Leukocyte-poor Platelet-rich Plasma Research Articles

Comparison of the efficacy of autologous Lp-PRP and Lr-PRP for treating intervertebral disc degeneration: in vitro and in vivo study

BackgroundIntervertebral disc degeneration (IDD) was the most common cause of low back pain. Platelet rich plasma (PRP) has the potential to repair IDD, however, there is still no conclusion on whether Leukocyte-poor platelet rich plasma (Lp-PRP) or Leukocyte-rich platelet rich plasma (Lr-PRP) is better for the treatment of IDD.MethodsFirst, we conducted an in vitro study to compare the effects of autologous Lp-PRP and Lr-PRP on human degenerated nucleus pulposus (NP) cells. Then we verified the in vivo effects of autologous Lp-PRP and Lr-PRP in treating disc degeneration through a rabbit IDD model.ResultsThe in vitro study showed both autologous Lp-PRP and Lr-PRP can promote the cell proliferation, the synthesis of COL II and Aggrecan of human degenerated NP cells, while Lp-PRP are better than Lr-PRP (P<0.05). In addition, only Lp-PRP can inhibit the apoptosis of human degenerated NP cells (P<0.05), whereas Lr-PRP activates the catabolism on the contrary (P<0.05). Further, the in vivo study through the rabbit IDD model verified that autologous Lp-PRP has better effects than autologous Lr-PRP in repairing IDD according to X-ray, MRI, histological, and immunohistochemical assessment (P<0.05, respectively). And the caspase-3 IHC results also showed that only autologous Lp-PRP treatment could inhibit apoptosis of NP cells in the rabbit IDD model (P<0.05).ConclusionCombining in vivo and in vitro studies, the present study confirmed that autologous Lp-PRP has a better effect than autologous Lr-PRP in repairing IDD, which may be due to the inflammatory factors (TNFα, IL-1β, etc.) in Lr-PRP antagonizing part of the repair effects and promoting the catabolism additionally. Therefore, our findings suggest that Lp-PRP may provide better results than Lr-PRP for treating IDD. Further randomized clinical trials will provide evidence to guide practice.

Platelet-Rich Plasma for Arthroscopic Rotator Cuff Repair: A 3-Arm Randomized Controlled Trial.

Although there has been some amount of research into the use of platelet-rich plasma (PRP) after arthroscopic rotator cuff repair, most studies have not fully demonstrated its benefits. In addition, PRP formulations containing different concentrations of leukocytes have not been directly compared for rotator cuff repair. The purpose of this article was to determine whether arthroscopic rotator cuff repair combined with PRP injection, either leukocyte-rich PRP (LR-PRP) or leukocyte-poor PRP (LP-PRP), is superior to the control. The null hypothesis was that the addition of any PRP formulation would not result in outcomes superior to the control group. Randomized controlled trial; Level of evidence, 1. Patients with full-thickness rotator cuff tears who underwent arthroscopic repair were assessed for eligibility. The included patients were randomized to 3 treatment groups: the LR-PRP, LP-PRP, and standard-care control groups. After the rotator cuff suture was fixed firmly, different groups of liquid PRP preparations prepared by centrifugation were injected into the tendon-to-bone interface. The functional outcomes were assessed using the University of California, Los Angeles (UCLA) score, the Constant score, the American Shoulder and Elbow Surgeons (ASES) score, the visual analog scale for pain during sleep and activity, and active range of motion at 3, 6, and 12 months after surgery. In addition, the visual analog scale score was obtained at weeks 2 and 6. Postoperative structural integrity was assessed by magnetic resonance imaging at 12 months using the Sugaya classification. Type III was considered partial retear, and types IV and V were considered complete retears. The safety of surgery was compared by the incidence of complications. The main analyses were performed in accordance with the intention-to-treat principle. Of 150 patients initially randomized, the functional outcomes in 142 (46 LR-PRP, 47 LP-PRP, 49 control) and the structural integrity in 133 (40 LR-PRP, 46 LP-PRP, 47 control) were analyzed. There was no significant difference in the primary outcome of the UCLA score among the 3 groups (P = .169). The trends in functional outcomes and range of motion were similar for the 3 groups, with no significant differences among the groups at 12 months. However, within 6 months after surgery, the ASES score was better in the LR-PRP group than in the control group (3 months: 85.8 ± 4.1 vs 81.6 ± 8.7; P = .011; 6 months: 90.0 ± 5.4 vs 86.2 ± 6.8; P = .003). At 12 months after surgery, the overall retear rate, including partial and complete retears, was 8%. There were no significant differences in the rates of overall retear (P = .755) or complete retear (P = .633) among the 3 groups. The only surgical complication was postoperative stiffness, which occurred in 3% of patients, and the incidence did not significantly differ among the groups (P = .790). The study did not reveal that shoulders treated with the LR-PRP or LP-PRP formulations had any superior functional or structural outcomes at 12 months compared with those of the control group. However, LR-PRP may offer better ASES scores than the control group up to 6 months after surgery, and its clinical benefit remains to be proven. ChiCTR2100045039 (Chinese Clinical Trial Register).

