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

Marx, 2001, Platelet-Rich Plasma (PRP): What Is PRP and What Is Not PRP?, Implant Dent., 10, 225, 10.1097/00008505-200110000-00002

Filardo, 2016, Platelet-rich plasma in tendon-related disorders: Results and indications, Knee Surg. Sports Traumatol. Arthrosc., 26, 1984, 10.1007/s00167-016-4261-4

Belk, J.W., Kraeutler, M.J., Houck, D.A., Goodrich, J.A., Dragoo, J.L., and McCarty, E.C. (2020). Platelet-Rich Plasma Versus Hyaluronic Acid for Knee Osteoarthritis: A Systematic Review and Meta-analysis of Randomized Controlled Trials. Am. J. Sports Med., 17.

Xuan, Z., Yu, W., Dou, Y., and Wang, T. (2020). Efficacy of Platelet-rich Plasma for Low Back Pain: A Systematic Review and Meta-analysis. J. Neurol. Surg. Part A Central Eur. Neurosurg.

Browning, 2012, Platelet-Rich Plasma Increases Matrix Metalloproteinases in Cultures of Human Synovial Fibroblasts, J. Bone Jt. Surg. Am. Vol., 94, e172-1, 10.2106/JBJS.K.01501

Hakan Dogan, K. (2019). Autologous Platelet-Rich Plasma and Mesenchymal Stem Cells for the Treatment of Chronic Wounds. Wound Healing—Current Perspectives, IntechOpen.

Sundman, 2011, Growth Factor and Catabolic Cytokine Concentrations Are Influenced by the Cellular Composition of Platelet-Rich Plasma, Am. J. Sports Med., 39, 2135, 10.1177/0363546511417792

Marrazzo, 2016, Highly Efficient In Vitro Reparative Behaviour of Dental Pulp Stem Cells Cultured with Standardised Platelet Lysate Supplementation, Stem Cells Int., 2016, 7230987, 10.1155/2016/7230987

Everts, 2006, Platelet-Rich Plasma and Platelet Gel: A Review, J. Extra Corpor. Technol., 38, 174, 10.1051/ject/200638174

Mahmood, C. (2020). The Rationale of Autologously Prepared Bone Marrow Aspirate Concentrate for use in Regenerative Medicine Applications. Regenerative Medicine, IntechOpen.

Hersant, 2019, Platelet-Rich Plasma Improves the Wound Healing Potential of Mesenchymal Stem Cells through Paracrine and Metabolism Alterations, Stem Cells Int., 2019, 1234263, 10.1155/2019/1234263

Johal, 2019, Impact of Platelet-Rich Plasma Use on Pain in Orthopaedic Surgery: A Systematic Review and Meta-analysis, Sports Health Multidiscip. Approach, 11, 355, 10.1177/1941738119834972

Giusti, I., D’Ascenzo, S., Macchiarelli, G., and Dolo, V. (2020). In vitro evidence supporting applications of platelet derivatives in regenerative medicine. Blood Transfus.

Andia, 2018, A contemporary view of platelet-rich plasma therapies: Moving toward refined clinical protocols and precise indications, Regen. Med., 13, 717, 10.2217/rme-2018-0042

Puzzitiello, 2020, Adverse Impact of Corticosteroids on Rotator Cuff Tendon Health and Repair: A Systematic Review of Basic Science Studies, Arthrosc. Sports Med. Rehabil., 2, e161, 10.1016/j.asmr.2020.01.002

Beitzel, 2014, US Definitions, Current Use, and FDA Stance on Use of Platelet-Rich Plasma in Sports Medicine, J. Knee Surg., 28, 29, 10.1055/s-0034-1390030

Everts, 2006, Differences in platelet growth factor release and leucocyte kinetics during autologous platelet gel formation, Transfus. Med., 16, 363, 10.1111/j.1365-3148.2006.00708.x

Mazzucco, 2009, Not every PRP-gel is born equal Evaluation of growth factor availability for tissues through four PRP-gel preparations: Fibrinet®, RegenPRP-Kit®, Plateltex® and one manual procedure, Vox Sang., 97, 110, 10.1111/j.1423-0410.2009.01188.x

Mosesson, 2006, The Structure and Biological Features of Fibrinogen and Fibrin, Ann. N. Y. Acad. Sci., 936, 11, 10.1111/j.1749-6632.2001.tb03491.x

Silverberg, 1977, A physiological sealant for cerebrospinal fluid leaks, J. Neurosurg., 46, 215, 10.3171/jns.1977.46.2.0215

Chahla, 2017, A Call for Standardization in Platelet-Rich Plasma Preparation Protocols and Composition Reporting, J. Bone Jt. Surg. Am. Vol., 99, 1769, 10.2106/JBJS.16.01374

Everts, 2008, What do we use: Platelet-rich plasma or platelet-leukocyte gel?, J. Biomed. Mater. Res. Part A, 85, 1135, 10.1002/jbm.a.31570

Kingsley, 1954, Blood Coagulation: Evidence of an Antagonist to Factor VI in Platelet-Rich Human Plasma, Nature, 173, 723, 10.1038/173723a0

