The effect of platelet-rich plasma injection on chronic Achilles tendinopathy and acute Achilles tendon rupture.

Several clinical trials exploring the effect of platelet-rich plasma (PRP) on Achilles tendon rupture (ATR) or Achilles tendinopathy (AT) have been published. However, current evidence is limited to small-sized trials. This study aims to evaluate whether PRP improves the outcomes of ATR or AT. PubMed, Web of Science, EMBASE, and Cochrane Library databases were searched to identify randomized controlled trials comparing PRP injection versus placebo for ATR or AT. Eleven studies with 574 patients were included. Quantitative synthesis suggested that compared with placebo, AT patients in PRP group had higher VISA-A score improvement at six-week follow-up (mean difference (MD) = 2.64; 95% CI) = 1.12 to 4.15). However, there was no significant difference between two groups for VISA-A score improvement at three-month follow-up (MD = 0.93; 95% CI = -2.75 to 4.62), or 6-month follow-up (MD = 5.46; 95% CI = -1.19 to 12.11). In ATR patients, quantitative synthesis suggested that no significant difference was seen between PRP and control group at 3-month, 6-month, and 1-year follow-up. In addition, no significant difference was detected between the two groups in improving tendon thickness and pain for AT patients, and no significant difference was seen in improving heel-rise work, maximum heel-rise height, dorsal and plantar flexion, rate of returning to sports activities, and complication for ATR patients. To conclude, no evidence indicates that PRP injection can improve the patient-reported/clinical/functional outcomes of AT or ATR. The increasing times of PRP injection could improve the outcomes, and further clinical randomized controlled trials are expected to be conducted to verify this hypothesis.

Autologous platelet-rich plasma treatment for moderate-severe Asherman syndrome: the first experience.

PURPOSE: Treatment of Asherman syndrome (AS) presents a significant clinical challenge. Based on our in vitro data showing that PRP could activate endometrial cell proliferation and migration, we hypothesized that intrauterine infusion of autologous platelet-rich plasma (PRP) may improve endometrial regeneration and fertility outcomes in patients with moderate-severe AS. MATERIALS AND METHODS: Subjects with moderate-severe AS were randomized to PRP or saline control administered following hysteroscopic adhesiolysis. Due to relative inability to randomize patients to the control group, after initial randomization of 10 subjects (6 in PRP and 4 in control groups), the remainder were prospectively enrolled in PRP group (n = 9), with 11 historic controls added to control group, for a total of 30 subjects (PRP n = 15; saline control n = 15). Right after hysteroscopy, 0.5-1 mL of PRP or saline was infused into the uterus via a Wallace catheter, followed by estrogen therapy. The primary outcomes were changes in endometrial thickness (EMT, checked in 3 weeks) and in menstrual flow; secondary outcomes were pregnancy and live birth rates. EMT and menstrual bleeding pattern were assessed before and after the intervention. Pregnancy was assessed over a 6-month period. RESULTS: There were no statistically significant differences in age, gravidity/parity, cause of AS, preoperative menses assessment, AS hysteroscopy score, and intrauterine balloon placement between the groups. There was no statistically significant difference (p = 0.79) in EMT pre-PRP infusion for control (5.7 mm, 4.0-6.0) and study arm (5.3 mm, 4.9-6.0). There was no statistically significant change (p = 0.78) in EMT after PRP infusion (1.4 mm, - 0.5-2.4) vs saline (1.0 mm, 0.0-2.5). Patients tolerated the procedure well, with no adverse effects. There was no difference in the predicted likelihood of pregnancy (p = 0.45) between the control (0.67, 0.41-0.85) and study arm (0.53, 0.29-0.76). CONCLUSIONS: PRP was well accepted and tolerated in AS patients. However, we did not observe any significant EMT increase or improved pregnancy rates after adding PRP infusion, compared to standard treatment only. The use of intrauterine PRP infusion may be a feasible option, and its potential use must be tested on a larger sample size of AS patients.

