{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T17:34:02Z","timestamp":1790703242558,"version":"4.1.0"},"reference-count":88,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2023,9,20]],"date-time":"2023-09-20T00:00:00Z","timestamp":1695168000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Research Foundation Flanders","award":["G0C1916N"],"award-info":[{"award-number":["G0C1916N"]}]},{"name":"Research Foundation Flanders","award":["12Z2620N"],"award-info":[{"award-number":["12Z2620N"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Leukocyte- and Platelet-Rich Fibrin (L-PRF) is a second-generation platelet concentrate that is prepared directly from the patient\u2019s own blood. It is widely used in the field of regenerative medicine, and to better understand its clinical applicability we aimed to further explore the biological properties and effects of L-PRF on cells from the central and peripheral nervous system. To this end, L-PRF was prepared from healthy human donors, and confocal, transmission, and scanning electron microscopy as well as secretome analysis were performed on these clots. In addition, functional assays were completed to determine the effect of L-PRF on neural stem cells (NSCs), primary cortical neurons (pCNs), and peripheral dorsal root ganglion (DRG) neurons. We observed that L-PRF consists of a dense but porous fibrin network, containing leukocytes and aggregates of activated platelets that are distributed throughout the clot. Antibody array and ELISA confirmed that it is a reservoir for a plethora of growth factors. Key molecules that are known to have an effect on neuronal cell functions such as brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), vascular endothelial growth factor (VEGF), and platelet-derived growth factor (PDGF) were slowly released over time from the clots. Next, we found that the L-PRF secretome had no significant effect on the proliferative and metabolic activity of NSCs, but it did act as a chemoattractant and improved the migration of these CNS-derived stem cells. More importantly, L-PRF growth factors had a detrimental effect on the survival of pCNs, and consequently, also interfered with their neurite outgrowth. In contrast, we found a positive effect on peripheral DRG neurons, and L-PRF growth factors improved their survival and significantly stimulated the outgrowth and branching of their neurites. Taken together, our study demonstrates the positive effects of the L-PRF secretome on peripheral neurons and supports its use in regenerative medicine but care should be taken when using it for CNS applications.<\/jats:p>","DOI":"10.3390\/ijms241814314","type":"journal-article","created":{"date-parts":[[2023,9,20]],"date-time":"2023-09-20T01:32:50Z","timestamp":1695173570000},"page":"14314","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["The Effect of Leukocyte- and Platelet-Rich Fibrin on Central and Peripheral Nervous System Neurons\u2014Implications for Biomaterial Applicability"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7520-0021","authenticated-orcid":false,"given":"Ivo","family":"Lambrichts","sequence":"first","affiliation":[{"name":"Cardio and Organ Systems, Biomedical Research Institute, UHasselt\u2014Hasselt University, 3590 Diepenbeek, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9277-6524","authenticated-orcid":false,"given":"Esther","family":"Wolfs","sequence":"additional","affiliation":[{"name":"Cardio and Organ Systems, Biomedical Research Institute, UHasselt\u2014Hasselt University, 3590 Diepenbeek, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annelies","family":"Bronckaers","sequence":"additional","affiliation":[{"name":"Cardio and Organ Systems, Biomedical Research Institute, UHasselt\u2014Hasselt University, 3590 Diepenbeek, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8320-1320","authenticated-orcid":false,"given":"Pascal","family":"Gervois","sequence":"additional","affiliation":[{"name":"Cardio and Organ Systems, Biomedical Research Institute, UHasselt\u2014Hasselt University, 3590 Diepenbeek, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Vangansewinkel","sequence":"additional","affiliation":[{"name":"Cardio and Organ Systems, Biomedical Research Institute, UHasselt\u2014Hasselt University, 3590 Diepenbeek, Belgium"},{"name":"VIB, Center for Brain & Disease Research, Laboratory of Neurobiology, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"eaaz2253","DOI":"10.1126\/scitranslmed.aaz2253","article-title":"A blueprint for translational regenerative medicine","volume":"12","author":"Armstrong","year":"2020","journal-title":"Sci. Transl. