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Restoring function to peripheral nerves with a gap is challenging, with <50% of patients undergoing nerve repair surgery recovering function. Sensory nerve grafts (autografts) are the clinical “gold standard” for bridging nerve gaps to restore sensory and motor function. They have significant limitations and restore meaningful function only across short gaps when repairs are performed soon after trauma and patients are young. When the value of any of these variables is large, the extent of recovery decreases precipitously, and when two or all are simultaneously large, there is little to no recovery. The extent of restored meaningful recovery has not increased in almost 70 years. Thus, novel techniques are needed that enhance both the extent of recovery and the percentage of patients who recover meaningful recovery. This paper reviews the limitations of autografts and other materials used to repair nerves. It also examines autologous platelet-rich plasma (PRP), a promising nerve gap repair technique that induces recovery in clinical settings where autografts are ineffective, including when the values of all three variables are simultaneously large.
Pan D, MacKinnon SE, Wood MD. Advances in the repair of segmental nerve injuries and trends in reconstruction. Muscle Nerve. 2020;61(6):726–739. https://doi.org/10.1002/mus.26797.
Ansaripour A, Thompson A, Styron JF, et al. Cost-effectiveness analysis of Avance® allograft for the treatment of peripheral nerve injuries in the USA. J Comp Eff Res. 2024;13(1):e230113. https://doi.org/10.57264/cer-2023-0113.
Hoben GM, Ee XP, Schellhardt L, et al. Increasing nerve autograft length increases senescence and reduces regeneration. Plast Reconstr Surg. 2018;142(4):952–961. https://doi.org/10.1097/PRS.0000000000004759.
Campodonico A, Pangrazi PP, De Francesco F, et al. Reconstruction of a long defect of the Median nerve with a free nerve conduit flap. Arch Plast Surg. 2020;47(2):187–193. https://doi.org/10.5999/aps.2019.00654.
Kornfeld T, Vogt PM, Radtke C. Nerve grafting for peripheral nerve injuries with extended defect sizes. Wien Med Wochenschr. 2019;169(9/10):240–251. https://doi.org/10.1007/s10354-018-0675-6.
Wolfe SW, Johnsen PH, Lee SK, et al. Long-nerve grafts and nerve transfers demonstrate comparable outcomes for axillary nerve injuries. J Hand Surg Am. 2014;39(7):1351–1357. https://doi.org/10.1016/j.jhsa.2014.02.032.
Karabeg R, Jakirlic M, Dujso V. Sensory recovery after forearm Median and ulnar nerve grafting. Med Arh. 2009;63(2):97–99.
Lans J, Eberlin KR, Evans PJ, et al. A systematic review and meta-analysis of nerve gap repair: comparative effectiveness of allografts, autografts, and conduits. Plast Reconstr Surg. 2023;151(5):814e–827e. https://doi.org/10.1097/PRS.0000000000010088.
Costales JR, Socolovsky M, Sánchez Lázaro JA, et al. Peripheral nerve injuries in the pediatric population: a review of the literature. Part Ⅰ: traumatic nerve injuries. Childs Nerv Syst. 2019;35(1):29–35. https://doi.org/10.1007/s00381-018-3974-8.
Foy CA, Micheo WF, Kuffler DP. Functional recovery following repair of long nerve gaps in senior patient 2.6 Years posttrauma. Plast Reconstr Surg Glob Open. 2021;9(9):e3831. https://doi.org/10.1097/GOX.0000000000003831.
Grinsell D, Keating CP. Peripheral nerve reconstruction after injury: a review of clinical and experimental therapies. BioMed Res Int. 2014;2014:698256. https://doi.org/10.1155/2014/698256.
McMorrow LA, Kosalko A, Robinson D, et al. Advancing our understanding of the chronically denervated schwann cell: a potential therapeutic target? Biomolecules. 2022;12(8):1128. https://doi.org/10.3390/biom12081128.
Zou HY, Ho C, Wong K, et al. Axotomy-induced Smad1 activation promotes axonal growth in adult sensory neurons. J Neurosci. 2009;29(22):7116–7123. https://doi.org/10.1523/JNEUROSCI.5397-08.2009.
Ronchi G, Cillino M, Gambarotta G, et al. Irreversible changes occurring in long-term denervated Schwann cells affect delayed nerve repair. J Neurosurg. 2017;127(4):843–856. https://doi.org/10.3171/2016.9.JNS16140.
Pellegatta M, Taveggia C. The complex work of proteases and secretases in wallerian degeneration: beyond neuregulin-1. Front Cell Neurosci. 2019;13:93. https://doi.org/10.3389/fncel.2019.00093.
El Soury M, Gambarotta G. Soluble neuregulin-1 (NRG1): a factor promoting peripheral nerve regeneration by affecting Schwann cell activity immediately after injury. Neural Regen Res. 2019;14(8):1374–1375. https://doi.org/10.4103/1673-5374.253516.
Nave KA, Salzer JL. Axonal regulation of myelination by neuregulin 1. Curr Opin Neurobiol. 2006;16(5):492–500. https://doi.org/10.1016/j.conb.2006.08.008.
Cornejo M, Nambi D, Walheim C, et al. Effect of NRG1, GDNF, EGF and NGF in the migration of a Schwann cell precursor line. Neurochem Res. 2010;35(10):1643–1651. https://doi.org/10.1007/s11064-010-0225-0.
