
AUTOLOGOUS PLATELET-RICH PLASMA AS A TREATMENT FOR KNEE OSTEOARTHRITIS.
Solange VISCHER1, Antoine TURZI2 1 Senior Scientific Advisor, Regen Lab SA, Switzerland ; 2 CEO, Regen Lab SA, Switzerland Article in FrenchSummary
Platelet-rich plasma (PRP) is an autologous biologic drug prepared from the patient’s blood and used as a treatment for wound healing and other lesions on the same patient. It is still considered by many to be an experimental treatment for osteoarthritis and is therefore not covered by insurance.
However, a growing number of scientific societies are recognizing PRP as a safe and effective treatment modality for knee osteoarthritis, based on a large number of studies published on this topic by clinicians around the world.
These clinical studies have been compiled and synthesized in various recent meta-analyses which are summarized here.
These meta-analyses demonstrate the safety, efficacy, and superiority of PRP compared to other
modalities of treatment of osteoarthritis of the knee by intra-articular injections.
Keywords: Knee osteoarthritis, platelet-rich plasma, PRP, medical devices, regulation, MDR 2017/745, FDA, MDSAP, ISO13485
INTRODUCTION
In the United States, as in the rest of the world, a variety of technologies are used for the preparation of PRP. Many preparation methods lack standardisation and repeatability from one patient to another, and there are even “homemade” processes, as transfusion specialists did 30 years ago.
However, the devices used for the isolation of PRP from the patient’s blood relate to the definition of a
medical device and must therefore comply with the regulations in force.
Over the past 20 years, multiple technologies for the preparation of PRP at the bedside have been approved by the health authorities of each country.
In the European Union, they are governed by Regulation 2017/745 (MDR), which has replaced Directive 93/42/EEC (MDD) since 2021.
In the United States, devices for the preparation of PRP are regulated by the Center for Biologics Evaluation and Research (CBER) of the Food and Drug Administration (FDA). They carry the product code ORG or PMQ (for those intended for wound care) and follow section 864.9246 of the Code of Federal Regulation Title 21 (21 CFR 864.9245) for automated blood cell separators.

The Centers for Medicare & Medicaid Services (CMS) decided in 2021 to reimburse PRP treatments for diabetic foot ulcers. For several years, TRICARE’s reimbursement has covered PRP treatments for military patients with knee osteoarthritis.


Regen Lab, Switzerland has been certified ISO13485 since 2003 for the manufacture and marketing of RegenKits internationally.
In Europe, RegenKits have already obtained their CE certificate according to MDR 2017/745.
RegenLab® USA received its first FDA clearance in May 2010 with RegenKit® THT®, which has been part of a family of medical devices manufactured in the United States since November 2021.
In accordance with the MDSAP ISO-13485 standard, the production of these medical devices follows the highest quality management standards.
The RegenKit® technology enables a fast and standardized PRP preparation process with a closed- loop system. This PRP (RegenPRP) has demonstrated its safety, reliability, and efficacy in more than 300 scientific and clinical publications in academic journals.
Autologous PRP is a suspension of platelets in plasma, prepared from the patient’s blood and used as a treatment for wound healing and other lesions on the same patient, thus minimizing the possibility of cross- reactivity and allergic reactions.
PRP contains live, functional platelets, so this biological preparation is different from other autologous blood-derived growth factor preparations such as clot extracts. Similarly, frozen/thawed PRP should not be considered equivalent to fresh PRP because most platelets do not survive this process [1].
RegenKit® technologies produce PRP treatments from fresh, minimally manipulated blood to harness and maximize the patient’s natural healing capacity.


Recent reviews, such as Li et al. 2022 [2], and meta-analyses, see below, have concluded that platelet- rich plasma is an effective and safe biological approach to treat osteoarthritis and more specifically knee osteoarthritis.
These studies show that PRP, compared to the two main intra-articular injectable therapies, corticosteroids (CS), hyaluronic acid (HA), provides superior pain relief and functional improvement [3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15].
Knee osteoarthritis treatments with CS and HA are currently covered by insurances in the United States. However, even though these treatments have been clinically shown to relieve pain, they have no impact on slowing the progression of knee osteoarthritis.
In addition, visco-supplementation with HA offers only a small reduction in pain symptoms compared to placebo [16].
Corticosteroids, on the other hand, are useful in patients with acute exacerbations of pain and joint effusion, but their long-term use has been associated with greater loss of cartilage volume [17].
Therefore, a growing number of scientific societies recognize PRP as a safe and effective treatment modality for knee osteoarthritis.
• The AAOS (American Academy of Orthopedic Surgeons) recognized that PRP demonstrated a significant improvement in patient- reported outcomes compared to placebo [18].
• The ASPN (American Society for Pain and Neuroscience), in the STEP guidelines, reached a strong consensus regarding the safety and efficacy of intra-articular PRP for pain treatment and improvement of joint functionality in patients with osteoarthritis, noting that it was at least as effective, if not more so, than an entire series of visco- supplementation with HA [19].
• ESSKA’s ORBIT Consensus (European Society for Sports Traumatology, Knee Surgery and Arthroscopy) concluded that there is sufficient preclinical and clinical evidence to support the use of PRP in knee osteoarthritis [20].
