Skip to main content

Advertisement

Log in

3D Coaxially Printing rGO Aerogel-Based Biocompatible Fiber for Peripheral Nerve Regeneration

  • Research Article
  • Published:
Advanced Fiber Materials Aims and scope Submit manuscript

Abstract

In this study, we developed a hollow aerogel fiber out of reduced graphene oxide (rGO), with a hierarchically ordered microstructure through a three-dimensional coaxial printing methodology, that enabled a physicochemically cooperative construction process at multiscale. The rGO hollow aerogel fiber was modified by depositing polycaprolactone (PCL) and melatonin (Mel). Attributable to its elaborately designed hierarchical structure and arched alignment of two-dimensional micro-sheets, the rGO/PCL/Mel hybrid aerogel bio-fiber demonstrated remarkable structural robustness in maintaining ordered pathways and high porosity (98.5% ± 0.24%), which facilitated nerve growth in a complex survival environment in vivo. Furthermore, the excellent combination of properties such as electrical conductivity, biocompatibility, and mechanical properties (elastic modulus: 7.06 ± 0.81 MPa to 26.58 ± 4.99 MPa) led to highly efficient regeneration of well-ordered PN tissue. Systematic evaluations of nerve regeneration and muscle function recovery in a Sprague–Dawley rat model with a long nerve defect (15 mm) validated the virtually identical performance of the rGO/PCL/Mel fiber compared to autogenous nerve graft. This study suggests a promising approach to the clinical repair of long PN defects through the combined regulation of rational multiscale structure design and indispensable chemical modification of rGO aerogel-based functional nerve regeneration fibers.

Graphical Abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Data availability

The data are available from the corresponding author on reasonable request.

References

  1. Li NY, Onor GI, Lemme NJ, Gil JA. Epidemiology of peripheral nerve injuries in sports, exercise, and recreation in the United States, 2009–2018. Phys Sportsmed. 2021;49:355.

    Article  PubMed  Google Scholar 

  2. Zhu L, Jia S, Liu T, Yan L, Huang D, Wang Z, Chen S, Zhang Z, Zeng W, Zhang Y, Yang H, Hao D. Aligned PCL fiber conduits immobilized with nerve growth factor gradients enhance and direct sciatic nerve regeneration. Adv Funct Mater. 2020;30:2002610.

    Article  CAS  Google Scholar 

  3. Wang Q, Wang H, Ma Y, Cao X, Gao H. Effects of electroactive materials on nerve cell behaviors and applications in peripheral nerve repair. Biomater Sci. 2022;10:6061.

    Article  CAS  PubMed  Google Scholar 

  4. Lu Q, Zhang F, Cheng W, Gao X, Ding Z, Zhang X, Lu Q, Kaplan DL. Nerve guidance conduits with hierarchical anisotropic architecture for peripheral nerve regeneration. Adv Healthc Mater. 2021;10:2100427.

    Article  CAS  Google Scholar 

  5. Zhang C, Gong J, Zhang J, Zhu Z, Qian Y, Lu K, Zhou S, Gu T, Wang H, He Y, Yu M. Three potential elements of developing nerve guidance conduit for peripheral nerve regeneration. Adv Funct Mater. 2023;33:2302251.

    Article  CAS  Google Scholar 

  6. Zhang H, Guo J, Wang Y, Shang L, Chai R, Zhao Y. Natural polymer-derived bioscaffolds for peripheral nerve regeneration. Adv Funct Mater. 2022;32:2203829.

    Article  CAS  Google Scholar 

  7. Huang L, Yang X, Deng L, Ying D, Lu A, Zhang L, Yu A, Duan B. Biocompatible chitin hydrogel incorporated with pedot nanoparticles for peripheral nerve repair. ACS Appl Mater Interfaces. 2021;13:16106.

    Article  CAS  PubMed  Google Scholar 

  8. Kong L, Gao X, Qian Y, Sun W, You Z, Fan C. Biomechanical microenvironment in peripheral nerve regeneration: from pathophysiological understanding to tissue engineering development. Theranostics. 2022;12:4993.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Daly W, Yao L, Zeugolis D, Windebank A, Pandit A. A biomaterials approach to peripheral nerve regeneration: bridging the peripheral nerve gap and enhancing functional recovery. J R Soc Interface. 2012;9:202.

    Article  CAS  PubMed  Google Scholar 

  10. Houshyar S, Bhattacharyya A, Shanks R. Peripheral nerve conduit: Materials and structures. ACS Chem Neurosci. 2019;10:3349.

    Article  CAS  PubMed  Google Scholar 

  11. Gu X, Ding F, Williams DF. Neural tissue engineering options for peripheral nerve regeneration. Biomaterials. 2014;35:6143.