Gambarotta G, Fregnan F, Gnavi S, et al. Neuregulin 1 role in Schwann cell regulation and potential applications to promote peripheral nerve regeneration. Int Rev Neurobiol. 2013;108:223–256. https://doi.org/10.1016/B978-0-12-410499-0.00009-5.
Shapira Y, Sammons V, Forden J, et al. Brief electrical stimulation promotes nerve regeneration following experimental In-continuity nerve injury. Neurosurgery. 2019;85(1):156–163. https://doi.org/10.1093/neuros/nyy221.
Koppes AN, Nordberg AL, Paolillo GM, et al. Electrical stimulation of schwann cells promotes sustained increases in neurite outgrowth. Tissue Eng. 2014;20(3/4):494–506. https://doi.org/10.1089/ten.TEA.2013.0012.
Gordon T. Electrical stimulation to enhance axon regeneration after peripheral nerve injuries in animal models and humans. Neurotherapeutics. 2016;13(2):295–310. https://doi.org/10.1007/s13311-015-0415-1.
Gordon T, Udina E, Verge VMK, et al. Brief electrical stimulation accelerates axon regeneration in the peripheral nervous system and promotes sensory axon regeneration in the central nervous system. Mot Control. 2009;13(4):412–441. https://doi.org/10.1123/mcj.13.4.412.
Jin HK, Hwang TY, Cho SH. Effect of electrical stimulation on blood flow velocity and vessel size. Open Med. 2017;12:5–11. https://doi.org/10.1515/med-2017-0002.
Juretic N, Jorquera G, Caviedes P, et al. Electrical stimulation induces calcium-dependent up-regulation of neuregulin-1β in dystrophic skeletal muscle cell lines. Cell Physiol Biochem. 2012;29(5–6):919–930. https://doi.org/10.1159/000188068.
Kao CH, Chen JJJ, Hsu YM, et al. High-frequency electrical stimulation can be a complementary therapy to promote nerve regeneration in diabetic rats. PLoS One. 2013;8(11):e79078. https://doi.org/10.1371/journal.pone.0079078.
Tagami Y, Kurimoto T, Miyoshi T, et al. Axonal regeneration induced by repetitive electrical stimulation of crushed optic nerve in adult rats. Jpn J Ophthalmol. 2009;53(3):257–266. https://doi.org/10.1007/s10384-009-0657-8.
Walsh JJ, Tschakovsky ME. Exercise and circulating BDNF: mechanisms of release and implications for the design of exercise interventions. Appl Physiol Nutr Metabol. 2018;43(11):1095–1104. https://doi.org/10.1139/apnm-2018-0192.
Gordon T, English AW. Strategies to promote peripheral nerve regeneration: electrical stimulation and/or exercise. Eur J Neurosci. 2016;43(3):336–350. https://doi.org/10.1111/ejn.13005.
Hoyng SA, de Winter F, Gnavi S, et al. A comparative morphological, electrophysiological and functional analysis of axon regeneration through peripheral nerve autografts genetically modified to overexpress BDNF, CNTF, GDNF, NGF, NT3 or VEGF. Exp Neurol. 2014;261:578–593. https://doi.org/10.1016/j.expneurol.2014.08.002.
Singh B, Xu QG, Franz CK, et al. Accelerated axon outgrowth, guidance, and target reinnervation across nerve transection gaps following a brief electrical stimulation paradigm. J Neurosurg. 2012;116(3):498–512. https://doi.org/10.3171/2011.10.JNS11612.
Jessen KR, Mirsky R. The repair Schwann cell and its function in regenerating nerves. J Physiol. 2016;594(13):3521–3531. https://doi.org/10.1113/JP270874.
Gordon T. The role of neurotrophic factors in nerve regeneration. Neurosurg Focus. 2009;26(2):E3. https://doi.org/10.3171/FOC.2009.26.2.E3.
Gordon T, Sulaiman O, Boyd JG. Experimental strategies to promote functional recovery after peripheral nerve injuries. J Peripher Nerv Syst. 2003;8(4):236–250. https://doi.org/10.1111/j.1085-9489.2003.03029.x.
Cattin AL, Burden JJ, Van Emmenis L, et al. Macrophage-induced blood vessels guide schwann cell-mediated regeneration of peripheral nerves. Cell. 2015;162(5):1127–1139. https://doi.org/10.1016/j.cell.2015.07.021.
Broeren BO, Duraku LS, Hundepool CA, et al. Nerve recovery from treatment with a vascularized nerve graft compared to an autologous nonvascularized nerve graft in animal models: a systematic review and meta-analysis. PLoS One. 2021;16(12):e0252250. https://doi.org/10.1371/journal.pone.0252250.
Zhu Y, Liu SW, Zhou SH, et al. Vascularized versus nonvascularized facial nerve grafts using a new rabbit model. Plast Reconstr Surg. 2015;135(2):331e–339e. https://doi.org/10.1097/PRS.0000000000000992.
Saffari TM, Bedar M, Hundepool CA, et al. The role of vascularization in nerve regeneration of nerve graft. Neural Regen Res. 2020;15(9):1573–1579. https://doi.org/10.4103/1673-5374.276327.
Rovak JM, Mungara AK, Aydin MA, et al. Effects of vascular endothelial growth factor on nerve regeneration in acellular nerve grafts. J Reconstr Microsurg. 2004;20(1):53–58. https://doi.org/10.1055/s-2004-818050.
Lee JY, Giusti G, Friedrich PF, et al. Effect of vascular endothelial growth factor administration on nerve regeneration after autologous nerve grafting. J Reconstr Microsurg. 2016;32(3):183–188. https://doi.org/10.1055/s-0035-1563709.