Effects of Platelet-Rich Plasma on Cellular Populations of the Central Nervous System: The Influence of Donor Age.

Platelet-rich plasma (PRP) is a biologic therapy that promotes healing responses across multiple medical fields, including the central nervous system (CNS). The efficacy of this therapy depends on several factors such as the donor's health status and age. This work aims to prove the effect of PRP on cellular models of the CNS, considering the differences between PRP from young and elderly donors. Two different PRP pools were prepared from donors 65‒85 and 20‒25 years old. The cellular and molecular composition of both PRPs were analyzed. Subsequently, the cellular response was evaluated in CNS in vitro models, studying proliferation, neurogenesis, synaptogenesis, and inflammation. While no differences in the cellular composition of PRPs were found, the molecular composition of the Young PRP showed lower levels of inflammatory molecules such as CCL-11, as well as the presence of other factors not found in Aged PRP (GDF-11). Although both PRPs had effects in terms of reducing neural progenitor cell apoptosis, stabilizing neuronal synapses, and decreasing inflammation in the microglia, the effect of the Young PRP was more pronounced. In conclusion, the molecular composition of the PRP, conditioned by the age of the donors, affects the magnitude of the biological response.

An Optimized Extract, Named Self-Growth Colony, from Platelet-Rich Plasma Shows Robust Skin Rejuvenation and Anti-Ageing Properties: A Novel Technology in Development of Cosmetics.

INTRODUCTION: Inspired by application of platelet-rich plasma (PRP) in skin treatment during injuries, an extracting method was developed here to recover high amounts of cytokines and growth factors from PRP; this prepared extract was named as self-growth colony (SGC). METHODS: In optimization of SGC preparation, various parameters were tested, for example, centrifugation force, freeze-thaw, sonication, and inclusion of calcium chelator. The amounts of cytokines and growth factors, including platelet factor 4, ß-thromboglobulin, epidermal growth factor, vascular endothelial growth factor, platelet-derived growth factor, were measured by ELISA assay. RESULTS: By comparing to PRP, the prepared SGC contained a significant higher amount of measured growth factors. In addition, the degradation of growth factors within SGC during the storage was calibrated, which showed better stability as compared to that of PRP preparation. Having possible application in skin care, the optimized SGC was chemically standardized by using the enrichment of growth factors. Application of SGC in cultured keratinocytes stimulated the wound healing of injured cultures. In line to this notion, SGC was applied onto human skin, and thereafter the robust improvement of skin properties was revealed. CONCLUSIONS: The potential application of SGC in treating skin rejuvenation and ageing, as well as its elaborated application for medical purpose, that is, wound healing, was illustrated.

Platelet-rich plasma for the treatment of burn wounds: A meta-analysis of randomized controlled trials.

BACKGROUND: To evaluate the efficacy and safety of platelet-rich plasma in the treatment of burn wounds through a meta-analysis of randomized controlled trials. METHODS: We conducted a comprehensive study from electronic medical journal databases. The primary outcome was healing rate, and the secondary outcomes were healing time, adverse events, pain score and scar score. The data was analyzed using Review Manager 5.3 and Stata 12. The odds ratio (OR) among different groups was calculated by using 95 % confidence interval (CI). RESULTS: We included 8 randomized controlled trials with a total of 539 patients. The results showed that platelet-rich plasma could improve the healing rate of burn wound (OR 4.43, 95 % CI 2.13-9.22). The wound healing time of the platelet-rich plasma treatment group was significantly shorter than that of the conventional treatment group (OR -4.23, 95 % CI -5.48 to -2.98), both the superficial burn (OR -3.80, 95 % CI -4.53 to -3.07) and the deep burn group (OR -4.65, 95 % CI -6.90 to -2.40) had shorter healing time. Otherwise, the incidences of adverse events (OR 0.30, 95 % CI 0.11-0.78), pain score (OR -0.80, 95 % CI -1.40 to -0.21) and scar score (OR -0.38, 95 % CI -0.69 to -0.07) were all better in the platelet rich plasma treatment group. CONCLUSION: Topical platelet-rich plasma treatment on burn wounds can improve wound healing and reduce the incidence of adverse events. Further research is needed to standardize the preparation and use of platelet-rich plasma and to evaluate the long-term clinical outcome of platelet-rich plasma in the treatment of burn wounds.