Influence of Platelet Concentration on the Clinical Outcome of Platelet-Rich Plasma Injections in Knee Osteoarthritis

Background: Platelet-rich plasma (PRP) is one of the most frequently used orthobiologic products for the injection treatment of patients affected by knee osteoarthritis (OA). Some preliminary evidence supports the influence of platelet concentration on patients’ clinical outcomes. Purpose: To analyze if platelet concentration can influence the safety and clinical efficacy of PRP injections for the treatment of patients with knee OA. Study Design: Cohort study; Level of evidence, 3. Methods: This study consisted of 253 patients with knee OA (142 men, 111 women; mean ± SD age, 54.8 ± 11.4 years; Kellgren-Lawrence grades 1-3) who were treated with 3 intra-articular injections of 5 mL of autologous leukocyte-rich or leukocyte-poor PRP. All patients were prospectively evaluated at baseline and at 2, 6, and 12 months. Patients were clinically assessed thorough the Knee injury and Osteoarthritis Outcome Score (KOOS) subscales and the International Knee Documentation Committee (IKDC) Subjective score. Platelet concentration was correlated with clinical outcome. Further analysis was performed by stratifying patients into 3 groups (homogeneous for OA severity) based on platelet concentration (high, medium, and low). All complications and adverse events were reported, as well as failures. Results: An overall statistically significant improvement in all clinical scores was documented from baseline to each follow-up evaluation. Platelet concentration positively correlated with clinical outcome. KOOS Pain improved more with higher platelet concentration at 2 months (P = .036; rho = 0.132), 6 months (P = .009; rho = 0.165), and 12 months (P = .014; rho = 0.155). The same trend was shown by the other KOOS subscales and by the IKDC Subjective score, as well as by the comparison of the groups of high-, medium-, and low-platelet PRP. The highest failure rate (15.0%) was found in the low-platelet group as compared with the medium-platelet group (3.3%) and the high-platelet group (3.3%). No differences were observed among the 3 groups in terms of adverse events. Conclusion: This study demonstrated that platelet concentration influences the clinical outcome of PRP injections in knee OA treatment. PRP with a higher platelet concentration provides a lower failure rate and higher clinical improvement as compared with PRP with a lower platelet concentration, with overall better results up to 12 months of follow-up in patients with knee OA.

Leukocytes Do Not Influence the Safety and Efficacy of Platelet-Rich Plasma Injections for the Treatment of Knee Osteoarthritis: A Double-Blind Randomized Controlled Trial