Xiao P, Zhang YL, Zeng YT, et al. Impaired angiogenesis in ageing: the central role of the extracellular matrix. J Transl Med. 2023;21(1):457. https://doi.org/10.1186/s12967-023-04315-z.
Gunin AG, Petrov VV, Golubtzova NN, et al. Age-related changes in angiogenesis in human dermis. Exp Gerontol. 2014;55:143–151. https://doi.org/10.1016/j.exger.2014.04.010.
Leckenby JI, Furrer C, Haug L, et al. A retrospective case series reporting the outcomes of avance nerve allografts in the treatment of peripheral nerve injuries. Plast Reconstr Surg. 2020;145(2):368e–381e. https://doi.org/10.1097/PRS.0000000000006485.
Safa B, Jain S, Desai MJ, et al. Peripheral nerve repair throughout the body with processed nerve allografts: results from a large multicenter study. Microsurgery. 2020;40(5):527–537. https://doi.org/10.1002/micr.30574.
Muangsanit P, Shipley RJ, Phillips JB. Vascularization strategies for peripheral nerve tissue engineering. Anat Rec. 2018;301(10):1657–1667. https://doi.org/10.1002/ar.23919.
Patel NP, Lyon KA, Huang JH. An update-tissue engineered nerve grafts for the repair of peripheral nerve injuries. Neural Regen Res. 2018;13(5):764–774. https://doi.org/10.4103/1673-5374.232458.
Wang WJ, Degrugillier L, Tremp M, et al. Nerve repair with fibrin nerve conduit and modified suture placement. Anat Rec. 2018;301(10):1690–1696. https://doi.org/10.1002/ar.23921.
Gontika I, Katsimpoulas M, Antoniou E, et al. Decellularized human umbilical artery used as nerve conduit. Bioengineering. 2018;5(4):100. https://doi.org/10.3390/bioengineering5040100.
Yılmaz MM, Akdere Ö E, Gümüşderelioğlu M, et al. Biological nerve conduit model with de-epithelialized human amniotic membrane and adiposederived mesenchymal stem cell sheet for repair of peripheral nerve defects. Cell Tissue Res. 2023;391(3):505–522. https://doi.org/10.1007/s00441-022-03732-8.
Das S, Thimukonda Jegadeesan J, Basu B. Advancing peripheral nerve regeneration: 3D bioprinting of GelMA-based cell-laden electroactive bioinks for nerve conduits. ACS Biomater Sci Eng. 2024;10(3):1620–1645. https://doi.org/10.1021/acsbiomaterials.3c01226.
di Summa PG, Kingham PJ, Campisi CC, et al. Collagen (NeuraGen®) nerve conduits and stem cells for peripheral nerve gap repair. Neurosci Lett. 2014;572:26–31. https://doi.org/10.1016/j.neulet.2014.04.029.
Sahin C, Karagoz H, Kulahci Y, et al. Minced nerve tissue in vein grafts used as conduits in rat tibial nerves. Ann Plast Surg. 2014;73(5):540–546. https://doi.org/10.1097/SAP.0000000000000060.
Chen ZX, Lu HB, Jin XL, et al. Skeletal muscle-derived cells repair peripheral nerve defects in mice. Neural Regen Res. 2020;15(1):152–161. https://doi.org/10.4103/1673-5374.264462.
Liu YX, Yu SJ, Gu XS, et al. Tissue-engineered nerve grafts using a scaffold-independent and injectable drug delivery system: a novel design with translational advantages. J Neural Eng. 2019;16(3):036030. https://doi.org/10.1088/1741-2552/ab17a0.
MacKinnon SE. Technical use of synthetic conduits for nerve repair. J Hand Surg Am. 2011;36(1):183. https://doi.org/10.1016/j.jhsa.2010.10.013.
Redolfi Riva E, Özkan M, Contreras E, et al. Beyond the limiting gap length: peripheral nerve regeneration through implantable nerve guidance conduits. Biomater Sci. 2024;12(6):1371–1404. https://doi.org/10.1039/d3bm01163a.
Periayah MH, Halim AS, Mat Saad AZ. Mechanism action of platelets and crucial blood coagulation pathways in hemostasis. Int J Hematol Oncol Stem Cell Res. 2017;11(4):319–327.
Golebiewska EM, Poole AW. Platelet secretion: from haemostasis to wound healing and beyond. Blood Rev. 2015;29(3):153–162. https://doi.org/10.1016/j.blre.2014.10.003.
Zumstein MA, Rumian A, Lesbats V, et al. 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. J Shoulder Elbow Surg. 2014;23(1):3–12. https://doi.org/10.1016/j.jse.2013.08.017.
Duerschmied D, Bode C, Ahrens I. Immune functions of platelets. Thromb Haemostasis. 2014;112(4):678–691. https://doi.org/10.1160/TH14-02-0146.
Forehand CC, Cribb J, May JR. Examination of the relationship between antimicrobials and thrombocytosis. Ann Pharmacother. 2012;46(10):1425–1429. https://doi.org/10.1345/aph.1R080.
Lichtenfels M, Colomé L, Sebben AD, et al. Effect of platelet rich plasma and platelet rich fibrin on sciatic nerve regeneration in a rat model. Microsurgery. 2013;33(5):383–390. https://doi.org/10.1002/micr.22105.
