An Evaluation of the Effect of Activation Methods on the Release of Growth Factors from Platelet-Rich Plasma.
Journal
Plastic and reconstructive surgery
ISSN: 1529-4242
Titre abrégé: Plast Reconstr Surg
Pays: United States
ID NLM: 1306050
Informations de publication
Date de publication:
01 Feb 2022
01 Feb 2022
Historique:
entrez:
25
1
2022
pubmed:
26
1
2022
medline:
22
3
2022
Statut:
ppublish
Résumé
Activation of platelets in platelet-rich plasma may improve growth factor release, thus enhancing regenerative properties. The authors investigated whether different methods of platelet-rich plasma activation affected growth factor release kinetics over time. Platelet-rich plasma from 20 healthy volunteers was processed by six different methods: (1) control (nonactivated); (2) activation with calcium chloride; (3) activation with calcium chloride and ethanol; (4) activation with calcium chloride and ethanol at 4°C; (5) activation with calcium chloride and ethanol with vitamin C; (6) activation with calcium chloride and ethanol with vitamin C at 4°C. Concentration of secreted vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and insulin-like growth factor over 24 hours was measured by immunoassay. Calcium chloride-activated platelet-rich plasma produced significantly more insulin-like growth factor at 1 hour compared to cold and vitamin C platelet-rich plasma, and calcium chloride plus ethanol produced significantly more at 24 hours compared to vitamin C platelet-rich plasma. The addition of vitamin C reduced release of PDGF over time. Activation with calcium chloride and ethanol with or without cold temperature produced a gradual PDGF release as opposed to calcium chloride alone, which caused higher PDGF within 4 hours. There were no significant differences between groups for VEGF, although calcium chloride and cooled platelet-rich plasma approached significance for producing more than vitamin C platelet-rich plasma. Activation of platelet-rich plasma does not significantly improve growth factor secretion, which is made worse by the addition of vitamin C, a platelet inhibitor. Ethanol does not negatively impact growth factor production and may offer a more gradual release. These findings will help guide platelet-rich plasma preparation methods where therapeutic growth factors are used. Therapeutic, V.
Sections du résumé
BACKGROUND
BACKGROUND
Activation of platelets in platelet-rich plasma may improve growth factor release, thus enhancing regenerative properties. The authors investigated whether different methods of platelet-rich plasma activation affected growth factor release kinetics over time.
METHODS
METHODS
Platelet-rich plasma from 20 healthy volunteers was processed by six different methods: (1) control (nonactivated); (2) activation with calcium chloride; (3) activation with calcium chloride and ethanol; (4) activation with calcium chloride and ethanol at 4°C; (5) activation with calcium chloride and ethanol with vitamin C; (6) activation with calcium chloride and ethanol with vitamin C at 4°C. Concentration of secreted vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and insulin-like growth factor over 24 hours was measured by immunoassay.
RESULTS
RESULTS
Calcium chloride-activated platelet-rich plasma produced significantly more insulin-like growth factor at 1 hour compared to cold and vitamin C platelet-rich plasma, and calcium chloride plus ethanol produced significantly more at 24 hours compared to vitamin C platelet-rich plasma. The addition of vitamin C reduced release of PDGF over time. Activation with calcium chloride and ethanol with or without cold temperature produced a gradual PDGF release as opposed to calcium chloride alone, which caused higher PDGF within 4 hours. There were no significant differences between groups for VEGF, although calcium chloride and cooled platelet-rich plasma approached significance for producing more than vitamin C platelet-rich plasma.
CONCLUSIONS
CONCLUSIONS
Activation of platelet-rich plasma does not significantly improve growth factor secretion, which is made worse by the addition of vitamin C, a platelet inhibitor. Ethanol does not negatively impact growth factor production and may offer a more gradual release.
CLINICAL RELEVANCE STATEMENT
CONCLUSIONS
These findings will help guide platelet-rich plasma preparation methods where therapeutic growth factors are used.
CLINICAL QUESTION/LEVEL OF EVIDENCE
METHODS
Therapeutic, V.