Background: Platelet-rich plasma (PRP) is increasingly used for the injection treatment of knee osteoarthritis (OA). However, the role of leukocytes contained in PRP is controversial, with some preclinical studies suggesting detrimental effects and others emphasizing their contribution in secreting bioactive molecules. Purpose: To compare the safety and effectiveness of leukocyte-rich PRP (LR-PRP) and leukocyte-poor PRP (LP-PRP) for the treatment of knee OA. Hypothesis: That leukocytes could influence results both in terms of adverse events and clinical outcomes. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: This double-blind randomized controlled trial included 132 patients with Kellgren-Lawrence grade 1-3 knee OA who were randomized to a 3-injection cycle of either LR-PRP or LP-PRP. Patients were prospectively assessed at baseline and at 2, 6, and 12 months with subjective evaluations comprising the International Knee Documentation Committee (IKDC) subjective score, the KOOS (Knee injury and Osteoarthritis Outcome Score), the WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index), the visual analog scale for pain, the EuroQol–visual analog scale, the EuroQol–5 dimensions, and the Tegner activity scale. Objective evaluations consisted of the IKDC objective score, active/passive range of motion, and circumference of the index and contralateral knees. Patient judgment of the treatment was recorded as well as adverse reactions and failures. Results: An overall improvement in subjective and objective outcomes was documented, with no differences between the 2 groups, except for the improvement in the IKDC subjective score at 2 months, which was greater for the LR-PRP group compared with the LP-PRP group (14.8 ± 14.8 vs 8.6 ± 13.3, respectively; P = .046), as well as for active (P = .021) and passive (P = .040) ROM of the index knee at 6 months, showing statistically significant higher values in the LP-PRP group; and for quadriceps circumference of the index (P = .042) and contralateral (P = .045) knees at 12 months, which were significantly greater in the LR-PRP group. The IKDC subjective score improved from 42.5 ± 17.6 at baseline to 55.6 ± 21.4 at 12 months for the LR-PRP group (P < .0005) and from 45.7 ± 16.4 to 55.3 ± 20.4 for the LP-PRP group (P = .001). No differences in terms of patient treatment judgment were observed at all follow-up time points. No severe adverse events related to the treatment were reported, but some mild adverse events related to the treatment were observed: 16 in the LR-PRP group and 17 in the LP-PRP group. Treatment failed in 5 patients in the LR-PRP group and 2 in the LP-PRP group. Conclusion: This double-blind randomized controlled trial demonstrated that leukocytes did not affect the safety and efficacy of intra-articular PRP injections for the treatment of patients with knee OA. Both LR-PRP and LP-PRP demonstrated comparable clinical outcomes at all follow-up time points, without showing differences in subjective and objective outcomes or in adverse events and treatment failures. Registration: NCT04187183 (ClinicalTrials.gov).

Novel Molecular Mechanisms Underlying the Ameliorative Effect of Platelet-Rich Plasma against Electron Radiation-Induced Premature Ovarian Failure.

Radiotherapy is one of the risk factors for radiation-induced premature ovarian failure and infertility in cancer patients. The development of methods for ovarian radioprotection remains relevant. Moreover, electrons are a little-studied and promising method of radiation with the least toxic effect on normal tissues. The assessment of intracellular mechanisms regulating the protective effects of leukocyte-poor platelet-rich plasma in a model of radiation-induced premature ovarian failure caused by electron irradiation. Wistar rats were divided into four groups, namely a control group, irradiation group (electron exposure), irradiation + leukocyte-poor platelet-rich plasma group, and only leukocyte-poor platelet-rich plasma group. Fragments of ovaries were removed and hormonal, oxidant, histological, and morphometric studies were carried out. The cell cycle of ovarian follicles and the inflammatory and vascular response were assessed using immunohistochemistry. The activity of MAPK, ERK, and PI3K pathways was also assessed using the RT-qPCR. We found that electron irradiation causes a decrease in the functional activity of the ovaries and the death of follicular cells through apoptosis. The administration of LP-PRP led to a partial restoration of the cytokine balance. In addition, minor ovarian damage and mild inflammation were observed in this group. Leukocyte-poor platelet-rich plasma components have anti-inflammatory, angiogenetic, and radioprotective effects, reducing the activation of the NOX4, caspase and cytokine cascades, and inflammatory response severity through the MAPK/p38/JNK signaling pathway. This leads to the induction of endogenous antioxidant protection, the repair of post-radiation follicular damage, and slowing down the development of radiation-induced premature ovarian failure after electron irradiation.

Leukocyte-Poor Platelet-Rich Plasma for the Management of Knee Osteoarthritis: A Retrospective Study With 12 Months of Follow-Up.

