Skip to main content
Log in

Efficacy of Large Groove Texture on Rat Sciatic Nerve Regeneration In Vivo Using Polyacrylonitrile Nerve Conduits

  • Original Article
  • Published:
Annals of Biomedical Engineering Aims and scope Submit manuscript

Abstract

Physical guidance cues play an important role in enhancing the efficiency of nerve conduits for peripheral nerve injury repair. However, very few in vivo investigations have been performed to evaluate the repair efficiency of nerve conduits with micro-grooved inner textures. In this study, polyacrylonitrile nerve conduits were prepared using dry-jet wet spinning, and micro-grooved textures were incorporated on the inner surface. The nerve conduits were applied to treat 10 mm sciatic nerve gaps in Sprague–Dawley (SD) rats. Sixteen weeks following implantation, nerve function was evaluated based on heat sensory tests, electrophysiological assessments and gastrocnemius muscle mass measurements. The thermal latency reaction and gastrocnemii weight of SD rats treated with grooved nerve conduits were almost 25% faster and 60% heavier than those of SD rats treated with smooth nerve conduits. The histological and immunohistochemical stain analyses showed the repair capacity of inner grooved conduits was found to be similar to that of autografts. These results suggest that grooved nerve conduits with groove width larger than 300 μm significantly improve peripheral nerve regeneration by introducing physical guidance cues. The obtained results can support the design of nerve conduits and lead to the improvement of nerve tissue engineering strategies.

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.

Institutional subscriptions

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8

Similar content being viewed by others

References

  1. Beigi, M. H., L. Ghasemi-Mobarakeh, M. P. Prabhakaran, K. Karbalaie, H. Azadeh, S. Ramakrishna, H. Baharvand, and M. H. Nasr-Esfahani. In vivo integration of poly (ε-caprolactone)/gelatin nanofibrous nerve guide seeded with teeth derived stem cells for peripheral nerve regeneration. J. Biomed. Mater. Res. Part A 102:4554–4567, 2014.

    Google Scholar 

  2. Cattin, A., J. J. Burden, L. Van Emmenis, F. E. Mackenzie, J. J. Hoving, N. G. Calavia, Y. Guo, M. McLaughlin, L. H. Rosenberg, V. Quereda, D. Jamecna, I. Napoli, S. Parrinello, T. TariqEnver, C. Ruhrberg, and A. C. Lloyd. Macrophage-induced blood vessels guide schwann cell-mediated regeneration of peripheral nerves. Cell 162:1127–1139, 2015.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Chang, Y., M. Chen, S. Liao, H. Wu, C. Kuan, J. Sun, and T. Wang. Multichanneled nerve guidance conduit with spatial gradients of neurotrophic factors and oriented nanotopography for repairing the peripheral nervous system. ACS Appl. Mater. Interfaces. 9:37623–37636, 2017.

    CAS  PubMed  Google Scholar 

  4. Chang, W., M. B. Shah, P. Lee, and X. Yu. Tissue-engineered spiral nerve guidance conduit for peripheral nerve regeneration. Acta Biomater. 73:302–311, 2018.

    PubMed  Google Scholar 

  5. Chua, J. S., C. P. Chng, A. A. K. Moe, J. Y. Tann, E. L. Goh, K. H. Chiam, and E. K. Yim. Extending neurites sense the depth of the underlying topography during neuronal differentiation and contact guidance. Biomaterials 35:7750–7761, 2014.

    CAS  PubMed  Google Scholar 

  6. Daly, W., L. Yao, D. Zeugolis, A. Windebank, and A. Pandit. A biomaterials approach to peripheral nerve regeneration: bridging the peripheral nerve gap and enhancing functional recovery. J. R. Soc. Interface. 9:202–221, 2011.

    PubMed  PubMed Central  Google Scholar 

  7. Dray, C., G. Rougon, and F. Debarbieux. Quantitative analysis by in vivo imaging of the dynamics of vascular and axonal networks in injured mouse spinal cord. Proc. Natl. Acad. Sci. 106:9459–9464, 2009.

