Effect Of Platelet-rich Plasma Research Articles

The protective effect of co-administration of platelet-rich plasma (PRP) and pentoxifylline (PTX) on cyclophosphamide-induced premature ovarian failure in mature and immature rats

Cyclophosphamide (CP), as an antineoplastic agent, causes premature ovarian failure (POF) due to ovarian toxicity and subsequent infertility in women. Platelet-rich plasma (PRP) has accumulated significant attention in regenerative medicine. Pentoxifylline (PTX) as a methylxanthine derivative has been shown to have antioxidant and antiapoptotic properties. The aim of this study was to evaluate the protective effect of PRP and PTX on CP-induced POF. Fifty mature and immature female rats were assigned into five groups: control, CP (75 mg/kg, intraperitoneal [ip] on days 1 and 10 to induce POF), CP + PRP (200 μl, ip, half an hour after CP injection on day 1 and 10), CP + PTX (50 mg/kg, orally, half an hour after CP injection daily for 21 day), and CP + PRP + PTX. At the end of experiments on day 21, measurement of body weight, ovarian parameters (ovarian volume, follicular granulosa cell layers diameter, oocyte diameter, and the number of granulosa cells), measurement of ovarian hormone in sera for estradiol (E2), and anti-Mullerian hormone (AMH), as well as biochemical assessment were performed. The results showed that CP significantly reduced the ovarian parameters, E2, AMH, superoxide dismutase (SOD) activity and increased Malondialdehyde (MDA) levels compared to the control group (p < 0.001). Our results also indicated that all histomorphometric parameters and biochemical markers in CP-induced POF, were preserved close to normal by PRP and PTX treatments in both mature and immature rats (p < 0.001). Therefore, it is concluded that the co-administration of PRP and PTX can protect the ovary from CP-induced POF.

The potential role of platelet-rich plasma and colchicine in experimentally induced muscle ischemia/reperfusion injury of adult male albino rats

Background Ischemia/reperfusion injury (IRI) in skeletal muscles is a pathophysiology that affects quality of life. The role of growth factors in the healing process encouraged the use of platelet-rich plasma (PRP). Aim This work aimed to evaluate the effect of PRP and colchicine in experimentally induced muscle IRI in rats. Materials and methods A total of 90 adult male rats were used in this study. Ten rats were used for blood collection to prepare PRP, and 80 rats were divided into four equal groups: group 1: control, group 2: gastrocnemius muscles of their right limbs were subjected to IRI and were left without treatment; group 3: gastrocnemius muscles were subjected to IRI as group 2 and immediately treated by intramuscular PRP; and group 4: colchicine was injected intraperitoneally immediately before IRI. Muscle specimens were taken from the control group and after 2 h and 7 days in the experimental groups for histological and immunohistochemical staining to detect antimyogenin and anti-CD34. The data were analyzed statistically. Results In the current study, group 2 showed disturbed normal histological architecture of skeletal muscles. PRP-treated group revealed early formation of many myotubes on the seventh day after injury and reduction of fibrosis. It showed significant increase in the number of centrally nucleated fibers, satellite cells, and new blood vessel formation. The colchicine group exhibited reduced muscle damage when compared with the IRI group. Conclusions PRP enhances tissue healing via myogenesis, neovascularization, and reduction of fibrosis. Colchicine attenuates IRI via its anti-inflammatory effects.

Platelet-rich plasma pretreatment protects anterior cruciate ligament fibroblasts correlated with PI3K-Akt-mTOR pathway under hypoxia condition.

