Research progress in auxiliary components of nerve conduit for treating peripheral nerve injuries_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

NONG Chaocao ¹ ,  LIN Haodong ^1,2

1. Trauma Center, Affiliated First People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 201600, P. R. China;
2. Department of Orthopedics, Jiading Branch of Affiliated First People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201803, P. R. China;

Corresponding author：

LIN Haodong, Email: haodonglin@hotmail.com

Keywords：

Nerve conduit; peripheral nerve injuries; nerve regeneration; guided tissue regeneration

DOI：

10.7507/1002-1892.202505083

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To review recent research progress in the use of auxiliary components of nerve conduits for the treatment of peripheral nerve injuries. Methods An extensive review of recent domestic and international literature was conducted to evaluate the role of auxiliary components in nerve conduits for peripheral nerve repair, with a focus on their effects and underlying mechanisms. Results By incorporating auxiliary components such as bioactive molecules, therapeutic cells, and their derivatives, nerve conduits can create a more biomimetic regenerative microenvironment. This is achieved by providing neurotrophic support, modulating the immune microenvironment, improving blood and oxygen supply, and offering directional guidance for nerve regeneration. Consequently, the nerve conduit is transformed from a simple physical scaffold into an active, bio-functional repair system, which enhances the therapeutic efficacy for PNI. Conclusion While nerve conduits augmented with auxiliary components demonstrate improved treatment efficacy, further advancements are required in drug delivery systems and the integration of cellular components. Moreover, most current studies are based on animal or in vitro experiments. Randomized controlled clinical trials are necessary to validate their clinical effectiveness.