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Farokhi, M., F. Mottaghitalab, M. A. Shokrgozar, D. L. Kaplan, H. Kim, and S. C. Kundu. Prospects of peripheral nerve tissue engineering using nerve guide conduits based on silk fibroin protein and other biopolymers. Int. Mater. Rev. 62:367–391, 2017.

    CAS  Google Scholar 

  9. Faroni, A., S. A. Mobasseri, P. J. Kingham, and A. J. Reid. Peripheral nerve regeneration: experimental strategies and future perspectives. Adv. Drug Deliv. Rev. 82:160–167, 2015.

    PubMed  Google Scholar 

  10. Gaudin, R., C. Knipfer, A. Henningsen, R. Smeets, M. Heiland, and T. Hadlock. Approaches to peripheral nerve repair: generations of biomaterial conduits yielding to replacing autologous nerve grafts in craniomaxillofacial surgery. Int BioMed Res 2016. https://doi.org/10.1155/2016/3856262.

    Article  Google Scholar 

  11. Gill, E. L., X. Li, M. A. Birch, and Y. Y. S. Huang. Multi-length scale bioprinting towards simulating microenvironmental cues. Bio-des. Manuf. 1:77–88, 2018.

    CAS  Google Scholar 

  12. Gordon, T., and G. H. Borschel. The use of the rat as a model for studying peripheral nerve regeneration and sprouting after complete and partial nerve injuries. Exp. Neurol. 287:331–347, 2017.

    CAS  PubMed  Google Scholar 

  13. Grinberg, Y., M. A. Schiefer, D. J. Tyler, and K. J. Gustafson. Fascicular perineurium thickness, size, and position affect model predictions of neural excitation. IEEE Trans. Neural Syst. Rehabil. Eng. 16:572–581, 2008.

    PubMed  PubMed Central  Google Scholar 

  14. Grinsell, D., and C. P. Keating. Peripheral nerve reconstruction after injury: a review of clinical and experimental therapies. BioMed Res. Int. 13:698256–698256, 2014. https://doi.org/10.1155/2014/698256.

    Article  Google Scholar 

  15. Gu, X., F. Ding, Y. Yang, and J. Liu. Construction of tissue engineered nerve grafts and their application in peripheral nerve regeneration. Prog. Neurobiol. 93:204–230, 2011.

    CAS  PubMed  Google Scholar 

  16. Guo, Q., C. Liu, B. Hai, T. Ma, W. Zhang, J. Tan, X. Fu, H. Wang, Y. Xu, and C. Song. Chitosan conduits filled with simvastatin/Pluronic F-127 hydrogel promote peripheral nerve regeneration in rats. J. Biomed. Mater. Res. Part B 106:787–799, 2018.

    CAS  Google Scholar 

  17. Hoffman-Kim, D., J. A. Mitchel, and R. V. Bellamkonda. Topography, cell response, and nerve regeneration. Annu. Rev. Biomed. Eng. 12:203–231, 2010.

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Holland, I., J. Logan, J. Shi, C. McCormick, D. Liu, and W. Shu. 3D biofabrication for tubular tissue engineering. Bio-des. Manuf. 1:89–100, 2018.

    Google Scholar 

  19. Hsu, S., C. Chen, P. S. Lu, C. Lai, and C. Chen. Oriented Schwann cell growth on microgrooved surfaces. Biotechnol. Bioeng. 92:579–588, 2005.

    CAS  PubMed  Google Scholar 

  20. Hsu, S., P. S. Lu, H. Ni, and C. Su. Fabrication and evaluation of microgrooved polymers as peripheral nerve conduits. Biomed. Microdevices 9:665–674, 2007.

