sustained and disease-modifying effects requires more studies in the future. | ||||||||||||||||||
13 | PRP | Intra-articular Injection of Platelet-Rich Plasma Is Superior to Hyaluronic Acid or Saline Solution in the Treatment of Mild to Moderate Knee Osteoarthritis: A Randomized, Double-Blind, Triple-Parallel, Placebo-Controlled Clinical Trial | Randomized, Double-Blind, Triple-Parallel, Placebo-Controlled Clinical Trial | Arthroscopy: The Journal of Arthroscopic and Related Surgery, 2019 Jan | KY. Lin et al. | Mild to Moderate Knee Osteoarthritis | 87 osteoarthritic knees (53 patients) were randomly assigned to 1 of 3 groups receiving 3 weekly injections of either leukocyte-poor PRP (31 knees), HA (29 knees), or Normal Saline (27 knees). | Intra-articular injections of leukocyte-poor PRP can provide clinically significant functional improvement for at least 1 year in patients with mild to moderate osteoarthritis of the knee. | ||||||||||||||||||
14 | PRP | Platelet‑rich plasma (PRP) in osteoarthritis (OA) knee: Correct dose critical for long term clinical efficacy | Prospective, double-blinded, randomized control (parallel designed with allocation 1:1 ratio), 12-month, study of 150 outpatients. | Nature, 2021 | H. Bansal et al. | Knee Osteoarthritis | A total of 150 patients were randomized to receive either PRP (10 billion platelets) or hyaluronic acid (HA; 4 ml; 75 patients in each group) and followed up till 1 year. | Significant improvements in WOMAC (51.94 ± 7.35 vs. 57.33 ± 8.92; P < 0.001), IKDC scores (62.8 ± 6.24 vs 52.7 ± 6.39; P < 0.001), 6-min pain free walking distance (+ 120 vs. + 4; P < 0.001) persisted in PRP compared to HA group at 1 year. Significant decline IL-6 and TNF-α levels observed in PRP group (P < 0.05) compared to HA at 1 month. Study demonstrated that an absolute count of 10 billion platelets is crucial in a PRP formulation to have long sustained chondroprotective effect upto one year in moderate knee OA. | ||||||||||||||||||
15 | Intra-articular injections | The efficacy of intra-articular injections in the treatment of knee osteoarthritis: A network meta-analysis of randomized controlled trials | A network meta-analysis of randomized controlled trials | The Knee, 2021 | U. Anil et al. | Knee Osteoarthritis | Seventy-nine RCTs with 8761 patients were included in this review. | Intra-articular injectables evaluated included autologous conditioned serum (ACS), bone marrow aspirate concentrate (BMAC), botulinum toxin, corticosteroids (CS), hyaluronic acid (HA), mesenchymal stem cells (MSC), ozone, saline placebo, platelet-rich plasma (PRP), plasma rich in growth factor (PRGF), and stromal vascular fraction (SVF).The most important finding of this study was that SVF resulted in the highest P-Score for VAS score at all time points, indicating that this had the greatest effect on pain post-injection at all time points. Furthermore, SVF had the highest WOMAC score at 12-months post-injection indicating that these patients also had the highest functional outcome scores following treatment. However, it is still worth noting that the majority of intra-articular injections had higher P-Scores than the saline placebo, and thus were shown to be efficacious. The only intra-articular injectable which was found to be consistently worse than the placebo was ozone. | ||||||||||||||||||
16 | PRP | PRP Injections for the Treatment of Knee Osteoarthritis: A Meta-Analysis of Randomized Controlled Trials | A Meta-Analysis of Randomized Controlled Trials | Cartilage, 2020 | G. Filardo et al. | Knee Osteoarthritis | 34 RCTs, including 1403 knees in PRP groups and 1426 in control groups | The effect of platelet concentrates goes beyond its mere placebo effect, and PRP injections provide better results than other injectable options. This benefit increases over time, being not significant at earlier follow-ups but becoming clinically significant after 6 to 12 months. However, although substantial, the improvement remains partial and supported by low level of evidence. This finding urges further research to confirm benefits and identify the best formulation and indications for PRP injections in knee OA. | ||||||||||||||||||
17 | PRP | Is platelet‑rich plasma effective for the treatment of knee osteoarthritis? A systematic review and meta‑analysis of level 1 and 2 randomized controlled trials | A systematic review and meta‑analysis of level 1 and 2 randomized controlled trials | European Journal of Orthopaedic Surgery & Traumatology, 2020 | E. Hohmann et al. | Knee Osteoarthritis | Twelve studies (1,248 cases; 636 PRP, 612 HA) met the eligibility criteria. | The results of this systematic review and meta-analysis suggest that PRP is superior to HA for symptomatic knee pain at 6 and 12 months. autologous platelet-rich plasma (ACP) appears to be clearly superior over HA for pain at both 6 and 12 months. There were no advantages of PRP over HA for clinical outcomes at both 6 and 12 months. | ||||||||||||||||||
18 | PRP | Platelet-Rich Plasma Versus Hyaluronic Acid for Knee Osteoarthritis | A Systematic Review and Meta-analysis of Randomized Controlled Trials | The American Journal of Sports Medicine, Clinical Sports Medicine Update, 2020 | J. W. Belk et al. | Knee Osteoarthritis | 18 studies (all level 1) met inclusion criteria, including 811 patients undergoing intra-articular injection with PRP (mean age, 57.6 years) and 797 patients with HA (mean age, 59.3 years). The mean follow-up was 11.1 months for both groups | Mean improvement was significantly higher in the PRP group (44.7%) than the HA group (12.6%) for WOMAC total scores (P\ .01). Of 11 studies based on the VAS, 6 reported PRP patients to have significantly less pain at latest follow-up when compared with HA patients (P\.05). Of 6 studies based on the Subjective IKDC outcome score, 3 reported PRP patients to have significantly better scores at latest follow-up when compared with HA patients (P\.05). Finally, leukocyte-poor PRP was associated with significantly better Subjective IKDC scores versus leukocyte-rich PRP (P\.05). Conclusion: Patients undergoing treatment for knee OA with PRP can be expected to experience improved clinical outcomes when compared with HA. Additionally, leukocyte-poor PRP may be a superior line of treatment for knee OA over leukocyterich PRP, although further studies are needed that directly compare leukocyte content in PRP injections for treatment of knee OA. | ||||||||||||||||||
19 | Stem Cell | Intra-Articular Injections of Platelet-Rich Plasma, Adipose Mesenchymal Stem Cells, and Bone Marrow Mesenchymal Stem Cells Associated With Better Outcomes Than Hyaluronic Acid and Saline in Knee Osteoarthritis: A Systematic Review and Network Meta-analysis | A Systematic Review and Network Meta-analysis, Level II, meta-analysis of Level I and II studies. | 2021 | D. Zhao et al. | Knee Osteoarthritis | 43 studies | Based on the results of current research findings, during 6 months of follow-up, AD-MSCs relieved pain the best; LP-PRP was most effective for functional improvement. During the 12-month follow-up, both AD-MSCs and LP-PRP showed potential clinical pain relief effects; functional improvement was achieved with LP-PRP. Unfortunately, AD-MSC/LP-PRP functional comparisons were only based on WOMAC scores due to missing IKDC scores. BM-MSCs seem to have potentially beneficial effects, but the wide credibility interval makes it impossible to draw a well-supported conclusion. HA viscosupplementation clinical efficacy was lower than that of biological agents during follow-up, which may be related to the properties of the drugs. Considering the evaluation of treatment-related adverse events, LP-PRP is the most advisable choice; although the adverse events of these treatments are not serious, they may affect treatment compliance and satisfaction. | ||||||||||||||||||
20 | PRP | Effects and safety of the combination of platelet-rich plasma (PRP) and hyaluronic acid (HA) in the treatment of knee osteoarthritis: a systematic review and meta-analysis | A systematic review and meta-analysis | BMC Musculoskeletal Disorders, 2020 | J. Zhao et al. | Knee Osteoarthritis | Seven studies (5 randomized controlled trials, 2 cohort studies) with a total of 941 patients were included. | Compared with intra-articular injection of PRP alone, that of PRP combined with HA can improve the WOMAC Function Scores, WOMAC Total Score, 6-month follow-up VAS ratings, and Lequesne Index scores. However, in terms of the incidence of adverse events, PRP combined with HA is not significantly different from PRP or HA alone. | ||||||||||||||||||
21 | PRP | Efficacy of Platelet-Rich Plasma in the Treatment of Knee Osteoarthritis: A Meta-analysis of Randomized Controlled Trials | Meta-analysis of Randomized Controlled Trials | Arthroscopy, 2016 Mar | WL. Dai et al. | Knee Osteoarthritis | 10 randomized controlled trials with a total of 1069 patients | Current evidence indicates that, compared with HA and saline, intra-articular PRP injection may have more benefit in pain relief and functional improvement in patients with symptomatic knee OA at 1 year postinjection. | ||||||||||||||||||
22 | PRP | The temporal effect of platelet-rich plasma on pain and physical function in the treatment of knee osteoarthritis: systematic review and meta-analysis of randomized controlled trials | Systematic review and Meta-analysis of Randomized Controlled Trials | Journal of Orthopaedic Surgery and Research, 2017 | L. Shen, et al. | Knee osteoarthritis | 14 RCTs comprising 1423 participants were included | Intra-articular PRP injections probably are more efficacious in the treatment of knee OA in terms of pain relief and self-reported function improvement at 3, 6 and 12 months follow-up, compared with other injections, including saline placebo, HA, ozone, and corticosteroids. | ||||||||||||||||||