• Similarly, the GRIIP (PRP Intra-articular Injection Research Group) stated that PRP is an effective symptomatic treatment for mild to moderate osteoarthritis of the knee and may be useful in severe osteoarthritis of the knee, with a high level of evidence [21].
• At least 75% of the experts of the “German Working Groupfor Clinical Tissue Regeneration”of the German Society of Orthopaedics and Traumatology (GSOT) have reached a consensus that PRP injection may be useful in patients with mild knee osteoarthritis (Kellgren-Lawrence II grade) [22].
• The SIOT (Italian Orthopaedic and Traumatology Society) working group supports the use of PRP injections in symptomatic osteoarthritis of the knee [23].
• Riboh’s meta-analysis concluded that leucocyte-poor PRP (LP-PRP) was the highest-ranked treatment compared to leucocyte-rich PRP (LR-PRP), HA, or placebo for both measures of clinical effectiveness (Western Ontario and McMaster University Osteoarthritis Index (WOMAC) and Subjective International Knee Documentation Committee (IKDC) scores) [24].

After reviewing and summarizing the literature published up to March 2023, Mende et al. 2024 came to the same conclusion and recommend the use of LP-PRP for Canadian Armed Forces (CAF) military members with mild to moderate osteoarthritis of the knee (Kellgren– Lawrence grades 1–3) to slow the progression of osteoarthritis and prolong the military careers of CAF members [25].
The U.S. Army is also providing intra-articular injections of PRP to military personnel and TRICARE beneficiaries [26].
Compared to other devices designed to prepare PRP, RegenLab® devices produce PRP with a standardised composition. The use of thixotropic separator gels with specific densities allows precise isolation at the cellular level of PRP from other blood components. This method of fractionating blood is highly reproducible due to the fact that it is independent of the operator and the patient.
The resulting PRP, RegenPRP, is a low-leukocyte PRP in which there is a specific depletion of pro- inflammatory neutrophil granulocytes. The platelet recovery rate in RegenPRP is greater than 80% with no specific loss of the largest and densest platelets that are known to be the richest in growth factors [27].
This standardised PRP has been shown to be effective in many different therapeutic areas. For knee osteoarthritis, 18 studies, involving a total of 1057 patients treated with RegenPRP, report a significant reduction in pain and improvement in function [28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45].
In addition, the study of Chen et al. has shown that RegenPRP injections positively modify the composition of synovial fluid, with a decrease in molecules related to inflammation and an increase in proteins associated with chelation and anti-aging physiological functions [31].
Russo et al. Conducted an economic evaluation of the intra-articular use of RegenPRP therapy in the treatment of knee osteoarthritis compared to hyaluronic acid (HA) which represents the standard intra- articular therapy (46). Both therapies can reduce pain, improve the patient’s quality of life, and help the patient delay joint surgery, which comes at a high cost to the national health system. A cost- effectiveness analysis was conducted using a decision tree model. Efficacy results were reported in terms of quality- adjusted life years (QALYs). Costs were reported in euros (€) assessed in 2016.
The analyses were carried out for three European countries: Germany, Italy and France. RegenPRP treatment was more expensive but also more effective than HA. Using a willingness-to-pay threshold of €10,000/QALY, PRP was found to be cost-effective compared to HA for patients with moderate to severe knee osteoarthritis considering a one-year horizon.
The main effectiveness of RegenPRP, in addition to improving quality of life, was that it could delay total knee replacement surgery and reduce the eventual revision of the prosthesis, thereby reducing the total costs of knee osteoarthritis and the economic burden on healthcare systems.
RECENT META-ANALYSES ON OSTEOARTHRITIS
In 2023, Cao et al. did a meta-analysis of randomized controlled trials (RCTs) to quantitatively evaluate PRP efficacy, compared with hyaluronic acid (HA), and to identify relevant factors that significantly affect the efficacy of PRP treatment for OA [3].
A total of 45 RCTs (3829 participants) involving 1805 participants injected with PRP were included in the analysis. Both conventional meta-analysis and pharmacodynamic maximal effect models showed that PRP was significantly more effective than HA for joint pain and function impairment (additional decrease of 1.1, 0.5, 4.3, and 1.1 scores compared to HA treatment at 12 months for WOMAC pain index, stiffness, function, and visual analog scale (VAS) pain scores, respectively). Higher baseline symptom scores, older age (≥ 60 years), higher BMI (≥ 30), lower Kellgren–Lawrence grade (≤ 2) and shorter OA duration (< 6 months) were significantly associated with greater efficacy of PRP treatment. These findings suggest that PRP is a more effective treatment for OA than the more well-known HA treatment.
Xiong et al. conducted a meta-analysis in 2023 examining relevant RCTs to determine the efficacy and safety of PRP injections for the treatment of OA [47]. They included 24 RCTs comprising 1344 patients with OA. Their results indicated that PRP injections were effective in improving VAS pain scores. Compared to controls, PRP injections were also effective in improving the Knee Injury and Osteoarthritis Outcome Score (KOOS), including the patient’s pain symptoms, activities of daily living (ADL), and adhesion symptomatology. PRP injections were effective in improving WOMAC scores, including pain, stiffness, and functional joint motion, in patients with OA when compared with the control group. In addition, subgroup analysis showed that leukocyte-poor (LP) PRP injections were more effective than leukocyte-rich (LR) PRP injections in improving pain symptoms in patients with OA. They concluded that PRP injection therapy can safely and effectively improve functional activity in patients with OA and produce positive analgesic effects in patients with OA. In addition, the analgesic effect of LP-PRP was greater than that of LR-PRP.