Introduction The knee, the most frequently affected joint in osteoarthritis (OA), impacts the life quality of millions of individuals globally, resulting in a considerable healthcare burden. Conservative treatments are preferred, turning to surgical intervention when necessary. Nonetheless, these conventional modalities have drawbacks. Recently, the use of regenerative medicine therapies, including autologous peripheral blood-derived orthobiologics (APBOs), such as leukocyte-poor platelet-rich plasma (LP-PRP), has evolved and demonstrated the ability to manage knee OA. The primary objective of this investigation was to evaluate the efficacy of LP-PRP via widely used patient-reported outcome measures (PROMs) in grade I or II (on the Kellgren-Lawrence scale) knee OA patients. The secondary objective was to characterize the formulated LP-PRP and determine the efficiency of the leukodepletion filter used for leukocyte removal and platelet recovery. Methods This investigation was a retrospective analysis of data collected from patients treated at a single center over a period of 15 months.Data from 40 patients included in this study were intra-articularly injected with 3mL of formulated LP-PRPunder ultrasound guidance. PROMs questionnaires, including Kujala and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores, were used and responses were documented at baseline and up to 12 months follow-up. The characterization of the formulated LP-PRP and the efficiency of the leukodepletion filter in removing leukocytes and recovering platelets were assessed via complete blood count (CBC) analysis. Results The intra-articular administration of LP-PRP resulted in statistically significant improvements in Kujala and WOMAC scores in patients with Grade I or II OA of the knee at all follow-up time points (four to 12 months) compared to the respective baseline scores. The subgroup analysis showed significant improvements in Kujala and WOMAC scores inboth male and female grade I or II knee OA patients with or without comorbidities, including diabetes and/or hypertension. The characterization of formulated PRP showedplatelet concentration to be at least 6x compared to the baseline whole blood levels, the absolute platelet count to be at least 5 billion, and total leukocytes, lymphocytes, neutrophils, and RBCs were depleted by over 88%, 82%, 98%, and 98%, respectively. In addition, the utilization of the PuriBlood leukocyte reduction filter (Puriblood Medical Co. Ltd., Baoshan Township, Taiwan) led to the depletion of approximately 93% of leukocytes and the recovery of about 83% of platelets. Conclusions Administration of LP-PRP resulted in significant improvements in pain and function of patients suffering from grade I or II OA of the knee. In addition, the leukodepletion filter used to formulate LP-PRP, successfully resulted in the depletion of leukocytes while recovering the platelets. More sufficiently powered, multi-center, prospective, non-randomized, and randomized controlled trials with long-term follow-up are needed to further establish the effectiveness of this formulation in knee OA patients.

Effect of Freeze-Thawing Treatment on Platelet-Rich Plasma Purified with Different Kits.

Osteoarthritis of the knee (OAK), a progressive degenerative disease affecting quality of life, is characterized by cartilage degeneration, synovial inflammation, and osteophyte formation causing pain and disability. Platelet-rich plasma (PRP) is an autologous blood product effective in reducing OAK-associated pain. PRP compositions depend on their purification. In clinical practice, PRP is typically administered immediately after purification, while cryopreserved PRP is used in research. Platelets are activated by freezing followed by release of their humoral factors. Therefore, PRP without any manipulation after purification (utPRP) and freeze-thawed PRP (fPRP) may differ in their properties. We purified leukocyte-poor PRP (LPPRP) and autologous protein solution (APS) to compare the properties of utPRPs and fPRPs and their effects on OAK target cells. We found significant differences in platelet activation and humoral factor content between utPRPs and fPRPs in both LPPRP and APS. Freeze-thawing affected the anti-inflammatory properties of LPPRP and APS in chondrocytes and synovial cells differed. Both utPRPs and fPRPs inhibited polarization toward M1 macrophages while promoting polarization toward M2 macrophages. Freeze-thawing specifically affected humoral factor production in macrophages, suggesting that evaluating the efficacy of PRPs requires considering PRP purification methods, properties, and conditions. Understanding these variations may enhance therapeutic application of PRPs in OAK.

52891 Preliminary Evaluation of the Efficacy and Safety of Leukocyte-Poor Platelet-Rich Plasma in the Treatment of Melasma in Asian Patients

52891 Preliminary Evaluation of the Efficacy and Safety of Leukocyte-Poor Platelet-Rich Plasma in the Treatment of Melasma in Asian Patients

Effectiveness of Injection Strategies on Patients With Patellar Tendonitis (Jumpers' Knee): A Network Meta-analysis of Randomized Controlled Trials.