23 | PRP | Comparison between intra‑articular infiltrations of placebo, steroids, hyaluronic and PRP for knee osteoarthritis: a Bayesian network meta‑analysis | Bayesian network meta‑analysis | Archives of Orthopaedic and Trauma Surgery, 2020 July | F. Migliorini et al. | Knee osteoarthritis | 30 RCTs (3463 patients) | Intra-articular injections of PRP demonstrated the best overall outcome compared to steroids, hyaluronic acid and placebo for patients with knee osteoarthrosis at 3, 6 and 12-months follow-up. Among CCS, hyaluronic acid and placebo, no discrepancies were detected. | ||||||||||||||||||
24 | Stem Cell | Improved outcomes after mesenchymal stem cells injections for knee osteoarthritis: results at 12‑months follow‑up: a systematic review of the literature | Systematic review, 12‑months follow‑up | Orthopaedic Surgery, 2019 Aug | F. Migliorini et al. | Knee osteoarthritis | 18 studies, comprising 1069 treated knees | Mesenchymal stem cells infiltrations for knee OA can represent a feasible option, leading to an overall remarkable improvement of all clinical and functional considered outcomes. Patients treated at earlier-degeneration stages reported statistically significant greater outcomes. The pain and function scores were improved considerably, thus, leading to a significant improvement of patient participation in recreational activities and quality of life. | ||||||||||||||||||
25 | PRP | Intra-articular platelet-rich plasma injection for knee osteoarthritis: a summary of metaanalyses | A summary of metaanalyses | Journal of Orthopaedic Surgery and Research, 2019 | P. Chen et al. | Knee osteoarthritis | 4 meta-analyses | For short-term follow-up (≤1 year), intra-articular PRP injection is more effective in terms of pain relief and function improvement in the treatment of KOA patients than HA and placebo, and there is no difference in the risk of an adverse event between PRP and HA or placebo. | ||||||||||||||||||
26 | PRP | Platelet-rich plasma versus hyaluronic acid in the treatment of knee osteoarthritis | A meta-analysis | Medicine, 2020 | Z. Chen et al. | Knee osteoarthritis | 14 randomized controlled trials (RCTs) involving 1350 patients | Compared with HA, PRP offers obvious advantages in the conservative treatment of knee osteoarthritis. Treatment with PRP can reduce long-term pain and improve knee joint function with no additional risks. Therefore, PRP can be widely used for the conservative treatment of knee osteoarthritis. | ||||||||||||||||||
27 | Surgical and tissue engineering strategies | Surgical and tissue engineering strategies for articular cartilage and meniscus repair | Surgical and tissue engineering strategies for articular cartilage and meniscus repair | Nature, 2019 | H. Kwon et al. | Articular cartilage and meniscus repair | Review of various studies | Tissue engineering approaches are emerging as alternatives to current surgical methods for cartilage and meniscus repair | ||||||||||||||||||
28 | PRP and Stem Cell (BMSC) | Comparative evaluation of leukocyte- and platelet-rich plasma and pure platelet-rich plasma for cartilage regeneration | In vivo research on rabbits | Nature, 2017 | Xu et al. | Cartilage regeneration | 27 New Zealand white rabbits wih 48 cartlilage defects | In conclusion, the results suggest that both P-PRP and L-PRP can exert a beneficial effect on the cartilage repair, but P-PRP promotes better rBMSC in chondrogenic differentiation in vitro and in vivo compared with L-PRP. These findings also revealed that the better behavior of P-PRP in cartilage regeneration reflects the removal of the leukocytes reduces the concentrations of IL-1β and TNF-α and inhibits the activation of the NF-κB pathway, which affects the repair of cartilage defects. Thus, P-PRP treatment may present a better alterna- tive for cartilage repair. | ||||||||||||||||||
29 | Stem Cell | Short-Term Outcomes in Treatment of Knee Osteoarthritis With 4 Bone Marrow Concentrate Injections | Preliminary research | Clinical Medicine Insights: Arthritis and Musculoskeletal Disorders, 2018 | B. Shaw et al. | Knee osteoarthritis | 15 patients (20 knees) | Patients experienced statistically significant improvements in active pain and functionality score after the first treatment. Additionally, patients experienced a mean decrease in resting pain after the first treatment, yet outcomes were not statistically significant until after the second treatment. On average, patients experienced an 84.31% decrease in resting pain, a 61.95% decrease in active pain, and a 55.68% increase in functionality score at the final follow-up. Patients also reported a mean 67% total overall improvement at study conclusion. Outcomes at the final follow-up after the fourth treatment were statistically significant compared to outcomes at baseline, after first treatment, after second treatment, and after third treatment. | ||||||||||||||||||
30 | Stem Cell | Transplantation of autologous bone marrow-derived mesenchymal stem cells under arthroscopic surgery with microfracture versus microfracture alone for articular cartilage lesions in the knee: A multicenter prospective randomized control clinical trial | A multicenter prospective randomized control clinical trial | Regenerative Therapy, 2019 | Y. Hashimoto et al. | Articular cartilage defect of the knee | 14 patient entered in the RCT | Compared with MFX alone, BMSCs with MFX provided a better quality of articular surface and KOOS QOL sub-score improvements in treatment of symptomatic cartilage defects of the knee. No remarkable adverse events or safety issues were noted in this heterogeneous patient population. However, a larger sample size and long-term studies are needed to confirm our findings | ||||||||||||||||||
31 | PRP | Effect of Intra-articular Platelet-Rich Plasma vs Placebo Injection on Pain and Medial Tibial Cartilage Volume in Patients With Knee Osteoarthritis: The RESTORE Randomized Clinical Trial | The RESTORE Randomized Clinical Trial | JAMA, 2021 | K. L. Bennell et al. | Knee osteoarthritis | Among 288 patients who were randomized (mean age, 61.9 [SD, 6.5] years; 169 [59%] women), 269 (93%) completed the trial. | Among patients with symptomatic mild to moderate radiographic knee OA, intra-articular injection of PRP, compared with injection of saline placebo, did not result in a significant difference in symptoms or joint structure at 12 months. These findings do not support use of PRP for the management of knee OA. | Comment & Response | Reply | Study protocol | |||||||||||||||
32 | Intra-articular Platelet-Rich Plasma vs Placebo Injection and Pain and Medial Tibial Cartilage Volume in Patients With Knee Osteoarthritis | K.L.Paterson et al., 2018 | ||||||||||||||||||||||||
33 | March 22/29, 2022 | March 22/29, 2022 | March 22/29, 2022 | March 22/29, 2022 | ||||||||||||||||||||||
34 | Z. Zhu et al. | J. Magalon et al. | M. R. Baria et al. | K. L. Bennell et al. | ||||||||||||||||||||||
35 | To the Editor We would like to draw attention to 3 concerns about the recent study1 of intra-articular PRP injection for knee OA. First, participants were asked to discontinue nonsteroidal anti-inflammatory drugs and other analgesics for knee pain (except acetaminophen rescue pain relief); however, more than 68% of participants in the PRP group and more than 60% of participants in the placebo group used pain medications, including nonrescue pain medication in more than 50% in the PRP group and almost 37% in the placebo group. This nonadherence to the study protocol may have had an important effect on the comparisons. Therefore, we believe that both intention-to-treat and per-protocol analyses should have been performed and presented. | To the Editor As representatives of the European Society for Clinical and Economic Aspects of Osteoporosis (ESCEO), the Groupe de Recherche International Sur Les Injections de Plaquettes (GRIIP), and the Société Française de Traumatologie du Sport (SFTS), which include groups of physicians and researchers interested in regenerative medicine, we have some possible explanations for the negative results of the recent study investigating the effect of PRP injections on knee OA. For the full text JAMA registration is required. | To the Editor A recent study1 found that intra-articular injection of platelet-rich plasma (PRP) did not significantly improve symptoms or joint structure at 12 months in patients with mild to moderate knee osteoarthritis (OA) compared with placebo injection. However, we have some concerns about this study’s methodology and nomenclature that should be discussed so that the results and conclusions are put into proper context. | In Reply Drs Baria and Flanigan consider the platelet concentration used in our study1 too low to be PRP, claiming it was 1.2 times baseline. It appears they miscalculated this using the participant baseline whole blood platelet count and the manufacturer PRP mean platelet volume.1 We were unable to assess our participants’ PRP platelet count, but data from the manufacturer and an independent study2 report a concentration of 1.6 times baseline, which exceeds the US Food and Drug Administration’s minimum platelet concentration for PRP3 and meets Marx’s definition.4 To our knowledge, no study has directly shown greater clinical efficacy with higher platelet concentrations; one found no relationship,5 while a systematic review found that high concentrations might be less effective.6 The study by Görmeli et al cited by Baria and Flanigan did not assess associations of platelet concentration and pain but found that 3 injections (the same number used in our study) were more effective than. | ||||||||||||||||||||||
36 | PRP & Stem Cell | Comparative effectiveness of nonsurgical interventions in the treatment of patients with knee osteoarthritis | A PRISMA-compliant systematic review and network meta-analysis | Medicine, 2021 | M. Naja et al. | Knee osteoarthritis | 19 RCTs (N=2488 patients) | In this systematic review and network meta-analysis, the outcomes of treatments using MSCs and PRP for the management of knee osteoarthritis were associated with long-term improvements in pain and function. More high quality RCTs would be needed to confirm the efficiency of MSCs and PRP for the treatment of patients with knee osteoarthritis. | ||||||||||||||||||
