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Synergistic Effects of Secretome and Surgical Angiogenesis in Acellular Nerve Allograft-Mediated Peripheral Nerve Repair in a Rat Model.

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Τίτλος: Synergistic Effects of Secretome and Surgical Angiogenesis in Acellular Nerve Allograft-Mediated Peripheral Nerve Repair in a Rat Model.
Συγγραφείς: Eker O; Department of Plastic, Reconstructive and Aesthetic Surgery, Selcuk University Faculty of Medicine, Konya, Turkey., Yıldıran G; Department of Plastic, Reconstructive and Aesthetic Surgery, Selcuk University Faculty of Medicine, Konya, Turkey., Çelik ZE; Department of Pathology, Selcuk University Faculty of Medicine, Konya, Turkey., Çiçek G; Department of Histology and Embryology, Necmettin Erbakan University Faculty of Medicine, Konya, Turkey., Bağcı FÖ; Department of Histology and Embryology, Necmettin Erbakan University Faculty of Medicine, Konya, Turkey., Akdeniz H; Department of Plastic, Reconstructive and Aesthetic Surgery, Selcuk University Faculty of Medicine, Konya, Turkey., Tosun Z; Department of Plastic, Reconstructive and Aesthetic Surgery, Selcuk University Faculty of Medicine, Konya, Turkey.
Πηγή: Annals of plastic surgery [Ann Plast Surg] 2026 Oct 01; Vol. 97 (4), pp. 461-469. Date of Electronic Publication: 2026 Aug 20.
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Little, Brown And Company Country of Publication: United States NLM ID: 7805336 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1536-3708 (Electronic) Linking ISSN: 01487043 NLM ISO Abbreviation: Ann Plast Surg Subsets: MEDLINE
Imprint Name(s): Publication: Boston Ma : Little, Brown And Company
Original Publication: Boston, Little, Brown.
Ιατρικοί όροι (MeSH): Nerve Regeneration*/physiology , Sciatic Nerve*/injuries , Sciatic Nerve*/transplantation , Sciatic Nerve*/surgery , Peripheral Nerve Injuries*/surgery , Mesenchymal Stem Cell Transplantation*/methods , Secretome* , Neovascularization, Physiologic*, Animals ; Male ; Rats, Wistar ; Rats ; Allografts ; Disease Models, Animal ; Random Allocation ; Recovery of Function
Περίληψη: Background: Critical-sized peripheral nerve defects remain a major reconstructive challenge. Although autografts are considered the gold standard, their use is limited by donor-site morbidity and graft availability. Acellular nerve allografts (ANAs) offer a promising alternative but are often hampered by inadequate revascularization and limited functional outcomes in large defects. This study investigates whether combining mesenchymal stem cell-derived secretome therapy with surgical angiogenesis can enhance the regenerative capacity of ANAs.
Methods: Forty male Wistar rats were randomly assigned to 5 groups (n=8): group 1 (reversed autograft), group 2 (ANA), group 3 (ANA+secretome), group 4 (ANA+surgical angiogenesis), and group 5 (ANA+secretome+surgical angiogenesis). A 10 mm sciatic nerve defect was created in all animals. Functional recovery was evaluated using the Sciatic Functional Index (SFI) at 6 and 9 weeks. Electrophysiological, histologic, immunohistochemical (CD34), and muscle weight/volume assessments were performed at 9 weeks.
Results: Group 5 demonstrated the highest functional recovery among ANA-based interventions, achieving outcomes comparable to autografts. Groups 4 and 5 showed significantly improved axonal regeneration compared with ANA alone. CD34 immunostaining revealed enhanced vascularization in groups 4 and 5, with levels similar to the autograft group. No significant differences were observed in electrophysiological or muscle mass parameters.
Conclusions: The combination of secretome therapy and surgical angiogenesis synergistically enhances the regenerative performance of acellular nerve allografts. This strategy may provide a clinically translatable alternative to autografts, particularly in challenging repair scenarios involving avascular or scarred recipient beds.
(Copyright © 2026 Wolters Kluwer Health, LLC. All rights reserved.)
Competing Interests: Conflicts of interest and sources of funding: This study was supported by the Selcuk University Scientific Research Projects Institution.
References: Pan D, Mackinnon SE, Wood MD. Advances in the repair of segmental nerve injuries and trends in reconstruction. Muscle Nerve. 2020;61:726–739.
Rivlin M, Sheikh E, Isaac R, et al. The role of nerve allografts and conduits for nerve injuries. Hand Clin. 2010;26:435–446.