Patellar tendonitis (PT) is a common degenerative disease of the patellar tendon that seriously affects the sports careers of elite athletes and activities of daily living of sports enthusiasts. Injection therapy is a prevalent invasive treatment for PT. This work comprehensively analyzes various injection treatments for PT that consider agent type and characteristics, frequency, and assessment timepoints by meta-analysis. PubMed, Embase, and the Cochrane Library were sources of data. Randomized controlled trials (RCTs) analyzing the effect of various injection strategies on the treatment of patients with PT were considered. Systematic review and meta-analysis. Level 2. First author, year of publication, research location, registration information, patient type, sample size, age, sex, intervention, control treatment, and follow-up period in each study were extracted. Nineteen RCTs were included in the analysis. In the network meta-analysis of Victorian Institute of Sports Assessment-Patellar (VISA-P) outcomes, polidocanol (standardized mean difference (SMD), 6.52; 95% CI 4.75, 8.30; P < 0.01), tenocyte-like cells (SMD, 4.08; 95% CI 2.92, 5.25; P < 0.01), and leukocyte-poor platelet-rich plasma (LP-PRP) plus high-volume image-guided injection (HVIGI) (SMD, 1.56; 95% CI 0.62, 2.50; P < 0.01) were significantly superior to noninjection conservative treatment, mainly at the 6-month follow-up timepoint. For visual analog scale results, multiple dry needling (DN) (SMD, -1.78; 95% CI -2.56, -1.00; P < 0.01), LP-PRP (SMD, -0.71; 95% CI -1.31, -0.12; P = 0.02), and LP-PRP plus HVIGI (SMD, -1.31; 95% CI -2.22, -0.39; P < 0.01) were significantly superior to blank, which was also mainly at the 6-month timepoint. Injection-related treatments: polidocanol, tenocyte-like cells, LP-PRP, and multiple DN showed potential short (1-3 months) or medium (6 months)-term treatment benefits. There is still no evidence for injection interventions with long-term therapeutic benefit.

The Effectiveness of Leukocyte-Poor Platelet-Rich Plasma Injections for Symptomatic Mild to Moderate Osteoarthritis of the Knee With Joint Effusion or Bone Marrow Lesions in a Japanese Population: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

Background: Intra-articular platelet-rich plasma (PRP) injections have been proposed for the treatment of knee osteoarthritis (OA); however, their effectiveness in Japanese patients remains unclear. Purpose: To investigate whether 3 intra-articular injections of leukocyte-poor PRP (LP-PRP) improve symptoms and joint function in symptomatic Japanese patients with mild to moderate knee OA. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: Of 72 patients screened, 30 were included and randomized to receive LP-PRP (n = 15) or saline (placebo; n = 15) injections between March 2019 and February 2023. Patients attended a screening visit and 3 treatment visits at 1 week apart, followed by 3 follow-up visits (at 4, 12, and 24 weeks) after the initial treatment visit. The primary efficacy outcome measure was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, whereas the secondary efficacy outcome measures were the proportion of patients showing a visual analog scale (VAS) improvement of ≥50%. Magnetic resonance imaging was performed to evaluate joint effusion and bone marrow lesions using the Whole-Organ Magnetic Resonance Imaging Score. Patients were followed for 24 weeks. Results: Patients in the PRP group (mean age, 65.9 years) had a mean hip-knee-ankle angle of 5.1°, with 7 and 8 patients demonstrating Kellgren-Lawrence grade 2 and 3 knee OA, respectively. Patients in the placebo group (mean age, 67.9 years) had a mean hip-knee-ankle angle of 3.8°, with 6 and 9 patients showing Kellgren-Lawrence grade 2 and 3 knee OA, respectively. No significant differences were identified in any baseline factors. The percentage change in Western Ontario and McMaster Universities Osteoarthritis Index scores from baseline to 24 weeks was significantly different (P= .032) between the PRP (median, 75.9%; quantile 1 [Q1], 49.6; quantile 3 [Q3], 94.1]) and placebo (median, 27.7%; Q1, –9.4; Q3, 80.9]) groups. Overall, 73.3% and 28.6% of the PRP group and placebo group, respectively, exhibited an improvement in visual analog scale scores of ≥50%, with a significant improvement observed in the PRP group (P = .027). Changes in bone marrow lesions from baseline to 24 weeks, as assessed on magnetic resonance imaging, significantly differed between groups (P = .017), with no significant differences in other secondary endpoints. Conclusion: In Japanese patients with knee OA, 3 intra-articular LP-PRP injections led to clinical improvements at 24-week follow-up and significant functional improvements and pain relief after 24 weeks.

Partial-Thickness Rotator Cuff Tears: Current Concepts.