Identifiants
pubmed: 35077415
doi: 10.1097/PRS.0000000000008772
pii: 00006534-202202000-00018
doi:
Substances chimiques
Platelet-Derived Growth Factor
0
Somatomedins
0
Ethanol
3K9958V90M
Calcium Chloride
M4I0D6VV5M
Ascorbic Acid
PQ6CK8PD0R
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
404-411Informations de copyright
Copyright © 2022 by the American Society of Plastic Surgeons.
Références
Nachman RL, Rafii S. Platelets, petechiae, and preservation of the vascular wall. N Engl J Med. 2008;359:1261–1270.
Pochini AC, Antonioli E, Bucci DZ, et al. Analysis of cytokine profile and growth factors in platelet-rich plasma obtained by open systems and commercial columns. Einstein (Sao Paulo). 2016;14:391–397.
Pallua N, Pulsfort AK, Suschek C, Wolter TP. Content of the growth factors bFGF, IGF-1, VEGF, and PDGF-BB in freshly harvested lipoaspirate after centrifugation and incubation. Plast Reconstr Surg. 2009;123:826–833.
Foster TE, Puskas BL, Mandelbaum BR, Gerhardt MB, Rodeo SA. Platelet-rich plasma: From basic science to clinical applications. Am J Sports Med. 2009;37:2259–2272.
Pierce GF, Mustoe TA, Altrock BW, Deuel TF, Thomason A. Role of platelet-derived growth factor in wound healing. J Cell Biochem. 1991;45:319–326.
Sánchez-González DJ, Méndez-Bolaina E, Trejo-Bahena NI. Platelet-rich plasma peptides: Key for regeneration. Int J Pept. 2012;2012:532519.
Uhl E, Rösken F, Sirsjö A, Messmer K. Influence of platelet-derived growth factor on microcirculation during normal and impaired wound healing. Wound Repair Regen. 2003;11:361–367.
Rees RS, Robson MC, Smiell JM, Perry BH. Becaplermin gel in the treatment of pressure ulcers: A phase II randomized, double-blind, placebo-controlled study. Wound Repair Regen. 1999;7:141–147.
Hoeben A, Landuyt B, Highley MS, Wildiers H, Van Oosterom AT, De Bruijn EA. Vascular endothelial growth factor and angiogenesis. Pharmacol Rev. 2004;56:549–580.
Hanft JR, Pollak RA, Barbul A, et al. Phase I trial on the safety of topical rhVEGF on chronic neuropathic diabetic foot ulcers. J Wound Care. 2008;1:34–37.
Rubin R, Baserga R. Insulin-like growth factor-I receptor: Its role in cell proliferation, apoptosis, and tumorigenicity. Lab Invest. 1995;73:311–331.
Ghiasi Z, Gray T, Tran P, et al. The effect of topical substance-P plus insulin-like growth factor-1 (IGF-1) on epithelial healing after photo refractive keratectomy in rabbits. Transl Vis Sci Technol. 2018;7:12.
Marx RE. Platelet-rich plasma: Evidence to support its use. J Oral Maxillofac Surg. 2004;62:489–496.
Gentile P, Cole JP, Cole MA, et al. Evaluation of not-activated and activated PRP in hair loss treatment: Role of growth factor and cytokine concentrations obtained by different collection systems. Int J Mol Sci. 2017;18:E408.
Gentile P, Garcovich S. Systematic review: The potential implications of different platelet-rich plasma (PRP) concentrations in regenerative medicine for tissue repair. Int J Mol Sci. 2020;21:E5702.
Sommeling CE, Heyneman A, Hoeksema H, Verbelen J, Stillaert FB, Monstrey S. The use of platelet-rich plasma in plastic surgery: A systematic review. J Plast Reconstr Aesthet Surg. 2013;66:301–311.
Martinez-Zapata MJ, Mart-Carvajal AJ, Sol I, et al. Autologous platelet rich plasma for treating chronic wounds. Cochrane Database Syst Rev. 2016;2016:CD006899.
Wasterlain AS, Braun HJ, Dragoo JL. Contents and formulations of platelet rich plasma. Oper Tech Orthop. 2012,22:33–42.
Schär MO, Diaz-Romero J, Kohl S, Zumstein MA, Nesic D. Platelet-rich concentrates differentially release growth factors and induce cell migration in vitro. Clin Orthop Relat Res. 2015;473:1635–1643.
