Author(s):
Nabila Maudy Salma, Ria Margiana, Lenny Setiawati, Dian Mediana
Email(s):
nabila@trisakti.ac.id
DOI:
10.52711/2349-2988.2026.00022 
Address:
Nabila Maudy Salma1*, Ria Margiana2,3,4,5,6, Lenny Setiawati1, Dian Mediana1
1Department of Anatomy, Faculty of Medicine, Universitas Trisakti, Jakarta, Indonesia.
2Department of Anatomy, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.
3Universitas Indonesia Academic Hospital, Depok, Indonesia.
4Permata Depok Hospital, Depok, Indonesia.
5Twins Fertility Clinic, Jakarta, Indonesia.
6Bocah Indonesia Fertility Center, Jakarta, Indonesia.
*Corresponding Author
Published In:
Volume - 18,
Issue - 2,
Year - 2026
ABSTRACT:
Introduction: Peripheral nerve injuries are a common condition seen in healthcare facilities; it has been discovered that almost one-third of peripheral nerve injury cases show insufficient recovery of nerve function. There are a number of contributory variables that delay the restoration of nerve function, such as insufficient molecular-level support, aging-related factors and regeneration. Considering the complexity of the process and the effects of peripheral nerve injury, this study aims to review the current literature on peripheral nerve regeneration, with a focus on research models, intervention strategies, evaluation parameters, and reported outcomes. Methods: Several databases, including PubMed, Google Scholar, Research Gate, and Web of Science, were used for the literature search. This systematic literature review was carried out using PRISMA guidelines as a basis for analysis. The articles were evaluated according to the year, type of injury, animal model, study intervention, and regeneration outcome. Result: Five rodent-based studies and human peripheral nerve injury published within the past 15 years. These studies involved either nerve compression or transection models and interventions such as aerobic exercise, electrical stimulation, and stem cell therapy. Regeneration was evaluated through histomorphology, immunohistochemistry, gait analysis, and electrophysiological tests, are characteristics that indicate satisfactory regeneration findings across all studies. Conclusion: This review highlights the diversity of experimental models and therapeutic approaches used in peripheral nerve regeneration research, proves essential for accurately determining regeneration outcomes. These findings support the continued development of integrated strategies to enhance and evaluate peripheral nerve repair in future studies.
Cite this article:
Nabila Maudy Salma, Ria Margiana, Lenny Setiawati, Dian Mediana. Advances in Peripheral Nerve Regeneration Study Methods: A Systematic Literature Review. Research Journal of Science and Technology. 2026; 18(2):156-4. doi: 10.52711/2349-2988.2026.00022
Cite(Electronic):
Nabila Maudy Salma, Ria Margiana, Lenny Setiawati, Dian Mediana. Advances in Peripheral Nerve Regeneration Study Methods: A Systematic Literature Review. Research Journal of Science and Technology. 2026; 18(2):156-4. doi: 10.52711/2349-2988.2026.00022 Available on: https://rjstonline.com/AbstractView.aspx?PID=2026-18-2-5
REFERENCES:
1. Lee, Steve K. MD; Wolfe, Scott W. MD Peripheral Nerve Injury and Repair. Journal of the American Academy of Orthopaedic Surgeons 2000; 8(4): 243-252.
2. Menorca RM, Fussell TS, Elfar JC. Nerve physiology: mechanisms of injury and recovery. Hand Clin. 2013; 29(3):317-330.
3. Ara.jo-Filho HG, Pereira EWM, Heimfarth L, Souza Monteiro B, Santos Passos FR, Siqueira-Lima P, et al. Limonene, a food additive, and its active metabolite perillyl alcohol improve regeneration and attenuate neuropathic pain after peripheral nerve injury: Evidence for IL-1β, TNF-α, GAP, NGF and ERK involvement. Int Immunopharmacol. 2020; 86:106766.
4. Wang ML, Rivlin M, Graham JG, Beredjiklian PK. Peripheral nerve injury, scarring, and recovery. Connect Tissue Res. 2019; 60(1):3-9.
5. Daradka MH, Bani Ismail ZA, Irsheid MA. Peripheral nerve regeneration: A comparative study of the effects of autologous bone marrow-derived mesenchymal stem cells, platelet-rich plasma, and lateral saphenous vein graft as a conduit in a dog model. Open Vet J. 2021; 11(4): 686-694.
6. Kamble N, Shukla D, Bhat D. Peripheral Nerve Injuries: Electrophysiology for the Neurosurgeon. Neurol India 2019; 67(6): 1419-1422.
7. Contreras E, Bol.var S, Navarro X, Udina E. New insights into peripheral nerve regeneration: The role of secretomes. Exp Neurol. 2022; 354:114069.
8. Fontana X, Hristova M, Da Costa C, Patodia S, Thei L, Makwana M, et al. C-Jun in Schwann cells promotes axonal regeneration and motoneuron survival via paracrine signaling. J Cell Biol. 2012; 198(1):127–41.
9. Yuan Q, Su H, Guo J, Yeung K, Cheah KSE, Chiu K, et al. Decreased c-Jun expression correlates with impaired spinal motoneuron regeneration in aged mice following sciatic nerve crush. EXG. 2012; 47(4):329–36.