» Partial-thickness rotator cuff tears (PTRCTs) are a common pathology with a likely high asymptomatic incidence rate, particularly in the overhead athlete.» The anatomy, 5-layer histology, and relationship to Ellman's classification of PTRCTs have been well studied, with recent interest in radiographic predictors such as the critical shoulder angle and acromial index.» Depending on the definition of tear progression, rates of PTRCT progression range from 4% to 44% and appear related to symptomatology and work/activity level.» Nearly all PTRCTs should be managed conservatively initially, particularly in overhead athletes, with those that fail nonoperative management undergoing arthroscopic debridement ± acromioplasty if <50% thickness or arthroscopic conversion repair or in situ repair if >50% thickness.» Augmentation of PTRCTs is promising, with leukocyte-poor platelet-rich plasma having the most robust body of supportive data. Mesenchymal signaling cell biologics and the variety of scaffold onlay augments require more rigorous studies before regular usage.

Evaluation of Patellar Tendon Structural Changes following Biological Treatments: Secondary Analysis of Double-Blinded Clinical Trial of Bone Marrow Mesenchymal Stromal Cells and Leukocyte-Poor Platelet-Rich Plasma.

Objective quantification of tendon structural changes through imaging is only achieved by evaluating tendon structure using ultrasound tissue characterization (UTC) technology. This study compares the effects of bone marrow mesenchymal stromal cells (BM-MSC) and leukocyte-poor platelet-rich plasma (Lp-PRP) on tendon structure and clinical outcomes in male patients with patellar tendinopathy measured with UTC at 3, 6, and 12 months after treatment. This is a double-blinded clinical trial with a randomized active control study with 20 male patients diagnosed with patellar tendinopathy who underwent BM-MSC and Lp-PRP. Bilateral ultrasound tissue characterization scans of the patellar tendon were carried out after 3, 6, and 12 months, as well as tests for strength and pain. UTC patellar tendon was analyzed at the insertion, proximal, and mid-tendon. BM-MSC showed a greater capacity to promote further positive changes than Lp-PRP. Lp-PRP presented higher disorganized echo-type II in the mid-tendon (p = 0.04; ES = 1.06) and III (p = 0.02; ES = -1.47) after 3 months in the Lp-PRP group. Similar results were seen after 6 and 12 months. Pain and strength data show improvement in the treated tendon. BM-MSC treatment demonstrates a superior capacity to promote tendon regeneration and organization, restore strength, and reduce pain compared to Lp-PRP, after 3, 6, and 12 months in male patients with patellar tendinopathy.

Platelet-Rich Plasma for Knee and Hip Osteoarthritis Pain: A Scoping Review.

Platelet-rich plasma (PRP) is an emerging biological intervention for osteoarthritis (OA), yet the outcomes remain uncertain. The purpose of this study was to review current literature regarding the use of PRP for knee and hip OA. Recent systematic reviews have found significant clinical improvements in outcomes after the administration of PRP compared to hyaluronic acid (HA) in patients with knee OA. One of these reviews included bone marrow aspirate concentrate (BMAC) as a comparison group and found no significant differences in outcomes between PRP and BMAC. Currently, the literature is lacking on whether leukocyte-rich or leukocyte-poor PRP is superior in patients with knee OA. The literature on PRP for hip OA has not provided consistent results as it has for the knee. Two recent systematic reviews evaluated RCTs for patients undergoing treatment with either PRP or HA for hip OA and found no significant differences in clinical outcomes between groups at final follow-up. Current literature regarding the association between OA grade and PRP efficacy has found varying results. The use of PRP injections in the treatment of knee OA appears to be favorable, resulting in clinically comparable or superior outcomes compared to other injection treatments. However, the clinical efficacy of PRP injections in hip OA is far less consistent. Evidence is lacking to suggest that the presence of leukocytes significantly influences clinical outcomes. Further randomized controlled trials on larger cohorts, with longer follow-up, and with comparable formulations are required before recommendations can be made regarding use of PRP for hip OA, the effect of leukocyte concentration, and clinical efficacy based on OA grade.

The Implications of Brain-Derived Neurotrophic Factor in the Biological Activities of Platelet-Rich Plasma.

