Leukocyte-rich Platelet-rich Plasma Research Articles

Comparison of bioactive substances in novel-developed freeze-dried platelet-rich plasma (PRP) and activated normal PRP, and investigation of bioactive substance levels after long-term storage

IntroductionIn recent years, biotherapy in orthopedics has become widespread, and platelet-rich plasma (PRP) has been readily used to treat sports injuries and osteoarthritis. Production of freeze-dried PRP (PRP-FD) results in PRP that is in powder form, allowing it to be stored for long periods at room temperature. Using this technology, we have developed Valuable Platelet-Derived Factor Concentrate Freeze Dry (VFD). However, whether VFD contains sufficient levels of bioactive substances (BS) remains unknown and retains the same levels of BS during long-term storage. In this study, we examined whether VFD contains sufficient amounts of BS and whether they retain these BS levels during long-term storage. MethodsPeripheral blood was collected from 10 healthy men (mean ± SD: 46.5 ± 15 years old) and various BS, including transforming growth factor β (TGF-β), basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), tissue inhibitors of metalloproteinases-1 (TIMP-1), interleukin-1 receptor antagonist (IL-1ra), matrix metallopeptidase-9 (MMP-9), and interleukin-6 (IL-6), were compared between VFD and normal PRP samples, including both leukocyte-rich PRP (LR-PRP) and leukocyte-poor PRP (LP-PRP). VFD was prepared using two rounds of centrifugation. LP-PRP and LR-PRP were activated by freezing and thawing before measurement. To evaluate the effects of long-term storage, the BS of VFD purified from five professional football players was compared between baseline and 1 year after storage. ResultsIn terms of the growth factors, the TGF-β and EGF levels were higher in LR-PRP than in VFD and LP-PRP (p < 0.05), while the bFGF levels were higher in VFD than in the LR-PRP and LP-PRP groups (p < 0.01). In terms of anti-inflammatory cytokines, the TIMP-1 level was lower in VFD than that in the other groups (p < 0.01), whereas the IL-1ra levels were higher in VFD than those in LP-PRP (p < 0.05) and lower than those in LR-PRP (p < 0.01). In terms of inflammatory enzymes and cytokines, the IL-1ra level was higher in VFD than that in LP-PRP (p < 0.05) and lower than that in LR-PRP (p < 0.01), whereas the IL-6 levels did not differ among the groups. Furthermore, the TGF-β, bFGF, TIMP-1, and IL-1ra levels were 5.61 → 3.38 (x103 pg/μL), 61.0 → 63.0 (pg/μL), 3.4 → 2.7 (x105 pg/μL), and 14.9 → 14.5 (x103 pg/μL) at baseline and 1 year later, respectively. No significant differences in the BS levels were observed between baseline and 1 year after storage. ConclusionsThe VFD samples prepared in this study exhibited higher levels of anti-inflammatory cytokines than LP-PRP and contained growth factor levels similar to LP-PRP and LR-PRP. In addition, the BS levels in VFD samples were maintained after one year of storage. These results suggest that VFD can be prepared and stored and may serve as a novel treatment strategy for sports injuries in high-risk groups, such as athletes.

A Comparative Study of Intra-Articular Knee Injection of Leukocyte-Poor Platelet-Rich Plasma Compared to Corticosteroids and Local Anesthetics in Patients with Knee Osteoarthritis

Background: Knee osteoarthritis (OA) is the most common reason for orthopedic secondary care referral. And it is one of the main causes of disability in adults worldwide. It is estimated to affect between 10 to 25% of patients over the age of 60. Intra-articular corticosteroid injection (IA CS) and physical therapy were the two choices in an attempt to provide symptomatic management or deferred surgery. There is a growing trend is intra-articular platelet-rich plasma (IA PRP) injection to reduce pain and improve function in OA patients. PRP is divided into two types: leukocyte-poor platelet-rich plasma (LP-PRP) and leukocyte-rich platelet-rich plasma (LR-PRP). It was shown that LR-PRP increases pro-inflammatory factors and also decreases anti-catabolic mediators, and LP-PRP has the opposite aspect.&#x0D; Methods: In our research 40 patients were divided into two equal groups, IA corticosteroid and leukocyte-poor platelet-rich plasma (LP-PRP) 40 cc of blood from the basilic vein of the upper limb is used with two step centrifugation. The final samples were 4 millilitres product injected intra-articular. group two (corticosteroid (CS)) received an intra-articular injection of triamcinolone acetate (Kenalog) 40 mg/ml along with 4 ml of lidocaine 0.02% (Abureyhan Co.) for a total of 5 ml. The needle used is a 22-gauge pencil-point Quincke needle (Dr. Japan Co, Ltd), which is performed with the Sonosite Edge II ultrasound guide and in an anterior-lateral manner in the knee joint. Pain was assessed on a visual analogue scale (VAS range 0-10 points) before, one week, one month, two month and 3 months after the operation. The WOMAC questionnaire was also filled before injection and three months following injection and other variables were examined.&#x0D; Results: There were no significant differences between the groups across all the baseline parameters including age, sex, body mass index and comorbidities including high blood pressure, diabetes and smoking. Both injection groups were effective in reducing patients' pain from one week to three months after injection. The level of pain in the first week after injection was significantly lower in the corticosteroid group than in the PRP group. In the first month and the third month after the injection, the pain reduction according to mean scores of VAS was the same in both groups.&#x0D; Conclusion: In short, one injection of PRP can reduce the pain of patients with osteoarthritis of the knee as much as corticosteroids during a three-month treatment process. Considering the possible side effects of corticosteroids, this alternative treatment can be considered with further investigation.