RECENT META-ANALYSES ON KNEE OSTEOARTHRITIS
2024
Jawanda et al. compared the efficacy of common intra-articular injections used in the treatment of knee osteoarthritis, including corticosteroid (CS), hyaluronic acid (HA), platelet-rich plasma (PRP), and bone marrow aspirate concentrate (BMAC), with a minimum follow-up of 6 months [4].
The literature search was conducted using the 2020 PRISMA guidelines in August 2022 in the following databases: PubMed/MEDLINE, Scopus, Cochrane Database of Controlled Trials and the Cochrane Database of Systematic Reviews. Forty-eight level I to II randomized clinical trials, with a minimum follow- up of 6 months, comprising a total of 9,338 knees were included.
The most studied intra-articular injection was HA (40.9%) followed by placebo (26.2%), PRP (21.5%), CS (8.8%) and then BMAC (2.5%). HA and PRP both led to a significant improvement in pain compared to placebo. HA, PRP, and BMAC all led to a significant improvement in function scores when compared to placebo. Surface under the cumulative ranking curves (SUCRA) of the interventions revealed that PRP, BMAC, and HA were the treatments with the highest likelihood of improvement in both pain and function with overall SUCRA scores of 91.54, 76.46, and 53.12 respectively. The overall SUCRA scores for CS and placebo were 15.18 and 13.70.
They concluded that at a minimum 6-month follow-up, PRP demonstrated significantly improved pain and function for patients with knee osteoarthritis compared to placebo. Additionally, PRP exhibited the highest SUCRA values for these outcomes when compared to BMAC, HA, and CS.
Khalid et al. compared the effectiveness of intra-articular injectable therapies, including PRP, HA, CS, and placebo, in knee osteoarthritis. Data extraction involved baseline characteristics and outcome measures (WOMAC, VAS, KOOS, and IKDC scores) at 1, 3, 6 and 12 months [5].
Statistical analysis, including subgroup analysis, assessment of heterogeneity, and publication bias, was conducted using Review Manager. Results showed that their meta-analysis of 42 studies involving 3696 patients demonstrated that PRP treatment resulted in significant pain relief compared to HA injections, as evidenced by improved WOMAC scores (MD: –0.74; 95% CI: –1.02 to –0.46; P ≤ 0.00001; I2 = 94%) and VAS pain scores (MD: -0.65; 95% CI: -1.24 to -0.06; P = 0.03; I2 = 97%). Similarly, PRP showed greater efficacy in reducing WOMAC scores (MD: -8.06; 95% CI: -13.62 to –2.51: P = 0.004; I2 = 96%) and VAS pain scores (MD: –1.11; 95% CI: –1.64 to –0.59; P ≤ 0.0001; I2 = 68%) when compared to CS injections, with the most significant improvement observed at 6 months. They concluded that PRP is an effective treatment for KOA. It provides symptomatic relief, has the potential to reduce disease progression, and has sustained effects up to 12 months. PRP offers superior pain relief and functional enhancement compared to CS and HA injections.
Oeding et al. did an analysis of the RCTs comparing PRP to alternative injections for knee OA to evaluate the statistical power of their conclusions [6].
This analysis included outcomes from 1993 patients. Based on random-effects meta-analyses, PRP demonstrated a significantly higher rate of successful outcomes when compared with hyaluronic acid (P = .002) as well as higher rates of patient-reported symptom relief (P = .019), not requiring a reintervention after the initial injection treatment (P = .002) and achieving the minimal clinically important difference
(MCID) for pain improvement (P = .007) when compared with all alternative nonoperative treatments. They concluded that the statistical significance of the pooled treatment outcome measures used to evaluate PRP for knee OA were more robust than approximately half of all comparable meta-analyses conducted in medicine and healthcare.
2023
Belk et al. did a systematic review and meta-analysis of the literature to identify level I studies that compare the efficacy and safety of PRP, bone marrow aspirate concentrate (BMAC), and hyaluronic acid injections for the treatment of knee osteoarthritis (OA) [7]. Twenty-seven of these level I studies met the inclusion criteria and included a total of 1,042 patients undergoing intra-articular injection(s) with PRP, 226 patients being treated with BMAC, and 1,128 patients with HA. Non-network meta-analyses demonstrated significantly better post-injection WOMAC scores (P < .001), VAS pain scores (P < .01), and IKDC scores (P < .001) in patients who received PRP compared with patients who received HA. There were no significant differences in post-injection outcome scores when comparing PRP with BMAC.
They concluded that patients undergoing treatment for knee OA with PRP or BMAC can be expected to experience improved clinical outcomes when compared with patients who receive HA.
Chen et al. compared the efficacy of PRP and HA for the treatment of OA (8). A total of 30 articles involving 2733 patients were included. The end-study WOMAC scores and IKDC scores of the PRP groups were found to be better than those of the HA groups, while there was no significant difference in AEs, satisfaction rate, and VAS between the two groups.
Kim et al. also performed a meta-analysis of level I studies [9]. A total of 138 studies were screened, and twenty-one level 1 RCTs were evaluated, encompassing a total of 2086 knees (1077 treated with PRP and 1009 treated with HA). PRP showed significant improvement in VAS pain scores compared to HA at 6 and 12 months. Regarding function, PRP injections led to significantly better improvement in total WOMAC scores compared with HA at 6 months. There was no significant difference in procedure- related knee pain or swelling between the PRP and HA groups.