The Role of Platelet Homeostasis in a Novel Topical PRP Formulation.

BACKGROUND: Topical platelet-rich plasma (PRP) must demonstrate stability to insure biologic activity in aesthetic medicine. OBJECTIVE: The objective of this research was to evaluate the role of platelet homeostasis in a novel PRP topical cosmetic formulation to provide facial appearance improvement. METHODS: The stability of the topical PRP formulation was evaluated in vitro followed by clinical in vivo testing. The in vitro evaluation examined platelet stability and morphology over a 90-day period within the preservative cosmetic base utilizing ELISA and light microscopy (LM)/scanning electron microscopy (SEM). The in vivo clinical study enrolled 20 subjects in a 120-day double blind split face study to evaluate the effect of 5–7x concentrated PRP compared to 2–3x concentrated PRP on facial photoaging. Cosmetic effect was evaluated by the subject and the dermatologist investigator on a 5-point ordinal scale at baseline, week 8, and week 16. RESULTS: 90-day stability for the topical PRP formulation was verified via ELISA and LM/SEM. ELISA showed the PRP was more inactive than control conditions via analyte concentration curves (PDGF-AB, EGF, and P-Selectin). LM/SEM demonstrated the PRP had less aggregation/activation over time within the cosmetic base and that refrigeration is superior to room-temperature storage thus delaying full platelet degranulation. The in vivo clinical study demonstrated parity between 20ml and 60ml PRP in terms of clinical efficacy. CONCLUSION: Platelets remain viable for up to 90 days in a refrigerated cosmetic vehicle with demonstrated topical clinical PRP facial benefits. PRP kits of 20ml and 60ml volumes for topical PRP are equally efficacious. J Drugs Dermatol. 2020;19(12): doi:10.36849/JDD.2020.5495.

Platelet-Rich Plasma: New Performance Understandings and Therapeutic Considerations in 2020.

Emerging autologous cellular therapies that utilize platelet-rich plasma (PRP) applications have the potential to play adjunctive roles in a variety of regenerative medicine treatment plans. There is a global unmet need for tissue repair strategies to treat musculoskeletal (MSK) and spinal disorders, osteoarthritis (OA), and patients with chronic complex and recalcitrant wounds. PRP therapy is based on the fact that platelet growth factors (PGFs) support the three phases of wound healing and repair cascade (inflammation, proliferation, remodeling). Many different PRP formulations have been evaluated, originating from human, in vitro, and animal studies. However, recommendations from in vitro and animal research often lead to different clinical outcomes because it is difficult to translate non-clinical study outcomes and methodology recommendations to human clinical treatment protocols. In recent years, progress has been made in understanding PRP technology and the concepts for bioformulation, and new research directives and new indications have been suggested. In this review, we will discuss recent developments regarding PRP preparation and composition regarding platelet dosing, leukocyte activities concerning innate and adaptive immunomodulation, serotonin (5-HT) effects, and pain killing. Furthermore, we discuss PRP mechanisms related to inflammation and angiogenesis in tissue repair and regenerative processes. Lastly, we will review the effect of certain drugs on PRP activity, and the combination of PRP and rehabilitation protocols.