Microfragmented Adipose Tissue Is Equivalent to Platelet-Rich Plasma for Knee Osteoarthritis at 12 Months Posttreatment: A Randomized Controlled Trial.

Platelet-rich plasma (PRP) is an effective treatment for knee osteoarthritis (OA). Microfragmented adipose tissue (MFAT) is another orthobiologic that holds promise, but data supporting its use are limited. Previous studies showed that MFAT created using the Lipogems device was equivalent to PRP created via noncommercial laboratory-based processes. To perform a comparison of commercially available MFAT and PRP systems for treatment of knee OA. Randomized controlled trial; Level of evidence, 2. A total of 71 patients with symptomatic knee OA (Kellgren-Lawrence grades 1-4) were randomized to receive a single injection of either leukocyte-rich PRP (Angel; Arthrex) or MFAT (Lipogems) under ultrasound guidance. Patient-reported outcomes (Knee injury and Osteoarthritis Outcome Score [KOOS], visual analog scale for pain with activities of daily living [VAS pain], and Tegner activity level) were recorded at baseline and at 1, 3, 6, and 12 months after injection. The primary outcome was the KOOS-Pain subscale score at 12 months after injection. Overall, 49 patients completed their 12-month follow-up (PRP group, n = 23; MFAT group, n = 26). All demographic features were similar between groups, except that more men were randomized to the PRP group and more women to the MFAT group. At 12 months posttreatment, KOOS-Pain scores improved in both groups, with no significant group difference (PRP, 78 ± 17.9 vs MFAT, 77.8 ± 19.3; P = .69). Similarly, other KOOS subscales, VAS pain scores, and Tegner scores improved at 12 months, with no differences between treatment groups. Both PRP and MFAT injections for knee OA resulted in improved patient-reported outcomes at 12 months posttreatment, with no differences found between treatments. NCT04351087 (ClinicalTrials.gov identifier).

A Comprehensive Summary of the Meta-Analyses and Systematic Reviews on Platelet-Rich Plasma Therapies for Knee Osteoarthritis.

Osteoarthritis (OA), including that of the knee joint, represents a significant proportion of musculoskeletal injuries in the Canadian Armed Forces (CAF) due to the frequent, high-stress physical activity for which member participation is necessary. Platelet-rich plasma (PRP) is a conservative, autologous treatment that has the potential to relieve symptoms and improve functionality of military members to decrease the impact of the disease and ultimately strengthen the CAF. A search of systematic reviews and meta-analyses was conducted to determine the efficacy of PRP injections in treating knee OA. The Scopus database, PubMed database, and Omni academic search tools were scoped for relevant publications. English literature, published up to and including March 2023, that investigated only clinically randomized controlled trials (RCTs) was eligible for inclusion. The results of network meta-analyses were investigated and summarized independent of reviews and non-network meta-analyses. A total of 225 unique systematic reviews and meta-analyses were initially identified, of which 39 publications, including 7 network meta-analyses, adhered to the defined inclusion and exclusion criteria. PRP was found to significantly alleviate symptoms of pain based on the visual analog scale and Western Ontario and McMaster Universities Arthritis Index pain scores within the 12-month follow-up. Function, activity, sport, quality of life, and stiffness were additionally determined to generally improve to a greater extent from PRP treatment compared to controls, while adverse effects were minor and temporary. PRP placed in the top 3 in 9 reported surface under the cumulative ranking curves, while individually reported rankings of leukocyte-poor and leukocyte-rich PRP both placed in the top 4. The clinical recommendations made were generally positive, with 17 publications acknowledging the benefits of PRP, 3 supporting possible efficacy, and an additional 8 recommending that it be an option for the conservative treatment of knee OA. The results of this review support the efficacy of PRP for relieving symptoms of pain and improving function, stiffness, and quality of life for patients experiencing knee OA within 12 months. As a result, leukocyte-poor-PRP could be considered for members of the CAF with mild to moderate knee OA (Kellgren-Lawrence grades 1-3) to slow the progression of OA and extend the military careers of CAF members. There continues to be a need for future studies to investigate the longer-term effects of PRP to verify sustained benefits at follow-up points greater than 12 months, including findings of improvement in a delayed fashion at the 3- and 6-month timeframe compared to hyaluronic acid treatment.