Background/Objective: Biological factors such as platelet-rich plasma (PRP) combined with anterior cruciate ligament (ACL) primary repair technology are used to treat ACL injury. However, the protective mechanism of PRP for ACL fibroblasts under hypoxia condition is still unknown. The aim of this study was to investigate the protective effect of PRP on ACL fibroblasts under hypoxia condition and illustrate the mechanism of PRP regulating the ACL fibroblasts under hypoxia condition.MethodsThe cells were divided into three groups: control group, hypoxia group and PRP pretreatment group. Lethal dose (LD) 50 for hypoxia induction time and the maximum efficacy of PRP concentration were confirmed by CCK-8 assay. The ability of cell apoptosis, cell proliferation, and cell migration were tested by flow cytometry, scratch assay and transwell assay, respectively. Extracellular matrix (ECM) synthesis and hypoxia-inducible factor 1α (HIF-1α) were identified by immunofluorescence staining, Masson's staining and transmission electron microscope analysis. Inflammatory cell infiltration was assessed by hematoxylin and eosin staining as well as immunofluorescence staining. Western blot analysis and real-time PCR were performed to assess the associated gene and protein expression, respectively. The ratio of phosphorylated/total PI3K, Akt and mTOR were also assessed by western blot analysis.Results① LD 50 of hypoxia was 48 ​h and the maximum efficacy of PRP concentration was 600 ​× ​109/L. ② ANNEXIN V-FITC/PI flow cytometry showed that the hypoxia condition significantly increased the apoptosis of cells (P ​< ​0.001) whereas PRP pretreatment significantly decreased the apoptosis of cells under hypoxia (P ​< ​0.001). The expressions of gene and protein of Bax, Bcl-2, cleaved-caspase 3 were consistent with the results of flow cytometric analysis. ③ Cell cycle analysis for flow cytometry showed the inhibitory effect of hypoxia and promotive effect of PRP pretreatment. ④ Immunofluorescence staining (HIF-1α, collagen I and III) showed the positive effect of hypoxia and negative effect of PRP on these parameters. Real-time PCR showed that type I and III collagen were 2.1 folds and 2.5 folds higher after 48 ​h hypoxia induction compared to the control group. PRP pretreatment significantly reduced the type I and III collagen mRNA expression of the hypoxia induced ACL fibroblasts to 78.5% and 77.7% at 48 ​h compared to hypoxia group (P ​< ​0.001), respectively.⑤ Cell migration assay showed that hypoxia condition significantly restrained cell migration compared with the control group. PRP could alleviate the inhibitory effect of hypoxia on fibroblasts. ⑥ Western blot analysis showed the ratio of phosphorylated/total PI3K, Akt and mTOR in hypoxia group increased to 31%, 20% and 44/% compared to control group, respectively. ⑦ The results of in vivo analysis was in accordance with the results of in vitro analysis.ConclusionPRP can protect ACL fibroblasts via decreasing apoptosis and increasing cell viability, cell migration and cell proliferation under hypoxia condition. And such PRP protective effect was correlated with PI3K/Akt/mTOR pathway.The translational potential of this articlePRP can be used to treat patients with ACL tear by injection under arthroscopy or ultrasound guiding.

Effects of intra-articular Platelet-Rich Plasma (PRP) injections on osteoarthritis in the thumb basal joint and scaphoidtrapeziotrapezoidal joint.

Intra-articular injection of platelet rich plasma (PRP) has been reported to decrease pain and improve function in knee osteoarthritis. There are few reports on the effect of PRP in the treatment of osteoarthritis in the hand. Our aim was to evaluate the effect of PRP-injections on pain and functional outcome in the short-term for osteoarthritis in the thumb basal joint and scaphoidtrapeziotrapezoidal (STT) joint. A retrospective analysis was performed of 29 patients treated with intra-articular PRP injection for painful osteoarthritis in the thumb basal joint (21 patients) or STT joint (eight patients). The patients received two consecutive, radiologically guided PRP injections at an interval of 3-4 weeks. Pain at rest and on load (numerical rating scale (NRS) 0-10), Patient-rated Wrist and Hand Evaluation (PRWHE) score (0-100), grip strength (Jamar) and key pinch were recorded pre-injection and 3 months after the second injection. Mean age was 63 (range 34-86) years and 17 patients were women. We used generalized estimating equations (GEE) to analyze the effect on the outcome variables. Possible predictors were included in the model (high pain level pre-injection, gender, age, manually demanding work, affected joint (thumb base or STT) and use of analgesic). The GEE analysis showed that PRP injections had no effect on reported pain, PRWHE score, grip strength or key pinch. 16/28 patients experience a positive effect according to a yes/no question. The short-term effect of PRP for osteoarthritis in the thumb base and STT-joint is doubtful and needs to be properly investigated in placebo-controlled studies.

The effect of mechanical skin damage on manifestations of endotoxicosis and immune response under the influence of skeletal trauma complicated by acute blood loss and PRP-therapy effectiveness