    CAS  PubMed  Google Scholar 

  21. Hsu, S. H., and H. C. Ni. Fabrication of the microgrooved/microporous polylactide substrates as peripheral nerve conduits and in vivo evaluation. Tissue Eng. Part A 15:1381–1390, 2008.

    Google Scholar 

  22. Huang, C., Y. Ouyang, H. Niu, N. He, Q. Ke, X. Jin, D. Li, J. Fang, W. Liu, C. Fan, and T. Lin. Nerve guidance conduits from aligned nanofibers: improvement of nerve regeneration through longitudinal nanogrooves on a fiber surface. ACS Appl. Mater. Interfaces. 7:7189–7196, 2015.

    CAS  PubMed  Google Scholar 

  23. Jin, J., S. Limburg, S. K. Joshi, R. Landman, M. Park, Q. Zhang, H. T. Kim, and A. C. Kuo. Peripheral nerve repair in rats using composite hydrogel-filled aligned nanofiber conduits with incorporated nerve growth factor. Tissue Eng. Part A 19:2138–2146, 2013.

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Johnson, B. N., K. Z. Lancaster, G. Zhen, J. He, M. K. Gupta, Y. L. Kong, E. A. Engel, K. D. Krick, A. Ju, F. Meng, L. W. Enquist, X. Jia, and M. C. Mcalpine. 3D printed anatomical nerve regeneration pathways. Adv. Funct. Mater. 25:6205–6217, 2015.

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Kim, S. M., M. S. Lee, J. Jeon, D. H. Lee, K. Yang, S. Cho, I. Han, and H. S. Yang. Biodegradable nerve guidance conduit with microporous and micropatterned poly(lactic-co-glycolic acid)-accelerated sciatic nerve regeneration. Macromol. Biosci. 18:1800290, 2018.

    Google Scholar 

  26. Krych, A. J., G. E. Rooney, B. Chen, T. C. Schermerhorn, S. Ameenuddin, L. Gross, M. J. Moore, B. L. Currier, R. J. Spinner, J. A. Friedman, M. J. Yaszemski, and A. J. Windebank. Relationship between scaffold channel diameter and number of regenerating axons in the transected rat spinal cord. Acta Biomater. 5:2551–2559, 2009.

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Lackington, W. A., A. J. Ryan, and F. J. Brien. Advances in nerve guidance conduit-based therapeutics for peripheral nerve repair. ACS Biomater. Sci. Eng. 3(1221–1235):2017, 2017.

    Google Scholar 

  28. Li, C. W., B. Davis, J. Shea, H. Sant, B. K. Gale, and J. Agarwal. Optimization of micropatterned poly (lactic-co-glycolic acid) films for enhancing dorsal root ganglion cell orientation and extension. Neural Regener. Res. 13:105, 2018.

    Google Scholar 

  29. Long, Y., N. Zhang, Y. Huang, and X. Wen. Formation of highly aligned grooves on inner surface of semipermeable hollow fiber membrane for directional axonal outgrowth. J. Manuf. Sci. Eng. 130:021011, 2008.

    Google Scholar 

  30. Ma, T., L. Zhu, Y. Yang, X. Quan, L. Huang, Z. Liu, Z. Sun, S. Zhu, J. Huang, and Z. Luo. Enhanced in vivo survival of Schwann cells by a synthetic oxygen carrier promotes sciatic nerve regeneration and functional recovery. J. Tissue Eng. Regener. Med. 12:e177–e189, 2018.

    CAS  Google Scholar 

  31. Mobasseri, A., A. Faroni, B. M. Minogue, S. Downes, G. Terenghi, and A. J. Reid. Polymer Scaffolds with preferential parallel grooves enhance nerve regeneration. Tissue Eng. Part A 21:1152–1162, 2015.

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Nectow, A. R., K. G. Marra, and D. L. Kaplan. Biomaterials for the development of peripheral nerve guidance conduits. Tissue Eng. Part B 18:40–50, 2012.