10. Jessen KR, Mirsky R. The Role of c-Jun and Autocrine Signaling Loops in the Control of Repair Schwann Cells and Regeneration. Front Cell Neurosci. 2022; 15:820216.
11. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021; 372:n71. doi: 10.1136/bmj.n71
12. Murray J, Farrington DP, Eisner MP. Drawing conclusions about causes from systematic reviews of risk factors: The Cambridge Quality Checklists. J Exp Criminol. 2009; 5(1):1–23.
13. Margiana R, Alawiyah K, Ima K, Fitriana R, Widodo AR, Wibowo TD. Improvement of walking analysis using the sciatic function index for sciatic nerve function in injured rat model treated with low-intensity aerobics. Open Access Maced J Med Sci. 2021; 9:1162–8.
14. Margiana R, Ima K, Fitriana R, Alawiyah K. Walking Analysis Using TFI , PFI , TOA and Q1-Q4 Angles for Sciatic Nerve Function in Sciatic Rat Model Treated with Low- Intensity Aerobics. 2021; 8(4):12299–314.
15. Huang J, Zhang Y, Lu L, Hu X, Luo Z. Electrical stimulation accelerates nerve regeneration and functional recovery in delayed peripheral nerve injury in rats. Eur J Neurosci. 2013; 38(12):3691–701.
16. Roh J, Schellhardt L, Keane GC, Hunter DA, Moore AM, Snyder-Warwick AK, et al. Short-Duration, Pulsatile, Electrical Stimulation Therapy Accelerates Axon Regeneration and Recovery following Tibial Nerve Injury and Repair in Rats. Plast Reconstr Surg. 2022; 149(4):681E-690E.
17. Margiana R, Aman RA, Pawitan JA, Jusuf AA, Ibrahim N, Wibowo H. The effect of human umbilical cord-derived mesenchymal stem cell conditioned medium on the peripheral nerve regeneration of injured rats. Electron J Gen Med. 2019; 16(6).
18. Widodo W, Dilogo IH, Kamal AF, Antarianto RD, Wuyung PE, Siregar NC, Octaviana F, Kekalih A, Suroto H, Latief W, Hutami WD. Functional outcome and histologic analysis of late onset total type brachial plexus injury treated with intercostal nerve transfer to median nerve with local umbilical cord-derived mesenchymal stem cells or secretome injection: a double-blinded, randomized control study. Eur J Orthop Surg Traumatol. 2024 Dec; 34(8):4073-4082. doi: 10.1007/s00590-024-04110-6.
19. Lee SY, Cho YS, Seo CH, Seo J, Joo SY. Clinical utility of extracorporeal shock wave therapy in restoring hand function of patients with nerve injury and hypertrophic scars due to burns: a prospective, randomized, double-blinded study. Int J Surg. 2024 Dec 1; 110(12):7487-7494. doi: 10.1097/JS9.
20. Carriel V, Garzón I, Alaminos M, Cornelissen M. Histological assessment in peripheral nerve tissue engineering. Neural Regen Res. 2014; 9(18):1657–60.
21. Cercignani, M, Giulietti, G, Dowell, N.G, Gabel, M, Broad, R., Leigh, P.N, Harrison, N.A, Bozzali, M. Characterizing axonal myelination within the healthy population: A tract-by-tract mapping of effects of age and gender on the fiber g-ratio. Neurobiol. Aging. 2017; 49:109–118.
22. Chen B, Chen Q, Parkinson DB, Dun XP. Analysis of Schwann Cell Migration and Axon Regeneration Following Nerve Injury in the Sciatic Nerve Bridge. Front Mol Neurosci. 2019; 12.
23. Ekanayake P, Ahn M, Kim J, Choi Y, Shin T. Immunohistochemical localization of nerve injury-induced protein-1 in mouse tissues. Anat Cell Biol. 2019; 52(4):455–61.
24. Muratori, L, Ronchi, G, Raimondo, S, Giacobini-Robecchi, M.G, Fornaro, M, Geuna, S. Can regenerated nerve fibers return to normal size? A long-term post-traumatic study of the rat median nerve crush injury model. Microsurgery. 2012; 32:383–387.
25. Ronchi G, Fregnan F, Muratori L, Gambarotta G, Raimondo S. Morphological Methods to Evaluate Peripheral Nerve Fiber Regeneration: A Comprehensive Review. Int J Mol Sci. 2023; 24(3).
26. Sarikcioglu L, Demirel BM, Utuk A. Walking track analysis: An assessment method for functional recovery after sciatic nerve injury in the rat. Folia Morphol (Warsz). 2009; 68(1):1–7.
27. Wang T, Ito A, Aoyama T, Nakahara R, Nakahata A, Ji X, et al. Functional evaluation outcomes correlate with histomorphometric changes in the rat sciatic nerve crush injury model: A comparison between sciatic functional index and kinematic analysis. PLoS One. 2018; 13(12).
28. Kamble N, Shukla D, Bhat D. Peripheral Nerve Injuries: Electrophysiology for the Neurosurgeon. Neurol India. 2019; 67(6):1419-1422.
29. Lawley A, Abbas A, Seri S, Rajabally YA. Peripheral nerve electrophysiology studies in relation to fatigue in patients with chronic inflammatory demyelinating polyneuropathy. Clin Neurophysiol. 2020; 131(12):2926-31.