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"14452","DOI":"10.1073\/pnas.1508520112","article-title":"Regenerative medicine: Current therapies and future directions","volume":"112","author":"Mao","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1126\/science.aar2955","article-title":"Biomaterials for tissue repair","volume":"363","author":"Christman","year":"2019","journal-title":"Science"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"114","DOI":"10.4161\/org.23306","article-title":"Bone grafts, bone substitutes and orthobiologics: The bridge between basic science and clinical advancements in fracture healing","volume":"8","author":"Roberts","year":"2012","journal-title":"Organogenesis"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1089\/wound.2015.0647","article-title":"Grafix(R), a Cryopreserved Placental Membrane, for the Treatment of Chronic\/Stalled Wounds","volume":"4","author":"Gibbons","year":"2015","journal-title":"Adv. Wound Care"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.biomaterials.2015.08.049","article-title":"Biomaterials with persistent growth factor gradients in vivo accelerate vascularized tissue formation","volume":"72","author":"Akar","year":"2015","journal-title":"Biomaterials"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Subramanian, A., Krishnan, U.M., and Sethuraman, S. (2009). Development of biomaterial scaffold for nerve tissue engineering: Biomaterial mediated neural regeneration. J. Biomed. Sci., 16.","DOI":"10.1186\/1423-0127-16-108"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"6143","DOI":"10.1016\/j.biomaterials.2014.04.064","article-title":"Neural tissue engineering options for peripheral nerve regeneration","volume":"35","author":"Gu","year":"2014","journal-title":"Biomaterials"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.nano.2012.08.009","article-title":"Nanofiber scaffolds facilitate functional regeneration of peripheral nerve injury","volume":"9","author":"Zhan","year":"2013","journal-title":"Nanomed. Nanotechnol. Biol. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.biomaterials.2017.07.020","article-title":"Electrical preconditioning of stem cells with a conductive polymer scaffold enhances stroke recovery","volume":"142","author":"George","year":"2017","journal-title":"Biomaterials"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"6810562","DOI":"10.1155\/2016\/6810562","article-title":"Biomaterial Applications in Cell-Based Therapy in Experimental Stroke","volume":"2016","author":"Boisserand","year":"2016","journal-title":"Stem Cells Int."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"203","DOI":"10.14336\/AD.2017.0305","article-title":"Combining Injectable Plasma Scaffold with Mesenchymal Stem\/Stromal Cells for Repairing Infarct Cavity after Ischemic Stroke","volume":"8","author":"Zhang","year":"2017","journal-title":"Aging Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1016\/j.mattod.2014.05.011","article-title":"Advanced biomaterials for repairing the nervous system: What can hydrogels do for the brain?","volume":"17","author":"Khaing","year":"2014","journal-title":"Mater. Today"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1089\/ten.2005.11.513","article-title":"Hyaluronic acid-poly-D-lysine-based three-dimensional hydrogel for traumatic brain injury","volume":"11","author":"Tian","year":"2005","journal-title":"Tissue Eng."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Li, Q., Pan, S., Dangaria, S.J., Gopinathan, G., Kolokythas, A., Chu, S., Geng, Y., Zhou, Y., and Luan, X. (2013). Platelet-rich fibrin promotes periodontal regeneration and enhances alveolar bone augmentation. BioMed Res. Int., 2013.","DOI":"10.1155\/2013\/638043"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.jse.2013.08.017","article-title":"Increased vascularization during early healing after biologic augmentation in repair of chronic rotator cuff tears using autologous leukocyte- and platelet-rich fibrin (L-PRF): A prospective randomized controlled pilot trial","volume":"23","author":"Zumstein","year":"2014","journal-title":"J. Shoulder Elb. Surg."