Platelet-rich plasma does not accelerate the healing of damaged muscle following muscle strain.

Although platelet-rich plasma (PRP)has been widely used regardless of the severity of muscle strain, there have been very few basic studies in which its effects on muscle injury were examined by using models that accurately mimic the clinical muscle strain injury process. Therefore, the aim of this study was to confirm by physiological and structural analyses whether PRP purified by a general preparation method has a muscle healing effect on muscle damage caused by eccentric contraction (ECC).Male Wistar rats were subjected to muscle injury induced by ECC in bilateral plantar flexor muscles using electrical stimulation and an automatically dorsiflexing footplate. The rats were randomly assigned to three groups by type of injection: phosphate-buffered saline (PBS),leukocyte-poor PRP (LP-PRP),or leukocyte-rich PRP (LR-PRP)injection into gastrocnemius muscles three times at weekly intervals. The platelet concentrations of the LP-PRPand LR-PRPwere three to five times higher than that of whole blood. The recovery process of torque strength in the plantar flexor muscle, signal changes in MRI images, and histological evaluation 3 weeks after injury showed no obvious differences among the three groups, and every muscle recovered well from the injury without marked fibrosis. The results that neither LP-PRPnor LR-PRPwas found to accelerate healing of muscle injuries suggested that conventional preparation and use of PRP for simple muscle injuries caused by muscle strain should be carefully considered, and further basic research using models that accurately mimic clinical practice should be carried out to determine the optimal use of PRP.

Elevated IL-1β and Comparable IL-1 Receptor Antagonist Levels Are Characteristic Features of L-PRP in Female College Athletes Compared to Male Professional Soccer Players.

Autologous platelet-rich plasma (PRP) therapy has been becoming popular for the treatment of musculotendinous injuries among athletes. However, for individual and practical variations, clinical success is hardly predictable. To overcome this difficulty, we have been exploring possible criterion candidates for monitoring its clinical effectiveness. In this study, we focused on sex-based differences in young elite athletes and compared the biochemical compositions of their PRP. Leukocyte-rich PRP (L-PRP) was manually prepared from blood samples collected from male professional soccer players (mPSPs) (n = 25) and female college athletes (fCAs) (n = 36). Platelet-derived growth factor-BB (PDGF-BB), transforming-growth factor-β1 (TGFβ1), platelet factor-4 (PF4), interleukin-1β (IL-1β), and IL-1 receptor antagonist (IL-1RA) were quantified using an enzyme-linked immunosorbent assay. The levels of PDGF-BB, TGFβ1, and PF4 in L-PRP were significantly higher in mPSPs than in fCAs. Conversely, IL-1β and IL-1RA were detected at significantly and slightly higher levels, respectively, in fCAs than in mPSPs. Our findings suggest that, even though L-PRP from fCAs may have lower potential to induce cell growth and differentiation than that of mPSPs, due to the latter's higher capacity to control inflammation, it does not necessarily imply that PRP treatment in fCAs is less effective. Thus, these cytokine levels should be checked before PRP therapy.

Is there structural change on MRI in gluteal tendinopathy after treatment? Single outcome measure extension of an RCT

BackgroundThe etiology of tendinopathy remains controversial and it is unknown whether degenerative structural changes in tendinopathies are reversible.HypothesisThere will be no structural change on magnetic resonance imaging (MRI) taken > 2-years after treatment for gluteal tendinopathy.Study DesignExtension of a single site, double-blind, prospective randomized-controlled trial to analyze the additional outcome measure; MRI changes.MethodsUniversity of Melbourne ethics approval number: 1852900, trial registration: ACTRN12613000677707. Participants with gluteal tendinopathy who had previously received a leukocyte-rich platelet-rich plasma injection (LR-PRP) or a corticosteroid injection (CSI) had a post treatment MRI between at least 2-years and up to 7 years following trial completion. A blinded, senior musculoskeletal radiologist graded all de-identified MRI scans using the Melbourne Hip Score (MHIP). The primary outcome measure was the change in overall pre- and post-treatment score.ResultsParticipants (n = 20) underwent MRI at mean time of 4.15 (SD 1.11; range 2–7) years after their initial treatment. There was no change in the overall mean MHIP score for the CSI group (Pre 4.3 (SD 2.3) Post 4.3 (SD 1.1), p = 1.00). Although there was an improvement in the LR-PRP group mean MHIP score (Pre 5.3 (SD 3.0) Post 4.77 (SD 2.5), p = 0.56) it was not statistically significant. However, in the LR-PRP intervention group, five out of nine of participants’ MHIP score improved, with four of these improving by 2–4 points.ConclusionThe hypothesis that there would be no improvement in MHIP scores following treatment of gluteal tendinopathy was supported. Findings of improvement in the LR-PRP group at 4 years would support further studies powered to look for structural improvement. These findings suggest that structural change following treatment for tendinopathy may be possible supporting the inclusion of MRI as a core outcome for future studies.Clinical relevanceThe study suggests that degenerative structural changes in tendons may be reversible.