They concluded that intra-articular injections of PRP improve pain and function in patients with knee osteoarthritis for up to 12 months and is superior to HA. The findings of this study support the routine clinical use of intra-articular injections of PRP for the treatment of knee osteoarthritis, regardless of the type and frequency of PRP injection.
Li et al. compared the clinical effectiveness of multiple injections of platelet-rich plasma (m-PRP) with multiple HA injections (m-HA) in the treatment of knee osteoarthritis (KOA) (10). Fourteen RCTs, assessing 1512 patients, had outcome measures that included postoperative VAS, WOMAC, IKDC, or EQ-VAS scores and were included in this systematic review. Compared with the group of intra-articular m-HA injections, the group of intra-articular m-PRP injections had better VAS pain scores at the 3- month and 12-month follow-ups. In addition, the group receiving intra-articular m-PRP injections had better WOMAC scores at 1-month, 3-month, 6-month, and 12-month follow-ups when compared to the m-HA group. Finally, the group receiving intra-articular m-PRP injections had higher IKDC scores at 3-month and 6-month follow-ups compared with the m-HA group.
Qiao et al. did a network meta-analysis using the Bayesian random-effects model on 35 studies with 3104 participants suffering from knee osteoarthritis [11]. They found that PRP and PRP combined with HA were the most successful in improving function and alleviating pain after 3, 6, and 12 months in comparison with corticosteroids, HA, and placebo. Also, the PRP and PRP-HA combination therapies did not result in an increase in the incidence of treatment-related side events when compared to placebo.
Tao et al. compared the efficacy of a single dose of platelet-rich plasma (PRP) with multiple doses of PRP therapy in the treatment of knee osteoarthritis (KOA) (48). Pooled analyses of VAS pain scores, WOMAC scores, and adverse events were conducted. Seven studies (all RCTs) of high methodologic quality involving 575 patients were included. The ages of the patients included in this study ranged from 20 to 80 years, and the sex ratio was balanced. Triple-dose PRP therapy resulted in significantly better VAS pain scores when compared with single-dose PRP therapy at 12 months (P < .0001), with no significant change observed in VAS scores between double-dose PRP and single-dose PRP at 12 months. Regarding adverse events, double-dose and triple-dose therapy showed no significant differences in safety from single-dose therapy.
Vilchez-Cavazos et al. conducted a meta-analysis using a random-effects model and the generic inverse variance method to evaluate whether the use of PRP would be as effective in studies with early- moderate knee OA patients compared to studies including patients with end-stage OA, based on the Kellgren–Lawrence classification [49]. They included 31 clinical trials that reported data of 2705 subjects. Meta-analysis revealed an overall significant improvement of both pain and function favoring PRP. Sub analysis for pain and functional improvement showed a 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.
Xue et al. compared the efficacy of different intra-articular (IA) injections for mild-to-moderate knee osteoarthritis [12]. They included 16 RCTs with a total of 1652 patients. Platelet-rich plasma injection therapy had the highest likelihood of being the best intervention in reducing WOMAC pain, stiffness, and function scores, according to the SUCRA. In the VAS pain score group, PRP outperformed hyaluronic acid and corticosteroids. PRP also outperformed corticosteroids in the WOMAC total score group. Furthermore, PRP outperformed other drugs in terms of reducing WOMAC function, stiffness, and function scores.
2022
Abbas et al. did a meta-analysis on studies comparing LP-PRP or LR-PRP (50). The follow-up periods were 6 months and 12 months. The primary outcome measure was the change in WOMAC score between baseline and follow-up. The secondary outcome measures were the changes in the WOMAC pain subscale, VAS pain scores, and IKDC scores between baseline and follow-up, and the incidence of local adverse reactions. Treatment outcomes were analyzed using the mean difference between treatments for continuous outcomes and the odds ratio for binary outcomes, with 95% credibility intervals. Treatment modalities were ranked using the surface under the cumulative ranking (SUCRA) probabilities. Twenty- three studies (20 RCTs and 3 prospective comparative studies) with a total of 2,260 patients and a mean follow-up period of 9.9 months were evaluated. They found no significant (p < 0.05) difference in all outcome measures and local adverse reactions between LP-PRP and LR-PRP. SUCRA rankings revealed that, for all outcome measures, LP-PRP is preferred to LR-PRP across follow- up periods.
Donovan et al. investigated the effects of recurrent intra-articular corticosteroid injections (IACIs) at 3 months and beyond in RCTs comparing IACIs with other injectables, placebo or no treatment (13). Ten RCTs were included (eight knee OA studies (n = 763) and two trapeziometacarpal OA studies (n = 121). Patients received between 2 and 8 injections, varying by trial. Trials compared recurrent IACIs with hyaluronic acid (HA), platelet-rich plasma (PRP), saline or orgotein with follow-up ranging from 3 to 24 months. Greater improvements in pain, function and quality of life throughout the 3–24-month follow- up range were noted for the comparators than with IACIs, with the comparators demonstrating an equal or superior effect. Recurrent IACIs demonstrated no benefits in pain or function over placebo at 12-24 months. No serious adverse events were recorded. They concluded that recurrent IACIs often provide inferior (or non-superior) symptom relief compared with other injectables (including placebo) at 3 months and beyond. Other injectables (HA, PRP) often yielded greater improvements in pain and function up to 24 months post-injection.
