scholarly journals Activation of platelet-rich plasma by pulse electric fields: Voltage, pulse width and calcium concentration can be used to control and tune the release of growth factors, serotonin and hemoglobin

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0249209
Author(s):  
Bogdan Neculaes ◽  
Andrew L. Frelinger ◽  
Anja J. Gerrits ◽  
Thomas Gremmel ◽  
Emma E. Forde ◽  
...  
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Electric Fields ◽  
Voltage Pulse ◽  
Pulse Width ◽  
Calcium Concentration ◽  
Platelet Rich Plasma ◽  
Clot Formation ◽  
Bovine Thrombin ◽  
Pulse Electric

Activated platelet-rich plasma (PRP) has been used in the clinical settings of wound healing and regenerative medicine, with activation typically induced by the addition of bovine thrombin. To eliminate issues with availability, cost and potential side effects associated with bovine thrombin, ex vivo PRP activation using pulse electric fields (PEF) has been proposed and demonstrated. The present study characterizes the effect of PEF voltage and pulse width, in combination with a range of calcium concentrations, on clot formation, growth factor release, and serotonin (5-HT) release from dense granules. The main findings are: 1) increasing calcium concentrations with most PEF conditions leads to increased levels of PDGF and 5-HT release; 2) whether EGF levels increase or decrease with increasing calcium concentration depends on the specific PEF parameters; 3) the pattern of PDGF and EGF levels in supernatants suggest that these molecules are localized differently within platelets; 4) significant levels of PDGF, EGF, and 5-HT can be released without inducing clot formation or hemoglobin release. In conclusion, voltage, pulse width and calcium concentration can be used to control and tune the release of growth factors, serotonin and hemoglobin from PEF-activated PRP. Because growth factor requirements vary for different types of wounds and for wounds at different stages of healing, the unique balance of factors in supernatants of PEF-activated PRP may provide more clinically advantageous than the current standard of bovine thrombin-activated PRP.

Platelet-Rich Plasma Powder: A New Preparation Method for the Standardization of Growth Factor Concentrations

2016 ◽  
Vol 45 (4) ◽  
pp. 954-960 ◽  
Author(s):  
Matthias Kieb ◽  
Frank Sander ◽  
Cornelia Prinz ◽  
Stefanie Adam ◽  
Anett Mau-Möller ◽  
...  
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Clinical Application ◽  
Whole Blood ◽  
Sports Medicine ◽  
Transforming Growth Factor ◽  
Platelet Rich Plasma ◽  
Transforming Growth Factor Β1 ◽  
Enzyme Linked Immunosorbent Assay ◽  
Tgf Β1

Background: Platelet-rich plasma (PRP) is widely used in sports medicine. Available PRP preparations differ in white blood cell, platelet, and growth factor concentrations, making standardized research and clinical application challenging. Purpose: To characterize a newly standardized procedure for pooled PRP that provides defined growth factor concentrations. Study Design: Controlled laboratory study. Methods: A standardized growth factor preparation (lyophilized PRP powder) was prepared using 12 pooled platelet concentrates (PCs) derived from different donors via apheresis. Blood samples and commercially available PRP (SmartPrep-2) served as controls (n = 5). Baseline blood counts were analyzed. Additionally, single PCs (n = 5) were produced by standard platelet apheresis. The concentrations of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), platelet-derived growth factor AB (PDGF-AB), transforming growth factor β1 (TGF-β1), insulin-like growth factor 1 (IGF-1), interleukin (IL)–1α, IL-1β, and IL-1 receptor agonist (IL-1RA) were analyzed by enzyme-linked immunosorbent assay, and statistical analyses were performed using descriptive statistics, mean differences, 95% CIs, and P values (analysis of variance). Results: All growth factor preparation methods showed elevated concentrations of the growth factors VEGF, bFGF, PDGF-AB, and TGF-β1 compared with those of whole blood. Large interindividual differences were found in VEGF and bFGF concentrations. Respective values (mean ± SD in pg/mL) for whole blood, SmartPrep-2, PC, and PRP powder were as follows: VEGF (574 ± 147, 528 ± 233, 1087 ± 535, and 1722), bFGF (198 ± 164, 410 ± 259, 151 ± 99, and 542), PDGF-AB (2394 ± 451, 17,846 ± 3087, 18,461 ± 4455, and 23,023), and TGF-β1 (14,356 ± 4527, 77,533 ± 13,918, 68,582 ± 7388, and 87,495). IGF-1 was found in SmartPrep-2 (1539 ± 348 pg/mL). For PC (2266 ± 485 pg/mL), IGF-1 was measured at the same levels of whole blood (2317 ± 711 pg/mL) but was not detectable in PRP powder. IL-1α was detectable in whole blood (111 ± 35 pg/mL) and SmartPrep-2 (119 ± 44 pg/mL). Conclusion: Problems with PRP such as absent standardization, lack of consistency among studies, and black box dosage could be solved by using characterized PRP powder made by pooling and lyophilizing multiple PCs. The new PRP powder opens up new possibilities for PRP research as well as for the treatment of patients. Clinical Relevance: The preparation of pooled PRP by means of lyophilization may allow physicians to apply a defined amount of growth factors by using a defined amount of PRP powder. Moreover, PRP powder as a dry substance with no need for centrifugation could become ubiquitously available, thus saving time and staff resources in clinical practice. However, before transferring the results of this basic science study to clinical application, regulatory issues have to be cleared.