Avaliação morfológica do concentrado autólogo de plaquetas em cães sob refrigeração e criopreservação em DMSO 6% / [Morphological evaluation of the autologous platelet concentrate in dogs under refrigeration and criopreservation in 6% DMSO]

The morphological characteristics of the autologous platelet concentrate (APC) of 31 dogs were evaluated after cooling and freezing in 6% DMSO. Blood from the jugular vein of each patient was collected and centrifuged at 191g for six minutes to obtain APC. In the fresh sample, the platelet count, MPV, PDW and cell morphology were evaluated. Four samples of each animal were sent for storage, one refrigerated at 4°C for seven days, another for 30 days and two more stored in a freezer at -80°C in the same time interval, using 6% DMSO as cryoprotectant. The conserved samples were submitted to the same laboratory analysis as the fresh sample. There was a difference between fresh and preserved samples for platelet count, cell concentration, MPV and PDW (P<0.05), except in the 30-day refrigerated group, which showed severe morphological changes. In the frozen group for seven days, no difference was observed in the percentage of activation (P>0.05). The results obtained lead to the conclusion that cryopreservation with 6% DMSO at -80°C for seven days is a favorable option for the maintenance of platelet concentrations and the morphological characteristics of APC in dogs.(AU)

Leukocyte-rich platelet-rich plasma application in post-traumatic osteoarthritis with popliteal cyst: a case report.

Aim: To describe the successful treatment of a Baker's cyst in the setting of post-traumatic osteoarthritis using ultrasound-guided injection of platelet-rich plasma. Setting: Outpatient sports clinic. Patient: 29-year old male basketball player. Case description: The patient presented with 2-months history of right knee pain, 17 months after undergoing right knee anterior cruciate ligament reconstruction surgery. Exam revealed medial joint line and medial collateral ligament tenderness with posterior knee swelling. After aspiration, a corticosteroid injection was administered with temporary symptom relief. Diagnostic ultrasound examination confirmed the Baker's cyst. The patient then underwent two serial leukocyte-rich platelet-rich plasma injections into his right knee. Results: The patient reported complete resolution of pain and cyst size. Conclusion: Leukocyte-rich platelet-rich plasma may be considered as a treatment option for patients with Baker's cysts in the setting of post-traumatic osteoarthritis.

Comparative efficacy of treatments for patients with knee osteoarthritis: a network meta-analysis.

BACKGROUND: Knee osteoarthritis is a common cause of musculoskeletal pain and a leading cause of disability and healthcare economic burden. The optimum treatment for knee osteoarthritis is still inconclusive. A network meta-analysis is required to assess the efficacy and safety of treatments and provide more scientific medical evidence. METHODS: Relevant studies were searched through PubMed, Embase, and Cochrane Library electronic databases from the inception to October 2018. Continuous outcomes such as pain, stiffness, physical function and total scores were expressed as the mean differences with 95% credible interval. Surface under the cumulative ranking curve illustrated the rank probability of each therapy under different outcomes. RESULTS: Nineteen studies were included in this study, with a total of 2395 patients. For knee pain, platelet-rich plasma (0.691) was ranked at the first place, followed by hyaluronic acid combined with platelet-rich plasma (0.670) and hyaluronic acid (0.402). In terms of stiffness, hyaluronic acid combined with platelet-rich plasma (0.743) enjoyed the highest value, platelet-rich plasma (0.603) was the next and hyaluronic acid (0.386) was the third. As for physical function, the rank was hyaluronic acid combined with platelet-rich plasma (0.772), platelet-rich plasma (0.608) and hyaluronic acid (0.343). For total scores, the order given by surface under the cumulative ranking was hyaluronic acid combined with platelet-rich plasma (0.765), platelet-rich plasma (0.624) and hyaluronic acid (0.37). CONCLUSIONS: Hyaluronic acid combined with platelet-rich plasma showed the best efficacy in improving stiffness, physical function, and total scores, while platelet-rich plasma appeared the best in terms of pain reduction.

Cord Blood Platelet Rich Plasma Derivatives for Clinical Applications in Non-transfusion Medicine.