Rasmusson, 2009, Classification of platelet concentrates: From pure platelet-rich plasma (P-PRP) to leucocyte- and platelet-rich fibrin (L-PRF), Trends Biotechnol., 27, 158, 10.1016/j.tibtech.2008.11.009

Delong, 2012, Platelet-Rich Plasma: The PAW Classification System, Arthrosc. J. Arthrosc. Relat. Surg., 28, 998, 10.1016/j.arthro.2012.04.148

Mishra, 2012, Sports Medicine Applications of Platelet Rich Plasma, Curr. Pharm. Biotechnol., 13, 1185, 10.2174/138920112800624283

Mautner, 2015, A Call for a Standard Classification System for Future Biologic Research: The Rationale for New PRP Nomenclature, PM&R, 7, S53, 10.1016/j.pmrj.2015.02.005

Magalon, 2016, DEPA classification: A proposal for standardising PRP use and a retrospective application of available devices, BMJ Open Sport Exerc. Med., 2, e000060, 10.1136/bmjsem-2015-000060

Lana, 2017, Contributions for classification of platelet rich plasma—Proposal of a new classification: MARSPILL, Regen. Med., 12, 565, 10.2217/rme-2017-0042

Harrison, 2018, The use of platelets in regenerative medicine and proposal for a new classification system: Guidance from the SSC of the ISTH, J. Thromb. Haemost., 16, 1895, 10.1111/jth.14223

Rossi, L.A., Murray, I.R., Chu, C.R., Muschler, G.F., Rodeo, S.A., and Piuzzi, N.S. (2019). Classification systems for platelet-rich plasma. Bone Jt. J., 891–896.

Ehrenfest, 2012, In Search of a Consensus Terminology in the Field of Platelet Concentrates for Surgical Use: Platelet-Rich Plasma (PRP), Platelet-Rich Fibrin (PRF), Fibrin Gel Polymerization and Leukocytes, Curr. Pharm. Biotechnol., 13, 1131, 10.2174/138920112800624328

The GRIP (Groupe de Recherche sur les Injections de PRP, PRP Injection Research Group), Eymard, P.A., Ornetti, P., Maillet, J., Noel, É., Adam, P., Legré-Boyer, V., Boyer, T., Allali, F., and Gremeaux, V. (2020). Intra-articular injections of platelet-rich plasma in symptomatic knee osteoarthritis: A consensus statement from French-speaking experts. Knee Surg. Sports Traumatol. Arthrosc.

Lana, 2019, Leukocyte-rich PRP for knee osteoarthritis: Current concepts, J. Clin. Orthop. Trauma, 10, S179, 10.1016/j.jcot.2019.01.011

Fadadu, 2019, Review of concentration yields in commercially available platelet-rich plasma (PRP) systems: A call for PRP standardization, Reg. Anesth. Pain Med., 44, 652, 10.1136/rapm-2018-100356

Amable, 2013, Platelet-rich plasma preparation for regenerative medicine: Optimization and quantification of cytokines and growth factors, Stem Cell Res. Ther., 4, 67, 10.1186/scrt218

Gentile, P., Calabrese, C., De Angelis, B., Dionisi, L., Pizzicanella, J., Kothari, A., De Fazio, D., and Garcovich, S. (2020). 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., 21.

Samadi, 2018, The Use of Platelet-Rich Plasma in Aesthetic and Regenerative Medicine: A Comprehensive Review, Aesthetic Plast. Surg., 43, 803, 10.1007/s00266-018-1293-9

Nguyen, P.A., and Pham, T.A.V. (2018). Effects of platelet-rich plasma on human gingival fibroblast proliferation and migration in vitro. J. Appl. Oral Sci., 26.

Vahabi, 2017, Comparison of the effect of activated or non-activated PRP in various concentrations on osteoblast and fibroblast cell line proliferation, Cell Tissue Bank., 18, 347, 10.1007/s10561-017-9640-7

Graziani, 2006, The in vitro effect of different PRP concentrations on osteoblasts and fibroblasts, Clin. Oral Implant. Res., 17, 212, 10.1111/j.1600-0501.2005.01203.x

Park, M.S., Moon, S.-H., Kim, T.-H., Oh, J.K., Yoon, W.Y., and Chang, H.G. (2018). Platelet-rich plasma for the spinal fusion. J. Orthop. Surg., 26.

Jahr, 2008, Can Platelet-Rich Plasma Enhance Tendon Repair?, Am. J. Sports Med., 36, 1171, 10.1177/0363546508314430

Yuan, 2019, Augmenting tendon and ligament repair with platelet-rich plasma (PRP), Muscle Ligaments Tendons J., 3, 139, 10.32098/mltj.03.2013.05

Gupta, 2019, Platelet-Rich Plasma as a Treatment for Androgenetic Alopecia, Dermatol. Surg., 45, 1262, 10.1097/DSS.0000000000001894

Kirmani, B.H., Jones, S.G., Datta, S., McLaughlin, E.K., and Hoschtitzky, A.J. (2016). A meta-analysis of platelet gel for prevention of sternal wound infections following cardiac surgery. Blood Transfus.