Enhanced Pain Relief and Function Improvement in Children with Osgood-Schlatter Disease: Leukocyte-Rich Platelet-Rich Plasma (LR-PRP) as a Complementary Treatment to Standard Conservative Therapy.

BACKGROUND Osgood-Schlatter disease (OSD) causes pain and loss of function of the knee in growing children. This study aimed to evaluate pain and function of the knee joint in 152 growing children with chronic OSD before and after treatment with LR-PRP when used with standard conservative treatment. MATERIAL AND METHODS Treatment efficacy was evaluated using the VAS, Tegner, Lyshom, and KOOS scales. Patient satisfaction, post-surgery athletic performance, and X-ray assessment were also used to determine the success of the procedure. RESULTS We found that 75% of the subjects were satisfied with the results of the treatment, and 72% of the subjects returned to full physical activity. The analysis showed a significant decrease in the median VAS score after treatment compared to the pre-treatment score (P<0.05), and an increase in the median scores of the Tegner, Lysholm, and KOOS scales compared to the pre-treatment score (P<0.05; P<0.05; P<0.05, respectively). The results showed that the shorter the duration of the disease, the better the treatment results were received. Return to activity and patient satisfaction were highest in the study group previously rehabilitated. CONCLUSIONS LR-PRP injection of the tibial tuberosity in patients with chronic OSD with open growth cartilage is an effective and uncomplicated method. We did not observe any adverse effects, which suggests the relatively high safety of the procedure. The use of PRP in the earlier phase of the disease and additional rehabilitation before treatment significantly increases the effectiveness of treatment.

Characterization of Leukocyte- and Platelet-Rich Plasma Derived from Female Collage Athletes: A Cross-Sectional Cohort Study Focusing on Growth Factor, Inflammatory Cytokines, and Anti-Inflammatory Cytokine Levels.

Platelet-rich plasma (PRP) has been increasingly used in sports medicine owing to its various advantages. The purpose of our project was to standardize the parameters before performing large-scale clinical trials in the near future to precisely evaluate individual PRP quality. To examine the effects of regular exercise on PRP quality, this study focused on young female athletes, who have been relatively less studied. Blood samples were obtained from female college athletes (n = 35) and ordinary healthy adults (n = 30), which were considered as controls, and leukocyte-rich PRP (L-PRP) was prepared manually. Body composition indices were determined using a bathroom weight scale equipped with an impedance meter. Growth factors and cytokines were quantified using ELISA kits. Platelet-derived growth factor-BB (PDGF-BB) and Transforming-growth factors β1 (TGFβ1) levels (per platelet) in L-PRP were significantly lower in female athletes than in controls. In contrast, Interleukin-1β and Interleukin 1 receptor antagonist (IL-1RA) levels (per platelet and L-PRP) in L-PRP were significantly higher in athletes, and this difference was more prominent in IL-1RA. These findings suggest that L-PRP from athletes may facilitate the inflammatory phase of the healing process by regulating the pro-inflammatory and anti-inflammatory balance. These chemical compositions can be adopted as "must-check" parameters to characterize individual PRP preparations prior to clinical trials.