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5.	Fadia NB, Bliley JM, DiBernardo GA, et al. Long-gap peripheral nerve repair through sustained release of a neurotrophic factor in nonhuman primates. Sci Transl Med, 2020, 12(527): eaav7753. doi: 10.1126/scitranslmed.aav7753.
6.	Sandoval-Castellanos AM, Claeyssens F, Haycock JW. Biomimetic surface delivery of NGF and BDNF to enhance neurite outgrowth. Biotechnol Bioeng, 2020, 117(10): 3124-3135.
7.	Rao F, Wang Y, Zhang D, et al. Aligned chitosan nanofiber hydrogel grafted with peptides mimicking bioactive brain-derived neurotrophic factor and vascular endothelial growth factor repair long-distance sciatic nerve defects in rats. Theranostics, 2020, 10(4): 1590-1603.
8.	González Porto SA, Domenech N, Blanco FJ, et al. Intraneural IFG-1 in cryopreserved nerve isografts increase neural regeneration and functional recovery in the rat sciatic nerve. Neurosurgery, 2019, 85(3): 423-431.
9.	Wan T, Li QC, Zhang FS, et al. Biomimetic ECM nerve guidance conduit with dynamic 3D interconnected porous network and sustained IGF-1 delivery for enhanced peripheral nerve regeneration and immune modulation. Mater Today Bio, 2024, 30: 101403. doi: 10.1016/j.mtbio.2024.101403.
10.	Song P, Han T, Wu Z, et al. Transplantation of neural stem cells loaded in an IGF-1 bioactive supramolecular nanofiber hydrogel for the effective treatment of spinal cord injury. Adv Sci (Weinh), 2024, 11(17): e2306577. doi: 10.1002/advs.202306577.
11.	Zhang D, Yang W, Wang C, et al. Methylcobalamin-loaded PLCL conduits facilitate the peripheral nerve regeneration. Macromol Biosci, 2020, 20(3): e1900382. doi: 10.1002/mabi.201900382.
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17.	Huang Y, Ye K, He A, et al. Dual-layer conduit containing VEGF-A-Transfected Schwann cells promotes peripheral nerve regeneration via angiogenesis. Acta Biomater, 2024, 180: 323-336.
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23.	Faroni A, Workman VL, Saiani A, et al. Self-assembling peptide hydrogel matrices improve the neurotrophic potential of human adipose-derived stem cells. Adv Healthc Mater, 2019, 8(17): e1900410. doi: 10.1002/adhm.201900410.
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1. Murphy RNA, de Schoulepnikoff C, Chen JHC, et al. The incidence and management of peripheral nerve injury in England (2005-2020). J Plast Reconstr Aesthet Surg, 2023, 80: 75-85.
2. Yi S, Xu L, Gu X. Scaffolds for peripheral nerve repair and reconstruction. Exp Neurol, 2019, 319: 112761. doi: 10.1016/j.expneurol.2018.05.016.
3. Stocco E, Barbon S, Emmi A, et al. Bridging gaps in peripheral nerves: From current strategies to future perspectives in conduit design. Int J Mol Sci, 2023, 24(11): 9170. doi: 10.3390/ijms24119170.
4. Ramburrun P, Kumar P, Ndobe E, et al. Gellan-xanthan hydrogel conduits with intraluminal electrospun nanofibers as physical, chemical and therapeutic cues for peripheral nerve repair. Int J Mol Sci, 2021, 22(21): 11555. doi: 10.3390/ijms222111555.
5. Fadia NB, Bliley JM, DiBernardo GA, et al. Long-gap peripheral nerve repair through sustained release of a neurotrophic factor in nonhuman primates. Sci Transl Med, 2020, 12(527): eaav7753. doi: 10.1126/scitranslmed.aav7753.
6. Sandoval-Castellanos AM, Claeyssens F, Haycock JW. Biomimetic surface delivery of NGF and BDNF to enhance neurite outgrowth. Biotechnol Bioeng, 2020, 117(10): 3124-3135.
7. Rao F, Wang Y, Zhang D, et al. Aligned chitosan nanofiber hydrogel grafted with peptides mimicking bioactive brain-derived neurotrophic factor and vascular endothelial growth factor repair long-distance sciatic nerve defects in rats. Theranostics, 2020, 10(4): 1590-1603.
8. González Porto SA, Domenech N, Blanco FJ, et al. Intraneural IFG-1 in cryopreserved nerve isografts increase neural regeneration and functional recovery in the rat sciatic nerve. Neurosurgery, 2019, 85(3): 423-431.
9. Wan T, Li QC, Zhang FS, et al. Biomimetic ECM nerve guidance conduit with dynamic 3D interconnected porous network and sustained IGF-1 delivery for enhanced peripheral nerve regeneration and immune modulation. Mater Today Bio, 2024, 30: 101403. doi: 10.1016/j.mtbio.2024.101403.
10. Song P, Han T, Wu Z, et al. Transplantation of neural stem cells loaded in an IGF-1 bioactive supramolecular nanofiber hydrogel for the effective treatment of spinal cord injury. Adv Sci (Weinh), 2024, 11(17): e2306577. doi: 10.1002/advs.202306577.