37 | PRP | The use of platelet-rich plasma in studies with early knee osteoarthritis versus advanced stages of the disease: a systematic review and meta-analysis of 31 randomized clinical trials | A systematic review and meta-analysis of 31 randomized clinical trials | 2021 | F. Vilchez-Cavazos et al. | Knee osteoarthritis | 31 clinical trials that reported data of 2705 subjects | Meta-analysis revealed an overall significant improvement of both pain (MD, -1.05 [95% CI -1.41 to -0.68]; I2 = 86%; P = < 0.00001) and function (SMD, -0.99 [95% CI -1.34, to -0.65]; I2 = 94%; P = < 0.00001), favoring PRP. Subanalysis for pain and functional improvement showed significant pain relief in studies with 1-3 and 1-4 Kellgren-Lawrence OA stages, and a significant functional improvement in studies with 1-2, 1-3, and 1-4 knee OA stages, favoring PRP. | ||||||||||||||||||
38 | PRP | Hyaluronic Acid Versus Platelet-Rich Plasma - A Prospective, Double-Blind Randomized Controlled Trial Comparing Clinical Outcomes and Effects on Intra-articular Biology for the Treatment of Knee Osteoarthritis | Prospective, Double-Blind Randomized Controlled Trial | The American Journal of Sports Medcine, 2016 | B. J. Cole et al. | Knee osteoarthritis | There were 49 patients randomized to treatment with PRP and 50 randomized to treatment with HA. | No difference was seen between the groups in the primary outcome measure (WOMAC pain score). In the secondary outcome measure, linear contrasts identified a significantly higher IKDC score in the PRP group compared with the HA group at 24 weeks (mean 6 standard error [SE], 65.5 6 3.6 vs 55.8 6 3.8, respectively; P = .013) and at final follow-up (52 weeks) (57.6 6 3.37 vs 46.6 6 3.76, respectively; P = .003). Linear contrasts also identified a statistically lower VAS score in the PRP group versus the HA group at 24 weeks (mean 6 SE, 34.6 6 3.24 vs 48.6 6 3.7, respectively; P = .0096) and 52weeks (44 6 4.6 vs 57.3 6 3.8, respectively; P = .0039). An examination of fixed effects showed that patients with mild OA and a lower body mass index had a statistically significant improvement in outcomes. We found no difference between HA and PRP at any time point in the primary outcome measure: the patient-reported WOMAC pain score. Significant improvements were seen in other patient-reported outcome measures, with results favoring PRP over HA. Preceding a significant difference in subjective outcomes favoring PRP, there was a trend toward a decrease in 2 proinflammatory cytokines, which suggest that the anti-inflammatory properties of PRP may contribute to an improvement of symptoms. | ||||||||||||||||||
39 | Stem Cell | Treatment of knee osteoarthritis with intraarticular injection of autologous adiposederived mesenchymal progenitor cells: a prospective, randomized, double-blind, active-controlled, phase IIb clinical trial | Prospective, randomized, double-blind, active-controlled, phase IIb clinical trial | Stem Cell Research & Therapy, 2019 | L. Lu et al. | Knee osteoarthritis | 53 patients were randomised | Significant improvements in joint function, pain, quality of life, and cartilage regeneration were observed in Re-Join®-treated knee OA patients with good tolerance in a period of 12 months. | ||||||||||||||||||
40 | Stem Cell (Bone marrow) | Intra-articular knee implantation of autologous bone marrow–derived mesenchymal stromal cells in rheumatoid arthritis patients with knee involvement: Results of a randomized, triple-blind, placebo-controlled phase 1/2 clinical trial | Randomized, triple-blind, placebo-controlled phase 1/2 clinical trial | Cytotherapy, 2018 | S. Shadmanfar et al. | Rheumatoid arthritis | A total of 30 patients, 15 in the MSC group and 15 in the placebo group | Intra-articular knee implantation of MSCs appeared to be safe and well tolerated. In addition, we observed a trend toward clinical efficacy. These results, in our opinion, have justified the need for further investigations over an extended assessment period with larger numbers of RA patients who have knee involvement. | ||||||||||||||||||
41 | PRP | The Use of Intra-articular Platelet-Rich Plasma as a Therapeutic Intervention for Hip Osteoarthritis: A Systematic Review and Meta-analysis | A Systematic Review and Meta-analysis, Level of evidence: 4 | The American Journal of Sports Medcine, Jun 2022 | A. Lim et al. (abstract only) | Hip Osteoarthritis | Eight studies were included in the analysis, with data from a total of 331 patients. | Results: PRP significantly reduced pain compared with the baseline at multiple time points, with the greatest effect at the 1- to 2-month follow-up, but PRP significantly improved function only at the 1- to 2-month follow-up. A significantly larger reduction in pain was achieved with a single injection of PRP compared with multiple injections, a total injected dose of PRP <15 mL compared with ≥15 mL, and use of a leukocyte-poor PRP preparation compared with leukocyte-rich PRP. There were no lasting adverse effects. Conclusion: Low- and moderate-quality evidence suggests that PRP reduces pain and improves function at the end-point follow-up of studies compared with the baseline. Moderate-quality evidence suggests that a larger reduction in pain is achieved with a single injection of PRP compared with multiple injections, and low-quality evidence attributes a larger reduction of pain with a total injected dose of PRP <15 mL compared with ≥15 mL and using leukocyte-poor PRP compared with leukocyte-rich PRP. | ||||||||||||||||||
42 | PRP | Effectiveness of platelet-rich plasma in the management of hip osteoarthritis: a systematic review and meta-analysis | A systematic review and meta-analysis | Clinical Rheumatology, 2020 | I. Medina-Porqueres et al. | Hip osteoarthritis | A total of 4 trials (334 participants, 340 hips) were included, all marked as “moderate risk of bias”. | Pain and function were assessed throughout the studies with visual analogue scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Harris Hip Score (HHS) tools. Intra-articular PRP injections were more effective at stages earlier than 3 months for both treatment groups with the exception of WOMAC score in one study. The superiority of PRP against comparative treatments was only reported in one study; longer-term evaluations from 4 to 12 months showed diverse results, with only one study reporting significantly better results for PRP. PRP may be beneficial and safe for patients with HOA at mid-term follow-up. However, its superiority over other procedures such as hyaluronic acid remains unclear. Further researches with high-quality designs and larger samples become imperative. | ||||||||||||||||||
43 | PRP | The effects of platelet-rich plasma injection in knee and hip osteoarthritis: a meta-analysis of randomized controlled trials | Meta-analysis of randomized controlled trials | Clinical Rheumatology, 2020 | Y. Dong et al. | Knee and Hip osteoarthritis | Twenty-four RCTs with 21 at knee OA and three at hip OA were included in this meta-analysis. | The PRP injections significantly improved the WOMAC score, VAS score, IKDC score, and HHS score as compared with comparators. The WOMAC pain, stiffness, and physical function scores were also significantly better in the PRP group than in the control group. Most of the evaluated parameters that favored PRP were observed in knee OA but not in hip OA, at short-term (at 1, 2, 3, 6, 12 months) but not long-term follow-up (at 18 months), in RCTs with low risk of bias. | ||||||||||||||||||
44 | PRP | Effect of Platelet-Rich Plasma Injections vs Placebo on Ankle Symptoms and Function in Patients With Ankle Osteoarthritis | A multicenter, block-randomized, double-blinded, placebo-controlled clinical trial | JAMA, 2021 | L. D. A. Paget et al. | Ankle Osteoarthritis | 6 sites in the Netherlands that included 100 patients with pain greater than 40 on a visual analog scale (range, 0-100) and tibiotalar joint space narrowing | Results: Among 100 randomized patients (mean age, 56 years; 45 [45%] women), no patients were lost to follow-up for the primary outcome. Compared with baseline values, the mean American Orthopaedic Foot and Ankle Society score improved by 10 points in the PRP group (from 63 to 73 points [95% CI, 6-14]; P < .001) and 11 points in the placebo group (from 64 to 75 points [95% CI, 7-15]; P < .001). The adjusted between-group difference over 26 weeks was −1 ([95% CI, –6 to 3]; P = .56). One serious adverse event was reported in the placebo group, which was unrelated to the intervention; there were 13 other adverse events in the PRP group and 8 in the placebo group. Conclusions and Relevance: Among patients with ankle osteoarthritis, intra-articular PRP injections, compared with placebo injections, did not significantly improve ankle symptoms and function over 26 weeks. The results of this study do not support the use of PRP injections for ankle osteoarthritis. | Comment & Response | Reply | ||||||||||||||||
45 | Platelet-Rich Plasma Injections vs Placebo for Patients With Ankle Osteoarthritis | |||||||||||||||||||||||||
46 | February 22, 2022 | February 22, 2022 | February 22, 2022 | February 22, 2022 | February 22, 2022 | |||||||||||||||||||||
47 | M. S. Barber et al. | T. Charnay et al. | P-J. Chu | G. P. Guyton | L. D. A. Paget et al. | |||||||||||||||||||||