Rahimzadeh et al. compared the effect of intra-articular PRP injection and oxygen-ozone therapy [51]. A meta-analysis was performed using the latest version of STATA version 16. A total of 12 studies were evaluated; 6 RCTs performed on 251 patients treated with ozone therapy versus 235 patients in the control groups, and 6 RCTs on 251 patients treated with PRP versus 230 patients in the control groups. The mean difference of VAS pain scores between the ozone and control groups in the first month after injection was -0.02 (P < 0.05). Mean differences of WOMAC pain, stiffness, and physical function score between baseline and after PRP were -3.53 (P = 0.00), -0.60 (P = 0.00), and -5.96 (P = 0.00), respectively. Their results showed that treating knee osteoarthritis using PRP shows better clinical results for a longer period of 6 to 12 months after the injection, while oxygen-ozone therapy has only short-term results.
Singh et al. assessed and compared the efficacy of different intra-articular (IA) injections used for the treatment of knee OA, including HA, CS, and PRP, with a minimum 6-month patient follow-up (14). Twenty-three studies were included in which 4604 injections were performed (592 with PRP, 2371 with HA, 521 with CS and 1120 with placebo). All IA treatments except CS were found to result in a statistically significant improvement in outcomes when compared with placebo. Regarding improvements in pain and function, PRP was found to possess the highest probability of efficacy, followed by HA, CS, and placebo.
Wang et al. systematically analyzed RCTs comparing the effectiveness of PRP vs. HA for the treatment of knee osteoarthritis (15). Studies were included as per the PICOS criteria and relevant event data were extracted. Risk of bias was analyzed, and a random-effects model was used to calculate the pooled odds ratio and risk ratio using RevMan software. A total of 14 studies were included in the meta-analysis ranging from the year 2000 to 2021, encompassing a total of 613 patients. The meta-analysis had a low risk of publication bias, and they obtained the pooled odds ratio (OR) of 2.55 (95% CI: 1.35–4.84) with a t2 value of 1.01, c2 value of 52.79, I2 value of 77%, Z value of 2.87 and p-value < 0.00001. The pooled risk ratio was 1.34 (95% CI: 1.09–1.65) with a t2 value of 0.09, c2 value of 73.48, I2 value of 84%, Z value of 2.80 and p-value < 0.00001. They concluded that their meta-analysis highly recommends the use of PRP for the treatment of knee osteoarthritis.
CONCLUSION
Osteoarthritis of the knee is a frequent source of musculoskeletal pain. As the population ages, knee osteoarthritis is expected to become an even more common cause of disability, resulting in a growing burden for individuals and a financial burden for our societies and healthcare systems.
Over the past decade, a growing number of studies have evaluated PRP for knee osteoarthritis.
Many of these studies and the resulting meta-analyses confirm that PRP is an effective and safe therapeutic option for the treatment of knee osteoarthritis.
Medico-economic evaluations also show that, by delaying arthroplasty, PRP reduces the total cost of knee osteoarthritis and hence the economic burden on healthcare systems.
These results are prompting learned scientific societies to gradually incorporate autologous PRP into their recommendations for the management of knee osteoarthritis, based on large volumes of published evidence that demonstrate efficacy, safety, and superiority over other covered treatment modalities
Regen Lab’s standardized technology, evaluated in numerous clinical trials, facilitates the reproducible point-of-care production of autologous PRP, guaranteeing the highest level of quality and safety for delivering these effective cost-efficient treatments to patients suffering from knee osteoarthritis.
REFERENCES
- Perut F, Filardo G, Mariani E, Cenacchi A, Pratelli L, Devescovi V, et Preparation method and growth factor content of platelet concentrate influence the osteogenic differentiation of bone marrow stromal cells. Cytotherapy 2013; 15(7): 830- http://www.ncbi.nlm.nih.gov/pubmed/23731763
- Li W, Pan J, Lu Z, Zhu H, Guo J, Xie D. The application of platelet-rich plasma in the treatment of knee osteoarthritis: A literature review. Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association 2022; 27(2): 420-8. https://www.ncbi.nlm.nih.gov/pubmed/33775509
- Cao Y, Luo J, Han S, Li Z, Fan T, Zeng M, et A model-based quantitative analysis of efficacy and associated factors of platelet rich plasma treatment for osteoarthritis. Int J Surg 2023; 109(6): 1742-52. https://www.ncbi.nlm.nih.gov/ pubmed/36999827