DeLeonibus A, Rezaei M, Fahradyan V, et al. A meta-analysis of functional outcomes in rat sciatic nerve injury models. Microsurgery. 2021;41:286–295.
Saffari TM, Mathot F, Friedrich PF, et al. Revascularization patterns of nerve allografts in a rat sciatic nerve defect model. J Plast Reconstr Aesthet Surg. 2020;73:460–468.
Estrada R, Li N, Sarojini H, et al. Secretome from mesenchymal stem cells induces angiogenesis via Cyr61. J Cell Physiol. 2009;219:563–571.
González-González A, García-Sánchez D, Dotta M, et al. Mesenchymal stem cells secretome: the cornerstone of cell-free regenerative medicine. World J Stem Cells. 2020;12:1529–1552.
Nevado-Sánchez E, Rodríguez-Díaz M, Núñez-Rodríguez S, et al. Effectiveness of stem cell secretomes in the regeneration and functional recovery of severed nerves in patients with nerve injuries: a systematic review. Cells. 2025;14:492.
Contreras E, Bolívar S, Navarro X, et al. New insights into peripheral nerve regeneration: the role of secretomes. Exp Neurol. 2022;354:114069.
Daneshmandi L, Shah S, Jafari T, et al. Emergence of the stem cell secretome in regenerative engineering. Trends Biotechnol. 2020;38:1373–1384.
Baez-Jurado E, Hidalgo-Lanussa O, Barrera-Bailón B, et al. Secretome of mesenchymal stem cells and its potential protective effects on brain pathologies. Mol Neurobiol. 2019;56:6902–6927.
Foo JB, Looi QH, Chong PP, et al. Comparing the therapeutic potential of stem cells and their secretory products in regenerative medicine. Stem Cells Int. 2021;2021:2616807.
Vizoso FJ, Eiro N, Cid S, et al. Mesenchymal stem cell secretome: toward cell-free therapeutic strategies in regenerative medicine. Int J Mol Sci. 2017;18:1852.
Karimian A, Khoshnazar SM, Kazemi T, et al. Role of secretomes in cell-free therapeutic strategies in regenerative medicine. Cell Tissue Bank. 2024;25:411–426.
Shin YH, Park SY, Kim JK. Comparison of systematically combined detergent and nuclease-based decellularization methods for acellular nerve graft: an ex vivo characterization and in vivo evaluation. J Tissue Eng Regen Med. 2019;13:1241–1252.
Moon GJ, Cho YH, Kim DH, et al. Serum-mediated activation of bone marrow-derived mesenchymal stem cells in ischemic stroke patients: a novel preconditioning method. Cell Transplant. 2018;27:485–500.
Ortiz A, de C, Fideles SOM, et al. Potential of fibrin glue and mesenchymal stem cells (MSCs) to regenerate nerve injuries: a systematic review. Cells. 2022;11:221.
Yu W, Zhou H, Feng X, et al. Mesenchymal stem cell secretome-loaded fibrin glue improves the healing of intestinal anastomosis. Front Bioeng Biotechnol. 2023;11:1103709.
Mehanna RA, Nabil I, Attia N, et al. The effect of bone marrow-derived mesenchymal stem cells and their conditioned media topically delivered in fibrin glue on chronic wound healing in rats. Biomed Res Int. 2015;2015:846062.
Bain JR, Mackinnon SE, Hunter DA. Functional evaluation of complete sciatic, peroneal, and posterior tibial nerve lesions in the rat. Plast Reconstr Surg. 1989;83:129–138.
Sumarwoto T, Suroto H, Mahyudin F, et al. Role of adipose mesenchymal stem cells and secretome in peripheral nerve regeneration. Ann Med Surg. 2021;67:102482.
Baraniak PR, McDevitt TC. Stem cell paracrine actions and tissue regeneration. Regen Med. 2010;5:121–143.
Konala VB, Mamidi MK, Bhonde R, et al. The current landscape of the mesenchymal stromal cell secretome: a new paradigm for cell-free regeneration. Cytotherapy. 2016;18:13–24.
Bedar M, Saffari TM, Johnson AJ, et al. The effect of mesenchymal stem cells and surgical angiogenesis on immune response and revascularization of acellular nerve allografts in a rat sciatic defect model. J Plast Reconstr Aesthet Surg. 2022;75:2809–2820.