48 | To the Editor After review of the recent clinical trial1 examining platelet-rich plasma (PRP) injections for ankle osteoarthritis, we think there are several methodological concerns that make its concluding statement of “not supporting the use of PRP injections for ankle osteoarthritis,” without qualifiers, appear to be an overstatement. First, differences in the biological parameters of PRP, especially platelet concentration, lead to varying inflammatory responses and outcomes; therefore, a detailed description of PRP preparation and characterization is essential.2 Seven PRP classification systems have been developed and recommended in the medical literature to address the heterogeneity in PRP and to facilitate both reproducibility and comparison among studies.2 Therefore, we were surprised that the authors did not characterize the PRP products used in this study1 and did not follow minimum standards recommended for reporting. The unknown content of the PRP products leads to uncertainty about whether patients received a supraphysiologic dose of platelets with their PRP treatment or a physiologic dose, unlikely to elicit clinical benefit. With the considerable variability in preparation methods and outcomes of studies investigating PRP, adequate description of the biologic characteristics of a PRP intervention ensures quality control and allows for comparison across studies.3 Failure to do so is a major flaw in research because reproducibility is compromised. | To the Editor We would like to clarify a few points about the recent trial1 comparing the effect of PRP injections and placebo on symptoms and function of patients with ankle osteoarthritis. First, the study failed to appropriately describe the biological characteristics of the PRP injected. The American Academy of Orthopaedic Surgeons defines “minimum information for studies evaluating biologics in orthopaedics,” which includes a list of 9 items about PRP preparation.2,3 In the Limitations section of this study,1 the authors justified the absence of PRP characterization by referring to a study that provided data about the PRP obtained with the device they used. However, a 2021 review of available data from 4 different studies that used this device showed substantial variation in PRP composition among these studies. | To the Editor A recent study1 provided evidence that intra-articular PRP injections did not significantly improve ankle symptoms and function over 26 weeks compared with placebo saline injections among patients with ankle osteoarthritis. However, I am concerned about some methodological issues. Because this was a multicenter, stratified, block-randomized, double-blind, placebo-controlled study, the baseline characteristics should have been well balanced between the PRP and placebo groups. The authors performed a multivariable analysis with stepwise backward elimination to make adjustments for baseline variables that were associated with the primary outcome. However, imbalances that may have led to confounding bias were seen in Table 1 in the article for several baseline characteristics of the 2 study groups.1 First, compared with patients in the placebo group, those in the PRP group had a higher body mass index, which is significantly associated with ankle osteoarthritis and worsening ankle symptoms.2,3 Second, a higher proportion of patients in the PRP group had more advanced stages of ankle osteoarthritis using several different radiological classification systems. Third, because ankle osteoarthritis leads to poorer mental and physical quality of life,4 it is understandable that patients in the PRP group with higher body mass index and more advanced stages of ankle osteoarthritis had lower frequency of playing sports than those in the placebo group. Therefore, I believe the authors should have included variables with significant between-group differences as covariates in the analyses of both primary and secondary outcomes. | To the Editor The study by Dr Paget and colleagues1 demonstrated lack of efficacy for PRP injections in ankle osteoarthritis, but I believe it is best interpreted through its validated secondary outcomes rather than its primary outcome variable, the American Orthopaedic Foot and Ankle Society (AOFAS) score.2 Although the authors noted that the Dutch version of the score has been validated,3 that was done in the context of acute ankle fracture rather than ankle osteoarthritis. Madeley et al4 found that the AOFAS score had criterion validity for ankle osteoarthritis compared with the 36-Item Short Form Survey. Those authors recommended against use of the AOFAS score because the investigator-determined portion of the measure has not been shown to be reliable. | In Reply We appreciate the opportunity to respond to the Letters to the Editor about the PRIMA study.1 Dr Barber and colleagues express concerns regarding the lack of detail describing PRP preparation and characterization, the exclusion of patients with polyarticular osteoarthritis and cointerventions, and recommendations made close to the intervention. As described in our protocol, analysis of PRP was not performed because the PRP content of the standardized Arthrex ACP system and protocol has been frequently analyzed.2,3 This system produces a leukocyte-poor PRP with approximately 2 to 3 times higher platelet concentration compared with whole blood. An “optimal” PRP preparation protocol has not yet been established.4 Analyzing the PRP content would not alter the outcome or conclusion of our trial. The generalizability of our findings to other PRP systems remains a limitation that was described in our study.1 Including patients with polyarticular osteoarthritis might mask a possible intervention effect on the outcome measures. For instance, a potential benefit of PRP on ankle function may be masked by limitations that knee osteoarthritis poses on a patient’s function in daily activities and walking distance. During design of the study, we used the best available evidence from knee osteoarthritis PRP studies for recommendations on activity and NSAID use. Knee osteoarthritis studies that reported a positive effect for PRP generally recommended reduced weight loading for 24 hours to 48 hours and no NSAID use. We recommended no NSAID use 24 hours before the injection and during the follow-up and avoidance of heavy or repetitive stress to the ankle joint for 48 hours after the intervention. We are not aware of any evidence supporting the belief of Barber and colleagues that patients need to abstain from activity for longer than 48 hours after PRP injection. | |||||||||||||||||||||
49 | PRP | Efficacy of Platelet-Rich Plasma in the Treatment of Fractures: A Meta-Analysis | Meta-Analysis | Computational and Mathematical Methods in Medicine, 2022 | Z. Xu et al. | Treatment of Fractures | The present meta-analysis included 10 randomized controlled trials (RCT) containing 652 patients. | In the fixed-effect meta-analysis of 10 RCTs, 8 RCTs found that fracture patients benefited from PRP treatment. The use of PRP reduced the time of fracture healing in 4 RCTs. Three RCTs found that PRP adjuvant therapy enhanced bone mineral density in the fracture trace and reduced the time of bone regeneration in mandibular fractures patients (standardized mean difference ðSMDÞ = −1:99, 95% confidence intervalðCIÞ = −2:64 – −1:35). And 3 RCTs found that PRP adjuvant therapy decreased the risk of revision surgery in fracture patients (SMD = 1:83, 95%CI = 1:10 – 3:04). Conclusion. PRP adjuvant therapy is beneficial for the treatment of fracture patients, particularly those with mandibular fractures, and decreased the risk of revision surgery in fracture patients. | ||||||||||||||||||
50 | Stem Cell & PRP & Cellular Therapies | Therapeutic Efficacy and Safety of Osteoinductive Factors and Cellular Therapies for Long Bone Fractures and Non-Unions: A Meta-Analysis and Systematic Review | Meta-Analysis and Systematic Review | Journal of Clinical Medicine, 2022 | A. Kaspiris et al. | Long Bone Fractures | 18 studies | Similarly, the application of PRP has also demonstrated an important role during the fracture repair process, due to its ability to induce complex inflammatory responses at the bone defect site, not only by activating angiogenesis but also by providing growth factors, such as VEGF, PDGF, TGF-β and IGF. Although our meta-analysis did not reveal significant differences in the healing rate of patients with long bone fractures that received PRP treatment compared to the control group, the examination of the included studies showed that PRP use was accompanied by increased success rates for non-union treatment, decreased fracture healing periods and very good overall functional outcomes. Our findings are in line with the results of a recent meta-analysis that detected higher healing rates and a shorter consolidation duration accompanied by significant pain relief after the treatment with PRP for long bone delayed union and nonunion. This was also supported by the study of Bielecki et al., where PRP use resulted in complete healing in all patients with delayed union fractures. Moreover, no complications such as damage to blood vessels, haematomas, delayed wound healing, permanent nerve damage and post-operative infections were observed. Studies (Table 2) also demonstrated that PRP is a useful growth factor in non-unions of long bones, boosting the healing process without reported complications, such as allergic reactions, deep infections, ectopic neo-formations, neoplastic transformations or re-fractures, in line with our meta-analysis. However, Calori et al. reported a superior osteoinductive activity of BMP-2 compared with PRP; this was consistent with our results. | ||||||||||||||||||
51 | Stem Cell (Bone marrow) | Percutaneous autologous concentrated bone marrow grafting in the treatment for nonunion | Case-series | European Journal of Orthopaedic Surgery & Traumatology, 2013 | H. Sugaya et al. | Bone nonunion | 17 cases those had atrophic changes due to continuous nonunion for over 9 months after injury and had undergone low-intensity pulsed ultrasound treatment for more than 3 months. | After grafting, all the patients showed pain alleviation, and bone union was observed in most cases, radiographically. Percutaneous autologous concentrated bone marrow grafting is an effective procedure for the treatment of patients with nonunion. | ||||||||||||||||||