Willemsen, 2017, The addition of PRP to facial lipofilling, Plast. Reconstr. Surg., 141, 331, 10.1097/PRS.0000000000004081

Muchedzi, 2018, A systematic review of the effects of platelet rich plasma on outcomes for patients with knee osteoarthritis and following total knee arthroplasty, Surgeon, 16, 250, 10.1016/j.surge.2017.08.004

Cengiz, 2019, The Clinical Use of Biologics in the Knee Lesions: Does the Patient Benefit?, Curr. Rev. Musculoskelet. Med., 12, 406, 10.1007/s12178-019-09573-3

Terry, 2015, Lumbar Intradiskal Platelet-Rich Plasma (PRP) Injections: A Prospective, Double-Blind, Randomized Controlled Study, PM&R, 8, 1

Mariani, E., and Pulsatelli, L. (2020). Platelet Concentrates in Musculoskeletal Medicine. Int. J. Mol. Sci., 21.

Manini, 2020, Role of Platelet-Rich Plasma in Spinal Fusion Surgery: Systematic Review and Meta-Analysis, Adv. Orthop., 2020, 1, 10.1155/2020/8361798

Haunschild, 2020, Platelet-Rich Plasma Augmentation in Meniscal Repair Surgery: A Systematic Review of Comparative Studies, Arthrosc. J. Arthrosc. Relat. Surg., 36, 1765, 10.1016/j.arthro.2020.01.038

Kushida, 2014, Platelet and growth factor concentrations in activated platelet-rich plasma: A comparison of seven commercial separation systems, J. Artif. Organs, 17, 186, 10.1007/s10047-014-0761-5

Senzel, 2009, The platelet proteome, Curr. Opin. Hematol., 16, 329, 10.1097/MOH.0b013e32832e9dc6

García, Á., and Senis, Y. (2011). Platelet Proteomics: Principles, Analysis, and Applications, John Wiley & Sons. Wiley-Interscience Series on Mass, Spectrometry.

Blair, 2009, Platelet α-granules: Basic biology and clinical correlates, Blood Rev., 23, 177, 10.1016/j.blre.2009.04.001

Iberg, 2020, Natural and Induced Tolerogenic Dendritic Cells, J. Immunol., 204, 733, 10.4049/jimmunol.1901121

Younas, 2013, IL-7 Modulates In Vitro and In Vivo Human Memory T Regulatory Cell Functions through the CD39/ATP Axis, J. Immunol., 191, 3161, 10.4049/jimmunol.1203547

Ganor, 2003, Human T cells express a functional ionotropic glutamate receptor GluR3, and glutamate by itself triggers integrin-mediated adhesion to laminin and fibronectin and chemotactic migration, J. Immunol., 170, 4362, 10.4049/jimmunol.170.8.4362

Everts, 2007, Reviewing the Structural Features of Autologous Platelet-Leukocyte Gel and Suggestions for Use in Surgery, Eur. Surg. Res., 39, 199, 10.1159/000101743

Xu, 2020, Platelet-rich plasma and regenerative dentistry, Aust. Dent. J., 65, 131, 10.1111/adj.12754

Zheng, 2016, Effect of platelet-rich plasma (PRP) concentration on proliferation, neurotrophic function and migration of Schwann cells in vitro, J. Tissue Eng. Regen. Med., 10, 428, 10.1002/term.1756

Hee, 2003, Do autologous growth factors enhance transforaminal lumbar interbody fusion?, Eur. Spine J., 12, 400, 10.1007/s00586-003-0548-5

Giusti, 2009, Identification of an optimal concentration of platelet gel for promoting angiogenesis in human endothelial cells, Transfusion (Paris), 49, 771, 10.1111/j.1537-2995.2008.02033.x

Creeper, 2009, The effect of platelet-rich plasma on osteoblast and periodontal ligament cell migration, proliferation and differentiation, J. Periodontal Res., 44, 258, 10.1111/j.1600-0765.2008.01125.x

Dale, 2008, The phagocytes: Neutrophils and monocytes, Blood, 112, 935, 10.1182/blood-2007-12-077917

Zirlik, 2007, CD40 Ligand Mediates Inflammation Independently of CD40 by Interaction with Mac-1, Circ., 115, 1571, 10.1161/CIRCULATIONAHA.106.683201

Herr, 2017, The Effects of Serotonin in Immune Cells, Front. Cardiovasc. Med., 4, 48, 10.3389/fcvm.2017.00048

Hara, 2014, Platelet-rich plasma in regenerative medicine, Biomed. Res. Ther., 1, 25

Zwaginga, 2008, Molecular and functional interactions among monocytes, platelets, and endothelial cells and their relevance for cardiovascular diseases, J. Leukoc. Biol., 85, 195

Bennett, 2005, Structure and function of the platelet integrin alphaIIbbeta3, J. Clin. Investig., 115, 3363, 10.1172/JCI26989

Soffer, 2004, Effects of platelet lysates on select bone cell functions, Clin. Oral Implant. Res., 15, 581, 10.1111/j.1600-0501.2004.01063.x

Helms, 2018, Erythrocytes and Vascular Function: Oxygen and Nitric Oxide, Front. Physiol., 9, 125, 10.3389/fphys.2018.00125

Schaer, 2013, Hemolysis and free hemoglobin revisited: Exploring hemoglobin and hemin scavengers as a novel class of therapeutic proteins, Blood, 121, 1276, 10.1182/blood-2012-11-451229

Repsold, 2018, Eryptosis: An Erythrocyte’s Suicidal Type of Cell Death, BioMed Res. Int., 2018, 1, 10.1155/2018/9405617

Fitzpatrick, J., Bulsara, M.K., McCrory, P.R., Richardson, M.D., and Zheng, M.H. (2017). Analysis of Platelet-Rich Plasma Extraction: Variations in Platelet and Blood Components between 4 Common Commercial Kits. Orthop. J. Sports Med., 5.