Cord blood platelet rich plasma (CB-PRP) derivatives have been investigated as potential therapeutic agents for the treatment of diverse conditions including ocular surface disease and skin ulcers. We have developed processes for the formulation of several CB-PRP preparations, which have different composition and attributes. Here we describe the molecular characteristics of these preparations and we make recommendations as to their most appropriate clinical application based on functional and immunomodulatory profiles. We show that incubation of adult peripheral blood mononuclear cells (PBMCs) with all three preparations dramatically reduced the production of INFγ and the expression of NKG2D and CD107a in NK, NKT, and T cells thus diminishing their activation, we propose that the likely mechanism is the high levels of soluble NKG2D ligands present in plasma. Of the three preparations we investigated, CB platelet lysate (PL) and platelet releaseate (PR) have higher concentrations of trophic and pro-angiogenic factors, CB platelet poor plasma (PPP) has the lowest concentration of all analytes measured. Based on these finding we propose that CB-PR is the most suitable raw material for skin wound patches, while CB-PL and PPP can be used to prepare eye drops for severe ocular surface pathologies and inflammatory conditions such as corneal ulcers or severe dry eye disease, respectively.

Platelet Concentrates in Musculoskeletal Medicine.

Platelet concentrates (PCs), mostly represented by platelet-rich plasma (PRP) and platelet-rich fibrin (PRF) are autologous biological blood-derived products that may combine plasma/platelet-derived bioactive components, together with fibrin-forming protein able to create a natural three-dimensional scaffold. These types of products are safely used in clinical applications due to the autologous-derived source and the minimally invasive application procedure. In this narrative review, we focus on three main topics concerning the use of platelet concentrate for treating musculoskeletal conditions: (a) the different procedures to prepare PCs, (b) the composition of PCs that is related to the type of methodological procedure adopted and (c) the clinical application in musculoskeletal medicine, efficacy and main limits of the different studies.

Application of high-sensitivity flow cytometry in combination with low-voltage scanning electron microscopy for characterization of nanosized objects during platelet concentrate storage.

Platelet concentrates are used in clinic for therapy and prophylaxis of conditions associated with platelet deficiency or malfunction. The characteristics of platelet concentrates gradually change during pretransfusion storage, affecting their clinical effectiveness and the risk of adverse transfusion reactions. The presence of platelet-derived membrane vesicles is an important characteristic of platelet concentrates. Due to their functionality, changes in the number and molecular compositions of platelet-derived vesicles have major effects on the clinical properties of platelet preparations. The existence of different subpopulations of membrane vesicles requires analytical methods capable of providing information at the individual vesicle level. Such methods include flow cytometry and electron microscopy. However, conventional flow cytometry has certain limitations, since the diameters of many platelet-derived membrane vesicles are smaller than its detection limit. The use of classical scanning electron microscopy is also limited due to the requirement for coating with a layer of conductive material, which impedes the detection of small extracellular vesicles. Here, a combination of high-sensitivity flow cytometry and low-voltage scanning electron microscopy was used to increase sensitivity and resolution in the detection of nanosized objects present in platelet concentrates during storage. Apheresis platelet concentrates from eight healthy adult donors were investigated on days 2 and 7 of storage. Fractions of nanosized objects were obtained by differential centrifugation. Fluorophore-conjugated antibodies were used to detect marker-positive vesicles derived from platelets (CD41), red blood cells (CD235a), leukocytes (CD45), and endothelial cells (VEGFR2). Near-spherical objects with diameters ranging from 25 to 700 nm were observed by low-voltage scanning electron microscopy in platelet concentrates and its fractions. On day 7 of storage, objects with diameters of less than 100 nm were attached to and clustered near the terminal ends of pseudopod-like projections. High-sensitivity flow cytometry showed that during storage numbers of CD41(pos) vesicles elevated more than fivefold and numbers of marker-negative nanosized objects, which did not carry any of the investigated cell type-specific markers elevated more than twofold. Major changes in both CD41(pos) vesicles and marker-negative nanosized objects abundances were observed for objects with diameters around 100 nm bead equivalents. Overall, these results emphasized the importance of application of high-sensitivity methods for monitoring the characteristics of cell-derived nanosized objects during platelet concentrate storage.