11. Zhang D, Yang W, Wang C, et al. Methylcobalamin-loaded PLCL conduits facilitate the peripheral nerve regeneration. Macromol Biosci, 2020, 20(3): e1900382. doi: 10.1002/mabi.201900382.
12. Wu F, Jiao C, Yang Y, et al. Nerve conduit based on HAP/PDLLA/PRGD for peripheral nerve regeneration with sustained release of valproic acid. Cell Biol Int, 2021, 45(8): 1733-1742.
13. Lackington WA, Kočí Z, Alekseeva T, et al. Controlling the dose-dependent, synergistic and temporal effects of NGF and GDNF by encapsulation in PLGA microparticles for use in nerve guidance conduits for the repair of large peripheral nerve defects. J Control Release, 2019, 304: 51-64.
14. Zhang F, Wu X, Li Q, et al. Dual growth factor methacrylic alginate microgels combined with chitosan-based conduits facilitate peripheral nerve repair. Int J Biol Macromol, 2024, 268(Pt 1): 131594. doi: 10.1016/j.ijbiomac.2024.131594.
15. Itai S, Suzuki K, Kurashina Y, et al. Cell-encapsulated chitosan-collagen hydrogel hybrid nerve guidance conduit for peripheral nerve regeneration. Biomed Microdevices, 2020, 22(4): 81. doi: 10.1007/s10544-020-00536-x.
16. Warren PM, Andrews MR, Smith M, et al. Secretion of a mammalian chondroitinase ABC aids glial integration at PNS/CNS boundaries. Sci Rep, 2020, 10(1): 11262. doi: 10.1038/s41598-020-67526-0.
17. Huang Y, Ye K, He A, et al. Dual-layer conduit containing VEGF-A-Transfected Schwann cells promotes peripheral nerve regeneration via angiogenesis. Acta Biomater, 2024, 180: 323-336.
18. Dietzmeyer N, Huang Z, Schüning T, et al. In vivo and in vitro evaluation of a novel hyaluronic acid-laminin hydrogel as luminal filler and carrier system for genetically engineered Schwann cells in critical gap length tubular peripheral nerve graft in rats. Cell Transplant, 2020, 29: 963689720910095. doi: 10.1177/0963689720910095.
19. Fang X, Zhang C, Yu Z, et al. GDNF pretreatment overcomes Schwann cell phenotype mismatch to promote motor axon regeneration via sensory graft. Exp Neurol, 2019, 318: 258-266.
20. Modrak M, Talukder MAH, Gurgenashvili K, et al. Peripheral nerve injury and myelination: Potential therapeutic strategies. J Neurosci Res, 2020, 98(5): 780-795.
21. Huang CW, Lu SY, Huang TC, et al. FGF9 induces functional differentiation to Schwann cells from human adipose derived stem cells. Theranostics, 2020, 10(6): 2817-2831.
22. Faroni A, Smith RJ, Lu L, et al. Human Schwann-like cells derived from adipose-derived mesenchymal stem cells rapidly de-differentiate in the absence of stimulating medium. Eur J Neurosci, 2016, 43(3): 417-430.
23. Faroni A, Workman VL, Saiani A, et al. Self-assembling peptide hydrogel matrices improve the neurotrophic potential of human adipose-derived stem cells. Adv Healthc Mater, 2019, 8(17): e1900410. doi: 10.1002/adhm.201900410.
24. Zorba Yildiz AP, Darici H, Yavuz B, et al. Preparation and characterization of graphene-based 3D biohybrid hydrogel bioink for peripheral neuroengineering. J Vis Exp, 2022, 16: (183)). doi: 10.3791/63622.
25. Li Y, Men Y, Wang B, et al. Co-transplantation of Schwann cells and neural stem cells in the laminin-chitosan-PLGA nerve conduit to repair the injured recurrent laryngeal nerve in SD rats. J Mater Sci Mater Med, 2020, 31(11): 99. doi: 10.1007/s10856-020-06436-z.
26. Chen YS, Ng HY, Chen YW, et al. Additive manufacturing of Schwann cell-laden collagen/alginate nerve guidance conduits by freeform reversible embedding regulate neurogenesis via exosomes secretion towards peripheral nerve regeneration. Biomater Adv, 2023, 146: 213276. doi: 10.1016/j.bioadv.2022.213276.
27. Li C, Liu SY, Zhang M, et al. Sustained release of exosomes loaded into polydopamine-modified chitin conduits promotes peripheral nerve regeneration in rats. Neural Regen Res, 2022, 17(9): 2050-2057.
28. Yue H, Wang Y, Fernandes S, et al. Bioprinting of GelMA/PEGDA hybrid bioinks for SH-SY5Y cell encapsulation: Role of molecular weight and concentration. Macromol Biosci, 2025, 25(6): e2400587. doi: 10.1002/mabi.202400587.
29. Wu Z, Li Q, Xie S, et al. In vitro and in vivo biocompatibility evaluation of a 3D bioprinted gelatin-sodium alginate/rat Schwann-cell scaffold. Mater Sci Eng C Mater Biol Appl, 2020, 109: 110530. doi: 10.1016/j.msec.2019.110530.
30. Ikeguchi R, Aoyama T, Noguchi T, et al. Peripheral nerve regeneration following scaffold-free conduit transplant of autologous dermal fibroblasts: a non-randomised safety and feasibility trial. Commun Med (Lond), 2024, 4(1): 12. doi: 10.1038/s43856-024-00438-6.