De Melo, B.A., Luzo, A.C.M., Lana, J.F., and Santana, M.H.A. (2019). Centrifugation Conditions in the L-PRP Preparation Affect Soluble Factors Release and Mesenchymal Stem Cell Proliferation in Fibrin Nanofibers. Molecules, 24.

Moojen, 2008, Antimicrobial activity of platelet-leukocyte gel against Staphylococcus aureus, J. Orthop. Res., 26, 404, 10.1002/jor.20519

Tang, 2002, Antimicrobial Peptides from Human Platelets, Infect. Immun., 70, 6524, 10.1128/IAI.70.12.6524-6533.2002

Kovtun, 2016, The crucial role of neutrophil granulocytes in bone fracture healing, eCells Mater., 32, 152, 10.22203/eCM.v032a10

Phillipson, 2019, The Healing Power of Neutrophils, Trends Immunol., 40, 635, 10.1016/j.it.2019.05.001

Zhou, 2016, PRP Treatment Efficacy for Tendinopathy: A Review of Basic Science Studies, BioMed Res. Int., 2016, 1

Fedorova, 2018, Neutrophils Release Metalloproteinases during Adhesion in the Presence of Insulin, but Cathepsin G in the Presence of Glucagon, Mediat. Inflamm., 2018, 1574928, 10.1155/2018/1574928

Ubezio, G., and Ghio, M. (2014). Bio-modulators in platelet-rich plasma: A comparison of the amounts in products from healthy donors and patients produced with three different techniques. Blood Transfus.

Italiani, 2014, From Monocytes to M1/M2 Macrophages: Phenotypical vs. Functional Differentiation, Front. Immunol., 5, 514, 10.3389/fimmu.2014.00514

Weirather, 2014, Foxp3 + CD4 + T Cells Improve Healing After Myocardial Infarction by Modulating Monocyte/Macrophage Differentiation, Circ. Res., 115, 55, 10.1161/CIRCRESAHA.115.303895

Das, 2015, Monocyte and Macrophage Plasticity in Tissue Repair and Regeneration, Am. J. Pathol., 185, 2596, 10.1016/j.ajpath.2015.06.001

Wynn, 2016, Macrophages in Tissue Repair, Regeneration, and Fibrosis, Immunity, 44, 450, 10.1016/j.immuni.2016.02.015

Ogle, 2016, Monocytes and macrophages in tissue repair: Implications for immunoregenerative biomaterial design, Exp. Biol. Med., 241, 1084, 10.1177/1535370216650293

2015, Understanding the Mysterious M2 Macrophage through Activation Markers and Effector Mechanisms, Mediat. Inflamm., 2015, 816460, 10.1155/2015/816460

Ferrante, 2012, Regulation of Macrophage Polarization and Wound Healing, Adv. Wound Care, 1, 10, 10.1089/wound.2011.0307

Riboh, 2015, Effect of Leukocyte Concentration on the Efficacy of Platelet-Rich Plasma in the Treatment of Knee Osteoarthritis, Am. J. Sports Med., 44, 792, 10.1177/0363546515580787

Mariani, E., Canella, V., Cattini, L., Kon, E., Marcacci, M., Di Matteo, B., Pulsatelli, L., and Filardo, G. (2016). Leukocyte-Rich Platelet-Rich Plasma Injections Do Not Up-Modulate Intra-Articular Pro-Inflammatory Cytokines in the Osteoarthritic Knee. PLoS ONE, 11.

Parrish, 2017, Physiology of Blood Components in Wound Healing: An Appreciation of Cellular Co-Operativity in Platelet Rich Plasma Action, J. Exerc. Sports Orthop., 4, 1, 10.15226/2374-6904/4/2/00156

Seta, 2007, Human circulating monocytes as multipotential progenitors, Keio J. Med., 56, 41, 10.2302/kjm.56.41

Perut, 2013, Preparation method and growth factor content of platelet concentrate influence the osteogenic differentiation of bone marrow stromal cells, Cytotherapy, 15, 830, 10.1016/j.jcyt.2013.01.220

Li, 2012, Crosstalk between Platelets and the Immune System: Old Systems with New Discoveries, Adv. Hematol., 2012, 384685, 10.1155/2012/384685

Morrell, 2014, Emerging roles for platelets as immune and inflammatory cells, Blood, 123, 2759, 10.1182/blood-2013-11-462432

Thon, 2012, T granules in human platelets function in TLR9 organization and signaling, J. Cell Biol., 198, 561, 10.1083/jcb.201111136