- Jawanda H, Khan ZA, Warrier AA, Acuna AJ, Allahabadi S, Kaplan DJ, et Platelet Rich Plasma, Bone Marrow Aspirate Concentrate and Hyaluronic Acid Injections Outperform Corticosteroids in Pain and Function Scores at a Minimum of 6 Months as Intra-Articular Injections for Knee Osteoarthritis: A Systematic Review and Network Meta-Analysis. Arthroscopy 2024. https://www.ncbi.nlm.nih.gov/pubmed/38331363
- Khalid S, Ali A, Deepak F, Zulfiqar MS, Malik LU, Fouzan Z, et Comparative effectiveness of intra-articular therapies in knee osteoarthritis: a meta-analysis comparing platelet-rich plasma (PRP) with other treatment modalities. Ann Med Surg (Lond) 2024; 86(1): 361-72. https://www.ncbi.nlm.nih.gov/pubmed/38222750
- Oeding JF, Varady NH, Fearington FW, Pareek A, Strickland SM, Nwachukwu BU, et al. Platelet-Rich Plasma Versus Alternative Injections for Osteoarthritis of the Knee: A Systematic Review and Statistical Fragility Index-Based Meta- analysis of Randomized Controlled Trials. The American journal of sports medicine 2024: 3635465231224463. https:// ncbi.nlm.nih.gov/pubmed/38420745
- Belk JW, Lim JJ, Keeter C, McCulloch PC, Houck DA, McCarty EC, et Patients With Knee Osteoarthritis Who Receive Platelet-Rich Plasma or Bone-Marrow Aspirate Concentrate Injections Have Better Outcomes Than Patients Who Receive Hyaluronic Acid: Systematic Review and Meta-analysis. Arthroscopy 2023. https://www.ncbi.nlm.nih.gov/ pubmed/36913992
- Chen L, Jin S, Yao Y, He S, He Comparison of clinical efficiency between intra-articular injection of platelet-rich plasma and hyaluronic acid for osteoarthritis: a meta-analysis of randomized controlled trials. Ther Adv Musculoskelet Dis 2023; 15: 1759720X231157043. https://www.ncbi.nlm.nih.gov/pubmed/36950089
- Kim JH, Park YB, Ha Are leukocyte-poor or multiple injections of platelet-rich plasma more effective than hyaluronic acid for knee osteoarthritis? A systematic review and meta-analysis of randomized controlled trials. Arch Orthop Trauma Surg 2023; 143(7): 3879-97. https://www.ncbi.nlm.nih.gov/pubmed/36173473
- Li S, Xing F, Yan T, Zhang S, Chen F. Multiple Injections of Platelet-Rich Plasma Versus Hyaluronic Acid for Knee Osteoarthritis: A Systematic Review and Meta-Analysis of Current Evidence in Randomized Controlled J Pers Med 2023; 13(3). https://www.ncbi.nlm.nih.gov/pubmed/36983613
- Qiao X, Yan L, Feng Y, Li X, Zhang K, Lv Z, et al. Efficacy and safety of corticosteroids, hyaluronic acid, and PRP and combination therapy for knee osteoarthritis: a systematic review and network meta-analysis. BMC Musculoskelet Disord 2023; 24(1): 926. https://www.ncbi.nlm.nih.gov/pubmed/38037038
- Xue Y, Wang X, Wang X, Huang L, Yao A, Xue A comparative study of the efficacy of intra-articular injection of different drugs in the treatment of mild to moderate knee osteoarthritis: A network meta-analysis. Medicine 2023; 102(12): e33339. https://www.ncbi.nlm.nih.gov/pubmed/36961175
- Donovan RL, Edwards TA, Judge A, Blom AW, Kunutsor SK, Whitehouse MR. Effects of recurrent intra-articular corticosteroid injections for osteoarthritis at 3 months and beyond: a systematic review and meta-analysis in comparison to other injectables. Osteoarthritis Cartilage 2022; 30(12): 1658-69. https://www.ncbi.nlm.nih.gov/pubmed/36108937
- Singh H, Knapik DM, Polce EM, Eikani CK, Bjornstad AH, Gursoy S, et al. Relative Efficacy of Intra-articular Injections in the Treatment of Knee Osteoarthritis: A Systematic Review and Network Meta-analysis. The American journal of sports medicine 2022; 50(11): 3140-8. https://www.ncbi.nlm.nih.gov/pubmed/34403285
- Wang L, Wei L, Ma H, Wang M, Rastogi S. Is platelet-rich plasma better than hyaluronic acid in the treatment of knee osteoarthritis? A meta-analysis of randomized controlled Wideochirurgia i inne techniki maloinwazyjne = Videosurgery and other miniinvasive techniques 2022; 17(4): 611-23. https://www.ncbi.nlm.nih.gov/pubmed/36818516
- Pereira TV, Jüni P, Saadat P, Xing D, Yao L, Bobos P, et Viscosupplementation for knee osteoarthritis: systematic review and meta-analysis. BMJ 2022; 378: e069722. https://www.bmj.com/content/bmj/378/bmj-2022-069722.full.pdf
- McAlindon TE, LaValley MP, Harvey WF, Price LL, Driban JB, Zhang M, et al. Effect of Intra-articular Triamcinolone vs Saline on Knee Cartilage Volume and Pain in Patients With Knee Osteoarthritis: A Randomized Clinical JAMA 2017; 317(19): 1967-75. http://www.ncbi.nlm.nih.gov/pubmed/28510679