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e45","DOI":"10.1016\/j.tripleo.2005.07.009","article-title":"Platelet-rich fibrin (PRF): A second-generation platelet concentrate. Part II: Platelet-related biologic features","volume":"101","author":"Dohan","year":"2006","journal-title":"Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endodontology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.2174\/138920112800624391","article-title":"Current knowledge and perspectives for the use of platelet-rich plasma (PRP) and platelet-rich fibrin (PRF) in oral and maxillofacial surgery part 1: Periodontal and dentoalveolar surgery","volume":"13","author":"Vervelle","year":"2012","journal-title":"Curr. Pharm. Biotechnol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e37","DOI":"10.1016\/j.tripleo.2005.07.008","article-title":"Platelet-rich fibrin (PRF): A second-generation platelet concentrate. Part I: Technological concepts and evolution","volume":"101","author":"Dohan","year":"2006","journal-title":"Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endodontology"},{"key":"ref_20","first-page":"e56","article-title":"Platelet-rich fibrin (PRF): A second-generation platelet concentrate","volume":"101","author":"Choukroun","year":"2006","journal-title":"Part IV: Clinical effects on tissue healingOral Surg. Oral Med. Oral Pathol. Oral Radiol. Endodontology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"8509","DOI":"10.3390\/ijms15058509","article-title":"Lyophilized platelet-rich fibrin (PRF) promotes craniofacial bone regeneration through Runx2","volume":"15","author":"Li","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"252","DOI":"10.3109\/09537104.2013.809060","article-title":"Growth-promoting action and growth factor release by different platelet derivatives","volume":"25","author":"Passaretti","year":"2014","journal-title":"Platelets"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1016\/j.jobcr.2022.08.020","article-title":"The impact of gender and peripheral blood parameters on the characteristics of L-PRF membranes","volume":"12","author":"Quirynen","year":"2022","journal-title":"J. Oral Biol. Craniofacial Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"855","DOI":"10.11607\/jomi.7275","article-title":"Characterization of the Leukocyte- and Platelet-Rich Fibrin Block: Release of Growth Factors, Cellular Content, and Structure","volume":"34","author":"Castro","year":"2019","journal-title":"Int. J. Oral Maxillofac. Implant."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"6038","DOI":"10.1038\/s41598-021-85736-y","article-title":"Impact of g force and timing on the characteristics of platelet-rich fibrin matrices","volume":"11","author":"Castro","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1635","DOI":"10.1007\/s11999-015-4192-2","article-title":"Platelet-rich concentrates differentially release growth factors and induce cell migration in vitro","volume":"473","author":"Schar","year":"2015","journal-title":"Clin. Orthop. Relat. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s40729-016-0052-4","article-title":"Growth factor and pro-inflammatory cytokine contents in platelet-rich plasma (PRP), plasma rich in growth factors (PRGF), advanced platelet-rich fibrin (A-PRF), and concentrated growth factors (CGF)","volume":"2","author":"Masuki","year":"2016","journal-title":"Int. J. Implant. Dent."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.2174\/138920112800624337","article-title":"Leukocyte- and platelet-rich fibrin (L-PRF) for long-term delivery of growth factor in rotator cuff repair: Review, preliminary results and future directions","volume":"13","author":"Zumstein","year":"2012","journal-title":"Curr. Pharm. Biotechnol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1089\/ten.tea.2010.0327","article-title":"Platelet-rich fibrin is a Bioscaffold and reservoir of growth factors for tissue regeneration","volume":"17","author":"Kang","year":"2011","journal-title":"Tissue Eng. Part A"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.2174\/138920112800624382","article-title":"Do the Fibrin Architecture and Leukocyte Content Influence the Growth Factor Release of Platelet Concentrates? An Evidence-based Answer Comparing a Pure Platelet-Rich Plasma (P-PRP) Gel and a Leukocyte- and Platelet-Rich Fibrin (L-PRF)","volume":"13","author":"Ehrenfest","year":"2012","journal-title":"Curr. Pharm. Biotechnol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1007\/s10561-012-9349-6","article-title":"Platelet rich fibrin: A new paradigm in periodontal regeneration","volume":"14","author":"Kumar","year":"2013","journal-title":"Cell Tissue Bank."