Rossaint, 2015, Platelets in leucocyte recruitment and function, Cardiovasc. Res., 107, 386, 10.1093/cvr/cvv048

Cruz, 2000, Mapping the Glycoprotein Ib-binding Site in the von Willebrand Factor A1 Domain, J. Biol. Chem., 275, 19098, 10.1074/jbc.M002292200

Zarbock, 2011, Leukocyte ligands for endothelial selectins: Specialized glycoconjugates that mediate rolling and signaling under flow, Blood, 118, 6743, 10.1182/blood-2011-07-343566

Furie, 1999, The Biology of P-Selectin Glycoprotein Ligand-1: Its Role as a Selectin Counterreceptor in Leukocyte-Endothelial and Leukocyte-Platelet Interaction, Thromb. Haemost., 81, 1, 10.1055/s-0037-1614407

Weber, 1997, Neutrophil accumulation on activated, surface-adherent platelets in flow is mediated by interaction of Mac-1 with fibrinogen bound to alphaIIbbeta3 and stimulated by platelet-activating factor, J. Clin. Investig., 100, 2085, 10.1172/JCI119742

Diacovo, 1994, A functional integrin ligand on the surface of platelets: Intercellular adhesion molecule-2, J. Clin. Investig., 94, 1243, 10.1172/JCI117442

Sommerfeld, 2020, Role of Inflammation and the Immune System in the Progression of Osteoarthritis, J. Orthop. Res., 38, 253, 10.1002/jor.24457

Newton, 2012, Signaling in Innate Immunity and Inflammation, Cold Spring Harb. Perspect. Biol., 4, a006049, 10.1101/cshperspect.a006049

Cognasse, 2019, Platelet Inflammatory Response to Stress, Front. Immunol., 10, 1478, 10.3389/fimmu.2019.01478

Clemetson, 2000, Functional expression of CCR1, CCR3, CCR4, and CXCR4 chemokine receptors on human platelets, Blood, 96, 4046, 10.1182/blood.V96.13.4046

Alberts, B. (2002). Molecular Biology of the Cell, Garland Science. [4th ed.].

Vasina, 2011, Microparticles from apoptotic platelets promote resident macrophage differentiation, Cell Death Dis., 2, e211, 10.1038/cddis.2011.94

Gros, 2015, Single platelets seal neutrophil-induced vascular breaches via GPVI during immune-complex–mediated inflammation in mice, Blood, 126, 1017, 10.1182/blood-2014-12-617159

Clark, 2007, Platelet TLR4 activates neutrophil extracellular traps to ensnare bacteria in septic blood, Nat. Med., 13, 463, 10.1038/nm1565

Kapur, 2015, Nouvelle Cuisine: Platelets Served with Inflammation, J. Immunol., 194, 5579, 10.4049/jimmunol.1500259

Scheuerer, 2000, The CXC-chemokine platelet factor 4 promotes monocyte survival and induces monocyte differentiation into macrophages, Blood, 95, 1158, 10.1182/blood.V95.4.1158.004k31_1158_1166

Napolitani, 2007, Interleukins 1β and 6 but not transforming growth factor-β are essential for the differentiation of interleukin 17–producing human T helper cells, Nat. Immunol., 8, 942, 10.1038/ni1496

Gaudino, 2019, Cross-Talk between Antigen Presenting Cells and T Cells Impacts Intestinal Homeostasis, Bacterial Infections, and Tumorigenesis, Front. Immunol., 10, 360, 10.3389/fimmu.2019.00360

Kaiko, 2008, Immunological decision-making: How does the immune system decide to mount a helper T-cell response?, Immunology, 123, 326, 10.1111/j.1365-2567.2007.02719.x

Sadtler, 2016, Developing a pro-regenerative biomaterial scaffold microenvironment requires T helper 2 cells, Science, 352, 366, 10.1126/science.aad9272

Henn, 1998, CD40 ligand on activated platelets triggers an inflammatory reaction of endothelial cells, Nature, 391, 591, 10.1038/35393

Yu, 2018, Recent advances in CD8+ regulatory T cell research (Review), Oncol. Lett., 15, 8187

Renshaw, 1994, Humoral immune responses in CD40 ligand-deficient mice, J. Exp. Med., 180, 1889, 10.1084/jem.180.5.1889

Semple, 2011, Platelets and the immune continuum, Nat. Rev. Immunol., 11, 264, 10.1038/nri2956

Arreola, 2015, Immunomodulatory Effects Mediated by Serotonin, J. Immunol. Res., 2015, 1

Berger, 2009, The Expanded Biology of Serotonin, Annu. Rev. Med., 60, 355, 10.1146/annurev.med.60.042307.110802

Venters, 2003, Differential effect of serotonin on cytokine production in lipopolysaccharide-stimulated human peripheral blood mononuclear cells: Involvement of 5-hydroxytryptamine2A receptors, Int. Immunol., 15, 233, 10.1093/intimm/dxg027

Tao, 2019, The Role of Descending Pain Modulation in Chronic Primary Pain: Potential Application of Drugs Targeting Serotonergic System, Neural Plast., 2019, 1389296, 10.1155/2019/1389296