Creating 2 Unique Platelet-rich Plasma Products From a Single Batch of Whole Blood With a Single Processing Kit

Introduction: Platelet-rich plasma (PRP) is effective for knee osteoarthritis (OA) and certain tendinopathies. Current recommendations support the use of leukocyte-poor PRP for OA and leukocyte-rich PRP for tendinopathy. If a patient presents with both OA and tendinopathy, very few systems can create multiple PRP products in the same treatment session. The Angel device processes multiple cycles to produce different PRP products. Methods: Ten healthy volunteers donated 156 mL whole blood (WB) that was mixed with 24 mL of anticoagulant citrate dextrose solution, solution A. The first PRP was produced by processing 120 mL at the 0% hematocrit setting and the second PRP was created by processing the remaining 60 mL at the 15% hematocrit setting. WB and PRP underwent complete blood counts and growth-factor analysis. Results: Ten patients donated WB for processing. The 0% setting yielded 3.7 ± 0.15 mL PRP, whereas the 15% setting produced 4.7 ± 0.33 mL. The 0% and 15% settings both concentrated platelets significantly more than WB (1101.5 ± 281.7 K/uL and 1357.8 ± 363.7 vs 184.3 ± 39.1 K/uL, P = 0.000). The 0% setting reduced total leukocytes, but this was not statistically significant. The 15% setting concentrated total leukocytes to 24 ± 8.72 K/uL, which was significantly higher than WB (P = 0.000). Neutrophil concentration was significantly reduced in the 0% PRP compared with 15% (0.032 ± .02 vs 6.75 ± 5.76 K/uL, P = 0.000). Discussion: Two unique PRP products were created from the same batch of WB using a single commercial kit by processing aliquots at different settings.

Leukocyte-poor platelet-rich plasma and leukocyte-rich platelet-rich plasma promote myoblast proliferation through the upregulation of cyclin A, cdk1, and cdk2.

Muscle injuries are common among athletes and often treated with platelet-rich plasma (PRP). However, whether the leukocyte concentration affects the efficacy of PRP in treating muscle injuries remains unclear. This study investigated the effects of leukocyte-poor platelet-rich plasma (LP-PRP) and leukocyte-rich platelet-rich plasma (LR-PRP) on myoblast proliferation and the molecular mechanisms underlying these effects. Myoblasts were treated with 0.5% LP-PRP, 0.5% LR-PRP, 1% LP-PRP, or 1% LR-PRP for 24 h. The gene expression of the LP-PRP- and LR-PRP-treated myoblasts was determined using RNA sequencing analysis. Cell proliferation was evaluated using an bromodeoxyuridine (BrdU) assay, and cell cycle progression was assessed through flow cytometry. The expression of cyclin A, cyclin-dependent kinase 1 (cdk1), and cdk2 was examined using Western blotting. The expression of myoblast determination protein 1 (MyoD1) was examined through Western blotting and immunofluorescence staining. The LP-PRP and LR-PRP both promoted the proliferation of myoblasts and increased differential gene expression of myoblasts. Moreover, the LP-PRP and LR-PRP substantially upregulated the expression of cyclin A, cdk1, and cdk2. MyoD1 expression was induced in the LP-PRP and LR-PRP-treated myoblasts. Our results corroborate the finding that LP-PRP and LR-PRP have similar positive effects on myoblast proliferation and MyoD1 expression.

Statistical Fragility of Randomized Controlled Trials Evaluating Platelet-Rich Plasma Use for Knee Osteoarthritis: A Systematic Review.

Numerous studies have been published on the use of platelet-rich plasma (PRP) for knee osteoarthritis (OA), with conflicting results. To determine the fragility index (FI) and fragility quotient (FQ) of randomized controlled trials (RCTs) that evaluated the use of PRP to treat knee OA. Systematic review. RCTs evaluating the efficacy of PRP injections for knee OA from 2000 to 2020 were included for analysis according to PRISMA guidelines. The FI was determined by calculating the number of outcome event reversals required to change the statistical significance. The associated FQ was determined by dividing the FI by the sample size. Our initial search resulted in 41,149 studies, of which 8 RCTs (678 patients, 72 outcome events) were included in the analysis. One study failed to report PRP formulation details, whereas 87.5% of studies reported using either leukocyte-rich or leukocyte-poor PRP. The platelet concentration was reported in 25% of the included trials. The overall FI of the 72 outcome events was 8.5. Accounting for sample size, the associated FQ was determined to be 0.14, suggesting that the reversal of 14% of outcome events was required to change outcome significance. There were 51 statistically significant outcomes, of which the FI and FQ were 12 and 0.164, respectively. Comprehensive fragility analysis suggested that the published literature evaluating the efficacy of PRP use for knee OA may lack statistical stability. We recommend the reporting of both an FI and FQ in addition to P value analysis to provide a clear and thorough understanding of the statistical integrity of studies reporting on PRP use for knee OA.

Poster 223: Patient Reported Outcomes Following Treatment with Leukocyte Rich Platelet Rich Plasma Injections for Proximal Hamstring Tendinopathy

Poster 223: Patient Reported Outcomes Following Treatment with Leukocyte Rich Platelet Rich Plasma Injections for Proximal Hamstring Tendinopathy

Cellular composition modifies the biological properties and stability of platelet rich plasma membranes for tissue engineering.