Summary. The frequency of emergencies in both peacetime and wartime conditions has significantly increased in recent years. Under those circumstances, severe multiple and combined traumas, caused by skeletal trauma, acute blood loss and massive soft-tissue and skin damage, predominate among the various kinds of injuries. The role of mechanical skin damage in the course of severe trauma is insufficiently presented in the existing studies and literature. There are no data on the effectiveness of platelet-rich plasma grafts (PRP-therapy) under those conditions, which can greatly accelerate the regeneration of damaged soft tissues and skin, and thus inhibit the manifestations of systemic disorders, in particular endotoxicosis and immune responses. The aim of the study – to establish the effect of mechanical skin damage on the dynamics of indicators of endogenous intoxication and immune responses under the influence of skeletal trauma complicated by acute blood loss and evaluate the PRP-therapy effectiveness. Materials and Methods. The experimental studies were performed on 186 nonlinear white male rats weighing 180–200 g. In the first experimental group, the animals were simulated a mechanical damage of skin (a skin flap of 2×2 cm on the back of the animal was cut). The animals of the second experimental group were subjected to a skeletal trauma complicated by acute blood loss. In the third experimental group, these lesions were combined. In the fourth experimental group, the animals with combined trauma were administered an intradermal injection of 0.1 ml of platelet-rich plasma in wound edges. After 3, 7, 14, 21 and 28 days of trauma infliction, the animals were removed from the experiment. Contents of middle molecular weight (MMW280) fraction and circulation immune complexes (CICs) were measured in serum. The control group consisted of intact animals. Results. The research findings have shown that the infliction of isolated damage to skin is accompanied by the accumulation of the MMW280fraction and CICs in serum, the contents were higher than control values at all experimental periods reaching their maximum after 7 days and starting to increase again after 21 days. The pattern of the dynamics of the studied indicators in conditions of skeletal trauma complicated by acute blood loss was similar, but with greater amplitude. A combined trauma model resulted in an even greater increase in the intensity of endogenous intoxication and immune responses at all experimental time points. The administration of the PRP-therapy led to the decrease in the contents of MMW280 fraction and CICs in serum of rats with the combined trauma model starting from 7thday and 21st day of the experiment, respectively, as compared to the animals with the trauma model without correction. Conclusions. The infliction of damage to skin provokes the significant increase in the contents of MMW280 fraction and CICs in serum and can enhance the endogenous intoxication and immune responses in the presence of skeletal trauma complicated by acute blood loss. Intradermal administration of allogeneic platelet-rich plasma injection under these conditions leads to the decrease in the contents of MMW280 fraction and CICs as compared to the untreated animals with trauma model

Effect of Platelet-Rich Plasma on Autologous Chondrocyte Implantation for Chondral Defects: Results Using an In Vivo Rabbit Model.

Background:Articular cartilage repair remains challenging despite the availability of techniques, including autologous chondrocyte implantation (ACI) for repairing large cartilage defects. Platelet-rich plasma (PRP) therapy, a novel therapy focused on chondrocyte regeneration, needs to be investigated regarding its potential to improve the outcomes of ACI.Purpose:To examine the effect of PRP therapy on the outcomes of cartilage repair using the ACI procedure in a rabbit model of knee joint cartilage damage.Study Design:Controlled laboratory study.Methods:A total of 30 knees in 15 Japanese White rabbits (joint cartilage damage model) were divided into nontreatment (n = 7), PRP (n = 8), ACI (n = 7), and combined ACI and PRP (n = 8) groups. At 4 weeks and 12 weeks postoperatively, histological and visual examination of the surgical site was performed, and the regenerated cartilage and calcified bone areas were measured by imaging the specimens.Results:Pretransplantation evaluation in the cultured cartilage showed the histological properties of hyaline cartilage. At 4 weeks postoperatively, the regenerated cartilage area at the surgical site showed a larger safranin O–positive area in the ACI group (2.73 ± 4.46 mm2) than in the combined ACI and PRP group (1.71 ± 2.04 mm2). Calcified bone formation in the ACI group was relatively lower than that in the other groups. Cartilage repair failure occurred in all groups at 12 weeks postoperatively.Conclusion:The authors found no positive effects of PRP on the outcomes of ACI in a rabbit model. There was a smaller safranin O–positive region with the addition of PRP to ACI compared with ACI alone. In the subchondral bone, bone formation might have been promoted by PRP.Clinical Relevance:Administering PRP at the time of ACI may not have a positive effect and may have deleterious effects on cartilage engraftment and regeneration.

Evaluation of Platelet-Rich Plasma Therapy for Peripheral Nerve Regeneration: A Critical Review of Literature.

Peripheral nerve injury (PNI) is a common disease in clinic, and the regeneration process of peripheral nerve tissue is slow, and patients with PNI often suffer from the loss of nerve function. At present, related research on the mechanism of peripheral nerve regeneration has become a hot spot, and scholars are also seeking a method that can accelerate the regeneration of peripheral nerve. Platelet-rich plasma (PRP) is a platelet concentrate extracted from autologous blood by centrifugation, which is a kind of bioactive substance. High concentration of platelets can release a variety of growth factors after activation, and can promote the proliferation and differentiation of tissue cells, which can accelerate the process of tissue regeneration. The application of PRP comes from the body, there is no immune rejection reaction, it can promote tissue regeneration with less cost, it is,therefore, widely used in various clinical fields. At present, there are relatively few studies on the application of PRP to peripheral nerve regeneration. This article summarizes the literature in recent years to illustrate the effect of PRP on peripheral nerve regeneration from mechanism to clinical application, and prospects for the application of PRP to peripheral nerve.