Pakala, 1994, Mitogenic effect of serotonin on vascular endothelial cells, Circulation, 90, 1919, 10.1161/01.CIR.90.4.1919

Mauler, 2018, Autocrine and paracrine regulatory functions of platelet serotonin, Platelets, 29, 541, 10.1080/09537104.2018.1478072

Wan, 2020, Serotonin: A Potent Immune Cell Modulator in Autoimmune Diseases, Front. Immunol., 11, 186, 10.3389/fimmu.2020.00186

Duerschmied, 2013, Platelet serotonin promotes the recruitment of neutrophils to sites of acute inflammation in mice, Blood, 121, 1008, 10.1182/blood-2012-06-437392

Balboa, 2003, Serotonin upregulates the activity of phagocytosis through 5-HT1Areceptors, Br. J. Pharmacol., 139, 457, 10.1038/sj.bjp.0705188

Everts, 2007, Exogenous Application of Platelet-Leukocyte Gel during Open Subacromial Decompression Contributes to Improved Patient Outcome, Eur. Surg. Res., 40, 203, 10.1159/000110862

Odem, 2018, Isolated nociceptors reveal multiple specializations for generating irregular ongoing activity associated with ongoing pain, Pain, 159, 2347, 10.1097/j.pain.0000000000001341

Sprott, 1998, Pain treatment of fibromyalgia by acupuncture, Rheumatol. Int., 18, 35, 10.1007/s002960050051

Sommer, 2004, Serotonin in Pain and Analgesia: Actions in the Periphery, Mol. Neurobiol., 30, 117, 10.1385/MN:30:2:117

Nicholson, 2003, Serotonin receptor mRNA expression in rat dorsal root ganglion neurons, Neurosci. Lett., 337, 119, 10.1016/S0304-3940(02)01256-9

Wu, 2003, The very-high-efficacy 5-HT1A receptor agonist, F 13640, preempts the development of allodynia-like behaviors in rats with spinal cord injury, Eur. J. Pharmacol., 478, 131, 10.1016/j.ejphar.2003.08.047

Rosenthal, 1998, Role of serotonin transporter promoter repeat length polymorphism (5-HTTLPR) in seasonality and seasonal affective disorder, Mol. Psychiatry, 3, 175, 10.1038/sj.mp.4000360

Patetsos, 2016, Treating Chronic Pain with SSRIs: What Do We Know?, Pain Res. Manag., 2016, 2020915, 10.1155/2016/2020915

Yoshida, 2016, Efficacy of autologous leukocyte-reduced platelet-rich plasma therapy for patellar tendinopathy in a rat treadmill model, Muscle Ligaments Tendons J., 6, 205, 10.32098/mltj.02.2016.07

Fu, 2017, Evaluation of platelet-rich plasma and fibrin matrix to assist in healing and repair of rotator cuff injuries: A systematic review and meta-analysis, Clin. Rehabil., 31, 158, 10.1177/0269215516634815

Verhaegen, 2016, Rotator cuff healing after needling of a calcific deposit using platelet-rich plasma augmentation: A randomized, prospective clinical trial, J. Shoulder Elb. Surg., 25, 169, 10.1016/j.jse.2015.10.009

Lin, M.-T., Wei, K.-C., and Wu, C.-H. (2020). Effectiveness of Platelet-Rich Plasma Injection in Rotator Cuff Tendinopathy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Diagnostics, 10.

Urits, 2020, Injection Techniques for Common Chronic Pain Conditions of the Foot: A Comprehensive Review, Pain Ther., 9, 145, 10.1007/s40122-020-00157-5

Kuffler, 2015, Platelet-Rich Plasma Promotes Axon Regeneration, Wound Healing, and Pain Reduction: Fact or Fiction, Mol. Neurobiol., 52, 990, 10.1007/s12035-015-9251-x

Mohammadi, 2017, Evaluation of platelet-rich plasma gel potential in acceleration of wound healing duration in patients underwent pilonidal sinus surgery: A randomized controlled parallel clinical trial, Transfus. Apher. Sci., 56, 226, 10.1016/j.transci.2016.12.032

Deppermann, 2018, Start a fire, kill the bug: The role of platelets in inflammation and infection, Innate Immun., 24, 335, 10.1177/1753425918789255

Lansdown, 2017, Platelet-Rich Plasma: Formulations, Preparations, Constituents, and Their Effects, Oper. Tech. Sports Med., 25, 7, 10.1053/j.otsm.2016.12.002

Walsh, 2014, The functional role of platelets in the regulation of angiogenesis, Platelets, 26, 199, 10.3109/09537104.2014.909022

Baka, 2006, A review of the latest clinical compounds to inhibit VEGF in pathological angiogenesis, Expert Opin. Ther. Targets, 10, 867, 10.1517/14728222.10.6.867

Marmé, D. (2019). The Role of the VEGF Signaling Pathway in Tumor Angiogenesis. Tumor Angiogenesis: A Key Target for Cancer Therapy, Springer International Publishing.