52 | Muscles, tendons, ligaments | PRP | The use of platelet-rich plasma in the treatment of greater trochanteric pain syndrome: a systematic literature review | Level I, systematic review of Level I studies | Journal of Hip Preservation Surgery, 2018 | Alie et al. | Greater trochanteric pain syndrome | 5 studies were included for analysis consisting of 3 RCTs and two case series. | Included studies used a variety of outcome measures. Improvement was observed during the first 3months after injection. Significant improvement was also noted when patients were followed up till 12 months post treatment. PRP seems a viable alternative injectable option for GTPS refractory to conservative measures. The current literature has revealed that PRP is relatively safe and can be effective. Considering the limitations in these studies, more large-sample and highquality randomized clinical trials are required in the future to provide further evidence of the efficacy for PRP as a treatment in GTPS. | |||||||||||||||||
53 | Stem Cell (Bone marrow) & PRP | Image-guided Injection of Anterior Cruciate Ligament Tears With Autologous Bone Marrow Concentrate and Platelets: Midterm Analysis From a Randomized Controlled Trial | Midterm Analysis From a Randomized Controlled Trial | Biologic Orthopedic Journal, Jan 2022 | C. Centeno et al. | Anterior Cruciate Ligament (ACL) tears | The sample comprised 50 patients, with 25 patients in the exercise therapy group and 25 in the treatment group. | Results: There was significant improvement in functional outcomes in the BMC group, compared to base-line for LEFS at time points 3 up to 24 months s = 0.000000005), and significant improvement in pain in the BMC group at 6 (p = 0.00054), 12 (p = 0.00127), and 24 months (p = 0.002). There was no significant improvement in pain or function at any time point in the exercise therapy group. There was significant improvement in ACL MRI ImageJ quantitative assessment in the BMC group (p = 0.001) and no difference in the exercise group (p > 0.05). No serious adverse events were reported.Conclusion: Autologous BMC and platelet product injection into ACL tears improved patient function compared to exercise, observed through 24 months. Patients treated with BMC demonstrated quantitative improvements in post-treatment MRI scans suggestive of interval ligament healing. | ||||||||||||||||||
54 | PRP | Comparative Effectiveness of Different Nonsurgical Treatments for Patellar Tendinopathy: A Systematic Review and Network Meta-analysis | Level I, Meta-analysis of Level I studies | Arthroscopy, 2019 Nov | P. C. Chen et al. | Patellar tendinopathy | 11 RCT studies with 430 affected patellar tendons were included | The network meta-analysis demonstrated that leukocyte-rich platelet-rich plasma (LR-PRP) has the greatest functional improvement and pain reduction for PT compared with other treatment options. | ||||||||||||||||||
55 | PRP | Platelet-Rich Plasma for Patellar Tendinopathy A Randomized Controlled Trial of Leukocyte-Rich PRP or Leukocyte-Poor PRP Versus Saline | A Randomized Controlled Trial | The American Journal of Sports Medicine, 2019 | A. Scott et al. | Patellar tendinopathy | 61 randomized patients | Study retention was 93% at 12 weeks and 79% after 1 year. There was no significant difference in mean change in VISA-P score, pain, or global rating of change among the 3 treatment groups at 12 weeks or any other time point. After 1 year, the mean (SD) outcomes for the LR-PRP, LP-PRP, and saline groups were as follows, respectively: VISA-P—58 (29), 71 (20), and 80 (18); pain—4.0 (2.4), 2.4 (2.3), and 2.0 (1.9); global rating of change—4.7 (1.6), 5.6 (1.0), and 5.7 (1.2) (P . .05 for all outcomes). Combined with an exercise-based rehabilitation program, a single injection of LR-PRP or LP-PRP was no more effective than saline for the improvement of patellar tendinopathy symptoms. | ||||||||||||||||||
56 | PRP | A systematic review and meta-analysis of platelet-rich plasma versus corticosteroid injections for plantar fasciopathy | Systematic review | International Orthopaedics (SICOT), 2017 Mar | P. Singh, S. Madanipour et al. | Plantar fasciopathy | 10 studies totalling 517 patients were included. Seven studies were randomised | PRP injections are associated with improved pain and function scores at three month follow-up when compared with corticosteroid injections. | ||||||||||||||||||
57 | PRP | Platelet-Rich Plasma Versus Corticosteroids for the Treatment of Plantar Fasciitis | A Systematic Review and Meta-analysis | The American Journal of Sports Medicine, Clinical Sports Medicine Update, 2020 | E. Hohmann et al. | Plantar Fasciitis | 15 studies | The results of this systematic review and meta-analysis suggest that PRP is superior to corticosteroid injections for pain control at 3 months and lasts up to 1 year. In the short term, there is no advantage of corticosteroid infiltration. However, the low study quality, high risk of bias, and different protocols for PRP preparation reduce the internal and external validity of these findings, and these results must be viewed with caution. | ||||||||||||||||||
58 | PRP | Platelet-Rich Plasma Versus Corticosteroids in the Treatment of Chronic Plantar Fasciitis: A Systematic Review and Meta-analysis of Prospective Comparative Studies | Systematic Review and Meta-analysis of Prospective Comparative Studies | The Journal of Foot & Ankle Surgery, 2019 | N. Alkhatib et al. | Plantar Fasciitis | 13 studies included | The American Orthopaedic Foot & Ankle Society score was significantly better in the PRP group at 6 months’ follow-up, with a lower visual analogue scale at 6- and 12-month intervals. The Foot and Ankle Disability Index and Roles-Maudsley score were similar in the 2 treatments at 3 and 6 months. PRP injection in the treatment of chronic plantar fasciitis is considered safe, with a favorable functional outcome and pain control at intermediate and long-term follow-up in comparison to corticosteroid injection. | ||||||||||||||||||
59 | PRP | Efficacy of platelet-rich plasma injections for symptomatic tendinopathy: systematic review and meta-analysis of randomised injectioncontrolled trials | Systematic review and Meta-analysis, Level I | BMJ Open Sport Exerc Med., 2017 Nov | L. E. Miller et al. | Symptomatic tendinopathy | A total of 16 RCTs (18 groups) of PRP versus control were included with a median sample size of 35 patients. | The results of this systematic review and meta-analysis provide level 1 evidence that injection of PRP is efficacious in patients with symptomatic tendinopathy. The treatment effects with PRP relative to controls in this meta-analysis suggest clinically meaningful improvements in patient symptoms. | ||||||||||||||||||
60 | PRP | Platelet-rich plasma for treatment of chronic proximal hamstring tendinopathy | Retrospective study | Regenerative Medicine, 2020 | M. J. Auriemma et al. | Hamstring tendinopathy | 22 patients | Pain and functional outcomes improved following injection of PRP. In 22 patients with a mean age of 48.7 years and mean symptom duration of 26.5 months, mean Numeric Pain Rating Scale and Victorian Institute of Sport Assessment Scale for Proximal Ham- string Tendinopathy subscores demonstrated statistically significant improvements (p < 0.05) at a mean of 7.91 months follow-up. Sixty-eight percent of patients demonstrated ≥50% reduction of pain. | ||||||||||||||||||
61 | PRP | Ultrasound-guided versus palpation-guided platelet-rich plasma injection for the treatment of chronic lateral epicondylitis: A prospective, randomized study | A prospective, randomized study | Arch Rheumatol 2023 | Sağlam et al. | Lateral Epicondylitis | 60 patients | Baseline sociodemographic and clinical variables were statistically similar between two groups (p>0.05). The VAS and DASH scores improved significantly after the injection at each control, as well as grip strength in both groups (p<0.001). No statistically significant difference was found between the groups regarding VAS and DASH scores, and grip strength at one, three, and six months post-injection (p>0.05). No significant complication related to the injection was observed in any of the groups. Conclusion: This study demonstrates that both palpation-guided and US-guided PRP injection protocols can improve clinical symptoms and functional parameters of patients with chronic LE. | Palpation vs. US | |||||||||||||||||
62 | PRP | Platelet-rich plasma therapy ensures pain reduction in the management of lateral epicondylitis - a PRISMA-compliant network meta-analysis of randomized controlled trials | PRISMA-compliant network meta-analysis of randomized controlled trials | Expert Opin Biol Ther, 2022 | S. Muthu et al. (abstract only) | Lateral Epicondylitis | 25 RCTs with 2040 patients were included in the network analysis. | Compared to saline control, only leukocyte-rich-PRP resulted in significant pain relief (WMD=-14.8,95% CI [-23.18,-6.39];low confidence) compared to steroid, local anesthetic, laser, and surgery. On analyzing DASH scores and PRETEE scores, none of the above-mentioned treatment methods were superior to saline control. In subgroup analysis, leucocyte-rich-PRP resulted in clinically significant improvement. Leucocyte-rich-PRP seems more promising with p-score of 0.415. Conclusion: PRP therapy offers significant pain relief compared to saline control in the management of LE without similar improvement in functional outcome. With available low-quality evidence, PRP was the most promising therapy that needs further exploration to explore its usefulness in lateral epicondylitis. | ||||||||||||||||||
63 | PRP | Effectiveness of Platelet-Rich Plasma for Lateral Epicondylitis | A Systematic Review and Meta-analysis Based on Achievement of Minimal Clinically Important Difference | The Orthopaedic Journal of Sports Medicine, 2022 | P. Niemiec et al. | Lateral Epicondylitis | A total of 26 studies were included in the analysis. | n: Based on comparisons with the MCID values of commonly used outcome scores, PRP seems to be an effective form of treatment for lateral epicondylitis. Both the LR- PRP and the LP- PRP systems were effective in the context of meeting the MCID. | ||||||||||||||||||