- Platelet-Rich Plasma (PRP) for Knee Osteoarthritis Technology Overview, 2021. https://www.aaos.org/globalassets/quality-and-practice-resources/biologics/technology-overview_prp- for-knee-oa.pdf
- Hunter CW, Deer TR, Jones MR, Chang Chien GC, D’Souza RS, Davis T, et al. Consensus Guidelines on Interventional Therapies for Knee Pain (STEP Guidelines) from the American Society of Pain and Journal of pain research 2022; 15: 2683-745. https://www.ncbi.nlm.nih.gov/pubmed/36132996
- Use of injectable orthobiologics for the treatment of knee osteoarthritis Part 1: blood-derived products (alias PRP). 2022. https://www.esska.org/page/Orthobiologic_Initiative_PRP_WG
- Eymard F, Ornetti P, Maillet J, Noel E, Adam P, Legre-Boyer V, et al. Intra-articular injections of platelet-rich plasma in symptomatic knee osteoarthritis: a consensus statement from French-speaking experts. Knee Surg Sports Traumatol Arthrosc 2021; 29(10): 3195-210. https://www.ncbi.nlm.nih.gov/pubmed/32583023
- Tischer T, Bode G, Buhs M, Marquass B, Nehrer S, Vogt S, et al. Platelet-rich plasma (PRP) as therapy for cartilage, tendon and muscle damage – German working group position J Exp Orthop 2020; 7(1): 64. https://www.ncbi. nlm.nih.gov/pubmed/32885339
- Pesare E, Vicenti G, Kon E, Berruto M, Caporali R, Moretti B, et Italian Orthopaedic and Traumatology Society (SIOT) position statement on the non-surgical management of knee osteoarthritis. Journal of orthopaedics and traumatology : official journal of the Italian Society of Orthopaedics and Traumatology 2023; 24(1): 47. https://www.ncbi.nlm.nih.gov/ pubmed/37679552
- Riboh JC, Saltzman BM, Yanke AB, Fortier L, Cole Effect of Leukocyte Concentration on the Efficacy of Platelet-Rich Plasma in the Treatment of Knee Osteoarthritis. The American journal of sports medicine 2016; 44(3): 792-800. https:// www.ncbi.nlm.nih.gov/pubmed/25925602
- Mende E, Love RJ, Young A Comprehensive Summary of the Meta-Analyses and Systematic Reviews on Platelet-
- Rich Plasma Therapies for Knee Osteoarthritis. Mil Med 2024. https://www.ncbi.nlm.nih.gov/pubmed/38421752
- Means GE, Muench Platelet-Rich Plasma Injections for the Treatment of Degenerative Orthopedic Conditions. Mil Med 2024. https://www.ncbi.nlm.nih.gov/pubmed/38349194
- Corash L, Tan H, Gralnick Heterogeneity of human whole blood platelet subpopulations. I. Relationship between buoyant density, cell volume, and ultrastructure. Blood 1977; 49(1): 71-87. http://www.ncbi.nlm.nih.gov/pubmed/830377
- Abate M, Verna S, Schiavone C, Di Gregorio P, Salini Efficacy and safety profile of a compound composed of platelet- rich plasma and hyaluronic acid in the treatment for knee osteoarthritis (preliminary results). European journal of orthopaedic surgery & traumatology : orthopedie traumatologie 2015; 25(8): 1321-6. https://www.ncbi.nlm.nih.gov/pubmed/26403468
- Amrilloevich Intra-articular platelet-rich plasma injections into the knee in patients with early osteoarthritis. Asian journal of pharmaceutical and biological research 2021; 10(3). https://www.ajpbr.org/index.php/ajpbr/article/view/53/60
- Chen CPC, Chen JL, Hsu CC, Pei YC, Chang WH, Lu HC. Injecting autologous platelet rich plasma solely into the knee joint is not adequate in treating geriatric patients with moderate to severe knee osteoarthritis. Experimental gerontology 2019; 119: 1-6. https://www.ncbi.nlm.nih.gov/pubmed/30664923
- Chen CPC, Cheng CH, Hsu CC, Lin HC, Tsai YR, Chen The influence of platelet rich plasma on synovial fluid volumes, protein concentrations, and severity of pain in patients with knee osteoarthritis. Experimental gerontology 2017; 93: 68- https://www.ncbi.nlm.nih.gov/pubmed/28433472
- Chen CPC, Hsu CC, Huang SC, Lin MY, Chen JL, Lin The application of thermal oscillation method to augment the effectiveness of autologous platelet rich plasma in treating elderly patients with knee osteoarthritis. Experimental gerontology 2020; 142: 111120. https://www.ncbi.nlm.nih.gov/pubmed/33091524
- Chen JL, Chen CH, Cheng CH, Chen CC, Lin KY, Chen CPC. Can the addition of ultrasound-guided genicular nerve block using 5% dextrose water augment the effect of autologous platelet rich plasma in treating elderly patients with knee osteoarthritis? Biomedical journal 2021; 44(6 Suppl 1): S144-S53. https://www.ncbi.nlm.nih.gov/pubmed/35289285
- Ciapini G, Simonettii M, Giuntoli M, Varchetta G, De Franco S, Ipponi E, et Is the Combination of Platelet-Rich Plasma and Hyaluronic Acid the Best Injective Treatment for Grade II-III Knee Osteoarthritis? A Prospective Study. Advances in orthopedics 2023; 2023: 1868943. https://www.ncbi.nlm.nih.gov/pubmed/36938102