    Article  CAS  PubMed  Google Scholar 

  12. Vijayavenkataraman S. Nerve guide conduits for peripheral nerve injury repair: a review on design, materials and fabrication methods. Acta Biomater. 2020;106:54.

    Article  CAS  PubMed  Google Scholar 

  13. Fregnan F, Ciglieri E, Tos P, Crosio A, Ciardelli G, Ruini F, Tonda-Turo C, Geuna S, Raimondo S. Chitosan crosslinked flat scaffolds for peripheral nerve regeneration. Biomed Mater. 2016;11: 045010.

    Article  CAS  PubMed  Google Scholar 

  14. Yang F, Murugan R, Ramakrishna S, Wang X, Ma YX, Wang S. Fabrication of nano-structured porous plla scaffold intended for nerve tissue engineering. Biomaterials. 1891;2004:25.

    Google Scholar 

  15. Yang Y, De Laporte L, Rives CB, Jang J-H, Lin W-C, Shull KR, Shea LD. Neurotrophin releasing single and multiple lumen nerve conduits. J Control Release. 2005;104:433.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Bozkurt A, Brook GA, Moellers S, Lassner F, Sellhaus B, Weis J, Woeltje M, Tank J, Beckmann C, Fuchs P, Damink LO, Schügner F, Heschel I, Pallua N. In vitro assessment of axonal growth using dorsal root ganglia explants in a novel three-dimensional collagen matrix. Tissue Eng. 2007;13:2971.

    Article  CAS  PubMed  Google Scholar 

  17. Jiang X, Lim SH, Mao H-Q, Chew SY. Current applications and future perspectives of artificial nerve conduits. Exp Neurol. 2010;223:86.

    Article  PubMed  Google Scholar 

  18. Tonda-Turo C, Cipriani E, Gnavi S, Chiono V, Mattu C, Gentile P, Perroteau I, Zanetti M, Ciardelli G. Crosslinked gelatin nanofibres: Preparation, characterisation and in vitro studies using glial-like cells. Mater Sci Eng C. 2013;33:2723.

    Article  CAS  Google Scholar 

  19. Liu K, Yan L, Li R, Song Z, Ding J, Liu B, Chen X. 3D printed personalized nerve guide conduits for precision repair of peripheral nerve defects. Adv Sci. 2022;9:2103875.

    Article  Google Scholar 

  20. Chen X, Ge X, Qian Y, Tang H, Song J, Qu X, Yue B, Yuan W-E. Electrospinning multilayered scaffolds loaded with melatonin and Fe3O4 magnetic nanoparticles for peripheral nerve regeneration. Adv Funct Mater. 2020;30:2004537.

    Article  CAS  Google Scholar 

  21. Qian Y, Zhao X, Han Q, Chen W, Li H, Yuan W. An integrated multi-layer 3D-fabrication of PDA/RGD coated graphene loaded PCL nanoscaffold for peripheral nerve restoration. Nat Commun. 2018;9:323.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Wang J, Xiong H, Zhu T, Liu Y, Pan H, Fan C, Zhao X, Lu WW. Bioinspired multichannel nerve guidance conduit based on shape memory nanofibers for potential application in peripheral nerve repair. ACS Nano. 2020;14:12579.

    Article  CAS  PubMed  Google Scholar 

  23. Xu H, Zhang L, Bao Y, Yan X, Yin Y, Li Y, Wang X, Huang Z, Xu P. Preparation and characterization of injectable chitosan–hyaluronic acid hydrogels for nerve growth factor sustained release. J Bioact Compat Polym. 2016;32:146.

    Article  CAS  Google Scholar 

  24. Bružauskaitė I, Bironaitė D, Bagdonas E, Bernotienė E. Scaffolds and cells for tissue regeneration: Different scaffold pore sizes-different cell effects. Cytotechnology. 2016;68:355.

    Article  PubMed  Google Scholar 

  25. Jiang Y, Xu Z, Huang T, Liu Y, Guo F, Xi J, Gao W, Gao C. Direct 3D printing of ultralight graphene oxide aerogel microlattices. Adv Funct Mater. 2018;28:1707024.

    Article  Google Scholar 

  26. Zhou G, Li M-C, Liu C, Wu Q, Mei C. 3d printed Ti3C2Tx MXene /cellulose nanofiber architectures for solid-state supercapacitors: Ink rheology, 3D printability, and electrochemical performance. Adv Funct Mater. 2022;32:2109593.