Bioactive Fibrin Scaffolds for Use in Musculoskeletal Regenerative Medicine

Abstract Autologous fibrin matrices derived from the Leukocyte and Platelet Rich Plasma (L-PRP) and Leukocyte and Platelet Rich Fibrin (L-PRF) techniques present great potential to act as a bioactive scaffold in regenerative medicine, contributing to the maintenance of cell viability, proliferation stimulus and differentiation. In contrast, there are few studies that characterize the bioactive potential of these fibrin scaffolds by considering the process of production. The objective of this work was to characterize the intrinsic potential of maintaining cell viability of different fibrin scaffolds containing platelets and leukocytes. In order to achieve that, blood samples from a volunteer were collected and processed to obtain fibrin clots using the suggested techniques. To characterize the potential for in vitro viability, mesenchymal stem cells from human infrapatellar fat were used. The scaffolds were cellularized (1x105 cells/scaffolds) and maintained for 5 and 10 days under culture conditions with Dulbecco's Modified Eagle Medium, without addition of fetal bovine serum, and subsequently subjected to analyses by Fourrier transform infra-red spectroscopy, circular dichroism and fluorescence microscopy. The results demonstrated distinct intrinsic potential viability between the scaffolds, and L-PRP was responsible for promoting higher levels of viability in both periods of analysis. No viable cells were identified in the fibrin matrix used as controls. These results allow us to conclude that both fibrin substrates have presented intrinsic potential for maintaining cell viability, with superior potential exhibited by L-PRP scaffold, and represent promising alternatives for use as bioactive supports in musculoskeletal regenerative medicine.

Pathogen reduction with riboflavin and ultraviolet light induces a quasi-apoptotic state in blood leukocytes.

BACKGROUND: Alloimmunization to platelet-rich plasma (PRP) transfusions can cause adverse reactions such as platelet refractoriness or transplant rejection. Pathogen reduction treatment with ultraviolet light and riboflavin (UV + R) of allogeneic PRP was shown to reduce allogeneic antibody responses and confer partial antigen-specific immune tolerance to subsequent transfusions in mice. Studies have shown that UV + R was effective at both rapidly killing donor white blood cells (WBCs) and reducing their ability to stimulate an allogeneic response in vitro. However, the manner in which UV + R induces WBC death and its associated role in the immune response to treated PRP is unknown. METHODS AND MATERIALS: This study evaluates whether UV + R causes WBC apoptosis by examining phosphatidylserine exposure on the plasma membrane, membrane asymmetry, caspase activity, and chromatin condensation by flow cytometry. The immunogenicity of WBCs killed with UV + R versus apoptotic or necrotic pathways was also examined in vivo. RESULTS: WBCs after UV + R exhibited early apoptotic-like characteristics including phosphatidylserine exposure on the outer leaflet of the plasma membrane and loss of membrane asymmetry, but unlike canonical apoptotic cells, caspase activity and chromatin condensation were not apparent. However, in vivo studies demonstrated, unlike untreated or necrotic WBCs, both apoptotic WBCs and UV + R-treated WBCs failed to prime alloantibody responses to subsequent untreated transfusions. CONCLUSION: Overall, the mechanism of WBC death following UV + R treatment shares some membrane characteristics of early apoptosis but is distinct from classic apoptosis. Despite these differences, UV + R-treated and apoptotic WBCs both offer some protection from alloimmunization.

The Current Status of Cell-Based Therapies for Primary Knee Osteoarthritis.