- Gobbi A, Karnatzikos G, Mahajan V, Malchira S. Platelet-rich plasma treatment in symptomatic patients with knee osteoarthritis: preliminary results in a group of active patients. Sports health 2012; 4(2): 162-72. https://www.ncbi.nlm. gov/pubmed/23016084
- Gobbi A, Karnatzikos G, Malchira S, Kumar Platelet Rich Plasma (PRP) in Osteoarthritis. In: Lana JFSD, Santana MHA, Belangero WD, Luzo ACM, editors. Platelet-Rich Plasma: Springer Berlin Heidelberg, 2014: 231-6. http://link.springer. com/chapter/10.1007%2F978-3-642-40117-6_11
- Gobbi A, Lad D, Karnatzikos G. The effects of repeated intra-articular PRP injections on clinical outcomes of early osteoarthritis of the knee. Knee Surg Sports Traumatol Arthrosc 2015; 23(8): 2170-7. https://www.ncbi.nlm.nih.gov/ pubmed/24748286
- Hegaze AH, Hamdi AS, Alqrache A, Hegazy Efficacy of Platelet-Rich Plasma on Pain and Function in the Treatment of Knee Osteoarthritis: A Prospective Cohort Study. Cureus 2021; 13(3): e13909. https://www.ncbi.nlm.nih.gov/ pubmed/33868853
- Huang PH, Wang CJ, Chou WY, Wang JW, Ko JY. Short-term clinical results of intra-articular PRP injections for early osteoarthritis of the knee. Int J Surg 2017; 42: 117-22. https://www.ncbi.nlm.nih.gov/pubmed/28476542
- Lin KY, Yang CC, Hsu CJ, Yeh ML, Renn 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. Arthroscopy 2019; 35(1): 106-17. https://www.ncbi.nlm.nih.gov/pubmed/30611335
- Mangone G, Orioli A, Pinna A, Pasquetti P. Infiltrative treatment with Platelet Rich Plasma (PRP) in gonarthrosis. Clinical cases in mineral and bone metabolism : the official journal of the Italian Society of Osteoporosis, Mineral Metabolism, and Skeletal Diseases 2014; 11(1): 67-72. https://www.ncbi.nlm.nih.gov/pubmed/25002882
- Napolitano M, Matera S, Bossio M, Crescibene A, Costabile E, Almolla J, et al. Autologous platelet gel for tissue regeneration in degenerative disorders of the knee. Blood Transfus 2012; 10(1): 72-7. https://www.ncbi.nlm.nih.gov/ pubmed/22044954
- Palco M, Fenga D, Basile GC, Rizzo P, Cavalieri B, Leonetti D, et Platelet-Rich Plasma Combined with Hyaluronic Acid versus Leucocyte and Platelet-Rich Plasma in the Conservative Treatment of Knee Osteoarthritis. A Retrospective Study. Medicina (Kaunas) 2021; 57(3). https://www.ncbi.nlm.nih.gov/pubmed/33802325
- Su F, Tong MW, Lansdown DA, Luke A, Ma CB, Feeley BT, et Leukocyte-Poor Platelet-Rich Plasma Injections Improve Cartilage T1ρ and T2 and Patient-Reported Outcomes in Mild-to-Moderate Knee Osteoarthritis. Arthroscopy, Sports Medicine, and Rehabilitation 2023. https://www.sciencedirect.com/science/article/pii/S2666061X23000676
- Wu YT, Hsu KC, Li TY, Chang CK, Chen Effects of Platelet-Rich Plasma on Pain and Muscle Strength in Patients With Knee Osteoarthritis. Am J Phys Med Rehabil 2018; 97(4): 248-54. https://www.ncbi.nlm.nih.gov/pubmed/29210705
- Russo S, Landa P, Landi S. The potential economic role of regenerative therapy in the treatment of knee osteoarthritis. Cost-utility analysis for the treatment of knee OA in three European countries: Platelet-Rich-Plasma dedicated kit versus Hyaluronic Department of Management, Università Ca’ Foscari Venezia 2019;Working Paper n. 2/2019. http://virgo.unive.it/wpideas/storage/2019wp02.pdf
- Xiong Y, Gong C, Peng X, Liu X, Su X, Tao X, et Efficacy and safety of platelet-rich plasma injections for the treatment of osteoarthritis: a systematic review and meta-analysis of randomized controlled trials. Front Med (Lausanne) 2023; 10: 1204144. https://www.ncbi.nlm.nih.gov/pubmed/37441691
- Tao X, Aw AAL, Leeu JJ, Bin Abd Razak Three Doses of Platelet-Rich Plasma Therapy Are More Effective Than One Dose of Platelet-Rich Plasma in the Treatment of Knee Osteoarthritis: A Systematic Review and Meta-analysis. Arthroscopy 2023. https://www.ncbi.nlm.nih.gov/pubmed/37236291
- Vilchez-Cavazos F, Blazquez-Saldana J, Gamboa-Alonso AA, Pena-Martinez VM, Acosta-Olivo CA, Sanchez-Garcia A, et al. 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 Arch Orthop Trauma Surg 2023; 143(3): 1393-408. https://www.ncbi.nlm.nih.gov/pubmed/35043252
- Abbas A, Du JT, Dhotar HS. The Effect of Leukocyte Concentration on Platelet-Rich Plasma Injections for Knee Osteoarthritis: A Network Meta-Analysis. J Bone Joint Surg Am 2022; 104(6): 559-70. https://www.ncbi.nlm.nih.gov/pubmed/34826301
- Rahimzadeh P, Imani F, Azad Ehyaei D, Faiz SHR. Efficacy of Oxygen-Ozone Therapy and Platelet-Rich Plasma for the Treatment of Knee Osteoarthritis: A Meta-analysis and Systematic Review. Anesth Pain Med 2022; 12(4): e127121. https://www.ncbi.nlm.nih.gov/pubmed/36937082