Platelet-rich plasma (PRP) is a biological blood-derived therapeutic obtained from whole blood that contains higher levels of platelets. PRP has been primarily used to mitigate joint degeneration and chronic pain in osteoarthritis (OA). This clinical applicability is based mechanistically on the release of several proteins by platelets that can restore joint homeostasis. Platelets are the primary source of brain-derived neurotrophic factor (BDNF) outside the central nervous system. Interestingly, BDNF and PRP share key biological activities with clinical applicability for OA management, such as anti-inflammatory, anti-apoptotic, and antioxidant. However, the role of BDNF in PRP therapeutic activities is still unknown. Thus, this work aimed to investigate the implications of BDNF in therapeutic outcomes provided by PRP therapy in vitro and in-vivo, using the MIA-OA animal model in male Wistar rats. Initially, the PRP was characterized, obtaining a leukocyte-poor-platelet-rich plasma (LP-PRP). Our assays indicated that platelets activated by Calcium release BDNF, and suppression of M1 macrophage polarization induced by LP-PRP depends on BDNF full-length receptor, Tropomyosin Kinase-B (TrkB). OA animals were given LP-PRP intra-articular and showed functional recovery in gait, joint pain, inflammation, and tissue damage caused by MIA. Immunohistochemistry for activating transcriptional factor-3 (ATF-3) on L4/L5 dorsal root ganglia showed the LP-PRP decreased the nerve injury induced by MIA. All these LP-PRP therapeutic activities were reversed in the presence of TrkB receptor antagonist. Our results suggest that the therapeutic effects of LP-PRP in alleviating OA symptoms in rats depend on BDNF/TrkB activity.

Nonoperative and Operative Soft-Tissue, Cartilage, and Bony Regeneration and Orthopaedic Biologics of the Elbow and Upper Extremity: An Orthoregeneration Network Foundation Review

Orthoregeneration is defined as a solution for orthopaedic conditions that harnesses the benefits of biology to improve healing, reduce pain, improve function, and, optimally, provide an environment for tissue regeneration. Options include drugs, surgical intervention, scaffolds, biologics as a product of cells, and physical and electromagnetic stimuli. The goal of regenerative medicine is to enhance the healing of tissue after musculoskeletal injuries as both isolated treatment and adjunct to surgical management, using novel therapies to improve recovery and outcomes. Various orthopaedic biologics (orthobiologics) have been investigated for the treatment of pathology involving the elbow and upper extremity, including the tendons (lateral epicondylitis, medial epicondylitis, biceps tendonitis, triceps tendonitis), articular cartilage (osteoarthritis, osteochondral lesions), and bone (fractures, nonunions, avascular necrosis, osteonecrosis). Promising and established treatment modalities include hyaluronic acid; botulinum toxin; corticosteroids; leukocyte-rich and leukocyte-poor platelet-rich plasma; autologous blood; bone marrow aspirate comprising mesenchymal stromal cells (alternatively termed medicinal signaling cells and frequently mesenchymal stem cells [MSCs]) and bone marrow aspirate concentrate; MSCs harvested from adipose and skin (dermis) sources; vascularized bone grafts; bone morphogenic protein scaffold made from osteoinductive and conductive β-tricalcium phosphate and poly-ε-caprolactone with hydrogels, human MSCs, and matrix metalloproteinases; and collagen sponge. Autologous blood preparations such as autologous blood injections and platelet-rich plasma show positive outcomes for nonresponsive tendinopathy. In addition, cellular therapies such as tissue-derived tenocyte-like cells and MSCs show a promising ability to regulate degenerative processes by modulating tissue response to inflammation and preventing continuous degradation and support tissue restoration.

Leukocyte-Poor Platelet-Rich Plasma as an Adjuvant to Arthroscopic Rotator Cuff Repair Reduces the Retear Rate But Does Not Improve Functional Outcomes: A Double-Blind Randomized Controlled Trial