Therapeutic effect of platelet-rich plasma on glucocorticoid-induced rat bone marrow mesenchymal stem cells in vitro

BackgroundGlucocorticoid-induced osteonecrosis of the femoral head (GIONFH) is a progressive and disabling disease caused by long-term or high-dose glucocorticoid use. Decreased osteogenesis and proliferation of bone marrow mesenchymal stem cells (BMSCs) are the main pathogenesis of GIONFH. Platelet-rich plasma (PRP) has been shown to play a promising role in bone regeneration. However, the effects of PRP on glucocorticoid-induced BMSCs inhibition remains elusive. The objective of this study was to explore whether PRP could improve the in vitro biological activities of BMSCs inhibited by high-dose glucocorticoid in vitro.MethodsIn this study, a dexamethasone (Dex)-induced in vitro cell model was established. The effects of PRP on proliferation, migration, cell cycle and apoptosis of rat BMSCs induced with high-dose Dex compared to BMSCCTRL, using CCK-8 assay, transwell, flow cytometry and TUNEL assay, respectively. We further performed the alkaline phosphatase (ALP) and alizarin red (ALR) staining to explore the influence of PRP on osteogenic differentiation. Western Blot was used to detect the expression of Bcl-2, Caspase-3, RUNX2 apoptosis, and osteogenic-related proteins.ResultsWe observed increased apoptosis rate and Caspase-3 expression, and the decreased migration and osteogenic differentiation, and down-regulation of RUNX-2 and Bcl-2 expression in Dex-induced BMSCs. PRP could reverse these inhibitory effects of Dex, and enhance the BMSCs proliferation, migration, and osteogenic ability in vitro.ConclusionOur vitro study showed that PRP significantly protected BMSCs from Dex-induced apoptosis, and further promoted BMSCs proliferation, migration, and osteogenic differentiation. This study provides a scientific basis for the prevention and treatment of GIONFH with PRP. Meanwhile, it also lays the foundation for the application of PRP in other musculoskeletal diseases.

Comparison effects of platelet-rich plasma on healing of infected and non-infected excision wounds by the modulation of the expression of inflammatory mediators: experimental research.

Microbial invasion in soft tissue is believed to cause infectious wounds and increase healthcare costs, anxiety, and distress. The current study was conducted to evaluate the effects of topical use of platelet-rich plasma (PRP) on infected wound-healing process in rats. Following the induction of a circular wound, the animals were divided into three groups, including (1) standard control: infected wounds treated with mupirocin (SDCL), (2) non-infected wounds treated with PRP (PRP), and (3) infected group in which the rats were infected with Staphylococcus epidermidis and Pseudomonas aeruginosa and treated with PRP (INF + PRP). To evaluate the effects of PRP on the wound-healing rate, total bacterial count, histopathological assessment, the serum concentrations of sialic acid, C-reactive protein, haptoglobin, and fibrinogen were assessed. Additionally, IL-1β, IL-6, TNF-α, IL-3, NF-κB, iNOS, PDGF, and EGF mRNA level expressions were assessed employing the qRT-PCR method. The results indicated that topical application of PRP could significantly decrease total bacterial count, the level of C-reactive protein, and pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) compared to the SDCL group. The administration of PRP also promoted re-epithelization rate by increasing the expression of EGF mRNA level. We could recommend the use of PRP for the treatment of infected wounds owing to its efficiency in decreasing colonization of tissue bacteria, tissue inflammation, and stimulating wound heal-up.

Application of Platelet-rich Plasma (PRP) with Different Scaffolds in Tissue Engineering

Background: Today, stem cells are the best candidates for cell therapy and tissue engineering. Adipose-derived Stem Cells (ADSCs) are an essential source of cells in replacement therapies of many diseases. Objectives: This study compared the proliferation of ADSCs in alginate and fibrin scaffolds. Methods: Adipose-derived stem cells were isolated from adipose tissue and cultured in alginate or fibrin scaffolds with a medium containing PRP 10% or FBS 10%. Then, the cell viability percentage was assessed by MTT assay and trypan blue staining. Also, the percentages of living, apoptotic, and necrotic cells were assessed by flow cytometry assay on the fourth and eighth days. Results: The cell viability rate was significantly higher in the fibrin scaffold group with PRP than in other groups on the fourth and eighth days (P &lt; 0.05). Moreover, the rate of necrotic cells was significantly lower in the fibrin scaffold group than in the other groups (P &lt; 0.05). Besides, the percentage of living cells was significantly higher in the fibrin scaffold group with PRP than in the other groups on the fourth and eighth days (P &lt; 0.05). Also, the percentage of early apoptotic cells was significantly lower in fibrin with PRP than in other groups on the fourth day. There was no significant difference in the rate of late apoptotic cells between the groups (P &gt; 0.05). Conclusions: These findings indicate the positive effect of PRP on the survival and proliferation of ADSCs compared with FBS. Therefore, PRP can be considered a suitable supplement to replace animal sera like FBS.