Teymur H, Tiftikcioglu YO, Cavusoglu T, et al. Effect of platelet-rich plasma on reconstruction with nerve autografts. Kaohsiung J Med Sci. 2017;33(2):69–77. https://doi.org/10.1016/j.kjms.2016.11.005.
Küçük L, Günay H, Erbaş O, et al. Effects of platelet-rich plasma on nerve regeneration in a rat model. Acta Orthop Traumatol Turcica. 2014;48(4):449–454. https://doi.org/10.3944/AOTT.2014.13.0029.
Zhang YY, Yi D, Hong Q, et al. Platelet-rich plasma-derived exosomes boost mesenchymal stem cells to promote peripheral nerve regeneration. J Contr Release. 2024;367:265–282. https://doi.org/10.1016/j.jconrel.2024.01.043.
Wang SL, Liu XL, Kang ZC, et al. Platelet-rich plasma promotes peripheral nerve regeneration after sciatic nerve injury. Neural Regen Res. 2023;18(2):375–381. https://doi.org/10.4103/1673-5374.346461.
Zheng CB, Zhu QT, Liu XL, et al. Improved peripheral nerve regeneration using acellular nerve allografts loaded with platelet-rich plasma. Tissue Eng. 2014;20(23/24):3228–3240. https://doi.org/10.1089/ten.TEA.2013.0729.
Chuang MH, Ho LH, Kuo TF, et al. Regenerative potential of platelet-rich fibrin releasate combined with adipose tissue-derived stem cells in a rat sciatic nerve injury model. Cell Transplant. 2020;29:963689720919438. https://doi.org/10.1177/0963689720919438.
Hama S., Yokoi T, Orita K, et al. Peripheral nerve regeneration by bioabsorbable nerve conduits filled with platelet-rich fibrin. Clin Neurol Neurosurg. 2024;236:108051. https://doi.org/10.1016/j.clineuro.2023.108051.
Lu CF, Wang B, Zhang PX, et al. Combining chitin biological conduits with small autogenous nerves and platelet-rich plasma for the repair of sciatic nerve defects in rats. CNS Neurosci Ther. 2021;27(7):805–819. https://doi.org/10.1111/cns.13640.
Kim JW, Kim JM, Choi ME, et al. Platelet-rich plasma loaded nerve guidance conduit as implantable biocompatible materials for recurrent laryngeal nerve regeneration. NPJ Regen Med. 2022;7(1):49. https://doi.org/10.1038/s41536-022-00239-2.
Zhu YQ, Peng N, Wang J, et al. Peripheral nerve defects repaired with autogenous vein grafts filled with platelet-rich plasma and active nerve microtissues and evaluated by novel multimodal ultrasound techniques. Biomater Res. 2022;26(1):24. https://doi.org/10.1186/s40824-022-00264-8.
García de Cortázar U, Padilla S, Lobato E, et al. Intraneural platelet-rich plasma injections for the treatment of radial nerve section: a case report. J Clin Med. 2018;7(2):13. https://doi.org/10.3390/jcm7020013.
Sánchez M, Yoshioka T, Ortega M, et al. Ultrasound-guided platelet-rich plasma injections for the treatment of common peroneal nerve palsy associated with multiple ligament injuries of the knee. Knee Surg Sports Traumatol Arthrosc. 2014;22(5):1084–1089. https://doi.org/10.1007/s00167-013-2479-y.
Fahandezh-Saddi Díaz H, Ríos Luna A, Villanueva Martínez M, et al. Surgical treatment of saphenous nerve injury assisted by plasma rich in growth factors (PRGF): lessons from a case report. Clin Pract. 2023;13(5):1090–1099. https://doi.org/10.3390/clinpract13050097.
Foy CA, Micheo WF, Kuffler DP. Sensory and motor recovery following the repair of three long nerve gap in a senior patient 2.6 Years post-trauma. Plast Reconstr Surg Glob Open. 2021;9(9):e3831. https://doi.org/10.1097/GOX.0000000000003831.
Micheo WF, Foy CA, Kuffler DP. A novel technique restores function while eliminating intractable neuropathic pain in a 71-year-old diabetic patient under challenging injury conditions. J Reconstr Microsurg Open. 2023;8(1):e23–e27. https://doi.org/10.1055/s-0042-1757323.
Tamez-Mata Y, Pedroza-Montoya FE, Martínez-Rodríguez HG, et al. Nerve gaps repaired with acellular nerve allografts recellularized with Schwann-like cells: preclinical trial. J Plast Reconstr Aesthetic Surg. 2022;75(1):296–306. https://doi.org/10.1016/j.bjps.2021.05.066.
Tajdaran K, Gordon T, Wood MD, et al. A glial cell line-derived neurotrophic factor delivery system enhances nerve regeneration across acellular nerve allografts. Acta Biomater. 2016;29:62–70. https://doi.org/10.1016/j.actbio.2015.10.001.
Rbia N, Bulstra LF, Lewallen EA, et al. Seeding decellularized nerve allografts with adipose-derived mesenchymal stromal cells: an in vitro analysis of the gene expression and growth factors produced. J Plast Reconstr Aesthetic Surg. 2019;72(8):1316–1325. https://doi.org/10.1016/j.bjps.2019.04.014.
Fitzpatrick J, Bulsara MK, McCrory PR, et al. Analysis of platelet-rich plasma extraction: variations in platelet and blood components between 4 common commercial kits. Orthop J Sports Med. 2017;5(1):2325967116675272. https://doi.org/10.1177/2325967116675272.