There is a growing interest in cell therapy for knee osteoarthritis. This study systematically reviews the current status of cell-based therapies. The authors review treatment modalities, clinical outcomes, and the economics of cell therapy. Inclusion criteria were articles containing cellular therapy, platelet-rich plasma, and knee osteoarthritis in the title. Letters, editorial material, abstracts not published, and manuscripts with incomplete data were excluded. Forty-two articles met these inclusion criteria and were critically reviewed. Cell-based therapy holds promise as a means of restoring deficient local cartilage cell populations. There is no evidence-based information for the use of cell-based therapies in knee osteoarthritis.

Haemostasis and analgesia with autologous platelet-rich plasma in tonsillectomy.

OBJECTIVE: A single-centre, single-blinded prospective experimental study was conducted to determine the effectiveness of autologous platelet-rich plasma applied to the tonsillar bed post-operatively in reducing post-operative pain and haemorrhage. METHODS: Platelet-rich plasma, prepared prior to surgery, was applied with calcium gluconate to one randomly chosen tonsillar fossa. Pain and haemorrhage were analysed, using a visual analogue scale and a pre-defined grading scale respectively, four times on the day of surgery at 2-hourly intervals, and thrice on the following day. RESULTS: The pain score and haemorrhage grade on the test side were lower than on the control side. These findings were statistically significant. CONCLUSION: This pilot study, conducted in India, revealed valid positive results for a promising new technology. The manual preparation of platelet-rich plasma could be automated in the future to allow a larger sample size.

Anti-Inflammatory Effects of Novel Standardized Platelet Rich Plasma Releasates on Knee Osteoarthritic Chondrocytes and Cartilage in vitro.

BACKGROUND: Platelet Rich Plasma (PRP) has recently emerged as a potential treatment for osteoarthritis (OA), but composition heterogeneity hampers comparison among studies, with the result that definite conclusions on its efficacy have not been reached. OBJECTIVES: 1) To develop a novel methodology to prepare a series of standardized PRP releasates (PRP-Rs) with known absolute platelet concentrations, and 2) To evaluate the influence of this standardization parameter on the anti-inflammatory properties of these PRP-Rs in an in vitro and an ex vivo model of OA. METHODS: A series of PRPs was prepared using the absolute platelet concentration as the standardization parameter. Doses of platelets ranged from 0% (platelet poor plasma, PPP) to 1.5·105 platelets/µl. PRPs were then activated with CaCl2 to obtain releasates (PRP-R). Chondrocytes were stimulated with 10% of each PRP-R in serum-free culture medium for 72 h to assess proliferation and viability. Cells were co-stimulated with interleukin (IL)-1ß (5 ng/ml) and 10% of each PRP-R for 48 h to determine the effects on gene expression, secretion and intra-cellular content of common markers associated with inflammation, catabolism and oxidative stress in OA. OA cartilage explants were co-stimulated with IL-1ß (5 ng/ml) and 10% of either PRP-R with 0.75·105 platelets/µl or PRP-R with 1.5·105 platelets/µl for 21 days to assess matrix inflammatory degradation. RESULTS: Chondrocyte viability was not affected, and proliferation was dose-dependently increased. The gene expression of all pro-inflammatory mediators was significantly and dose-independently reduced, except for that of IL-1ß and IL-8. Immunoblotting corroborated this effect for inducible NO synthase (NOS2). Secreted matrix metalloproteinase-13 (MMP-13) was reduced to almost basal levels by the PRP-R from PPP. Increasing platelet dosage led to progressive loss to this anti-catabolic ability. Safranin O and toluidine blue stains supported the beneficial effect of low platelet dosage on cartilage matrix preservation. CONCLUSION: We have developed a methodology to prepare PRP releasates using the absolute platelet concentration as the standardization parameter. Using this approach, the composition of the resulting PRP derived product is independent of the donor initial basal platelet count, thereby allowing the evaluation of its effects objectively and reproducibly. In our OA models, PRP-Rs showed antiinflammatory, anti-oxidant and anti-catabolic properties. Platelet enrichment could favor chondrocyte proliferation but is not necessary for the above effects and could even be counter-productive.