Comparisons of Ultrasound-Guided Platelet-Rich Plasma Intra-Articular Injection and Extracorporeal Shock Wave Therapy in Treating ARCO I-III Symptomatic Non-Traumatic Femoral Head Necrosis: A Randomized Controlled Clinical Trial.

Background and ObjectiveOsteonecrosis of the femoral head (ONFH) is a devastating disease, and there is some evidence that extracorporeal shock wave therapy (ESWT) and intra-articular platelet-rich plasma (PRP) injection might alleviate pain and improve joint function in individuals with ONFH. The objective of this study was to compare the effectiveness and safety of PRP and ESWT in symptomatic ONFH patients.MethodsA total of 60 patients aged 40–79 with unilateral ONFH at Association Research Circulation Osseous (ARCO) stages I, II, and III were randomly assigned to the PRP (N=30) or the ESWT group (N=30). Four treatment sessions were provided in both groups. Assessments were performed at baseline, and 1-, 3-, 6-, and 12-month. Primary outcomes were measured by the visual analogue scale (VAS), and pressure pain thresholds (PPTs). Secondary outcomes were assessed by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Harris Hip Score (HHS), and magnetic resonance imaging (MRI). The linear mixed-model analysis was used to evaluate the differences between groups and within groups and the “group by time” interaction effects.ResultsThere were significant differences between groups in terms of changes over time for VAS, PPTs, WOMAC, and HHS since 3-month and maintained up to 12-month (P<0.05, except for PPTs at 12-month). The simple main effects showed that the patients in PRP group had greater improvements in VAS (mean difference = −0.82, 95% CI [−1.39, −0.25], P=0.005), WOMAC (mean difference = −4.19, 95% CI [−7.00, −1.37], P=0.004), and HHS (mean difference = 5.28, 95% CI [1.94, 8.62], P=0.002). No related adverse events were reported.ConclusionThis study supported the effectiveness and safety of both the PRP injection and ESWT in treating ONFH patients. For symptomatic patients with ONFH, intra-articular PRP injection appeared superior to ESWT in pain relief and functional improvement.

Leukocyte-Rich versus Leukocyte-Poor Platelet-Rich Plasma for the Treatment of Knee Osteoarthritis: A Double-Blind Randomized Trial

Background: Platelet-rich plasma (PRP) is gaining large interest in clinical practice as a minimally invasive injective treatment for knee osteoarthritis (OA). Different preparation methods are available, and the presence of leukocytes, deemed detrimental in some preclinical studies, is one of the most debated aspects regarding PRP efficacy. 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. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: A total of 192 patients with symptomatic knee OA (Kellgren-Lawrence grade 1-3) were randomly allocated to 3 weekly injections of LR-PRP or LP-PRP. LP-PRP was obtained with a filter for leukodepletion. LR-PRP and LP-PRP were divided into aliquots of 5 mL, with a mean platelet concentration of 1146.8 × 109/L and 1074.9 × 109/L and a mean leukocyte concentration of 7991.4 × 106/L and 0.1 × 106/L, respectively. Patients were evaluated at baseline and thereafter at 2, 6, and 12 months for the primary outcome, the International Knee Documentation Committee (IKDC) subjective score; and for secondary outcomes, the Knee injury and Osteoarthritis Outcome Score (KOOS) subscales, EuroQol–visual analog scale (EQ-VAS), and Tegner score. Results: No differences between groups were observed in terms of absolute values or improvement of the clinical scores across all follow-up intervals. The mean IKDC subjective score at baseline and 12 months improved from 45.6 to 60.7 in the LR-PRP group as compared with 46.8 to 62.9 in the LP-PRP group (P = .626). No severe adverse events were described in either group, although 15 mild adverse events (knee pain or swelling) were reported: 12.2% for LR-PRP and 4.7% for LP-PRP (P = .101). No statistically significant difference was also found between LR-PRP and LP-PRP in terms of failures (7.8% vs 3.5%, P = .331). Conclusion: This double-blind randomized trial showed that 3 intra-articular LR-PRP or LP-PRP injections produced similar clinical improvement in the 12 months of follow-up in patients with symptomatic knee OA. Both treatment groups reported a low number of adverse events, without intergroup differences. The presence of leukocytes did not significantly affect the clinical results of PRP injections. Registration: NCT02923700 (ClinicalTrials.gov identifier).