Background: Whether the use of PRP as an adjuvant of rotator cuff repairs leads to improved tendon healing and better functional outcomes remains unclear in clinical evidence. Purpose: The main purpose of this study was to assess whether the use of leukocyte-poor platelet-rich plasma (LP-PRP) as an adjuvant to arthroscopic rotator cuff repair (ARCR) decreases the rate of retears compared with a control group. The secondary objective was to analyze whether LP-PRP improves patient-reported outcomes. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: This was a double-blind randomized controlled trial at a single center. A consecutive series of 96 patients with rotator cuff tears <3 cm were enrolled and randomly allocated to the control group (double-row suture-bridge ARCR alone [n = 48]) and the PRP group (double-row suture-bridge repair, followed by 1 LP-PRP injection during surgery [n = 48]). The visual analog scale (VAS) for pain, the American Shoulder and Elbow Surgeons (ASES) score, the Single Assessment Numeric Evaluation (SANE), and the Pittsburgh Sleep Quality Index (PSQI) were administered preoperatively and at 6- and 12-month follow-up. Magnetic resonance imaging (MRI) was performed to evaluate tendon integrity at 6-month follow-up. Both patients and assessors were blinded to the intervention received during surgery. Results: The mean patient age was 56.1 ± 2.98 years. Of the 96 patients, 90 had MRI performed at 6 months after surgery (94% radiological follow-up). The retear rate in the PRP group was 15.2% (7/46 [95% CI, 6%-28%]), which was lower than that in the control group of 34.1% (15/44 [95% CI, 20%-49%]) (P = .037). Therefore, the risk ratio of ruptures in patients exposed to LP-PRP was 0.44 (95% CI, 0.2-0.9; P = .037). Overall, the ASES, VAS, SANE, and PSQI scores showed a statistical improvement after surgery (P < .001). There were no significant differences in functional scores between the groups. Most of the patients exceeded the minimal clinically important difference for the ASES, SANE, and VAS without significant differences between the groups. Conclusion: In patients with rotator cuff tears <3 cm undergoing double-row suture-bridge repair, a 5-mL dose of LP-PRP injected at the tendon-bone interface significantly reduced the retear rate. However, the use of LP-PRP in terms of postoperative pain and patient-reported outcomes failed to show clinically meaningful effects. Registration: NCT04703998 (ClinicalTrials.gov identifier).

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.

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.

Study of centrifuge conditions for preparing rabbit leukocyte-poor platelet-rich plasma by single centrifugation

To explore the best centrifuge condition for preparing rabbit leukocyte-poor platelet-rich plasma (LP-PRP) by using single centrifugation method. Sixteen healthy New Zealand rabbits, aged 3-4 months, were utilized in the investigation. A total of 15 mL anticoagulated blood was extracted from the central ear artery of each rabbit, with a repeat of the blood collection procedure after 1 and 2 months. The obtained blood specimens were individually subjected to centrifugation at a radius of 16.7 cm and speeds of 1 200, 1 300, 1 400, and 1 500 r/min (equivalent to centrifugal forces of 269× g, 315× g, 365× g, and 420× g) for durations of 2, 3, 4, and 5 minutes, resulting in a total of 16 groups. Following centrifugation, collect plasma from each group to a distance of 1.5 mL from the separation plane. The volumes, platelet enrichment coefficient, and platelet recovery rates of LP-PRP in each group, under varying centrifugation conditions, were methodically computed and subsequently compared. The volume of LP-PRP obtained under all centrifugation conditions ranged from 1.8 to 7.6 mL. At a consistent centrifugal speed, an extension of centrifugation time leaded to a significant increase in the volume of LP-PRP, accompanied by a declining trend in the platelet enrichment coefficient of LP-PRP. When centrifuged for 2 minutes, the volume of LP-PRP at speeds of 1 200 and 1 300 r/min was less than 2.0 mL, while the volume of LP-PRP obtained under other conditions was more than 2.0 mL. When centrifuged for 4 and 5 minutes, the volume of LP-PRP obtained at each speed was more than 4 mL. LP-PRP with a platelet enrichment coefficient more than 2.0 could be prepared by centrifuging at 1 200 r/min for each time group and 1 300 r/min for 2 and 3 minutes, and the highest LP-PRP platelet enrichment coefficient could be obtained by centrifugation for 2 minutes at a speed of 1 200 r/min. The platelet recovery rates of LP-PRP obtained by centrifugation at 1 200 r/min for 4 and 5 minutes, as well as centrifugation at 1 400 r/min for 5 minutes, were both greater than 60%. There was no significant difference between the groups when centrifuged at 1 200 r/min for 4 and 5 minutes ( P>0.05). In the process of preparing rabbit LP-PRP using a single centrifugation method, collecting 15 mL of blood and centrifuging at a radius of 16.7 cm and speed of 1 200 r/min for 4 minutes can prepare LP-PRP with a volume exceeding 2.0 mL, platelet enrichment coefficient exceeding 2.0, and platelet recovery rate exceeding 60%. This centrifugal condition can achieve the optimal LP-PRP action parameters in the shortest possible time.