Brill, 2004, Differential role of platelet granular mediators in angiogenesis, Cardiovasc. Res., 63, 226, 10.1016/j.cardiores.2004.04.012

Bir, 2011, Therapeutic treatment with sustained-release platelet-rich plasma restores blood perfusion by augmenting ischemia-induced angiogenesis and arteriogenesis in diabetic mice, J. Vasc. Res., 48, 195, 10.1159/000318779

Richardson, 2001, Polymeric system for dual growth factor delivery, Nat. Biotechnol., 19, 1029, 10.1038/nbt1101-1029

Marushima, 2020, Balanced single-vector co-delivery of VEGF/PDGF-BB improves functional collateralization in chronic cerebral ischemia, J. Cereb. Blood Flow Metab., 40, 404, 10.1177/0271678X18818298

Jeon, 2017, Local clearance of senescent cells attenuates the development of post-traumatic osteoarthritis and creates a pro-regenerative environment, Nat. Med., 23, 775, 10.1038/nm.4324

2014, The role of senescent cells in ageing, Nature, 509, 439, 10.1038/nature13193

Ritschka, 2017, The senescence-associated secretory phenotype induces cellular plasticity and tissue regeneration, Genes Dev., 31, 172, 10.1101/gad.290635.116

Biran, 2017, Quantitative identification of senescent cells in aging and disease, Aging Cell, 16, 661, 10.1111/acel.12592

Michaloglou, 2005, BRAFE600-associated senescence-like cell cycle arrest of human naevi, Nature, 436, 720, 10.1038/nature03890

Farr, 2017, Targeting cellular senescence prevents age-related bone loss in mice, Nat. Med., 23, 1072, 10.1038/nm.4385

Patil, 2019, Systemic clearance of p16 INK4a -positive senescent cells mitigates age-associated intervertebral disc degeneration, Aging Cell, 18, e12927, 10.1111/acel.12927

Walters, 2020, Rising from the ashes: Cellular senescence in regeneration, Curr. Opin. Genet. Dev., 64, 94, 10.1016/j.gde.2020.06.002

Desprez, 2010, The Senescence-Associated Secretory Phenotype: The Dark Side of Tumor Suppression, Annu. Rev. Pathol. Mech. Dis., 5, 99, 10.1146/annurev-pathol-121808-102144

Baar, 2018, Musculoskeletal senescence: A moving target ready to be eliminated, Curr. Opin. Pharmacol., 40, 147, 10.1016/j.coph.2018.05.007

Panda, 2009, Human innate immunosenescence: Causes and consequences for immunity in old age, Trends Immunol., 30, 325, 10.1016/j.it.2009.05.004

Wang, J.H.-C., and Nirmala, X. (2016). Perspectives on Improving the Efficacy of PRP Treatment for Tendinopathy. J. Musculoskelet. Disord. Treat., 2, Available online: https://clinmedjournals.org/articles/jmdt/journal-of-musculoskeletal-disorders-and-treatment-jmdt-2-015.php?jid=jmdt.

Stolzing, 2008, Age-related changes in human bone marrow-derived mesenchymal stem cells: Consequences for cell therapies, Mech. Ageing Dev., 129, 163, 10.1016/j.mad.2007.12.002

Liu, 2014, Delayed animal aging through the recovery of stem cell senescence by platelet rich plasma, Biomaterials, 35, 9767, 10.1016/j.biomaterials.2014.08.034

Wang, 2014, Can PRP effectively treat injured tendons?, Muscle Ligaments Tendons J., 4, 35, 10.32098/mltj.01.2014.07

Moussa, 2017, Platelet rich plasma (PRP) induces chondroprotection via increasing autophagy, anti-inflammatory markers, and decreasing apoptosis in human osteoarthritic cartilage, Exp. Cell Res., 352, 146, 10.1016/j.yexcr.2017.02.012

Jia, 2017, Platelet-rich plasma ameliorates senescence-like phenotypes in a cellular photoaging model, RSC Adv., 7, 3152, 10.1039/C6RA26725D

Oberlohr, 2020, Biologics for Skeletal Muscle Healing: The Role of Senescence and Platelet-Based Treatment Modalities, Oper. Tech. Sports Med., 28, 150754, 10.1016/j.otsm.2020.150754

Zhu, 2015, The Achilles’ heel of senescent cells: From transcriptome to senolytic drugs, Aging Cell, 14, 644, 10.1111/acel.12344

Caplan, 2006, Mesenchymal stem cells as trophic mediators, J. Cell. Biochem., 98, 1076, 10.1002/jcb.20886

Kim, 2018, Effects of bone marrow aspirate concentrate and platelet-rich plasma on patients with partial tear of the rotator cuff tendon, J. Orthop. Surg. Res., 13, 1, 10.1186/s13018-017-0693-x

Zhao, 2013, Combined treatment with platelet-rich plasma and brain-derived neurotrophic factor-overexpressing bone marrow stromal cells supports axonal remyelination in a rat spinal cord hemi-section model, Cytotherapy, 15, 792, 10.1016/j.jcyt.2013.04.004

Hede, K., Christensen, B.B., Jensen, J., Foldager, C.B., and Lind, M. (2019). Combined Bone Marrow Aspirate and Platelet-Rich Plasma for Cartilage Repair: Two-Year Clinical Results. Cartillage.