Scaffolds should provide structural support for tissue regeneration, allowing their gradual biodegradation and interacting with cells and bioactive molecules to promote remodeling. Thus, the scaffold's intrinsic properties affect cellular processes involved in tissue regeneration, including migration, proliferation, differentiation, and protein synthesis. In this sense, due to its biological effect and clinical potential, Platelet Rich Plasma (PRP) fibrin could be considered a successful scaffold. Given the high variability in commercial PRPs formulations, this research focused on assessing the influence of cellular composition on fibrin membrane stability and remodeling cell activity. The stability and biological effect were evaluated at different time points via D-dimer, type I collagen and elastase quantification in culture media conditioned by Plasma Rich in Growth Factors - Fraction 1 (PRGF-F1), Plasma Rich in Growth Factors - Whole Plasma (PRGF-WP) and Leukocyte-rich Platelet Rich Plasma (L-PRP) membranes, and by gingival fibroblast cells seeded on them, respectively. Ultrastructure of PRP membranes was also evaluated. Histological analyses were performed after 5 and 18 days. Additionally, the effect of fibrin membranes on cell proliferation was determined. According to the results, L-PRP fibrin membranes degradation was complete at the end of the study, while PRGF membranes remained practically unchanged. Considering fibroblast behavior, PRGF membranes, in contrast to L-PRP ones, promoted extracellular matrix biosynthesis at the same time as fibrinolysis and enhanced cell proliferation. In conclusion, leukocytes in PRP fibrin membranes drastically reduce scaffold stability and induce behavioral changes in fibroblasts by reducing their proliferation rate and remodeling ability.

Leukocyte-Rich Platelet-Rich Plasma Is Predominantly Anti-inflammatory Compared With Leukocyte-Poor Platelet-Rich Plasma in Patients With Mild-Moderate Knee Osteoarthritis: A Prospective, Descriptive Laboratory Study

Background: Platelet-rich plasma (PRP) has been used extensively in clinical practice to treat patients with symptomatic knee osteoarthritis (OA). Leukocyte-poor PRP (LP-PRP) has been clinically preferred over leukocyte-rich PRP (LR-PRP); however, it is unclear which cytokine mediators of pain and inflammation are present in LR-PRP and LP-PRP from patients with mild to moderate knee OA in order to rationalize a specific formulation. Hypothesis: LP-PRP would be predominantly anti-inflammatory and have reduced nociceptive pain mediators compared with LR-PRP from the same individual with mild to moderate knee OA. Study Design: Controlled laboratory study. Methods: A total of 24 unique samples of PRP were prepared in order to assess 48 samples of LR-PRP and LP-PRP taken from 12 patients (6 male and 6 female) with symptomatic knee OA of Kellgren-Lawrence grade 2 to 3. Patients underwent blood collection for LR-PRP and LP-PRP preparation through a double-spin protocol to obtain baseline whole blood, platelet concentration, and white blood cell subtypes. LR-PRP and LP-PRP from the same patient were produced at the same time and underwent a comprehensive panel through Luminex (multicytokine profiling) to assess key mediators of inflammation: interleukin 1 receptor antagonist (IL-1Ra), interleukin 4, 6, 8, and 10 (IL-4, IL-6, IL-8, and IL-10), IL-1β, tissue necrosis factor α (TNF-α), and matrix metalloproteinase 9 (MMP-9). To assess mediators of nociceptive pain, nerve growth factor (NGF) and tartrate resistant acid phosphatase 5 (TRAP5) were also assessed. Results: LR-PRP from patients with mild to moderate knee OA expressed significantly more IL-1Ra, IL-4, IL-8, and MMP-9 compared with LP-PRP formulations from the same patients. No significant differences were found between LR-PRP and LP-PRP in mediators of nociceptive pain—namely, NGF and TRAP5. Other mediators including TNF-α, IL-1β, IL-6, and IL-10 were also found to have no significant expression differences between LR-PRP and LP-PRP. Conclusion: LR-PRP expressed significantly more IL-1Ra, IL-4, and IL-8, suggesting that LR-PRP may be more anti-inflammatory than LP-PRP. MMP-9 was expressed in higher concentrations in LR-PRP, suggesting that LR-PRP may be more chondrotoxic than LP-PRP. Clinical Relevance: LR-PRP was found to have a robust expression of anti-inflammatory mediators compared with LP-PRP and may be beneficial to patients with long-term knee OA where chronic low-grade inflammation is present. Mechanistic clinical trials are needed to elucidate the key mediators in both LR-PRP and LP-PRP to assess their effect on long-term progression of knee OA.