    Article  CAS  Google Scholar 

  27. Zhang S, Wang J, Zheng Z, Yan J, Zhang L, Li Y, Zhang J, Li G, Wang X, Kaplan D. Porous nerve guidance conduits reinforced with braided composite structures of silk/magnesium filaments for peripheral nerve repair. Acta Biomater. 2021;134:116.

    Article  CAS  PubMed  Google Scholar 

  28. Shen J, Wang J, Liu X, Sun Y, Yin A, Chai Y, Zhang K, Wang C, Zheng X. In situ prevascularization strategy with three-dimensional porous conduits for neural tissue engineering. ACS Appl Mater Interfaces. 2021;13:50785.

    Article  CAS  PubMed  Google Scholar 

  29. Chen F, Wu M, Wu P, Xiao A, Ke M, Huselstein C, Cai L, Tong Z, Chen Y. Natural flammulina velutipes-based nerve guidance conduit as a potential biomaterial for peripheral nerve regeneration: In vitro and in vivo studies. ACS Biomater Sci Eng. 2021;7:3821.

    Article  CAS  PubMed  Google Scholar 

  30. Dursun Usal T, Yesiltepe M, Yucel D, Sara Y, Hasirci V. Fabrication of a 3D printed pcl nerve guide: In vitro and in vivo testing. Macromol Biosci. 2022;22:2100389.

    Article  CAS  Google Scholar 

  31. Bu Y, Xu H-X, Li X, Xu W-J, Yin Y, Dai H-L, Wang X-B, Huang Z-J, Hu P. A conductive sodium alginate and carboxymethyl chitosan hydrogel doped with polypyrrole for peripheral nerve regeneration. RSC Adv. 2018;8:10806.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Salehi M, Naseri-Nosar M, Ebrahimi-Barough S, Nourani M, Khojasteh A, Hamidieh A-A, Amani A, Farzamfar S, Ai J. Sciatic nerve regeneration by transplantation of schwann cells via erythropoietin controlled-releasing polylactic acid/multiwalled carbon nanotubes/gelatin nanofibrils neural guidance conduit. J Biomed Mater Res Part B. 2018;106:1463.

    Article  CAS  Google Scholar 

  33. Pawelec KM, Koffler J, Shahriari D, Galvan A, Tuszynski MH, Sakamoto J. Microstructure and in vivo characterization of multi-channel nerve guidance scaffolds. Biomed Mater. 2018;13: 044104.

    Article  CAS  PubMed  Google Scholar 

  34. Salehi M, Naseri-Nosar M, Ebrahimi-Barough S, Nourani M, Khojasteh A, Farzamfar S, Mansouri K, Ai J. Polyurethane/gelatin nanofibrils neural guidance conduit containing platelet-rich plasma and melatonin for transplantation of schwann cells. Cell Mol Neurobiol. 2018;38:703.

    Article  CAS  PubMed  Google Scholar 

  35. Santos D, Wieringa P, Moroni L, Navarro X, Valle JD. PEOT/PBT guides enhance nerve regeneration in long gap defects. Adv Healthc Mater. 2017;6:1600298.

    Article  Google Scholar 

  36. Lee JH, Kim YJ. Effect of bimodal pore structure on the bioactivity of poly(lactic-co-glycolic acid)/poly(γ-glutamic acid)/pluronic 17r4 nerve conduits. J Mater Sci. 2017;52:4923.

    Article  CAS  Google Scholar 

  37. Pooshidani Y, Zoghi N, Rajabi M, Haghbin Nazarpak M, Hassannejad Z. Fabrication and evaluation of porous and conductive nanofibrous scaffolds for nerve tissue engineering. J Mater Sci-Mater Med. 2021;32:46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Li G, Li S, Zhang L, Chen S, Sun Z, Li S, Zhang L, Yang Y. Construction of biofunctionalized anisotropic hydrogel micropatterns and their effect on schwann cell behavior in peripheral nerve regeneration. ACS Appl Mater Interfaces. 2019;11:37397.

    Article  CAS  PubMed  Google Scholar 

  39. Si J, Yang Y, Xing X, Yang F, Shan P. Controlled degradable chitosan/collagen composite scaffolds for application in nerve tissue regeneration. Polym Degrad Stabil. 2019;166:73.

    Article  CAS  Google Scholar 

  40. Dursun Usal T, Yucel D, Hasirci V. A novel gelma-phema hydrogel nerve guide for the treatment of peripheral nerve damages. Int J Biol Macromol. 2019;121:699.

    Article  CAS  PubMed  Google Scholar 

  41. Dehnavi N, Parivar K, Goodarzi V, Salimi A, Nourani MR. Systematically engineered electrospun conduit based on PGA/collagen/bioglass nanocomposites: The evaluation of morphological, mechanical, and bio-properties. Polym Adv Technol. 2019;30:2192.