The Efficacy of Platelet-Rich Plasma for Ligament Injuries: A Systematic Review of Basic Science Literature With Protocol Quality Assessment.

Background:Despite the existence of many clinical studies on platelet-rich plasma (PRP) interventions for ligamentous pathology, basic science consensus regarding the indications, mechanisms, and optimal composition of PRP for treating ligament injuries is lacking.Purpose:To (1) compare the efficacy of PRP in animal models of ligament injury with placebo and (2) describe the potential variability in PRP preparation using accepted classification systems.Study Design:Systematic review.Methods:The Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, PubMed, Embase, and Ovid MEDLINE were queried in April 2020 for in vivo and in vitro basic science studies regarding PRP use for ligament injury. Study design, results, PRP composition, and analyzed cellular and molecular markers were extracted, and outcomes relative to control models were documented. Bias was assessed using the SYRCLE risk-of-bias tool.Results:Included were 43 articles (31 in vivo and 12 in vitro studies) investigating the anterior cruciate ligament/cranial cruciate ligament (n = 32), medial collateral ligament (n = 6), suspensory ligament (n = 3), patellar ligament (n = 1), and Hock ligament (n = 1). Platelet concentration was reported in 34 studies (77.3%); leukocyte composition, in 12 (27.3%); and red blood cell counts, in 7 (15.9%). With PRP treatment, 5 of 12 in vitro studies demonstrated significant increases in cell viability, 6 of 12 in gene expression, 14 of 32 in vivo studies reported superior ligament repair via histological evaluation, and 13 in vivo studies reported superior mechanical properties. Variability in PRP preparation methods was observed across all articles, and only 1 study reported all necessary information to be classified by the 4 schemes we used to evaluate reporting. Among the in vivo studies, detection and performance bias were consistently high, whereas selection, attrition, reporting, and other biases were consistently low.Conclusion:Conflicting data on the cellular and molecular effects of PRP for ligament injuries were observed secondary to the finding that included studies were heterogeneous, limiting interpretation across studies and the ability to draw meaningful conclusions. Clinical trials and any causal relationship between PRP use in ligament injuries and its potential for regeneration and healing should be pursued with caution if based solely on basic science data.

Protective Effects of Platelet-rich plasma for in vitro Fertilization of Rats with Ovarian Failure Induced by Cyclophosphamide.

Premature ovarian insufficiency (POI) contributes significantly to female infertility. Cyclophosphamide (CYC has adverse effects on folliculogenesis. Platelet-rich plasma (PRP) is an autologous product rich in many growth factors. We evaluated the protective effect of PRP on in vitro fertilization in female rats with CYC-induced ovarian damage. Twenty-eight adult female Sprague-Dawley rats were randomly divided into four groups. Group 1 (control-sodium chloride 0.9%; 1 mL/kg, single-dose intraperitoneal [IP] injection); group 2 (CYC), 75 mg/kg, single-dose IP injection and sodium chloride 0.9% (1 mL/kg, single-dose IP injection); group 3 CYC plus PRP, CYC (75 mg/kg, single-dose and PRP (200 μl, single-dose) IP injection); and group 4 (PRP, 200 μl, single-dose IP injection). In the comparisons in terms of M1 and M2 oocytes, it was observed that the CYC group presented a significantly lower amount than the control, CYC/PRP, and PRP groups. (for M1, p = 0.000, p = 0.029, p = 0.025; for M2, p = 0.009, p = 0.004, p = 0.000, respectively). The number of fertilized oocytes and two-celled good quality embryos was found to be statistically significant between the CYC and control groups, CYC + PRP and PRP groups (p = 0.009, p = 0.001, p = 0.000 for oocytes, respectively. For embryos; p = 0.016, p = 0.002, p = 0.000). Platelet-rich plasma can protect the ovarian function against damage caused by CYC, and, in addition, it improves oocyte count and the development of embryos as a result of oocyte stimulation during the IVF procedure.

The use of platelet-rich plasma in studies with early knee osteoarthritis versus advanced stages of the disease: a systematic review and meta-analysis of 31 randomized clinical trials.

Reports have concluded that platelet-rich plasma (PRP) is an effective and safe biological approach to treating knee osteoarthritis (OA). However, the effectiveness of PRP in advanced stages of the disease is not entirely clear. The purpose of this study was 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. A comprehensive search in MEDLINE, EMBASE, Scopus, and Web of Science databases was conducted to identify randomized controlled trials (RCTs) comparing the effect of PRP injections versus other intra-articular treatments on pain and functionality. A meta-analysis was conducted using a random-effects model and the generic inverse variance method. We included 31 clinical trials that reported data of 2705 subjects. Meta-analysis revealed an overall significant improvement of both pain [MD, - 1.05 (95% CI - 1.41 to - 0.68); I2 = 86%; P ≤ 0.00001] and function [SMD, - 1.00 (95% CI - 1.33, to - 0.66); I2 = 94%; P ≤ 0.00001], favoring PRP. Subanalysis 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. Our results indicate that including patients with advanced knee OA does not seem to affect the outcomes of clinical trials in which the effectiveness of the PRP in knee OA is assessed.