64 | PRP | Treatment of Lateral Epicondylitis With Autologous Blood, Platelet-Rich Plasma, or Corticosteroid Injections | Systematic Review of Overlapping Meta-analyses | The Orthopaedic Journal of Sports Medicine, 2019 | D. A. Houck et al. | Lateral Epicondylitis | 9 meta-analyses (two level 1 studies, seven level 2 studies) containing 8656 patients | The current best available evidence suggests that Corticosteroid Injections improve functional outcomes and pain relief in the short term, while Autologous Blood and PRP are the most effective treatments in the intermediate term. | ||||||||||||||||||
65 | PRP | Platelet-Rich Plasma Versus Corticosteroid Injections in the Management of Elbow Epicondylitis and Plantar Fasciitis | An Updated Systematic Review and Meta-analysis | The American Journal of Sports Medicine, 2019 | K. Huang et al. | Elbow Epicondylitis and Plantar Fasciitis | Twenty trials with 1268 participants were included. | The use of PRP yields statistically and clinically better improvement in long-term pain than does CS in the treatment of elbow epicondylitis (EE). The use of PRP yields statistically and clinically better long-term functional improvement than that of CS in the treatment of plantar fasciitis (PF). | ||||||||||||||||||
66 | PRP | Pain in donor site after BTB-ACL reconstruction with PRGF: a randomized trial | Double-blinded randomized clinical trial | Arthroscopy and Sports Medicine, 2016 | R. Seijas et al. | Bone-patellar tendon-bone (BTB) autograft anterior cruciate ligament (ACL) reconstruction | 43 patients were included comparing two patient groups who underwent ACL reconstruction using patellar tendon graft. | The autologous plasma rich in growth factors group showed decreased donor site pain in comparison to the control group, with significant differences in the first two months of follow-up. | ||||||||||||||||||
67 | PRP | Effect of Platelet-Rich Plasma Injection vs Sham Injection on Tendon Dysfunction in Patients With Chronic Midportion Achilles Tendinopathy | A participant-blinded, multicenter Randomized Clinical Trial | JAMA, 2021 | R. S. Kearney et al. | Chronic Midportion Achilles Tendinopathy | 240 people, 221 (92%) completed the trial at 6-month follow-up. | Among patients with chronic midportion Achilles tendinopathy, treatment with a single injection of intratendinous platelet-rich plasma, compared with insertion of a subcutaneous dry needle, did not reduce Achilles tendon dysfunction at 6 months. These findings do not support the use of this treatment for chronic midportion Achilles tendinopathy. | ||||||||||||||||||
68 | PRP | Platelet-rich plasma injection for adults with acute Achilles tendon rupture: the PATH-2 RCT | A multicentre, parallel-group, participant- and outcome assessor-blinded randomised controlled trial (RCT) comparing PRP with placebo | National Institute for Health Research, 2019 Nov | J. Alsousou et al. | Achilles tendon rupture | A total of 230 participants were randomised: 114 to the PRP group (103 treated) and 116 to the placebo group (all treated). | This trial design and standardised PRP preparation gives the first robust RCT evidence about PRP’s role in managing ATR, which suggests that PRP offers no patient benefit. Equally robust evidence to investigate PRP application in tendon and soft tissue injuries is required. The 24-month follow-up will be completed in April 2020. | ||||||||||||||||||
69 | PRP | Platelet-rich plasma injection for the treatment of chronic Achilles tendinopathy | A meta-analysis | Medicine, 2019 | C. Liu et al. | Achilles tendinopathy (AT) | Five RCTs (n=189)were included in this meta-analysis. | In conclusion, this meta-analysis revealed that PRP injection around the Achilles tendon is a treatment option for chronic AT. Research on the mechanism of action of PRP has shown that PRP has unique potential for relieving pain and improving function among patients with AT. Thus, its application will be extensive. The present results still require verification with a large number of well-designed, homogeneous RCT studies. | ||||||||||||||||||
70 | PRP | Anterior Cruciate Ligament Reconstruction with Platelet-Rich Plasma: A Systematic Review of Randomized Control Trials | Level I, Systematic review of Level I evidence | Arthroscopy Association of North America, 2019 | M.S. Davey et al. | Anterior Cruciate Ligament (ACL) reconstruction | 13 RCTs involving 765 patients | PRP did not result in any clinical improvement when used alongside soft-tissue grafts in graft integration. In addition, PRP did not improve donor-site morbidity when used at the site of BPTB harvest, although there was a transient reduction in pain in the early postoperative period. | ||||||||||||||||||
71 | PRP | Platelet-rich plasma in non-operative management of mild to moderate carpal tunnel syndrome – A systematic review & meta-analysis of short-term outcomes | Level of evidence: II; Systematic Review & Meta-Analysis of Prospective Trials | Journal of Orthopaedics, 2021 | M.S. Davey, M.G. Davey et al. | Carpal tunnel syndrome | 8 prospective trials with 404 patients | This study indicates that there may be a potential role for the use of PRP in the non-operative management of mild to moderate CTS results in improvements in pain scores, functional outcomes as well as CSA measurements of the MN at short-term follow-up. However, PRP does not result in improvements in NCS. | ||||||||||||||||||
72 | PRP | Leucocyte-Rich Platelet-Rich Plasma Treatment of Gluteus Medius and Minimus Tendinopathy | Double-Blind Randomized Controlled Trial With 2-Year Follow-up | The American Journal of Sports Medicine, 2019 | J. Fitzpatrick et al. | Gluteus Medius and Minimus Tendinopathy | 80 patients | Among patients with chronic gluteal tendinopathy and a length of symptoms .15 months, a single intratendinous LR-PRP injection performed under ultrasound guidance results in greater improvement in pain and function than a single CSI. The improvement after LR-PRP injection is sustained at 2 years, whereas the improvement from a CSI is maximal at 6 weeks and not maintained beyond 24 weeks. | ||||||||||||||||||
73 | PRP | Platelet-rich Plasma Injection Can Be a Viable Alternative to Corticosteroid Injection for Conservative Treatment of Rotator Cuff Disease: A Meta-analysis of Randomized Controlled Trials | A Meta-analysis of Randomized Controlled Trials, Level of evidence: Systematic review of Level I and II studies. | Arthroscopy, Jul 2022 | L. P. Bachelor et al. (abstract only) | Rotator Cuff Disease | 13 non-surgical RCTs with 725 patients were included. | Without the drawbacks of CS injection, PRP injection is not worse than CS injection in pain relief and function recovery at any time point of the follow-up. PRP injection may reduce rates of subsequent injection or surgery, and might provide better improvement in pain and function in the medium- to long-term. PRP injection can be a viable alternative to CS injection for conservative treatment of rotator cuff disease. | ||||||||||||||||||
74 | PRP | Platelet-Rich Plasma Augmentation of Arthroscopic Rotator Cuff Repair Lowers Retear Rates and Improves Short-Term Postoperative Functional Outcome Scores: A Systematic Review of Meta-Analyses | A Systematic Review of Meta-Analyses, Level III, systematic review of Level I-III studies. | Arthroscopy, Sports Medicine, and Rehabilitation, 2022 | Z. Ahmad et al. (abstract only) | Arthroscopic Rotator Cuff Repair | A total of 1,800 patients with an average follow up of 12 to 36 months. | Our study shows that PRP is effective in reducing retears after rotator cuff repair and improving functional outcome scores and reducing short-term pain. | ||||||||||||||||||
75 | PRP | Clinical efficacy and safety of platelet-rich plasma in arthroscopic full-thickness rotator cuff repair: A meta-analysis | Meta-analysis | 2019 | C. Wang et al. | Full-thickness rotator cuff tear (following arthroscopic repair) | 8 randomized controlled trials involving 566 patients | Platelet-rich plasma injection can effectively improve the short-term outcomes following arthroscopic repair of full-thickness rotator cuff tears, thus reducing the rate of retears, alleviating pain, and improving patients’ shoulder function. | ||||||||||||||||||
76 | PRP | Double Row Repair with PRP Optimizes Retear Rates after Small to Medium Full-Thickness Rotator Cuff Repair: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials | A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials | Arthroscopy, 2022 | O. Lavoie-Gagne et al. (abstract only) | Small to Medium Full-Thickness Rotator Cuff Repair | A total of 18 studies comprising 2,046 shoulders (47% females, mean age 61 ± 3 years, mean follow-up 21 ± 5 months) were included. | Based on a network meta-analysis of level 1 studies, arthroscopic rotator cuff repair with a SR or DR construct demonstrates similar retear rates, PROs, and clinical outcomes. The highest-ranking treatment for minimizing retears was arthroscopic repair with DR constructs and PRP augmentation, although open repair and arthroscopic SR remain reliable options with excellent clinical outcomes. Addition of PRP to DR constructs trended towards a 56% decreased risk of retear as compared to DR repair alone. While no single treatment emerged superior, several interventions offered excellent clinical improvements in pain, ROM, and PROs exceeding minimal clinically important difference thresholds. | ||||||||||||||||||