Zhang L, Chen S, Chang P, et al. Harmful effects of leukocyte-rich platelet-rich plasma on rabbit tendon stem cells in vitro. Am J Sports Med. 2016;44(8):1941–1951. https://doi.org/10.1177/0363546516644718.
Fitzpatrick J, Bulsara MK, O'Donnell J, et al. The effectiveness of platelet-rich plasma injections in gluteal tendinopathy: a randomized, double-blind controlled trial comparing a single platelet-rich plasma injection with a single corticosteroid injection. Am J Sports Med. 2018;46(4):933–939. https://doi.org/10.1177/0363546517745525.
Mishra AK, Skrepnik NV, Edwards SG, et al. Efficacy of platelet-rich plasma for chronic tennis elbow: a double-blind, prospective, multicenter, randomized controlled trial of 230 patients. Am J Sports Med. 2014;42(2):463–471. https://doi.org/10.1177/0363546513494359.
Wang ZQ, Mudalal M, Sun Y, et al. The effects of leukocyte-platelet rich fibrin (L-PRF) on suppression of the expressions of the pro-inflammatory cytokines, and proliferation of schwann cell, and neurotrophic factors. Sci Rep. 2020;10(1):2421. https://doi.org/10.1038/s41598-020-59319-2.
Mazzucco L, Balbo V, Cattana E, et al. Platelet-rich plasma and platelet gel preparation using Plateltex. Vox Sang. 2008;94(3):202–208. https://doi.org/10.1111/j.1423-0410.2007.01027.x.
Zhu YQ, Jin Z, Wang J, et al. Ultrasound-guided platelet-rich plasma injection and multimodality ultrasound examination of peripheral nerve crush injury. NPJ Regen Med. 2020;5(1):21. https://doi.org/10.1038/s41536-020-00101-3.
Marx RE. Platelet-rich plasma: evidence to support its use. J Oral Maxillofac Surg. 2004;62(4):489–496. https://doi.org/10.1016/j.joms.2003.12.003.
Micheo WF, Foy CA, Kuffler DP. Novel technique for restoring function and eliminating chronic neuropathic pain to a 71-year-old diabetic patient with a 12 cm peripheral nerve gap repaired 1.3 years post-trauma. J Reconstruc Microsurg Open. 2022 (in press).
Rittner HL, Machelska H, Stein C. Leukocytes in the regulation of pain and analgesia. J Leukoc Biol. 2005;78(6):1215–1222. https://doi.org/10.1189/jlb.0405223.
Machelska H, Stein C. Leukocyte-derived opioid peptides and inhibition of pain. J Neuroimmune Pharmacol. 2006;1(1):90–97. https://doi.org/10.1007/s11481-005-9002-2.
Celik MÖ, Labuz D, Henning, et al. Leukocyte opioid receptors mediate analgesia via Ca(2+)-regulated release of opioid peptides. Brain Behav Immun. 2016;57:227–242. https://doi.org/10.1016/j.bbi.2016.04.018.
Keating FK, Sobel BE, Schneider DJ. Effects of increased concentrations of glucose on platelet reactivity in healthy subjects and in patients with and without diabetes mellitus. Am J Cardiol. 2003;92(11):1362–1365. https://doi.org/10.1016/j.amjcard.2003.08.033.
Fitzpatrick J, Bulsara M, Zheng MH. The effectiveness of platelet-rich plasma in the treatment of tendinopathy: a meta-analysis of randomized controlled clinical trials. Am J Sports Med. 2017;45(1):226–233. https://doi.org/10.1177/0363546516643716.
Engström M, Schött U, Romner B, et al. Acidosis impairs the coagulation: a thromboelastographic study. J Trauma. 2006;61(3):624–628. https://doi.org/10.1097/01.ta.0000226739.30655.75.
Zavoico GB, Cragoe Jr EJ, Feinstein MB. Regulation of intracellular pH in human platelets. Effects of thrombin, A23187, and ionomycin and evidence for activation of Na+/H+ exchange and its inhibition by amiloride analogs. J Biol Chem. 1986;261(28):13160–13167.
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. https://doi.org/10.1155/2016/6591717.
Mazzocca AD, McCarthy MBR, Chowaniec DM, et al. Platelet-rich plasma differs according to preparation method and human variability. J Bone Joint Surg Am. 2012;94(4):308–316. https://doi.org/10.2106/JBJS.K.00430.
Belch JJ, McArdle BM, Burns P, et al. The effects of acute smoking on platelet behaviour, fibrinolysis and haemorheology in habitual smokers. Thromb Haemostasis. 1984;51(1):6–8.
Mukamal KJ, Massaro JM, Ault KA, et al. Alcohol consumption and platelet activation and aggregation among women and men: the Framingham Offspring Study. Alcohol Clin Exp Res. 2005;29(10):1906–1912. https://doi.org/10.1097/01.alc.0000183011.86768.61.
Shen MY, Hsiao G, Liu CL, et al. Inhibitory mechanisms of resveratrol in platelet activation: pivotal roles of p38 MAPK and NO/cyclic GMP. Br J Haematol. 2007;139(3):475–485. https://doi.org/10.1111/j.1365-2141.2007.06788.x.
Olas B, Wachowicz B, Saluk-Juszczak J, et al. Effect of resveratrol, a natural polyphenolic compound, on platelet activation induced by endotoxin or thrombin. Thromb Res. 2002;107(3/4):141–145. https://doi.org/10.1016/s0049-3848(02)00273-6.