    CAS  Google Scholar 

  33. Nguyen, A. T., S. R. Sathe, and E. K. Yim. From nano to micro: topographical scale and its impact on cell adhesion, morphology and contact guidance. J. Phys. 28:183001, 2016.

    Google Scholar 

  34. Oh, S. H., J. G. Kang, T. H. Kim, U. Namgung, K. S. Song, B. H. Jeon, and J. H. Lee. Enhanced peripheral nerve regeneration through asymmetrically porous nerve guide conduit with nerve growth factor gradient. J. Biomed. Mater. Res. Part A 106:52–64, 2018.

    CAS  Google Scholar 

  35. Pawelec, K. M., J. Koffler, D. Shahriari, A. R. Galvan, M. H. Tuszynski, and J. Sakamoto. Microstructure and in vivo characterization of multi-channel nerve guidance scaffolds. Biomed. Mater. 13:044104, 2018.

    CAS  PubMed  Google Scholar 

  36. Quan, Q., H. Y. Meng, B. Chang, G. B. Liu, X. Q. Cheng, H. Tang, Y. Wang, J. Peng, Q. Zhao, and S. B. Lu. Aligned fibers enhance nerve guide conduits when bridging peripheral nerve defects focused on early repair stage. Neural Regener. Res. 14:903, 2019.

    Google Scholar 

  37. Roach, P., T. Parker, N. Gadegaard, and M. R. Alexander. Surface strategies for control of neuronal cell adhesion: a review. Surf. Sci. Rep. 65:145–173, 2010.

    CAS  Google Scholar 

  38. Sarker, M., S. Naghieh, A. D. Mcinnes, D. J. Schreyer, and X. B. Chen. Strategic design and fabrication of nerve guidance conduits for peripheral nerve regeneration. Biotechnol. J. 13:1700635, 2018.

    Google Scholar 

  39. Sarker, M. D., S. Naghieh, A. D. McInnes, D. J. Schreyer, and X. Chen. Regeneration of peripheral nerves by nerve guidance conduits: influence of design, biopolymers, cells, growth factors, and physical stimuli. Prog. Neurobiol. 171:125–150, 2018.

    CAS  PubMed  Google Scholar 

  40. Seidl, A. H. Regulation of conduction time along axons. Neuroscience 276:126–134, 2014.

    CAS  PubMed  Google Scholar 

  41. Simitzi, C., A. Ranella, and E. Stratakis. Controlling the morphology and outgrowth of nerve and neuroglial cells: the effect of surface topography. Acta Biomater. 51:21–52, 2017.

    CAS  PubMed  Google Scholar 

  42. Suo, H., Z. Wang, G. Dai, J. Fu, J. Yin, and L. Chang. Polyacrylonitrile nerve conduits with inner longitudinal grooved textures to enhance neuron directional outgrowth. IEEE\/ASME J. Microelectromech. Syst. 27:457–463, 2018.

    CAS  Google Scholar 

  43. Tao, J., Y. Hu, S. Wang, J. Zhang, X. Liu, Z. Gou, H. Cheng, Q. Liu, Q. Zhang, S. You, and M. Gou. A 3D-engineered porous conduit for peripheral nerve repair. Sci. Rep. 7(1):46038, 2017.

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Tao, J., J. Zhang, T. Du, X. Xu, X. Deng, S. Chen, J. Liu, Y. Chen, X. Liu, M. Xiong, Y. Luo, H. Cheng, J. Mao, L. Cardon, M. Gou, and Y. Wei. Rapid 3D printing of functional nanoparticle-enhanced conduits for effective nerve repair. Acta Biomater. 90:49–59, 2019.

    CAS  PubMed  Google Scholar 

  45. Vleggeert-Lankamp, C. L. The role of evaluation methods in the assessment of peripheral nerve regeneration through synthetic conduits: a systematic review. J. Neurosurg. 107:1168–1189, 2007.