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.tmrv.2014.11.001","article-title":"Platelet derivatives in regenerative medicine: An update","volume":"29","author":"Sommese","year":"2015","journal-title":"Transfus. Med. Rev."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.tibtech.2008.11.009","article-title":"Classification of platelet concentrates: From pure platelet-rich plasma (P-PRP) to leucocyte- and platelet-rich fibrin (L-PRF)","volume":"27","author":"Rasmusson","year":"2009","journal-title":"Trends Biotechnol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Marenzi, G., Riccitiello, F., Tia, M., di Lauro, A., and Sammartino, G. (2015). Influence of Leukocyte- and Platelet-Rich Fibrin (L-PRF) in the Healing of Simple Postextraction Sockets: A Split-Mouth Study. BioMed Res. Int., 2015.","DOI":"10.1155\/2015\/369273"},{"key":"ref_35","first-page":"e119","article-title":"Use of leukocyte and platelet-rich fibrin (L-PRF) in periodontally accelerated osteogenic orthodontics (PAOO): Clinical effects on edema and pain","volume":"8","author":"Munoz","year":"2016","journal-title":"J. Clin. Exp. Dent."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1111\/jcpe.13463","article-title":"Effect of different platelet-rich fibrin matrices for ridge preservation in multiple tooth extractions: A split-mouth randomized controlled clinical trial","volume":"48","author":"Castro","year":"2021","journal-title":"J. Clin. Periodontol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.11607\/jomi.7371","article-title":"Simultaneous sinus floor elevation and implant placement using leukocyte- and platelet-rich fibrin as a sole graft material","volume":"34","author":"Molemans","year":"2019","journal-title":"Int. J. Oral Maxillofac. Implant."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Bai, M.Y., Vy, V.P.T., Tang, S.L., Hung, T.N.K., Wang, C.W., Liang, J.Y., Wong, C.C., and Chan, W.P. (2023). Current Progress of Platelet-Rich Derivatives in Cartilage and Joint Repairs. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241612608"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1080\/09537104.2017.1327654","article-title":"Leucocyte- and platelet-rich fibrin (L-PRF) as a regenerative medicine strategy for the treatment of refractory leg ulcers: A prospective cohort study","volume":"29","author":"Pinto","year":"2018","journal-title":"Platelets"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"7532637","DOI":"10.1155\/2023\/7532637","article-title":"Impact of a Novel Hydrogel with Injectable Platelet-Rich Fibrin in Diabetic Wound Healing","volume":"2023","author":"Bai","year":"2023","journal-title":"J. Diabetes Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1016\/j.tem.2020.10.003","article-title":"Autologous Platelet-Rich Plasma for Diabetic Foot Ulcer","volume":"31","author":"Shao","year":"2020","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"121","DOI":"10.4103\/JCAS.JCAS_116_22","article-title":"A Comparative Study on Therapeutic Efficacy of Autologous Platelet-rich Plasma, Autologous Platelet-rich Fibrin Matrix, Recombinant Human Epidermal Growth Factor, and Collagen Particles in Nonhealing Leg Ulcers","volume":"16","author":"Gehlawat","year":"2023","journal-title":"J. Cutan. Aesthetic Surg."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/ijos.2017.1","article-title":"Platelet-rich plasma for regeneration of neural feedback pathways around dental implants: A concise review and outlook on future possibilities","volume":"9","author":"Huang","year":"2017","journal-title":"Int. J. Oral Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1002\/micr.22105","article-title":"Effect of Platelet Rich Plasma and Platelet Rich Fibrin on sciatic nerve regeneration in a rat model","volume":"33","author":"Lichtenfels","year":"2013","journal-title":"Microsurgery"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1080\/14712598.2017.1259409","article-title":"Platelet-rich plasma, a source of autologous growth factors and biomimetic scaffold for peripheral nerve regeneration","volume":"17","author":"Sanchez","year":"2017","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1002\/term.1756","article-title":"Effect of platelet-rich plasma (PRP) concentration on proliferation, neurotrophic function and migration of Schwann cells in vitro","volume":"10","author":"Zheng","year":"2016","journal-title":"J. Tissue Eng. Regen. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/S0168-3659(00)00296-0","article-title":"Controlled release of nerve growth factor from a heparin-containing fibrin-based cell ingrowth matrix","volume":"69","author":"Hubbell","year":"2000","journal-title":"J. Control. Release Off. J. Control. Release Soc."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/j.jconrel.2006.05.005","article-title":"Delivery of neurotrophin-3 from fibrin enhances neuronal fiber sprouting after spinal cord injury","volume":"113","author":"Taylor","year":"2006","journal-title":"J. Control. Release Off. J. Control. Release Soc."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"5127","DOI":"10.1039\/c0sm00173b","article-title":"Tissue-engineered fibrin scaffolds containing neural progenitors enhance functional recovery in a subacute model of SCI","volume":"6","author":"Johnson","year":"2010","journal-title":"Soft Matter"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"14632","DOI":"10.1038\/s41598-018-32936-8","article-title":"Angiogenic Properties of \u2018Leukocyte- and Platelet-Rich Fibrin\u2019","volume":"8","author":"Ratajczak","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2195","DOI":"10.1089\/neu.2017.5497","article-title":"Differential Response in Novel Stem Cell Niches of the Brain after Cervical Spinal Cord Injury and Traumatic Brain Injury","volume":"35","author":"Falnikar","year":"2018","journal-title":"J. Neurotrauma"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1125785","DOI":"10.3389\/fncel.2023.1125785","article-title":"Endogenous neural stem cells characterization using omics approaches: Current knowledge in health and disease","volume":"17","author":"Murtaj","year":"2023","journal-title":"Front. Cell. Neurosci."},{"key":"ref_53","first-page":"53","article-title":"Therapeutic Application of Stem Cells in the Repair of Traumatic Brain Injury","volume":"15","author":"Adugna","year":"2022","journal-title":"Stem Cells Cloning"},{"key":"ref_54","first-page":"1071","article-title":"The influence of platelet-rich fibrin on angiogenesis in guided bone regeneration using xenogenic bone substitutes: A study of rabbit cranial defects","volume":"42","author":"Yoon","year":"2014","journal-title":"J. Cranio-Maxillofac. Surg. Off. Publ. Eur. Assoc. Cranio-Maxillofac. Surg."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1055\/s-0036-1584894","article-title":"Role of Leukocyte-Platelet-Rich Fibrin in Endoscopic Endonasal Skull Base Surgery Defect Reconstruction","volume":"78","author":"Soldatova","year":"2017","journal-title":"J. Neurol. Surg. Part B Skull Base"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1843","DOI":"10.1172\/JCI200317977","article-title":"VEGF-induced neuroprotection, neurogenesis, and angiogenesis after focal cerebral ischemia","volume":"111","author":"Sun","year":"2003","journal-title":"J. Clin. Investig."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1016\/j.neuroscience.2004.11.056","article-title":"Platelet-derived growth factor (PDGF-BB) and brain-derived neurotrophic factor (BDNF) induce striatal neurogenesis in adult rats with 6-hydroxydopamine lesions","volume":"132","author":"Mohapel","year":"2005","journal-title":"Neuroscience"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"8219","DOI":"10.3390\/ijms13078219","article-title":"The neuroprotective functions of transforming growth factor beta proteins","volume":"13","author":"Dobolyi","year":"2012","journal-title":"Int. J. Mol. Sci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1528","DOI":"10.1038\/jcbfm.2009.75","article-title":"Postischemic IGF-1 gene transfer promotes neurovascular regeneration after experimental stroke","volume":"29","author":"Zhu","year":"2009","journal-title":"J. Cereb. Blood Flow Metab. Off. J. Int. Soc. Cereb. Blood Flow Metab."