Concentrations of Blood Components in Commercial Platelet-Rich Plasma Separation Systems: A Review of the Literature

2018 ◽  
Vol 47 (2) ◽  
pp. 479-487 ◽  
Author(s):  
Bart W. Oudelaar ◽  
Joost C. Peerbooms ◽  
Rianne Huis in ‘t Veld ◽  
Anne J.H. Vochteloo
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Platelet Rich Plasma ◽  
Therapeutic Option ◽  
Transforming Growth Factor Β1 ◽  
Future Research ◽  
Cochrane Central Register ◽  
Blood Components ◽  
Separation Systems

Background: Platelet-rich plasma (PRP) has proven to be a very safe therapeutic option in the treatment of tendon, muscle, bone, and cartilage injuries. Currently, several commercial separation systems are available for the preparation of PRP. The concentrations of blood components in PRP among these separation systems vary substantially. Purpose: To systematically review and evaluate the differences between the concentrations of blood components in PRP produced by various PRP separation systems. Study Design: Systematic review. Methods: MEDLINE/PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), and EMBASE were searched for studies that compared the concentrations of blood components and growth factors in PRP between various separation systems and studies that reported on the concentrations of blood components and growth factors of single separation systems. The primary outcomes were platelet count, leukocyte count, and concentration of growth factors (eg, platelet-derived growth factor–AB [PDGF-AB], transforming growth factor–β1 [TGF-β1], and vascular endothelial growth factor [VEGF]). Furthermore, the preparation protocols and prices of the systems were compared. Results: There were 1079 studies found, of which 19 studies were selected for inclusion in this review. The concentrations of platelets and leukocytes in PRP differed largely between, and to a lesser extent within, the studied PRP separation systems. Additionally, large differences both between and within the studied PRP separation systems were found for all the growth factors. Furthermore, preparation protocols and prices varied widely between systems. Conclusion: There is a large heterogeneity between PRP separation systems regarding concentrations of platelets, leukocytes, and growth factors in PRP. The choice for the most appropriate type of PRP should be based on the specific clinical field of application. As the ideal concentrations of blood components and growth factors for the specific fields of application are yet to be determined for most of the fields, future research should focus on which type of PRP is most suitable for the specific field.

Effects of Aspirin on Growth Factor Release From Freshly Isolated Leukocyte-Rich Platelet-Rich Plasma in Healthy Men: A Prospective Fixed-Sequence Controlled Laboratory Study

2019 ◽  
Vol 47 (5) ◽  
pp. 1223-1229 ◽  
Author(s):  
Prathap Jayaram ◽  
Peter Yeh ◽  
Shiv J. Patel ◽  
Racel Cela ◽  
Theodore B. Shybut ◽  
...  
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Whole Blood ◽  
Low Dose ◽  
Platelet Rich Plasma ◽  
Healthy Men ◽  
Growth Factor Release ◽  
Tgf Β1 ◽  
Cox 1 ◽  
Factor Release

Background: The benefits of platelet-rich plasma (PRP) are believed to be in part dependent on growth factor release after platelet activation. Platelet activation is complex and involves multiple mechanisms. One important mechanism is driven by cyclooxygenase 1 (COX-1)–mediated conversion of arachidonic acid (AA) to precursor prostaglandins that then mediate proinflammatory responses that trigger growth factor release. Acetylsalicylic acid (ASA; also known as aspirin) is known to irreversibly inhibit COX-1, thereby blocking AA-mediated signaling; however, it is unclear whether ASA use alters growth factor release from freshly isolated PRP. Purpose: To assess the effects of low-dose ASA use on activation of growth factor release from freshly isolated human PRP via AA and thrombin (TBN). Study Design: Controlled laboratory study. Methods: Twelve healthy men underwent blood collection and leukocyte-rich PRP (LR-PRP) preparation through a double-spin protocol to obtain baseline whole blood and PRP counts the same day. PRP was aliquoted into 3 groups: nonactivated, AA activated, and TBN activated. Immediately after activation, the concentrations of transforming growth factor β1 (TGF-β1), vascular endothelial growth factor (VEGF), and platelet-derived growth factor AB (PDGF-AB) were measured using enzyme-linked immunosorbent assays (ELISAs). The same 12 participants were then placed on an 81-mg daily dose of oral ASA for 14 days. Repeat characterization of whole blood and PRP analyses was done on day 14, followed by repeat ELISAs of growth factors under the same nonactivated and activated settings as previously stated. Results: Fourteen days of daily ASA had no effect on the number of platelets and leukocytes measured in whole blood and LR-PRP. Compared with nonactivated LR-PRP, AA- and TBN-mediated activation led to significant release of VEGF and PDGF-AB. In contrast, release of TGF-β1 from LR-PRP was observed only with activation by AA, not with TBN. Consistent with its inhibitory role in AA signaling, ASA significantly inhibited AA-mediated release of all 3 growth factors measured in this study. Although ASA had no effect on TBN-mediated release of VEGF and TGF-β1 from LR-PRP, ASA did partially block TBN-mediated release of PDGF-AB, although the mechanism remains unclear. Conclusion: Daily use of low-dose ASA reduces VEGF, PDGF-AB, and TGF-β1 expression in freshly isolated human LR-PRP when activated with AA. Clinical Relevance: Reduction in growth factor release attributed to daily use of low-dose ASA or other COX inhibitors can be mitigated when PRP samples are activated with TBN. Clinical studies are needed to determine whether activation before PRP injection is needed in all applications where ASA is in use and to what extent ASA may inhibit growth factor release in vivo at the site of injury.