Frary CD, Johnson RK, Wang MQ. Food sources and intakes of caffeine in the diets of persons in the United States. J Am Diet Assoc. 2005;105(1):110–113. https://doi.org/10.1016/j.jada.2004.10.027.
Williams JK, Clarkson TB. Dietary soy isoflavones inhibit in-vivo constrictor responses of coronary arteries to collagen-induced platelet activation. Coron Artery Dis. 1998;9(11):759–764. https://doi.org/10.1097/00019501-199809110-00009.
Hubbard GP, Wolffram S, Lovegrove JA, et al. Ingestion of quercetin inhibits platelet aggregation and essential components of the collagen-stimulated platelet activation pathway in humans. J Thromb Haemostasis. 2004;2(12):2138–2145. https://doi.org/10.1111/j.1538-7836.2004.01067.x.
Alvarez-Suarez JM, Giampieri F, Tulipani S, et al. One-month strawberry-rich anthocyanin supplementation ameliorates cardiovascular risk, oxidative stress markers and platelet activation in humans. J Nutr Biochem. 2014;25(3):289–294. https://doi.org/10.1016/j.jnutbio.2013.11.002.
Sudic D, Razmara M, Forslund M, et al. High glucose levels enhance platelet activation: involvement of multiple mechanisms. Br J Haematol. 2006;133(3):315–322. https://doi.org/10.1111/j.1365-2141.2006.06012.x.
de Lorgeril M, Renaud S, Mamelle N, et al. Mediterranean alpha-linolenic acid-rich diet in secondary prevention of coronary heart disease. Lancet. 1994; 343(8911):1454–1459. https://doi.org/10.1016/s0140-6736(94)92580-1.
Grozovsky R, Giannini S, Falet H, et al. Regulating billions of blood platelets: glycans and beyond. Blood. 2015;126(16):1877–1884. https://doi.org/10.1182/blood-2015-01-569129.
Yokogoshi H, Wurtman RJ. Meal composition and plasma amino acid ratios: effect of various proteins or carbohydrates, and of various protein concentrations. Metabolism. 1986;35(9):837–842. https://doi.org/10.1016/0026-0495(86)90225-8.
Ahmed Y, van Iddekinge B, Paul C, et al. Retrospective analysis of platelet numbers and volumes in normal pregnancy and in pre-eclampsia. Br J Obstet Gynaecol. 1993;100(3):216–220. https://doi.org/10.1111/j.1471-0528.1993.tb15233.x.
Schlienger RG, Meier CR. Effect of selective serotonin reuptake inhibitors on platelet activation: can they prevent acute myocardial infarction? Am J Cardiovasc Drugs. 2003;3(3):149–162. https://doi.org/10.2165/00129784-200303030-00001.
George JN. Platelets. Lancet. 2000;355(9214):1531–1539. https://doi.org/10.1016/S0140-6736(00)02175-9.
Barkin RL, Fawcett J. The management challenges of chronic pain: the role of antidepressants. Am J Therapeut. 2000;7(1):31–47. https://doi.org/10.1097/00045391-200007010-00006.
Sommer C. Serotonin in pain and analgesia: actions in the periphery. Mol Neurobiol. 2004;30(2):117–125, 10.1385/MN: 30: 2: 117.
Çirci E, Akman YE, Şükür E, et al. Impact of platelet-rich plasma injection timing on healing of Achilles tendon injury in a rat model. Acta Orthop Traumatol Turcica. 2016;50(3):366–372. https://doi.org/10.3944/AOTT.2015.15.0271.
Ebert JR, Wang A, Smith A, et al. A midterm evaluation of postoperative platelet-rich plasma injections on arthroscopic supraspinatus repair: a randomized controlled trial. Am J Sports Med. 2017;45(13):2965–2974. https://doi.org/10.1177/0363546517719048.
Zayni R, Thaunat M, Fayard JM, et al. Platelet-rich plasma as a treatment for chronic patellar tendinopathy: comparison of a single versus two consecutive injections. Muscles Ligaments Tendons J. 2015;5(2):92–98.
Patel S, Dhillon MS, Aggarwal S, et al. Treatment with platelet-rich plasma is more effective than placebo for knee osteoarthritis: a prospective, double-blind, randomized trial. Am J Sports Med. 2013;41(2):356–364. https://doi.org/10.1177/0363546512471299.
Görmeli G, Görmeli CA, Ataoglu B, et al. Multiple PRP injections are more effective than single injections and hyaluronic acid in knees with early osteoarthritis: a randomized, double-blind, placebo-controlled trial. Knee Surg Sports Traumatol Arthrosc. 2017;25(3):958–965. https://doi.org/10.1007/s00167-015-3705-6.
Golzadeh A, Mohammadi R. Effect of local administration of platelet-derived growth factor B on functional recovery of peripheral nerve regeneration: a sciatic nerve transection model. Dent Res J. 2016;13(3):225–232. https://doi.org/10.4103/1735-3327.182181.
Zheng CB, Zhu QT, Liu XL, et al. Effect of platelet-rich plasma (PRP) concentration on proliferation, neurotrophic function and migration of Schwann cells in vitro. J Tissue Eng Regen Med. 2016;10(5):428–436. https://doi.org/10.1002/term.1756.
Sowa Y, Kishida T, Tomita K, et al. Reply: involvement of PDGF-BB and IGF-1 in activation of human schwann cells by platelet-rich plasma. Plast Reconstr Surg. 2020;146(6):826e–827e. https://doi.org/10.1097/PRS.0000000000007407.