Efficacy of Platelet-Rich Plasma for Chronic Lateral Ankle Instability After Modified Broström-Gould surgery: A Randomized, Single-Blinded, Prospective Controlled Trial

Modified Broström-Gould (MBG) surgery is frequently used for chronic lateral ankle instability (CLAI). However, conventional postoperative management (CPOM) due to prolonged immobilization may have adverse effects on tendons, ligaments, and joints, causing stiffness. This prospective, randomized controlled trial aimed to determine outcomes among patients randomized to receive CPOM plus ultrasonography-guided triple injections of leukocyte-rich platelet-rich plasma (LR-PRP) compared to patients who receive only CPOM after MBG surgery. The present study included 40 patients with symptomatic CLAI who were candidates for the MBG surgery. The patients were randomized into 2 groups of 20, the control and PRP groups. In the PRP group, patients were injected with 3 doses of LR-PRP solution using ultrasonographic guidance. In the first injection, 2 mL of LR-PRP was injected near the injury site, and in the second and third injections, 4 mL of LR-PRP was injected in the tibiotalar joint. All patients received a short leg splint for 2 weeks, followed by 4 weeks in a walking boot. The primary outcome measure was the visual analog scale (VAS), and the secondary outcome measures were the American Orthopaedic Foot & Ankle Society (AOFAS) ankle-hindfoot scale and ankle total range of motion (total ROM). The assessment was performed at baseline and 3 and 6 months after surgery. The mean VAS and AOFAS scores improved significantly in both groups 6 months after surgery (P < .001). However, the PRP group did not significantly improve in VAS or AOFAS scores compared with the control group. No clinically significant difference was observed between the 2 groups regarding the total ROM scores at month 3. The application of LR-PRP after MBG surgery did not show any superior clinical or functional improvement over CPOM. Level II, prospective randomized trial.

Comparison of Leukocyte-Rich and Leukocyte-Poor Platelet-Rich Plasma on Pressure Ulcer in a Rat Model.

Pressure ulcer (PU) is a common type of chronic wound that is difficult to treat. Platelet-rich plasma (PRP) is rich in cytokines and growth factors, and it can be divided into two categories according to its leukocyte content: leukocyte-poor PRP (P-PRP) and leukocyte-rich PRP (L-PRP). PRP has been applied in a variety of wound treatments, due to its strong ability to promote repair. This study aims to investigate the therapeutic effects of PRP on PU and elucidate the role of leukocytes in the treatment process. Sprague-Dawley rats were used to establish PU models of ischemia-reperfusion injury by applying magnets externally. L-PRP, P-PRP, and saline were injected into the dermal wounds. Wound healing analysis and sampling were performed on days 3, 7, 11, and 15 after treatment. Histological examinations, real-time PCR, immunohistochemical examinations, and biomechanical assay were carried out on the wound samples. The PRP groups exhibited greater wound inflammatory response than the control group in the early stage but the response reduced rapidly as the wound healed. On days 7, 11, and 15, the PRP groups also yielded better wound healing rates and histological outcomes than the control group, with superior biomechanical properties observed on day 15. Among both PRP groups, the L-PRP group attained a higher wound healing rate than the P-PRP group on day 7, with greater significant early inflammatory responses, and more prominent angiogenesis. Therefore, PRP is proven to accelerate the healing of PU, with L-PRP being more effective in regulating inflammation and promoting angiogenesis than P-PRP.

Comparison of clinical efficiency between intra-articular injection of platelet-rich plasma and hyaluronic acid for osteoarthritis: a meta-analysis of randomized controlled trials.

Platelet-rich plasma (PRP) and hyaluronic acid (HA) are non-surgical treatments for osteoarthritis (OA), but the comparison of their efficiency is still inconclusive. The objectives of this study were to compare the efficacy of PRP and HA in the treatment of OA by meta-analysis and to explore the effects of different injection times and leukocyte concentration on the efficacy of PRP. Meta-analysis and subgroup analysis were conducted. The data were analyzed by Review Manager v5.4.1. Articles were retrieved and screened from PubMed, the Cochrane Library, Web of Science, and Embase. The outcome included the total Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), the visual analog scale (VAS), adverse events (AEs), the International Knee Documentation Committee (IKDC), and the satisfaction rate. A total of 30 articles involving 2733 patients were included. The total WOMAC score and IKDC score of the PRP group were better than those of the HA group at the last follow-up time, while there was no significant difference in AEs, satisfaction rate, and VAS between the two groups. In our subgroup analysis, there was no significant difference between single-injection PRP and triple-injection PRP. Leukocyte-poor PRP (LP-PRP) was better than leukocyte-rich PRP (LR-PRP) in IKDC, but there was no significant difference between them in the other scores. In the treatment of OA, compared with HA, PRP performed better in the improvement of the patient's function. There was no significant difference in VAS and AEs between the two groups, and the safety was comparable. LP-PRP looked to be superior to LR-PRP in functional recovery, but there appeared to be no significant difference in pain relief between them. There was no significant difference between single PRP and triple PRP in the subgroup analysis.