scholarly journals Basic Studies on the Clinical Applications of Platelet-Rich Plasma

2003 ◽  
Vol 12 (5) ◽  
pp. 509-518 ◽  
Author(s):  
Masaki Yazawa ◽  
Hisao Ogata ◽  
Tatsuo Nakajima ◽  
Taisuke Mori ◽  
Naohide Watanabe ◽  
...  
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Fibrin Glue ◽  
Transforming Growth Factor ◽  
Platelet Rich Plasma ◽  
Transforming Growth Factor Β ◽  
Clinical Applications ◽  
Platelet Concentrate ◽  
Platelet Concentrates ◽  
Basic Studies

Platelets, which contain many growth factors such as platelet-derived growth factor (PDGF) and transforming growth factor-β (TGF-β), are being used in clinical applications as platelet-rich plasma (PRP). Only a few studies, however, have been conducted on the growth factors present in PRP and on the clinical applications using the drug delivery system (DDS). For the purpose of clinical application, we first modified the PRP preparation method and assessed the amounts of growth factors contained in the human platelet concentrates. Furthermore, we assessed fibrin glue as a DDS of platelet concentrates. Platelet precipitations were made by twice centrifuging human whole blood. The precipitated platelet was resuspended to yield the platelet concentrates. The growth factor concentrations were measured. Fibrin glue sheets containing this platelet concentrate were implanted in rabbit pinna and samples were obtained for immunostaining (anti-PDGF antibody) to assess the use of PRP over time using the fibrin glue as the DDS. The mean concentration of growth factors present in the platelet concentrates was three times or greater than that of conventional PRP. Furthermore, the results indicated that when the platelet concentrate was used with fibrin glue as a carrier, the contents were released over a period of about 1 week. This raises the possibility that this system may be useful in clinical applications.

scholarly journals Review of the Dynamics of Coalescence and Demulsification by High-Voltage Pulsed Electric Fields

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Ye Peng ◽  
Tao Liu ◽  
Haifeng Gong ◽  
Xianming Zhang
Keyword(s):  
Electric Field ◽  
Electric Fields ◽  
High Voltage ◽  
Industrial Application ◽  
Voltage Pulse ◽  
Pulse Electric Field ◽  
Pulsed Electric Fields ◽  
High Voltage Pulse ◽  
Technological Method ◽  
Pulse Electric

The coalescence of droplets in oil can be implemented rapidly by high-voltage pulse electric field, which is an effective demulsification dehydration technological method. At present, it is widely believed that the main reason of pulse electric field promoting droplets coalescence is the dipole coalescence and oscillation coalescence in pulse electric field, and the optimal coalescence pulse electric field parameters exist. Around the above content, the dynamics of high-voltage pulse electric field promoting the coalescence of emulsified droplets is studied by researchers domestically and abroad. By review, the progress of high-voltage pulse electric field demulsification technology can get a better understanding, which has an effect of throwing a sprat to catch a whale on promoting the industrial application.

scholarly journals Influence of storage conditions on the release of growth factors in platelet-rich blood derivatives

2016 ◽  
Vol 2 (1) ◽  
pp. 311-314 ◽  
Author(s):  
Katharina Düregger ◽  
Anqi Peng ◽  
Markus Eblenkamp
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Platelet Rich Plasma ◽  
Storage Conditions ◽  
Platelet Derived Growth Factor ◽  
Prolonged Storage ◽  
Wound Treatment ◽  
Time Dependency ◽  
Processing And Storage ◽  
And Storage

AbstractThrombocytes can be concentrated in blood derivatives and used as autologous transplants e.g. for wound treatment due to the release of growth factors such as platelet derived growth factor (PDGF). Conditions for processing and storage of these platelet-rich blood derivatives influence the release of PDGF from the platelet-bound α-granules into the plasma. In this study Platelet rich plasma (PRP) and Platelet concentrate (PC) were produced with a fully automated centrifugation system. Storage of PRP and PC for 1 h up to 4 months at temperatures between −20°C and +37°C was applied with the aim of evaluating the influence on the amount of released PDGF. Storage at −20°C resulted in the highest release of PDGF in PRP and a time dependency was determined: prolonged storage up to 1 month in PRP and 10 days in PC increased the release of PDGF. Regardless of the storage conditions, the release of PDGF per platelet was higher in PC than in PRP.

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