Cytokine Profiling and Intra-Articular Injection of Autologous Platelet-Rich Plasma in Knee Osteoarthritis.

Osteoarthritis (OA) is a degenerative joint disease leading to joint pain and stiffness. Due to lack of effective treatments, physical and psychological disabilities caused by OA have a detrimental impact on the patient’s quality of life. Emerging evidence suggests that intra-articular injection of platelet-rich plasma (PRP) may provide favorable results since PRP comprises not only a high level of platelets but also a huge amount of cytokines, chemokines, and growth factors. However, the precise mechanism and standardization method remain uncertain. This study aimed to examine cytokine profiling in both PRP and platelet-poor plasma (PPP) of knee OA patients and to determine the effects of PRP on OA chondrocytes and knee OA patients. PRP contained a wide variety of cytokines, chemokines, growth factors, and autologous intra-articular PRP injection resulted in favorable outcomes in knee OA patients. Significant increases in levels of IL-1, IL-2, IL-7, IL-8, IL-9, IL-12, TNF-α, IL-17, PDGF-BB, bFGF, and MIP-1β were detected in PRP compared to PPP (p < 0.001). An in vitro study showed a marked increase in proliferation in OA chondrocytes cultured with PRP, compared to PPP and fetal bovine serum (p < 0.001). In a clinical study, knee OA patients treated with PRP showed improvement of physical function and pain, assessed by physical performance, Western Ontario and McMaster Universities Arthritis Index and visual analog scale. Our findings from both in vitro and clinical studies suggest that intra-articular PRP injection in knee OA patients may be a potential therapeutic strategy for alleviating knee pain and delaying the need for surgery.

Application Effect of Different Concentrations of Platelet-Rich Plasma Combined with Quadriceps Training on Cartilage Repair of Knee Osteoarthritis.

We investigated the application effect of different concentrations of platelet-rich plasma (PRP) combined with quadriceps training on cartilage repair of knee osteoarthritis. Data of 37 patients with knee osteoarthritis (KOA) treated in our hospital (November 2019–February 2021) were retrospectively analyzed and the patients were divided into low concentration group (LCG) (n = 12), medium concentration group (MCG) (n = 12), and high concentration group (HCG) (n = 13) according to the order of admission. All patients received quadriceps training. Three groups above received knee injection of PRP, and the platelet concentrations were 1000–1400 × 109/L, 1400–1800 × 109/L, and 1800–2100 × 109/L, respectively. Articular cartilage thickness of the medial and lateral femur, knee joint function scores, inflammatory factor levels, and matrix metalloproteinases (MMPs) levels were compared. After treatment, compared with the MCG and HCG, articular cartilage thickness of the medial and lateral femur of the diseased side in the LCG was obviously lower (P < 0.05). At 2 months after treatment (T3), compared with the HCG, articular cartilage thickness of the medial and lateral femur of the diseased side in the MCG was obviously higher (P < 0.05), without remarkable difference in articular cartilage thickness of the medial and lateral femur of the healthy side among three groups (P > 0.05). After treatment, compared with the LCG, knee joint function scores of the MCG and HCG were obviously better (P < 0.001). Compared with the HCG, the knee function score at T3 in the MCG was obviously better (P < 0.001). After treatment, compared with the LCG, inflammatory factor levels and levels of MMPs in the MCG and HCG were obviously lower (P < 0.05). Compared with the HCG, inflammatory factor levels and levels of MMPs at T3 in the MCG were obviously lower (P < 0.05). PRP combined with quadriceps training can accelerate cartilage repair of patients with KOA and reduce inflammatory factor levels and levels of MMPs, but the treatment effect of PRP depends on platelet concentration, with the best range of 1400–1800 × 109/L. Too high or too low platelet concentrations will affect recovery of knee function.