Platelet-Rich Plasma Gel Matrix (PRP-GM): Description of a New Technique.

Several musculoskeletal conditions are triggered by inflammatory processes that occur along with imbalances between anabolic and catabolic events. Platelet-rich plasma (PRP) is an autologous product derived from peripheral blood with inherent immunomodulatory and anabolic properties. The clinical efficacy of PRP has been evaluated in several musculoskeletal conditions, including osteoarthritis, tendinopathy, and osteonecrosis. When used in combination with hyaluronic acid (HA), a common treatment alternative, the regenerative properties of PRP are significantly enhanced and may provide additional benefits in terms of clinical outcomes. Recently, a new PRP-derived product has been reported in the literature and is being referred to as "plasma gel". Plasma gels are obtained by polymerizing plasmatic proteins, which form solid thermal aggregates cross-linked with fibrin networks. Plasma gels are considered to be a rich source of growth factors and provide chemotactic, migratory, and proliferative properties. Additionally, clot formation and the associated fibrinolytic reactions play an additional role in tissue repair. There are only a few scientific articles focusing on plasma gels. Historically, they have been utilized in the fields of aesthetics and dentistry. Given that the combination of three products (PRP, HA, and plasma gel) could enhance tissue repair and wound healing, in this technical note, we propose a novel regenerative approach, named "PRP-HA cellular gel matrix" (PRP-GM), in which leukocyte-rich PRP (LR-PRP) is mixed with a plasma gel (obtained by heating the plasma up) and HA in one syringe using a three-way stopcock. The final product contains a fibrin-albumin network entangled with HA's polymers, in which the cells and biomolecules derived from PRP are attached and released gradually as fibrinolytic reactions and hyaluronic acid degradation occur. The presence of leukocytes, especially monocytes and macrophages, promotes tissue regeneration, as type 2 macrophages (M2) possess an anti-inflammatory feature. In addition, HA promotes the viscosuplementation of the joint and induces an anti-inflammatory response, resulting in pain relief. This unique combination of biological molecules may contribute to the optimization of regenerative protocols suitable for the treatment of degenerative musculoskeletal diseases.

Effect of Combined Bone Marrow Aspirate, Lipoaspirate, and Platelet-Rich Plasma Injections on Pain, Function, and Perceived Change Amongst Individuals with Glenohumeral Osteoarthritis

Purpose: This study was conducted to investigate the efficacy of a combined minimally processed bone marrow aspirate (BMA), adipose graft, and leukocyte-rich platelet-rich plasma (PRP) intra-articular injection series on pain, function, and global rating of change (GROC) among patients with glenohumeral osteoarthritis (GHOA) and record any complications or adverse events associated with the protocol. Methods: Ten adults (mean age 65 years) previously recalcitrant to conservative care with clinical and radiographic evidence of GHOA were included. At the initial visit, patients were assessed for eligibility of treatment. All patients were assessed pre- and post-treatment with numerical pain rating and patient-specific functional scales (PSFS). All study participants were treated with 4–6 ml of PRP, 6 ml adipose graft, and 12 ml of BMA, which were administered via a landmark-based anterior intra-articular injection. Patients were requested to return twice over 4-week intervals for booster PRP injections. At each follow-up, the GROC and prior outcome measures were completed. Results: Patients returned after an average of 27 days for first (F1) and 68 days for the second (F2) PRP injection. Friedman Chi Square analysis indicated significant improvements in best and worse pain and PSFS from baseline initial visit to F1 and F2 (P ≤ .002). Post-hoc Wilcoxon signed-rank testing with Bonferroni correction (α = 0.017) identified significant improvements from baseline to F1 and F2 for the PSFS (P ≤ 0.012). Improvements in best and worse pain were significant at F2 (P ≤ 0.016), not F1 (P ≥ 0.02), compared to baseline. Effect sizes were large, ranging from r = 0.57 to 0.84 for pain and function. Improvements in pain, GROC, and PSFS met minimum clinically important differences at F2 based on previously validated clinimetrics. The only adverse events reported are related to administration of injectate that was temporary and managed in all cases with over-the-counter analgesics. Conclusion: A minimally processed adipose graft with BMA and three PRP injections improved pain and function among individuals with GHOA who were recalcitrant to conservative care. Although significant functional improvement at both follow-up points occurred, clinically important and significant changes in pain did not occur until F2. A one-group design and multimodal approach limit generalization of results. Level of Evidence: IV