    PubMed  Google Scholar 

  46. Wang, Y., W. Wang, Y. Wo, T. Gui, H. Zhu, X. Mo, C. Chen, Q. Li, and W. Ding. Orientated guidance of peripheral nerve regeneration using conduits with a microtube array sheet (MTAS). ACS Appl. Mater. Interfaces. 7:8437–8450, 2015.

    CAS  PubMed  Google Scholar 

  47. Wen, X., and P. A. Tresco. Effect of filament diameter and extracellular matrix molecule precoating on neurite outgrowth and Schwann cell behavior on multifilament entubulation bridging device in vitro. J. Biomed. Mater. Res., Part A 76:626–637, 2006.

    Google Scholar 

  48. Xu, X., J. Tao, S. Wang, L. Yang, J. Zhang, J. Zhang, H. Liu, H. Cheng, J. Xu, M. Gou, and Y. Wei. 3D printing of nerve conduits with nanoparticle-encapsulated RGFP966. Appl. Mater. Today 16:247–256, 2019.

    CAS  Google Scholar 

  49. Yao, L., S. Wang, W. Cui, R. Sherlock, C. O’Connell, G. Damodaran, A. Gorman, A. Windebank, and A. Pandit. Effect of functionalized micropatterned PLGA on guided neurite growth. Acta Biomater. 5:580–588, 2009.

    CAS  PubMed  Google Scholar 

  50. Yin, J., Z. Wang, W. Chai, G. Dai, H. Suo, N. Zhang, X. Wen, and Y. Huang. Fabrication of inner grooved hollow fiber membranes using microstructured spinneret for nerve regeneration. J. Manuf. Sci. Eng. 139:111007, 2017.

    Google Scholar 

  51. Zhao, Y., Q. Zhang, L. Zhao, L. Gan, L. Yi, Y. Zhao, J. Xue, L. Luo, Q. Du, R. Geng, Z. Sun, N. Benkirane-Jessel, P. Chen, and Y. Li. Enhanced peripheral nerve regeneration by a high surface area to volume ratio of nerve conduits fabricated from hydroxyethyl cellulose/soy protein composite sponges. ACS Omega. 2:7471–7481, 2017.

    CAS  PubMed  Google Scholar 

  52. Zhong, Y., L. Wang, J. Dong, Y. Zhang, P. Luo, J. Qi, X. Liu, and C. J. Xian. Three-dimensional reconstruction of peripheral nerve internal fascicular groups. Sci. Rep. 5:17168–17168, 2015.

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Zhu, S., J. Ge, Y. Wang, F. Qi, T. Ma, M. Wang, Y. Yang, Z. Liu, J. Huang, and Z. Luo. A synthetic oxygen carrier-olfactory ensheathing cell composition system for the promotion of sciatic nerve regeneration. Biomaterials 35:1450–1461, 2014.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

Authors sincerely thank Chaonan Yu for preparing and housing SD rats. This study was partially supported by the National Key Research and Development Program of China (Grant No. 2018YFA0703000), the Key Research and Development Program of Zhejiang Province (Grant No. 2017C01063), the Science Fund for Creative Research Groups of the National Natural Science Foundation of China (Grant No. 51821093), the National Natural Science Foundation of China (Grant No. U1609207, 81873911), the Public Projects of Zhejiang Province (Grant No. 2019C03033), the Zhejiang Medical Science and Technology Project (Grant No. 2019KY569), and the Natural Foundation of Ningbo (Grant No. 2017A610215).

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Peng Wei, Kedi Xu or Jun Yin.

Additional information

Associate Editor Xiaoxiang Zheng oversaw the review of this article.

Publisher's Note

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

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, Z., Wu, Y., Xiang, Y. et al. Efficacy of Large Groove Texture on Rat Sciatic Nerve Regeneration In Vivo Using Polyacrylonitrile Nerve Conduits. Ann Biomed Eng 49, 394–406 (2021). https://doi.org/10.1007/s10439-020-02560-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10439-020-02560-7

Keywords

Navigation