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1002\/jnr.490340105","article-title":"Transforming Growth-Factor-Beta as a Neuronoglial Signal during Peripheral Nervous-System Response to Injury","volume":"34","author":"Rogister","year":"1993","journal-title":"J. Neurosci. Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1002\/glia.10074","article-title":"Platelet-derived growth factor-b expression induced after rat peripheral nerve injuries","volume":"38","author":"Oya","year":"2002","journal-title":"Glia"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1046\/j.1471-4159.1995.64020850.x","article-title":"Interleukin-6 production by Schwann cells and induction in sciatic nerve injury","volume":"64","author":"Bolin","year":"1995","journal-title":"J. Neurochem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1002\/mus.21485","article-title":"Effect of locally delivered IGF-1 on nerve regeneration during aging: An experimental study in rats","volume":"41","author":"Apel","year":"2010","journal-title":"Muscle Nerve"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1111\/j.1365-2990.2011.01159.x","article-title":"Enhancement of sciatic nerve regeneration after vascular endothelial growth factor (VEGF) gene therapy","volume":"37","author":"Lisboa","year":"2011","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1146\/annurev.matsci.31.1.81","article-title":"Biological responses to materials","volume":"31","author":"Anderson","year":"2001","journal-title":"Annu. Rev. Mater. Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"21071","DOI":"10.1038\/srep21071","article-title":"Synergistic interactions of blood-borne immune cells, fibroblasts and extracellular matrix drive repair in an in vitro peri-implant wound healing model","volume":"6","author":"Burkhardt","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Zou, J., Swieringa, F., de Laat, B., de Groot, P.G., Roest, M., and Heemskerk, J.W.M. (2022). Reversible Platelet Integrin alphaIIbbeta3 Activation and Thrombus Instability. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232012512"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"7858","DOI":"10.1074\/jbc.M115.706861","article-title":"The Platelet Integrin alphaIIbbeta3 Differentially Interacts with Fibrin Versus Fibrinogen","volume":"291","author":"Litvinov","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_69","first-page":"3","article-title":"Classification of platelet concentrates (Platelet-Rich Plasma-PRP, Platelet-Rich Fibrin-PRF) for topical and infiltrative use in orthopedic and sports medicine: Current consensus, clinical implications and perspectives","volume":"4","author":"Andia","year":"2014","journal-title":"Muscles Ligaments Tendons J."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1111\/jocd.13742","article-title":"Injectable Platelet-Rich Fibrin (PRF): The newest biomaterial and its use in various dermatological conditions in our practice: A case series","volume":"20","author":"Shashank","year":"2021","journal-title":"J. Cosmet. Dermatol."},{"key":"ref_71","first-page":"e28647","article-title":"Injectable Platelet-Rich Fibrin\u2014A Revolution in Periodontal Regeneration","volume":"14","author":"Gollapudi","year":"2022","journal-title":"Cureus"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1111\/jre.12991","article-title":"Mechanical properties and cellular content of leukocyte- and platelet-rich fibrin membranes of patients on antithrombotic drugs","volume":"57","author":"Ockerman","year":"2022","journal-title":"J. Periodontal Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1002\/(SICI)1098-1136(199911)28:2<114::AID-GLIA3>3.0.CO;2-O","article-title":"Neuronal death in cytokine-activated primary human brain cell culture: Role of tumor necrosis factor-alpha","volume":"28","author":"Downen","year":"1999","journal-title":"Glia"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1497","DOI":"10.1007\/s00701-018-3579-8","article-title":"Plasma-rich fibrin in neurosurgery: A feasibility study","volume":"160","author":"Theys","year":"2018","journal-title":"Acta Neurochir."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1744","DOI":"10.1096\/fj.201601121R","article-title":"Ionotropic glutamate receptors activate cell signaling in response to glutamate in Schwann cells","volume":"31","author":"Campana","year":"2016","journal-title":"FASEB J."