Platelet-rich plasma improves lipopolysaccharide-induced inflammatory response by upgrading autophagy

Objectives Platelet-rich plasma (PRP) plays an important role at all stages of wound healing, including the inflammatory stage. Macrophage autophagy has been found to influence the inflammatory response process. However, it is unclear whether PRP can affect inflammatory responses via macrophage autophagy. In the present study, we explored the effect of PRP on inflammatory responses and researched the underlying mechanism. Methods RAW 264.7 macrophages were treated with PRP and/or lipopolysaccharide (LPS). The effects of PRP on the expression of inflammatory factors were determined by ELISA and qRT-PCR. Macrophage autophagosomes were also assessed by TEM and immunofluorescence. Autophagy and NLRP3-related proteins were investigated using Western blot analysis. Results PRP reduced the levels of inflammatory factors and increased autophagy in RAW 264.7 cells. Pretreatment with 3-MA, which is an autophagy inhibitor, abolished the impact of PRP on the inflammatory response. Moreover, PRP induced macrophage autophagy by activating the NLRP3 inflammasome. Conclusions These results show that PRP can attenuate LPS-induced inflammatory responses by enhancing autophagy via NLRP3. These study also provides a new perspective on the molecular mechanism of PRP therapy in wound healing.

Effects of Platelet-Rich Plasma on Clinical Outcomes After Anterior Cruciate Ligament Reconstruction: A Systematic Review and Meta-analysis.

Background:Many studies have documented the use of platelet-rich plasma (PRP) alongside anterior cruciate ligament (ACL) reconstruction (ACLR) in the management of ACL injury, but evidence on the benefits of PRP in improving the clinical outcomes of ACLR is inconsistent.Purpose:To help in our understanding, we undertook a systematic review and meta-analysis of randomized controlled trials (RCTs) that evaluated the effects of PRP on patient-reported functional scores, the clinical assessments of knee function and structure, and complications.Study Design:Systematic review; Level of evidence, 1.Methods:We searched 9 online databases for RCTs published in English or Chinese that examined the effects of PRP on ACLR. The primary outcome measures were visual analog scale (VAS) for pain and International Knee Documentation Committee (IKDC) scores. The secondary outcomes included KT-1000 arthrometer, pivot-shift test, Lysholm and Tegner scores, tunnel widening, graft characterization, and complications. Subgroup analyses were performed according to time of assessments. Fixed- and random-effects models were selected for data analysis.Results:A total of 14 studies were included. When PRP was injected to graft tunnels, the pooled VAS scores of the 2 groups were similar (P = .31), and the subgroup analysis found that VAS and IKDC only improved at 3 months postoperatively (P = .0003 and P < .00001, respectively). When PRP was used at the bone–patellar tendon–bone harvest sites, VAS was decreased in the first 6 months postoperatively (P < .00001), whereas IKDC score was not remarkably different (P = .07). After PRP injection, Lysholm scores at 3 months postoperatively was different between the 2 groups (P < .00001), but the Tegner scores (P = .86), KT-1000 measurements (P = .12), the positive rate of pivot-shift test (P = .64), the enlargement of tunnels (femoral, P = .91; tibial, P = .80), and the characterization of grafts (P = .05) were not different. No difference in complications was found in either group.Conclusion:PRP applied alongside ACLR could reduce postoperative pain and improve knee function in the short and medium terms but is ineffective in the long term. PRP does not improve knee stability and the enlargement of tunnels and does not accelerate the healing of grafts. Further studies would be required.

Real-world evidence to assess the effectiveness of platelet-rich plasma in the treatment of knee degenerative pathology: a prospective observational study.

Objective:The present work aims to analyse the effectiveness of platelet-rich plasma (PRP) in degenerative knee pathology based on real-world data and to evaluate possible factors influencing the response to treatment.Methods:In total, 531 cases were analysed collecting data on gender, age, body mass index, pathology location, severity, number of cycles and route of administration. Clinical outcome was evaluated at 6 and 15 months after treatment, using the Knee injury and Osteoarthritis Outcome Score (KOOS) and obtaining percentages of Minimal Clinically Important Improvement (MCII). Blood and PRP samples were randomly tested as a quality control measure to ensure the correct properties. Comparative statistical tests and multivariate regression were performed for the analysis of the variables.Results:The PRP applied had a platelet concentration factor of 1.67, with no leukocytes or erythrocytes. The percentage of patients with MCII at 6 and 15 months after PRP application was 59.32% and 70.62%, respectively. Patients with MCII were younger (p = 0.0246) and with lower body mass index (p = 0.0450). The treatment had a better response in mild/moderate cases than in severe cases (p = 0.0002). Intraosseous PRP application in severe cases improved the effect of intraarticular PRP (p = 0.0358). The application of a second cycle of PRP only improved the response in patients without MCII at 6 months (p = 0.0029), especially in mild/moderate cases (p = 0.0357).Conclusion:The applications of PRP in degenerative knee pathologies is an effective treatment, but this effectiveness nonetheless depends on several variables. Real-world data can complement that from clinical trials to provide valuable information.