Oya T, Zhao YL, Takagawa K, et al. Platelet-derived growth factor-b expression induced after rat peripheral nerve injuries. Glia. 2002;38(4):303–312. https://doi.org/10.1002/glia.10074.
Dahlgren LA, Mohammed HO, Nixon AJ. Temporal expression of growth factors and matrix molecules in healing tendon lesions. J Orthop Res. 2005;23(1):84–92. https://doi.org/10.1016/j.orthres.2004.05.007.
Cao RH, Bråkenhielm E, Li XR, et al. Angiogenesis stimulated by PDGF-CC, a novel member in the PDGF family, involves activation of PDGFR-alphaalpha and-alphabeta receptors. Faseb J. 2002;16(12):1575–1583. https://doi.org/10.1096/fj.02-0319com.
Cheng HL, Steinway ML, Russell JW, et al. GTPases and phosphatidylinositol 3-kinase are critical for insulin-like growth factor-Ⅰ-mediated Schwann cell motility. J Biol Chem. 2000;275(35):27197–27204. https://doi.org/10.1074/jbc.M002534200.
Laurino L, Wang XX, de la Houssaye BA, et al. PI3K activation by IGF-1 is essential for the regulation of membrane expansion at the nerve growth cone. J Cell Sci. 2005;118(Pt 16):3653–3662. https://doi.org/10.1242/jcs.02490.
Rabinovsky ED. The multifunctional role of IGF-1 in peripheral nerve regeneration. Neurol Res. 2004;26(2):204–210. https://doi.org/10.1179/016164104225013851.
Nieto-Estévez V, Defterali Ç, Vicario-Abejón C. IGF-Ⅰ: a key growth factor that regulates neurogenesis and synaptogenesis from embryonic to adult stages of the brain. Front Neurosci. 2016;10:52. https://doi.org/10.3389/fnins.2016.00052.
Apel PJ, Ma JJ, Callahan M, et al. Effect of locally delivered IGF-1 on nerve regeneration during aging: an experimental study in rats. Muscle Nerve. 2010;41(3):335–341. https://doi.org/10.1002/mus.21485.
Qin J, Wang L, Sun Y, et al. Concentrated growth factor increases Schwann cell proliferation and neurotrophic factor secretion and promotes functional nerve recovery in vivo. Int J Mol Med. 2016;37(2):493–500. https://doi.org/10.3892/ijmm.2015.2438.
Qin J, Wang L, Zheng L, et al. Concentrated growth factor promotes Schwann cell migration partly through the integrin β1-mediated activation of the focal adhesion kinase pathway. Int J Mol Med. 2016;37(5):1363–1370. https://doi.org/10.3892/ijmm.2016.2520.
Moyle M, Napier MA, McLean JW. Cloning and expression of a divergent integrin subunit beta 8. J Biol Chem. 1991;266(29):19650–19658.
Ma L, Shen FX, Jun K, et al. Integrin β8 deletion enhances vascular dysplasia and hemorrhage in the brain of adult Alk1 heterozygous mice. Transl Stroke Res. 2016;7(6):488–496. https://doi.org/10.1007/s12975-016-0478-2.
Xia B, Lv YG. Dual-delivery of VEGF and NGF by emulsion electrospun nanofibrous scaffold for peripheral nerve regeneration. Mater Sci Eng C. 2018;82:253–264. https://doi.org/10.1016/j.msec.2017.08.030.
Raimondo TM, Li HH, Kwee BJ, et al. Combined delivery of VEGF and IGF-1 promotes functional innervation in mice and improves muscle transplantation in rabbits. Biomaterials. 2019;216:119246. https://doi.org/10.1016/j.biomaterials.2019.119246.
Scheib JL, Höke A. An attenuated immune response by Schwann cells and macrophages inhibits nerve regeneration in aged rats. Neurobiol Aging. 2016;45:1–9. https://doi.org/10.1016/j.neurobiolaging.2016.05.004.
Painter MW, Brosius Lutz A, Cheng YC, et al. Diminished Schwann cell repair responses underlie age-associated impaired axonal regeneration. Neuron. 2014;83(2):331–343. https://doi.org/10.1016/j.neuron.2014.06.016.
Wynn TA, Barron L. Macrophages: master regulators of inflammation and fibrosis. Semin Liver Dis. 2010;30(3):245–257. https://doi.org/10.1055/s-0030-1255354.
Böttner M, Krieglstein K, Unsicker K. The transforming growth factor-betas: structure, signaling, and roles in nervous system development and functions. J Neurochem. 2000;75(6):2227–2240. https://doi.org/10.1046/j.1471-4159.2000.0752227.x.
Maldonado LAG, Nascimento CR, Rodrigues Fernandes NA, et al. Influence of tumor cell-derived TGF-β on macrophage phenotype and macrophagemediated tumor cell invasion. Int J Biochem Cell Biol. 2022;153:106330. https://doi.org/10.1016/j.biocel.2022.106330.
Islam A, Choudhury ME, Kigami Y, et al. Sustained anti-inflammatory effects of TGF-β1 on microglia/macrophages. Biochim Biophys Acta, Mol Basis Dis. 2018;1864(3):721–734. https://doi.org/10.1016/j.bbadis.2017.12.022.
Kim JS, Kim JG, Moon MY, et al. Transforming growth factor-beta1 regulates macrophage migration via RhoA. Blood. 2006;108(6):1821–1829. https://doi.org/10.1182/blood-2005-10-009191.