Luck J, Smith OJ, Mosahebi A. A systematic review of autologous platelet-rich plasma and fat graft preparation methods. Plast Reconstr Surg Glob Open. 2017;5:e1596.
Dohan Ehrenfest DM, Rasmusson L, Albrektsson T. Classification of platelet concentrates: From pure platelet-rich plasma (P-PRP) to leucocyte- and platelet-rich fibrin (L-PRF). Trends Biotechnol. 2009;27:158–167.
Gentile P, Calabrese C, De Angelis B, et al. Impact of the different preparation methods to obtain autologous non-activated platelet-rich plasma (A-PRP) and activated platelet-rich plasma (AA-PRP) in plastic surgery: Wound healing and hair regrowth evaluation. Int J Mol Sci. 2020;21:431.
Gentile P, Garcovich S. Autologous activated platelet-rich plasma (AA-PRP) and non-activated (A-PRP) in hair growth: A retrospective, blinded, randomized evaluation in androgenetic alopecia. Expert Opin Biol Ther. 2020;20:327–337.
Gentile P, Scioli MG, Bielli A, et al. Platelet-rich plasma and micrografts enriched with autologous human follicle mesenchymal stem cells improve hair re-growth in androgenetic alopecia: Biomolecular pathway analysis and clinical evaluation. Biomedicines. 2019;7:E27.
Spronk HM, Dielis AW, De Smedt E, et al. Assessment of thrombin generation II: Validation of the calibrated automated thrombogram in platelet-poor plasma in a clinical laboratory. Thromb Haemost. 2008;100:362–364.
Toyoda T, Isobe K, Tsujino T, et al. Direct activation of platelets by addition of CaCl2 leads coagulation of platelet-rich plasma. Int J Implant Dent. 2018;4:23.
Kumar V, Madsen T, Zhu H, Semple E. Stability of human thrombin produced from 11 ml of plasma using the thrombin processing device. J Extra Corpor Technol. 2005;37:390–395.
Kuo YP, Lee YL, Tseng YH, Su CH, Burnouf T, Su CY. Influence of ethanol on the release of growth factors in human blood-derived platelet gels. Biologicals. 2010;38:120–127.
Marinaro JA, Neumann GM, Russo VC, Leeding KS, Bach LA. O-glycosylation of insulin-like growth factor (IGF) binding protein-6 maintains high IGF-II binding affinity by decreasing binding to glycosaminoglycans and susceptibility to proteolysis. Eur J Biochem. 2000;267:5378–5386.
Radek KA, Kovacs EJ, Gallo RL, DiPietro LA. Acute ethanol exposure disrupts VEGF receptor cell signaling in endothelial cells. Am J Physiol Heart Circ Physiol. 2008;295:H174–H184.
Jensen RL, Ragel BT, Whang K, Gillespie D. Inhibition of hypoxia inducible factor-1α (HIF-1α) decreases vascular endothelial growth factor (VEGF) secretion and tumor growth in malignant gliomas. J Neurooncol. 2006;78:233–247.
Oliver AE, Tablin F, Walker NJ, Crowe JH. The internal calcium concentration of human platelets increases during chilling. Biochim Biophys Acta. 1999;1416:349–360.
Gousset K, Tsvetkova NM, Crowe JH, Tablin F. Important role of raft aggregation in the signaling events of cold-induced platelet activation. Biochim Biophys Acta. 2004;1660:7–15.
Watts DD, Trask A, Soeken K, Perdue P, Dols S, Kaufmann C. Hypothermic coagulopathy in trauma: Effect of varying levels of hypothermia on enzyme speed, platelet function, and fibrinolytic activity. J Trauma. 1998;44:846–854.
Strandberg G, Sellberg F, Sommar P, et al. Standardizing the freeze-thaw preparation of growth factors from platelet lysate. Transfusion. 2017;57:1058–1065.
Kikuchi N, Yoshioka T, Taniguchi Y, et al. Optimization of leukocyte-poor platelet-rich plasma preparation: A validation study of leukocyte-poor platelet-rich plasma obtained using different preparer, storage, and activation methods. J Exp Orthop. 2019;6:24.