77 | PRP | Injection of Leukocyte-Poor Platelet-Rich Plasma for Moderate-to-Large Rotator Cuff Tears Does Not Improve Clinical Outcomes but Reduces Retear Rates and Fatty Infiltration: A Prospective, Single-Blinded Randomized Study | A Prospective, Single-Blinded Randomized Study, Level of evidence: II | Arthroscopy, Aug 2022 | C. Zhang et al. (abstract only) | Moderate-to-Large Rotator Cuff Tears | 104 patients with moderate-to-large rotator cuff tears -> a total of 89 patients were available for 24 months follow-up. | Results: The mean UCLA score increased from 14.80 ± 2.53 to 29.37 ± 2.06 in control group and from 13.74 ± 3.30 to 30.14 ± 2.32 in study group (P = .103). The mean Constant score increased from 46.56 ± 5.90 to 86.83 ± 4.94 in control group and from 44.37 ± 7.92 to 88.80 ± 4.92 in study group (P = .063). The VAS score decreased from 3.22 ± 1.24 to 0.97 ± 1.12 in control group and in 3.49 ± 1.52 to 1.16 ± 0.99 in study group (P = .41). All differences in UCLA score, Constant score, and VAS between pre- and postoperation achieved minimal clinically important differences proposed for arthroscopic rotator cuff repair. Of the 89 patients, 76 had magnetic resonance imaging performed at 24 months after surgery. The retear rate was 17.6% in study group, which was lower than that in control group (38.1%, P = .049). In addition, the Goutallier grade was found to be significant difference between groups postoperatively (Kendall tau-b -0.24, P = .03) but no significant difference preoperatively (Kendall tau-b -0.18, P = .11). There were no complications in the patients. Conclusions: Our procedures involving repeated injections of Lp-PRP during surgery and at days 7 and 14, as described in this study, have positive effects on reducing retear rate and promoting Goutallier grade in patients following arthroscopic rotator cuff repair and could also provide substantial clinical outcomes that reach the minimal clinically important difference for surgical treatment. However, given the numbers available for analysis, it did not promote better clinical results when compared with the control group. | Editorial Commentary: Platelet-Rich Plasma Reduces Retear Rates Following Rotator Cuff Repair but Does Not Improve Clinical Outcomes, Erik Hohmann; DOI: 10.1016/j.arthro.2022.03.019 Platelet-rich plasma (PRP) is a novel biologic treatment in orthopaedic sports medicine that may enhance surgical repairs and improve clinical and functional outcomes. Studies investigating the effect of PRP on shoulder rotator cuff healing, clinical outcomes, and retear rates suggest that PRP has no effect on outcome and healing but potentially reduces retear rates. However, study quality is compromised by low samples sizes, inadequate randomization protocols, and heterogeneity. In addition, other factors influence outcomes and could cause bias when collecting data. PRP preparation varies among studies, and a variety of patient factors such as smoking; comorbidity; rotator cuff tear size, configuration, and grade; and functional demands are difficult to control even if a randomized study protocol is undertaken. Until there are reliable and valid data available, the use of PRP in rotator cuff repair is not strongly supported and is at the discretion of the treating surgeon. The current evidence shows the superiority of PRP over hyaluronic acid and corticosteroids, and there is promise that PRP could be a useful adjunct promoting rotator cuff healing following surgical repair. | |||||||||||||||||
78 | PRP | Use of Platelet-Rich Plasma for the Improvement of Pain and Function in Rotator Cuff Tears: A Systematic Review and Meta-analysis With Bias Assessment | A Systematic Review and Meta-analysis With Bias Assessment | The American Journal of Sports Medicine, 2020 | X. Chen et al. | Rotator Cuff Tear | A total of 18 level 1 studies were included in this review, 17 (1116 patients) of which could be included in quantitative analysis. | Long-term retear rates were significantly decreased in patients with rotator cuff–related abnormalities who received PRP. Significant improvements in PRP-treated patients were noted for multiple functional outcomes, but none reached their respective minimal clinically important differences. Overall, our results suggest that PRP may positively affect clinical outcomes, but limited data, study heterogeneity, and poor methodological quality hinder firm conclusions. | ||||||||||||||||||
79 | PRP | Efficacy of Platelet-Rich Plasma Injection in the Management of Rotator Cuff Tendinopathy: A Review of the Current Literature | Review of the Current Literature | Cureus, Jun 2022 | K. Bhan et al. | Rotator Cuff Tendinopathy | 9 studies (Level I to Level IV) were reviewed | It can be agreed that PRP injection offers an efficient alternative for improving the shoulder function and range of motion in patients suffering from rotator cuff tendinopathy. In patients with restricted shoulder movements, the improvements in DASH, ASES, or WORC scores have shown that PRP as a standalone treatment option can help improve the shoulder range of motion. However, the absence of any long-term follow-up data means that no comments about refractory rotator cuff tendinopathy after a PRP injection can be made. Moreover, since rotator cuff tendinopathy is a chronic condition, short-term improvement in the range of motion may not imply that the condition will not worsen over time. Nonetheless, PRP may be safely suggested to improve the shoulder range of motion in periods up to at least one year after injection in the majority of patients without major adverse effects. More definitive studies with standardized methods of preparations and follow-ups are required to make a conclusive recommendation. | ||||||||||||||||||
80 | PRP | Effectiveness of Platelet-Rich Plasma Injection in Rotator Cuff Tendinopathy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials | Systematic Review and Meta-Analysis of Randomized Controlled Trials | Diagnostics, 2020 | MT. Lin et al. | Rotator Cuff Tendinopathy | 5 studies included, the comparison between the PRP and control group in this study comprised 283 patients. | PRP injection may provide benefit over the control group (sham injection, no injection, or physiotherapy alone) in reducing pain at long-term follow-up for patients with rotator cu tendinopathy. | ||||||||||||||||||
81 | Stem Cell and PRP | Do Regenerative Medicine Therapies Provide Long-Term Relief in Chronic Low Back Pain: A Systematic Review and Metaanalysis | Systematic Review and Metaanalysis | Pain Physician, 2018 | J. Sanapati et al. | Chronic Low Back Pain | This review encompassed 7 articles on regenerative therapies that studied a combined population of only 104 patients | Results: Evidence synthesis based on a single-arm metaanalysis, randomized controlled trials (RCTs), and observational studies, disc injections of PRP and MSCs showed Level 3 evidence (on a scale of Level I through V). Evidence for epidural injections based on single-arm metaanalysis, a single randomized controlled trial and other available studies demonstrated Level 4 (on a scale of Level I through V) evidence. Similarly, evidence for lumbar facet joint injections and sacroiliac joint injections without metaanalysis demonstrated Level 4 evidence (on a scale of Level I through V). Limitations: Lack of high quality RCTs. Conclusion: The findings of this systematic review and single-arm metaanalysis shows that MSCs and PRP may be effective in managing discogenic low back pain, radicular pain, facet joint pain, and sacroiliac joint pain, with variable levels of evidence in favor of these techniques. | ||||||||||||||||||
82 | PRP | Platelet-Rich Plasma in the Treatment of Facet Mediated Low Back Pain: A Comprehensive Review | Comprehensive Review | Orthopedic Reviews, 2022 | A. Patel et al. | Low Back Pain | N/A | Results: PRP injections for facet mediated or modulated pain are an alternative to conventional pharmacotherapies and interventional injections/radiofrequency. There are limited numbers of studies in world literature at present. Limitations: Small number of articles in the world literature and small numbers of patients in those published studies. Conclusions: At present, there are limited studies in the literature; however, larger well-designed studies are warranted to precisely understand efficacy, potential side effects and best practice techniques for PRP injections for facet mediated or modulated pain. | ||||||||||||||||||
83 | Back pain & Spine | PRP | Lumbar Intradiskal Platelet-Rich Plasma (PRP) Injections: A Prospective, Double-Blind, Randomized Controlled Study | Prospective, Double-Blind, Randomized Controlled Study | PM&R by the American Academy of Physical Medicine and Rehabilitation, 2016 | Yetsa A. Tuakli-Wosornu et al. | Symptomatic degenerative intervertebral disks | 47 participants | Participants who received intradiskal PRP showed significant improvements in FRI, NRS Best Pain, and NASS patient satisfaction scores over 8 weeks compared with controls. Those who received PRP maintained significant improvements in FRI scores through at least 1 year of follow-up. | |||||||||||||||||
84 | PRP | Treatment of symptomatic degenerative intervertebral discs with autologous platelet-rich plasma: follow-up at 5–9 years | 5- to 9-year follow-up of a previous randomized controlled trial | Regenerative, Medicine, 2019 | J. Cheng et al. | Symptomatic degenerative intervertebral discs | 29 patients in the intradiscal PRP arm of the previous study were included in this follow-up study | This subset of patients demonstrated statistically and clinically significant improvements in pain and function at 5–9 years postinjection. | ||||||||||||||||||
85 | PRP | Platelet-Rich Plasma for the Treatment of Low Back Pain: a Comprehensive Review | Comprehensive Review | Current Pain and Headache Reports, 2019 | I. Urits et al. | Low Back Pain | Multiple studies on: Discogenic Pain, Sacroiliac Joint Pain, Facet Arthropathy | Despite considerable advances in recent decades, low back pain remains highly prevalent and difficult to treat. Plateletrich plasma may be a safe and effective therapy for patients with chronic low back pains secondary to degenerative conditions of the spine and the lower back. Limited small studies have demonstrated PRP to be beneficial in application to degenerative disc disease, sacroiliac joint-related pain, and facet joint arthropathy. Further large clinical trials are required however to better assess safety and efficacy of this treatment in the future. | ||||||||||||||||||