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.regpep.2012.10.005","article-title":"Neuregulin-1beta regulates tyrosine kinase receptor expression in cultured dorsal root ganglion neurons with excitotoxicity induced by glutamate","volume":"180","author":"Yue","year":"2013","journal-title":"Regul. Pept."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1055\/s-0037-1603355","article-title":"Platelet-Rich Fibrin Conduits as an Alternative to Nerve Autografts for Peripheral Nerve Repair","volume":"33","author":"Roth","year":"2017","journal-title":"J. Reconstr. Microsurg."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1097\/SCS.0000000000007003","article-title":"Effects of Platelet-Rich Fibrin\/Collagen Membrane on Sciatic Nerve Regeneration","volume":"32","author":"Vares","year":"2021","journal-title":"J. Craniofacial Surg."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.hansur.2022.12.001","article-title":"Peripheral nerve regeneration in rats using nerve graft in a vein conduit pre-filled with platelet-rich fibrin (PRF)","volume":"42","author":"Fernandes","year":"2023","journal-title":"Hand Surg. Rehabil."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.alcohol.2020.03.005","article-title":"The mouse-equivalent of the human BDNF VAL66MET polymorphism increases dorsal hippocampal volume and does not interact with developmental ethanol exposure","volume":"86","author":"Bird","year":"2020","journal-title":"Alcohol"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.bbapap.2014.12.005","article-title":"A comparative analysis of the structural, functional and biological differences between Mouse and Human Nerve Growth Factor","volume":"1854","author":"Paoletti","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2582080","DOI":"10.1155\/2017\/2582080","article-title":"The Angiogenic Potential of DPSCs and SCAPs in an In Vivo Model of Dental Pulp Regeneration","volume":"2017","author":"Hilkens","year":"2017","journal-title":"Stem Cells Int."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"8589149","DOI":"10.1155\/2019\/8589149","article-title":"Preconditioning of Human Dental Pulp Stem Cells with Leukocyte- and Platelet-Rich Fibrin-Derived Factors Does Not Enhance Their Neuroregenerative Effect","volume":"2019","author":"Gervois","year":"2019","journal-title":"Stem Cells Int."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1634","DOI":"10.1096\/fj.13-243980","article-title":"Human dental pulp stem cells can differentiate into Schwann cells and promote and guide neurite outgrowth in an aligned tissue-engineered collagen construct in vitro","volume":"28","author":"Martens","year":"2014","journal-title":"FASEB J."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Conti, L., Pollard, S.M., Gorba, T., Reitano, E., Toselli, M., Biella, G., Sun, Y., Sanzone, S., Ying, Q.L., and Cattaneo, E. (2005). Niche-independent symmetrical self-renewal of a mammalian tissue stem cell. PLoS Biol., 3.","DOI":"10.1371\/journal.pbio.0030283"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"851","DOI":"10.3727\/096368910X543411","article-title":"Clinical potential of intravenous neural stem cell delivery for treatment of neuroinflammatory disease in mice?","volume":"20","author":"Reekmans","year":"2011","journal-title":"Cell Transplant."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Banker, G., and Goslin, K. (1998). Culturing Nerve Cells, MIT Press. [2nd ed.].","DOI":"10.7551\/mitpress\/4913.001.0001"},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Vangansewinkel, T., Lemmens, S., Tiane, A., Geurts, N., Dooley, D., Vanmierlo, T., Pejler, G., and Hendrix, S. (2023). Therapeutic administration of mouse mast cell protease 6 improves functional recovery after traumatic spinal cord injury in mice by promoting remyelination and reducing glial scar formation. FASEB J., 37.","DOI":"10.1096\/fj.202201942RR"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/18\/14314\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:54:10Z","timestamp":1760129650000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/18\/14314"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,20]]},"references-count":88,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2023,9]]}},"alternative-id":["ijms241814314"],"URL":"https:\/\/doi.org\/10.3390\/ijms241814314","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,20]]}}}