Lacoste E, Martineau I, Gagnon G. Platelet concentrates: Effects of calcium and thrombin on endothelial cell proliferation and growth factor release. J Periodontol. 2003;74:1498–1507.
Mohammed BM, Fisher BJ, Kraskauskas D, et al. Vitamin C promotes wound healing through novel pleiotropic mechanisms. Int Wound J. 2016;13:572–584.
Barbosa E, Faintuch J, Machado Moreira EA, et al. Supplementation of vitamin E, vitamin C, and zinc attenuates oxidative stress in burned children: A randomized, double-blind, placebo-controlled pilot study. J Burn Care Res. 2009;30:859–866.
Pielesz A, Biniaś D, Bobiński R, Sarna E, Paluch J, Waksmańska W. The role of topically applied l-ascorbic acid in ex-vivo examination of burn-injured human skin. Spectrochim Acta A Mol Biomol Spectrosc. 2017;185:279–285.
Gökşen S, Balabanli B, Coşkun-Cevher Ş. Application of platelet derived growth factor-BB and diabetic wound healing: The relationship with oxidative events. Free Radic Res. 2017;51:498–505.
Cordova C, Musca A, Violi F, Perrone A, Alessandri C. Influence of ascorbic acid on platelet aggregation in vitro and in vivo. Atherosclerosis. 1982;41:15–19.
Raghavan SA, Sharma P, Dikshit M. Role of ascorbic acid in the modulation of inhibition of platelet aggregation by polymorphonuclear leukocytes. Thromb Res. 2003;110:117–126.
Cavallo C, Roffi A, Grigolo B, et al. Platelet-rich plasma: The choice of activation method affects the release of bioactive molecules. Biomed Res Int. 2016;2016:6591717.
Kobayashi E, Flückiger L, Fujioka-Kobayashi M, et al. Comparative release of growth factors from PRP, PRF, and advanced-PRF. Clin Oral Investig. 2016;20:2353–2360.
Nagata MJ, Messora MR, Furlaneto FA, et al. Effectiveness of two methods for preparation of autologous platelet-rich plasma: An experimental study in rabbits. Eur J Dent. 2010;4:395–402.
Choi HM, Kim SH, Kim CK, et al. The cheapest and easiest way to make platelet-rich plasma preparation. Arch Aesthetic Plast Surg. 2015;21:12–17.
Margolis J. Glass surface and blood coagulation. Nature. 1956;178:805–806.
My Assays. Four parameter logistic curve. Available at: https://myassays.com/four-parameter-logistic-curve.assay . Accessed January 8, 2021.
Hosnuter M, Aslan C, Isik D, Caliskan G, Arslan B, Durgun M. Functional assessment of autologous platelet-rich plasma (PRP) after long-term storage at -20 °C without any preservation agent. J Plast Surg Hand Surg. 2017;51:235–239.
Su CY, Kuo YP, Nieh HL, Tseng YH, Burnouf T. Quantitative assessment of the kinetics of growth factors release from platelet gel. Transfusion. 2008;48:2414–2420.
Hamilton B, Tol JL, Knez W, Chalabi H. Exercise and the platelet activator calcium chloride both influence the growth factor content of platelet-rich plasma (PRP): Overlooked biochemical factors that could influence PRP treatment. Br J Sports Med. 2015;49:957–960.
Oudelaar BW, Peerbooms JC, Huis In ’t Veld R, Vochteloo AJH. Concentrations of blood components in commercial platelet-rich plasma separation systems: A review of the literature. Am J Sports Med. 2019;47:479–487.
Martineau I, Lacoste E, Gagnon G. Effects of calcium and thrombin on growth factor release from platelet concentrates: Kinetics and regulation of endothelial cell proliferation. Biomaterials. 2004;25:4489–4502.
Scherer SS, Tobalem M, Vigato E, et al. Nonactivated versus thrombin-activated platelets on wound healing and fibroblast-to-myofibroblast differentiation in vivo and in vitro. Plast Reconstr Surg. 2012;129:46e–54e.
McClain AK, McCarrel TM. The effect of four different freezing conditions and time in frozen storage on the concentration of commonly measured growth factors and enzymes in equine platelet-rich plasma over six months. BMC Vet Res. 2019;15:292.