    Article  CAS  Google Scholar 

  42. Li G, Xiao Q, Mcnaughton R, Han L, Zhang L, Wang Y, Yang Y. Nanoengineered porous chitosan/catio3 hybrid scaffolds for accelerating schwann cells growth in peripheral nerve regeneration. Colloid Surf B-Biointerfaces. 2017;158:57.

    Article  CAS  Google Scholar 

  43. Mohamadi F, Ebrahimi-Barough S, Reza Nourani M, Ali Derakhshan M, Goodarzi V, Sadegh Nazockdast M, Farokhi M, Tajerian R, Faridi Majidi R, Ai J. Electrospun nerve guide scaffold of poly(ε-caprolactone)/collagen/nanobioglass: An in vitro study in peripheral nerve tissue engineering. J Biomed Mater Res Part A. 1960;2017:105.

    Google Scholar 

  44. Qian Y, Song J, Zhao X, Chen W, Ouyang Y, Yuan W, Fan C. 3D fabrication with integration molding of a graphene oxide/polycaprolactone nanoscaffold for neurite regeneration and angiogenesis. Adv Sci. 2018;5:1700499.

    Article  Google Scholar 

  45. Zhang S, Vijayavenkataraman S, Chong GL, Fuh JYH, Lu WF. Computational design and optimization of nerve guidance conduits for improved mechanical properties and permeability. J. Biomech. Eng. 2019, 141.

  46. Chiono V, Tonda-Turo C. Trends in the design of nerve guidance channels in peripheral nerve tissue engineering. Prog Neurobiol. 2015;131:87.

    Article  PubMed  Google Scholar 

  47. Wang L, Lu C, Yang S, Sun P, Wang Y, Guan Y, Liu S, Cheng D, Meng H, Wang Q, He J, Hou H, Li H, Lu W, Zhao Y, Wang J, Zhu Y, Li Y, Luo D, Li T, Chen H, Wang S, Sheng X, Xiong W, Wang X, Peng J, Yin L. A fully biodegradable and self-electrified device for neuroregenerative medicine. Sci Adv. 2020;6:eabc6686.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Geim AK. Graphene: Status and prospects. Science. 2009;324:1530.

    Article  CAS  PubMed  Google Scholar 

  49. Huang Q, Cai Y, Zhang X, Liu J, Liu Z, Li B, Wong H, Xu F, Sheng L, Sun D, Qin J, Luo Z, Lu X. Aligned graphene mesh-supported double network natural hydrogel conduit loaded with netrin-1 for peripheral nerve regeneration. ACS Appl Mater Interfaces. 2021;13:112.

    Article  CAS  PubMed  Google Scholar 

  50. Zhang D, Yao Y, Duan Y, Yu X, Shi H, Nakkala JR, Zuo X, Hong L, Mao Z, Gao C. Surface-anchored graphene oxide nanosheets on cell-scale micropatterned poly(d, l-lactide-co-caprolactone) conduits promote peripheral nerve regeneration. ACS Appl Mater Interfaces. 2020;12:7915.

    Article  CAS  PubMed  Google Scholar 

  51. Zhang Q, Xu X, Lin D, Chen W, Xiong G, Yu Y, Fisher TS, Li H. Hyperbolically patterned 3D graphene metamaterial with negative Ppoisson’s ratio and superelasticity. Adv Mater. 2016;28:2229.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by the National Science Fund for Distinguished Young Scholars (No. 11925204), the Fundamental Research Funds for Central Universities (Nos. lzujbky-2022-ey02, lzujbky-2023-eyt03), the Science and Technology Program of Gansu (NO.23ZDKA0001), the Fok Ying-Tong Education Foundation for Young Teachers in the Higher Education Institutions of China (No. 171107), the National Natural Science Foundation of China (No. 82202718), Beijing Natural Science Foundation (No. L212050), the Military Medical Science and Technology Youth Development Program (No. 21QNPY112), and the China Postdoctoral Science Foundation (No. 2019M664007 and 2021T140793).

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Jizeng Wang, Peifu Tang or Qiangqiang Zhang.

Ethics declarations

Conflicts of Interest

The authors declare that they have no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 13148 KB)

Supplementary file2 (MP4 17687 KB)

Supplementary file3 (MP4 13929 KB)

Supplementary file4 (MP4 4702 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhang, J., Liu, Z., Wang, J. et al. 3D Coaxially Printing rGO Aerogel-Based Biocompatible Fiber for Peripheral Nerve Regeneration. Adv. Fiber Mater. 6, 713–726 (2024). https://doi.org/10.1007/s42765-023-00352-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s42765-023-00352-x

Keywords

Navigation