31. Zheng C, Yang Z, Chen S, et al. Nanofibrous nerve guidance conduits decorated with decellularized matrix hydrogel facilitate peripheral nerve injury repair. Theranostics, 2021, 11(6): 2917-2931.
32. Wang Y, Shi G, Huang TCT, et al. Enhancing functional recovery after segmental nerve defect using nerve allograft treated with plasma-derived exosome. Plast Reconstr Surg, 2023, 152(6): 1247-1258.
33. Hu T, Chang S, Qi F, et al. Neural grafts containing exosomes derived from Schwann cell-like cells promote peripheral nerve regeneration in rats. Burns Trauma, 2023, 11: tkad013. doi: 10.1093/burnst/tkad013.
34. Yang Z, Yang Y, Xu Y, et al. Biomimetic nerve guidance conduit containing engineered exosomes of adipose-derived stem cells promotes peripheral nerve regeneration. Stem Cell Res Ther, 2021, 12(1): 442. doi: 10.1186/s13287-021-02528-x.
35. Jeske R, Liu C, Duke L, et al. Upscaling human mesenchymal stromal cell production in a novel vertical-wheel bioreactor enhances extracellular vesicle secretion and cargo profile. Bioact Mater, 2022, 25: 732-747.
36. Liu Z, Tong H, Li J, et al. Low-stiffness hydrogels promote peripheral nerve regeneration through the rapid release of exosomes. Front Bioeng Biotechnol, 2022, 10: 922570. doi: 10.3389/fbioe.2022.922570.
37. Li C, Li X, Shi Z, et al. Exosomes from LPS-preconditioned bone marrow MSCs accelerated peripheral nerve regeneration via M2 macrophage polarization: Involvement of TSG-6/NF-κB/NLRP3 signaling pathway. Exp Neurol, 2022, 356: 114139. doi: 10.1016/j.expneurol.2022.114139.
38. Huo Y, Cheng Y, Dong X, et al. Pleiotropic effects of nitric oxide sustained-release system for peripheral nerve repair. Acta Biomater, 2024, 182: 28-41.
39. Wang JY, Yuan Y, Zhang SY, et al. Remodeling of the intra-conduit inflammatory microenvironment to improve peripheral nerve regeneration with a neuromechanical matching protein-based conduit. Adv Sci (Weinh), 2024, 11(17): e2302988. doi: 10.1002/advs.202302988.
40. 武小煜, 李海波, 尹健健, 等. 替米沙坦/胶原蛋白/聚己内酯神经导管的构建及其修复大鼠坐骨神经缺损效果的实验研究. 中国修复重建外科杂志, 2022, 36(3): 352-361.
41. Qian Y, Yao Z, Wang X, et al. (-)-Epigallocatechin gallate-loaded polycaprolactone scaffolds fabricated using a 3D integrated moulding method alleviate immune stress and induce neurogenesis. Cell Prolif, 2020, 53(1): e12730. doi: 10.1111/cpr.12730.
42. Ma T, Yang Y, Quan X, et al. Oxygen carrier in core-shell fibers synthesized by coaxial electrospinning enhances Schwann cell survival and nerve regeneration. Theranostics, 2020, 10(20): 8957-8973.
43. Liu L, Wan J, Dai M, et al. Effects of oxygen generating scaffolds on cell survival and functional recovery following acute spinal cord injury in rats. J Mater Sci Mater Med, 2020, 31(12): 115. doi: 10.1007/s10856-020-06453-y.
44. Thibodeau A, Galbraith T, Fauvel CM, et al. Repair of peripheral nerve injuries using a prevascularized cell-based tissue-engineered nerve conduit. Biomaterials, 2022, 280: 121269. doi: 10.1016/j.biomaterials.2021.121269.
45. Shen M, Ye X, Zhou Q, et al. Angiogenesis-promoting effect of SKP-SC-EVs-derived miRNA-30a-5p in peripheral nerve regeneration by targeting LIF and ANGPT2. J Biol Chem, 2025, 301(2): 108146. doi: 10.1016/j.jbc.2024.108146.
46. Mayer JM, Krug C, Saller MM, et al. Hypoxic pre-conditioned adipose-derived stem/progenitor cells embedded in fibrin conduits promote peripheral nerve regeneration in a sciatic nerve graft model. Neural Regen Res, 2023, 18(3): 652-656.
47. 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(4): 2254. doi: 10.3390/ijms23042254.
48. Park J, Kim J, Choe G, et al. Conductive hydrogel luminal filler for peripheral nerve regeneration. Biomaterials, 2025, 317: 123103. doi: 10.1016/j.biomaterials.2025.123103.
49. Zhang F, Zhang M, Liu S, et al. Application of hybrid electrically conductive hydrogels promotes peripheral nerve regeneration. Gels, 2022, 8(1): 41. doi: 10.3390/gels8010041.
50. Kim J, Jeon J, Lee JY, et al. Electroceuticals for regeneration of long nerve gap using biodegradable conductive conduits and implantable wireless stimulator. Adv Sci (Weinh), 2023, 10(24): e2302632. doi: 10.1002/advs.202302632.
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Latest ArticlesResearch progress in auxiliary components of nerve conduit for treating peripheral nerve injuries

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