Saffari TM, Mathot F, Thaler R, et al. Microcomputed analysis of nerve angioarchitecture after combined stem cell delivery and surgical angiogenesis to nerve allograft. J Plast Reconstr Aesthet Surg. 2021;74:1919–1930.
Hobson MI. Increased vascularisation enhances axonal regeneration within an acellular nerve conduit. Ann R Coll Surg Engl. 2002;84:47–53.
Bedar M, Saffari TM, Mathot F, et al. Functional outcomes of nerve allografts augmented with mesenchymal stem cells and surgical angiogenesis in a rat sciatic nerve defect model. J Plast Reconstr Aesthet Surg. 2023;87:329–338.
Man RC, Sulaiman N, Idrus RBH, et al. Insights into the effects of the dental stem cell secretome on nerve regeneration: towards cell-free treatment. Stem Cells Int. 2019;2019:4596150.
Krug C, Beer A, Hartmann B, et al. Fibrin glue displays promising in vitro characteristics as a potential carrier of adipose progenitor cells for tissue regeneration. J Tissue Eng Regen Med. 2019;13:359–368.
Yu M, Gu G, Cong M, et al. Repair of peripheral nerve defects by nerve grafts incorporated with extracellular vesicles from skin-derived precursor Schwann cells. Acta Biomater. 2021;134:190–203.
Margiana R, Aman RA, Pawitan JA, et al. 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:em171.
Saffari TM, Bedar M, Hundepool CA, et al. The role of vascularization in nerve regeneration of nerve graft. Neural Regen Res. 2020;15:1573.
Da Silva K, Kumar P, Choonara YE. The paradigm of stem cell secretome in tissue repair and regeneration: present and future perspectives. Wound Repair Regen. 2025;33:e13251.
Muangsanit P, Shipley RJ, Phillips JB. Vascularization strategies for peripheral nerve tissue engineering. Anat Rec. 2018;301:1657–1667.
Taylor GI, Ham FJ. The free vascularized nerve graft: a further experimental and clinical application of microvascular techniques. Plast Reconstr Surg. 1976;57:413.
Townsend PL, Taylor GI. Vascularised nerve grafts using composite arterialised neuro-venous systems. Br J Plast Surg. 1984;37:1–17.
S D’Arpa, Claes KY, Stillaert F, et al. Vascularized nerve “grafts”: just a graft or a worthwhile procedure? Plast Aesthet Res 2015;2:183.
Doi K, Kuwata N, Sakai K, et al. A reliable technique of free vascularized sural nerve grafting and preliminary results of clinical applications. J Hand Surg Am. 1987;12(5 Pt 1):677–684.
Cattin AL, Burden JJ, Van Emmenis L, et al. Macrophage-induced blood vessels guide schwann cell-mediated regeneration of peripheral nerves. Cell. 2015;162:1127–1139.
Fornasari BE, Zen F, Nato G, et al. Blood vessels: the pathway used by schwann cells to colonize nerve conduits. Int J Mol Sci. 2022;23:2254.
Kanaya F, Firrell JC, Breidenbach WC. Sciatic function index, nerve conduction tests, muscle contraction, and axon morphometry as indicators of regeneration. Plast Reconstr Surg. 1996;98:1264–1271.
Myckatyn TM, Mackinnon SE. A review of research endeavors to optimize peripheral nerve reconstruction. Neurol Res. 2004;26:124–138.
Luís AL, Amado S, Geuna S, et al. Long-term functional and morphological assessment of a standardized rat sciatic nerve crush injury with a non-serrated clamp. J Neurosci Methods. 2007;163(1-2):92–104.
Czarnecki P, Huber J, Szymankiewicz-Szukała A, et al. End-to-side vs. free graft nerve reconstruction—experimental study on rats. Int J Mol Sci. 2023;24:10428.
Iwai T, Ikeguchi R, Aoyama T, et al. Nerve regeneration using a Bio 3D conduit derived from umbilical cord-derived mesenchymal stem cells in a rat sciatic nerve defect model. PLoS One. 2024;19:e0310711.
Contributed Indexing: Keywords: acellular nerve allograft; mesenchymal stem cell secretome; peripheral nerve regeneration; rat sciatic nerve model; surgical angiogenesis
Entry Date(s): Date Created: 20260820 Date Completed: 20260910 Latest Revision: 20260910
Update Code: 20260910
DOI: 10.1097/SAP.0000000000004835
PMID: 42623489
Βάση Δεδομένων: MEDLINE
Περιγραφή
ISSN:1536-3708
DOI:10.1097/SAP.0000000000004835