86 | Stem Cell and PRP | Biologics for Lumbar Discogenic Pain: 18 Month Follow-up for Safety and Efficacy | Prospective case series, 18‑months follow‑up | Interventional Pain Management Reports, 2018 | A. Navani et al. | Lumbar discogenic pain | 20 patients | Study supports the safety of a single intradiscal biologic injection and provides additional evidence for its efficacy in the management of lumbar discogenic pain, with improvements in both pain and function, and decreased utilization of medications and medical services thereby decreasing health care costs. | ||||||||||||||||||
87 | Stem Cell and PRP | Responsible, Safe, and Effective Use of Biologics in the Management of Low Back Pain: American Society of Interventional Pain Physicians (ASIPP) Guidelines | (ASIPP) Guidelines, review of evidence | Pain Physician, 2019 | A. Navani et al. | Low Back Pain | Evidence synthesis of randomized controlled trials (RCTs), multiple moderate-quality observational studies, single-arm meta-analyses and systematic reviews | Based on the evidence synthesis summarized above, there is Level III evidence for intradiscal injections of PRP and MSCs, whereas the evidence is considered Level IV for lumbar facet joint, lumbar epidural, and sacroiliac joint injections of PRP, (on a scale of Level I through V) using a qualitative modified approach to the grading of evidence based on best evidence synthesis. | ||||||||||||||||||
88 | PRP | Effectiveness of plasma rich in growth factors in the management of chronic spinal pain: a case series of 32 patients | Case-series | Regenerative Medicine, 2022 | M. Barbieri, A. Stogicza et al. | Chronic spinal pain | 32 patients | PRGF is a potential treatment in a specific subpopulation of difficult-to-treat patients affected by chronic LBP. | ||||||||||||||||||
89 | Stem Cell (Bone marrow) | Percutaneous Injection of Autologous Bone Marrow Concentrate Cells Significantly Reduces Lumbar Discogenic Pain Through 12 Months | 12 months follow-up | Stem Cells, 2015 | K. A. Pettine et al. | Degenerative disc disease | 26 patients | This study provides evidence of safety and feasibility in the nonsurgical treatment of DDD with autologous BMC and indicates an effect of mesenchymal cell concentration on discogenic pain reduction. | ||||||||||||||||||
90 | Stem Cell (Bone marrow) | Treatment of discogenic back pain with autologous bone marrow concentrate injection with minimum two year follow-up | 2 year follow up | International Orthopaedics, 2015 | K. A. Pettine et al. | Degenerative disc disease | 26 patients | This study provides evidence of safety and feasibility in the non-surgical treatment of discogenic pain with autologous BMC, with durable pain relief (71 % VAS reduction) and ODI improvements (>64 %) through two years. | ||||||||||||||||||
91 | Stem Cell (Bone marrow) | Autologous bone marrow concentrate intradiscal injection for the treatment of degenerative disc disease with three-year follow-up | Prospective, open-label, non-randomized, single-arm study, 3-year follow-up | International Orthopaedics, 2017 | K. A. Pettine et al. | Degenerative disc disease | 26 patients | There were no adverse events related to marrow aspiration or injection, and this study provides evidence of safety and feasibility of intradiscal BMC therapy. Patient improvement and satisfaction with this surgical alternative supports further study of the therapy. | ||||||||||||||||||
92 | Nerve & Neuropatic | PRP | Prospects for Improving the Extent of Recovery following Peripheral Nerve Trauma: A Review | Review | Puerto Rico Helalth Sciences Journal, May 2022 | C. Foy et al. (abstract only) | Restoring function to damaged peripheral nerves | N/A | This review discusses the limitations of sensory nerve grafts and other techniques currently being used to repair nerves. It also discusses the use of autologous platelet-rich plasma (PRP), which appears to be the most promising technique for inducing sensory and motor recovery even when the values of all three variables are significantly greater than when sensory nerve grafts alone are not effective. Thus, there is finally the promise that patients who presently have limited to no chance of any recovery may recover good to excellent sensory and motor function. | |||||||||||||||||
93 | PRP | Platelet-rich plasma and cytokines in neuropathic pain: A narrative review and a clinical perspective | Review | European Journal of Pain, 2021 | Y. Bohren et al. | Neuropathic pain | Over 300 articles including meta analyses | Data from the literature show that cytokines are involved in the development and maintenance of neuropathic pain. Their modulation appears to be an interesting therapeutic option. However, due to the possible adverse effects of systemic immunomodulatory treatments, such as biotherapies against TNF-α, their potential use seems to be very limited. Moreover, the ‘cytokine candidate’ approach, targeting a precise cytokine, may likely be difficult to generalize to the different aetiologies of neuropathic pain. Animal studies showed regulation of the cytokinergic balance, such as a pro-/ anti-inflammatory shift, induced by PRP therapy. By analogy to inflammatory pathologies, the use of PRP in neuropathic pain seems to be a promising option, pending major controlled trials. Its use could be of particularly interest with locoregional administration, applying PRP on the concerned tissue only. This hypothesis would be supported by the fact that the patients with chronic pain often display a localized, but not general, imbalance between pro-/ anti-inflammatory cytokines. On the other hand, the optimal frequency of PRP injections should likely be determined according to neuropathic pain's aetiologies. | ||||||||||||||||||
94 | PRP | Novel perineural approach of platelet-rich plasma application in idiopathic trigeminal neuralgia treatment: a six-month follow-up pilot study | Pilot study | International Journal of Oral and Maxillofacial Surgery, 2017 | A. Stamatoski et al. (abstract only) | Trigeminal neuralgia | 29 patients aged above 35 years with TNP | PRP was applied five times on seven days interval. The comparison of the intensity of pain during seven examinations suggests excellent effects of the procedure being performed as the mean visual analogue scale score was 9.1 before application I; 7.6 before application II; 3.0 before application III; 0.6 before application IV; 0.1 before application V, 0.0 at third month examination and 0.0 and at sixth month examination 0.0. Conclusion: The significant reduction in pain suggests that future, larger and longer cohort studies in which will be used newest TNP pain scales are required to evaluate the effectiveness of the present methodology. | https://www.ijoms.com/article/S0901-5027(17)31320-6/fulltext | |||||||||||||||||
95 | PRP | Platelet-rich plasma in treating peripheral neuropathic pain. | Preliminary report, prospective study | Revista de la Sociedad Española del Dolor: Rev. Soc. Esp. Dolor., 2018 | J. C. Lopez et al. | Neuropathic pain: Post herpetic neuralgia (PHN) braquial plexus Post herpetic neuralgia (PHN) occipital nerve Post herpetic neuralgia (PHN) intercostal nerve Chronic post-surgical abdominal pain (CPSP) ilioinguinal involvement Peripheral nerve injury following trauma | 45 patients with shooting, burning, electric, or lancinating pain and allodynia, with refractory multimodal-approach to pharmacologic management for more than 3 months were included in the study | All patients had a diagnosis of peripheral neuropathic pain. Patients received a sonographic- guided injection of PRP at the affected dermatome site. Results: At the end of three-month follow-up, the pain score was reduced up to 70 % in 39 out of the 45 patients, permitting the lowering of pain medication and improving their quality of life. Conclusion: These positive and promising results with PRP in treating peripheral neuropathic pain in the present study encourage us for further clinical investigations of this novel proposal. % patients with improvement: Post herpetic neuralgia (PHN) braquial plexus: 88% Post herpetic neuralgia (PHN) occipital nerve: 100% Post herpetic neuralgia (PHN) intercostal nerve: 91% Chronic post-surgical abdominal pain (CPSP) ilioinguinal involvement: 87% Peripheral nerve injury following trauma: 78% | ||||||||||||||||||
96 | PRP | Trigeminal Neuralgia Treatment: A Case Report on Short-TermFollow up After Ultrasound Guided Autologous Platelet RichPlasma Injections. | Case Report | Webmed, 2012 | A. X. Doss | Trigeminal neuralgia | 1 40 year old female patient | Five injections of PRP. She was discharged immediately after each procedure and resumed normal activities without any need for recovery. She maintained a pain diary for most days from the start of symptoms. Since the PRP injections, she has been on 50 mg of Tegretol twice a day for about 3 months. She continued with oral vitamin, omega three fatty acid supplements during the follow up period. For 6 months post PRP, she has had a normal social and work life with resolution of symptoms and no clinical features to suggest peripheral nerve damage. As far as the author is aware this is the first report of ultrasound guided PRP of the distal branches of the trigeminal nerve in Trigeminal Neuralgia. In comparison to other percutaneous or surgical procedures, DTNT is a very low risk, out patient clinic procedure that can be repeated and should be further evaluated in a large patient group with long term follow up. | https://www.webmedcentral.com/article_view/3381 | |||||||||||||||||
97 | ||||||||||||||||||||||||||
98 | Legend: | Created by: | ||||||||||||||||||||||||
99 | PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses | Pro-regenerative treatment | ||||||||||||||||||||||||
100 | KOOS: Knee Injury and Osteoarthritis Outcome Score | Not in support of regenerative treatment | ||||||||||||||||||||||||