Lian, 2014, Synergistic Effect of Bone Marrow-Derived Mesenchymal Stem Cells and Platelet-Rich Plasma in Streptozotocin-Induced Diabetic Rats, Ann. Dermatol., 26, 1, 10.5021/ad.2014.26.1.1

Betsch, M., Schneppendahl, J., Thuns, S., Herten, M., Sager, M., Jungbluth, P., Hakimi, M., and Wild, M. (2013). Bone Marrow Aspiration Concentrate and Platelet Rich Plasma for Osteochondral Repair in a Porcine Osteochondral Defect Model. PLoS ONE, 8.

Kim, G.B., Seo, M.-S., Park, W.T., and Lee, G.W. (2020). Bone Marrow Aspirate Concentrate: Its Uses in Osteoarthritis. Int. J. Mol. Sci., 21.

Cassano, 2016, Bone marrow concentrate and platelet-rich plasma differ in cell distribution and interleukin 1 receptor antagonist protein concentration, Knee Surg. Sports Traumatol. Arthrosc., 26, 333, 10.1007/s00167-016-3981-9

Gharibi, 2012, Effects of Medium Supplements on Proliferation, Differentiation Potential, and In Vitro Expansion of Mesenchymal Stem Cells, Stem Cells Transl. Med., 1, 771, 10.5966/sctm.2010-0031

Delgado, 2016, Modulation of Synovial Fluid-Derived Mesenchymal Stem Cells by Intra-Articular and Intraosseous Platelet Rich Plasma Administration, Stem Cells Int., 2016, 1247950, 10.1155/2016/1247950

Sassoli, 2018, Combined use of bone marrow-derived mesenchymal stromal cells (BM-MSCs) and platelet rich plasma (PRP) stimulates proliferation and differentiation of myoblasts in vitro: New therapeutic perspectives for skeletal muscle repair/regeneration, Cell Tissue Res., 372, 549, 10.1007/s00441-018-2792-3

Andia, 2013, Platelet-rich plasma for managing pain and inflammation in osteoarthritis, Nat. Rev. Rheumatol., 9, 721, 10.1038/nrrheum.2013.141

Jayaram, 2019, 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, Am. J. Sports Med., 47, 1223, 10.1177/0363546519827294

Frey, C., Yeh, P.C., and Jayaram, P. (2020). Effects of Antiplatelet and Nonsteroidal Anti-inflammatory Medications on Platelet-Rich Plasma: A Systematic Review. Orthop. J. Sports Med., 8.

Schippinger, G., Prüller, F., Divjak, M., Mahla, E., Fankhauser, F., Rackemann, S., and Raggam, R.B. (2015). Autologous Platelet-Rich Plasma Preparations. Orthop. J. Sports Med., 3.

Reed, 2000, Molecular mechanisms of platelet exocytosis: Insights into the “secrete” life of thrombocytes, Blood, 96, 10

Bartrons, 2000, Inhibition of cyclooxygenase-2 decreases DNA synthesis induced by platelet-derived growth factor in Swiss 3T3 fibroblasts, J. Pharmacol. Exp. Ther., 293, 509

Tarnawski, 2003, Inhibition of angiogenesis by NSAIDs: Molecular mechanisms and clinical implications, J. Mol. Med., 81, 627, 10.1007/s00109-003-0479-y

Mannava, 2019, The Influence of Naproxen on Biological Factors in Leukocyte-Rich Platelet-Rich Plasma: A Prospective Comparative Study, Arthrosc. J. Arthrosc. Relat. Surg., 35, 201, 10.1016/j.arthro.2018.07.030

Neph, 2020, Role of Mechanical Loading for Platelet-Rich Plasma-Treated Achilles Tendinopathy, Curr. Sports Med. Rep., 19, 209, 10.1249/JSR.0000000000000719

Ekinci, D. (2015). Current Concepts and Translational Uses of Platelet Rich Plasma Biotechnology. Biotechnology, InTech.

Filardo, G., Previtali, D., Napoli, F., Candrian, C., Zaffagnini, S., and Grassi, A. (2020). PRP Injections for the Treatment of Knee Osteoarthritis: A Meta-Analysis of Randomized Controlled Trials. Cartilage.

Virchenko, 2006, How can one platelet injection after tendon injury lead to a stronger tendon after 4 weeks? Interplay between early regeneration and mechanical stimulation, Acta Orthop., 77, 806, 10.1080/17453670610013033

Harshwardhan, 2020, Assessment of clinical outcomes of PRP therapy in OA knee, Int. J. Orthop. Sci., 6, 201, 10.22271/ortho.2020.v6.i1d.1862

Bek, 2012, Home-based general versus center-based selective rehabilitation in patients with posterior tibial tendon dysfunction, Acta Orthop. Traumatol. Turc., 46, 286, 10.3944/AOTT.2012.2488

Huber, 2012, Supervised versus Uncontrolled Rehabilitation of Patients after Rotator Cuff Repair-Clinical and Neurophysiological Comparative Study, Int. J. Artif. Organs, 35, 45, 10.5301/ijao.5000037