Huynh MLN, Fadok VA, Henson PM. Phosphatidylserine-dependent ingestion of apoptotic cells promotes TGF-beta1 secretion and the resolution of inflammation. J Clin Invest. 2002;109(1):41–50. https://doi.org/10.1172/JCI11638.
Sulaiman W, Nguyen DH. Transforming growth factor beta 1, a cytokine with regenerative functions. Neural Regen Res. 2016;11(10):1549–1552. https://doi.org/10.4103/1673-5374.193223.
Liang GY, Cline GW, Macica CM. IGF-1 stimulates de novo fatty acid biosynthesis by Schwann cells during myelination. Glia. 2007;55(6):632–641. https://doi.org/10.1002/glia.20496.
Muscella A, Vetrugno C, Cossa LG, et al. TGF-β1 activates RSC96 Schwann cells migration and invasion through MMP-2 and MMP-9 activities. J Neurochem. 2020;153(4):525–538. https://doi.org/10.1111/jnc.14913.
Ogata T, Yamamoto SI, Nakamura K, et al. Signaling axis in schwann cell proliferation and differentiation. Mol Neurobiol. 2006;33(1):51–62, 10.1385/mn: 33: 1: 051.
Margul DJ, Park J, Boehler RM, et al. Reducing neuroinflammation by delivery of IL-10 encoding lentivirus from multiple-channel bridges. Bioeng Transl Med. 2016;1(2):136–148. https://doi.org/10.1002/btm2.10018.
Conti P, Kempuraj D, Kandere K, et al. IL-10, an inflammatory/inhibitory cytokine, but not always. Immunol Lett. 2003;86(2):123–129. https://doi.org/10.1016/s0165-2478(03)00002-6.
Vidal PM, Lemmens E, Dooley D, et al. The role of “anti-inflammatory” cytokines in axon regeneration. Cytokine Growth Factor Rev. 2013;24(1):1–12. https://doi.org/10.1016/j.cytogfr.2012.08.008.
Murakami M, Simons M. Fibroblast growth factor regulation of neovascularization. Curr Opin Hematol. 2008;15(3):215–220. https://doi.org/10.1097/MOH.0b013–3282f97d98.
Rozman P, Bolta Z. Use of platelet growth factors in treating wounds and soft-tissue injuries. Acta Dermatovenerol Alpina Pannonica Adriatica. 2007;16(4):156–165.
Li JW, Wang QQ, Cai HX, et al. FGF1 improves functional recovery through inducing PRDX1 to regulate autophagy and anti-ROS after spinal cord injury. J Cell Mol Med. 2018;22(5):2727–2738. https://doi.org/10.1111/jcmm.13566.
Midha R, Munro CA, Dalton PD, et al. Growth factor enhancement of peripheral nerve regeneration through a novel synthetic hydrogel tube. J Neurosurg. 2003;99(3):555–565. https://doi.org/10.3171/jns.2003.99.3.0555.
Cheng HL, Steinway M, Delaney CL, et al. IGF-Ⅰ promotes Schwann cell motility and survival via activation of Akt. Mol Cell Endocrinol. 2000;170(1/2):211–215. https://doi.org/10.1016/s0303-7207(00)00324-5.
Pecchi E, Priam S, Gosset M, et al. Induction of nerve growth factor expression and release by mechanical and inflammatory stimuli in chondrocytes: possible involvement in osteoarthritis pain. Arthritis Res Ther. 2014;16(1):R16. https://doi.org/10.1186/ar4443.
Aoki Y, Ohtori S, Takahashi K, et al. Innervation of the lumbar intervertebral disc by nerve growth factor-dependent neurons related to inflammatory pain. Spine. 2004;29(10):1077–1081. https://doi.org/10.1097/00007632-200405150-00005.
Hoyng SA, De Winter F, Gnavi S, et al. Gene delivery to rat and human Schwann cells and nerve segments: a comparison of AAV 1-9 and lentiviral vectors. Gene Ther. 2015;22(10):767–780. https://doi.org/10.1038/gt.2015.47.
Chu TH, Li SY, Guo AC, et al. Implantation of neurotrophic factor-treated sensory nerve graft enhances survival and axonal regeneration of motoneurons after spinal root avulsion. J Neuropathol Exp Neurol. 2009;68(1):94–101. https://doi.org/10.1097/NEN.0b013-31819344a9.
Godinho MJ, Teh L, Pollett MA, et al. Immunohistochemical, ultrastructural and functional analysis of axonal regeneration through peripheral nerve grafts containing Schwann cells expressing BDNF, CNTF or NT3. PLoS One. 2013;8(8):e69987. https://doi.org/10.1371/journal.pone.0069987.
Boyd JG, Gordon T. Glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor sustain the axonal regeneration of chronically axotomized motoneurons in vivo. Exp Neurol. 2003;183(2):610–619. https://doi.org/10.1016/s0014-4886(03)00183-3.
Weibrich G, Kleis WKG, Buch R, et al. The Harvest Smart PRePTM system versus the Friadent-Schütze platelet-rich plasma kit. Clin Oral Implants Res. 2003;14(2):233–239. https://doi.org/10.1034/j.1600-0501.2003.140215.x.
Leitner GC, Gruber R, Neumüller J, et al. Platelet content and growth factor release in platelet-rich plasma: a comparison of four different systems. Vox Sang. 2006;91(2):135–139. https://doi.org/10.1111/j.1423-0410.2006.00815.x.
Mazzucco L, Balbo V, Cattana E, et al. 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. 2009;97(2):110–118. https://doi.org/10.1111/j.1423-0410.2009.01188.x.
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