Injeção de agregados plaquetários no rejuvenescimento facial: uma revisão sistemática / Injection of platelet aggregates in facial rejuvenation: a systematic review

Introdução: Essa revisão sistemática foi conduzida para avaliar se a associação da aplicação da injeção de agregados plaquetários quando comparada a outras terapias faciais favorece no rejuvenescimento facial em pacientes adultos. Métodos: A pesquisa buscou ensaios clínicos randomizados que compararam uso de técnicas de rejuvenescimento facial isoladas com as mesmas técnicas aliadas à injeção de agregados plaquetários. A busca foi realizada em bases de dados indexadas e literatura cinzenta. A ferramenta de risco de viés da "Cochrane Collaboration" foi aplicada para a avaliação da qualidade dos estudos. Resultados: Foram identificados 7137 artigos. Apenas quatro estudos permaneceram na síntese qualitativa, e os demais foram considerados com risco indefinido de viés nos domínios chaves. Conclusão: Existem poucos estudos na literatura que comparam o uso de agregados plaquetários em rejuvenescimento facial e os que estão disponíveis têm risco de viés "indefinido" ou "alto". Há necessidade de realizar mais estudos clínicos bem delineados que comparem o uso de injeção de agregados plaquetários associados ou não às técnicas de rejuvenescimento facial.

Introduction: This systematic review was conducted to assess whether the use of a platelet aggregate injection with or without associated facial rejuvenation techniques favors facial rejuvenation in adult patients. Methods: Randomized clinical trials that compared the use of techniques for facial rejuvenation alone with the same techniques coupled with the injection of platelet aggregates were searched. The search was performed in indexed databases and in the gray literature. The Cochrane Collaboration bias risk tool was applied to assess the quality of the studies. Results: In total, 7137 articles were identified. Only four studies remained in the qualitative synthesis, and the others were considered as having undefined bias risk in the key domains. Conclusion: There are few studies in the literature that compare the use of platelet aggregates in facial rejuvenation and those that are available have a risk of "undefined" or "high" bias. There is a need for more well-designed clinical studies comparing the use of platelet aggregate injection with or without associated facial rejuvenation techniques.

Development of Autologous Platelet-Rich Plasma Mixed-Microfat as an Advanced Therapy Medicinal Product for Intra-Articular Injection of Radio-Carpal Osteoarthritis: From Validation Data to Preliminary Clinical Results.

Wrist osteoarthritis (OA) is one of the most common conditions encountered by hand surgeons with limited efficacy of non-surgical treatments. The purpose of this study is to describe the Platelet-Rich Plasma (PRP) mixed-microfat biological characteristics of an experimental Advanced Therapy Medicinal Product (ATMP) needed for clinical trial authorization and describe the clinical results obtained from our first three patients 12 months after treatment (NCT03164122). Biological characterization of microfat, PRP and mixture were analysed in vitro according to validated methods. Patients with stage four OA according to the Kellgren Lawrence classification, with failure to conservative treatment and a persistent daily painful condition >40 mm according to the visual analog scale (VAS) were treated. Microfat-PRP ATMP is a product with high platelet purity, conserved viability of stromal vascular fraction cells, chondrogenic differentiation capacity in vitro and high secretion of IL-1Ra anti-inflammatory cytokine. For patients, the only side effect was pain at the adipose tissue harvesting sites. Potential efficacy was observed with a pain decrease of over 50% (per VAS score) and the achievement of minimal clinically important differences for DASH and PRWE functional scores at one year in all three patients. Microfat-PRP ATMP presented a good safety profile after an injection in wrist OA. Efficacy trials are necessary to assess whether this innovative strategy could delay the necessity to perform non-conservative surgery.