Finite element analysis of glucose diffusivity in cellulose nanofibril peripheral nerve conduits

Abstract

Peripheral neuropathy arising from physical trauma is estimated to afflict 20 million people in the United States alone. In one common surgical intervention, neural conduits are placed over the nerve stumps to bridge the gap and create a microenvironment conducive to regeneration. It has been proposed that a biocompatible material such as cellulose nanofiber may serve as a viable conduit material, providing a non-inflammatory and mechanically stable system. Preliminary studies have shown that cellulose nanofiber conduits successfully aid neural regeneration and further, that the dimensions of the conduit relative to the nerve gap have an impact on efficacy in murine models. It has been hypothesized that the reliance of regeneration upon the physical dimensions of the conduit may be related to modified modes of diffusion and/or distances of key cellular nutrients and waste metabolites to/from the injury site. The present work investigates the concentration profile of glucose within the conduit via finite element analysis as a function of the physical dimensions of the conduit. It was determined that the magnitude of glucose diffusion was greater through the conduit walls than through the luminal space between the nerve and the inner wall of the conduit, and that as such radial diffusion is dominant over axial diffusion.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

References

  1. Allen JS, Damasio H, Grabowski TJ (2002) Normal neuroanatomical variation in the human brain: an MRI-volumetric study. Am J Phys Anthropol 358:341–58. https://doi.org/10.1002/ajpa.10092

    Article  Google Scholar 

  2. Barton MJ, Morley JW, Stoodley MA, Lauto A, Mahns DA (2014) Nerve repair: toward a sutureless approach. Neurosurg Rev 37(4):585–595. https://doi.org/10.1007/s10143-014-0559-1

    Article  PubMed  Google Scholar 

  3. Berg JM, Tymoczko JL, Stryer L (2002) Biochemistry. W H Freeman, New York

    Google Scholar 

  4. Dahlin LB, Wiberg M (2017) Nerve Injuries of the Upper Extremity and Hand. EFORT Open Rev 2(5):158–170. https://doi.org/10.1302/2058-5241.2.160071

    Article  PubMed  PubMed Central  Google Scholar 

  5. Gaudet AD, Popovich PG, Ramer MS (2011) Wallerian degeneration: gaining perspective on inflammatory events after peripheral nerve injury. J Neuroinflammat 8(1):110. https://doi.org/10.1186/1742-2094-8-110

    Article  Google Scholar 

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

    Article  PubMed  PubMed Central  Google Scholar 

  7. Grinsell D, Keating CP (2014) Peripheral nerve reconstruction after injury: a review of clinical and experimental therapies. Biomed Res Int. https://doi.org/10.1155/2014/698256

    Article  PubMed  PubMed Central  Google Scholar 

  8. Han P, Bartels DM (1996) Temperature dependence of oxygen diffusion in H2O and D2O. J Phys Chem 100:5597–5602. https://doi.org/10.1021/jp952903y

    CAS  Article  Google Scholar 

  9. Harrison PJ, Freemantle N, Geddes JR (2003) Meta-analysis of brain weight in schizophrenia. Schizophrenia Res 64:25–34. https://doi.org/10.1016/S0920-9964(02)00502-9

    Article  Google Scholar 

  10. Haug A (2009) US food and drug administration/conformit Europe-approved absorbable nerve conduits for clinical repair of peripheral and cranial nerves. Ann Plast Surg 62(6):710

    CAS  Article  Google Scholar 

  11. Jensen VFH, Mølck AM, Bøgh IB, Lykkesfeldt J (2014) Effect of insulin-induced hypoglycaemia on the peripheral nervous system: focus on adaptive mechanisms, pathogenesis and histopathological changes. J Neuroendocrinol 26(8):482–496. https://doi.org/10.1111/jne.12170

    CAS  Article  PubMed  Google Scholar 

  12. Kehoe S, Zhang XF, Boyd D (2012) FDA approved guidance conduits and wraps for peripheral nerve injury: a review of materials and efficacy. Injury 43(5):553–572. https://doi.org/10.1016/j.injury.2010.12.030

    CAS  Article  PubMed  Google Scholar 

  13. Khalil E, Kretsos K, Kasting GB (2006) Glucose partition coefficient and diffusivity in the lower skin layers. Pharm Res 23(6):1227–1234. https://doi.org/10.1007/s11095-006-0141-9

    CAS  Article  PubMed  Google Scholar 

  14. Kokai LE, Lin YC, Oyster NM, Marra KG (2009) Diffusion of soluble factors through degradable polymer nerve guides: controlling manufacturing parameters. Acta Biomater 5(7):2540–2550. https://doi.org/10.1016/j.actbio.2009.03.009

    CAS  Article  PubMed  Google Scholar 

  15. Lim TKY, Rone MB, Lee S, Antel JP, Zhang J (2015a) Mitochondrial and bioenergetic dysfunction in trauma-induced painful peripheral neuropathy. Mol Pain. https://doi.org/10.1186/s12990-015-0057-7

    Article  PubMed  PubMed Central  Google Scholar 

  16. Lim TKY, Shi XQ, Johnson JM, Rone MB, Antel JP, David S, Zhang J (2015b) Peripheral nerve injury induces persistent vascular dysfunction and endoneurial hypoxia, contributing to the genesis of neuropathic pain. J Neurosci 35(8):3346–3359. https://doi.org/10.1523/JNEUROSCI.4040-14.2015

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  17. Lohrasbi S, Mirzaei E, Karimizade A, Takallu S, Rezaei A (2020) Collagen/cellulose nanofiber hydrogel scaffold: physical, mechanical and cell biocompatibility properties. Cellulose 27(2):927–940. https://doi.org/10.1007/s10570-019-02841-y

    CAS  Article  Google Scholar 

  18. Meek MF, Jansen K (2009) Two years after in vivo implantation of Poly(DL-Lactide-ε- Caprolactone) nerve guides: has the material finally resorbed? J Biomed Mater Res Part A 89(3):734–738. https://doi.org/10.1002/jbm.a.32024

    CAS  Article  Google Scholar 

  19. Mergenthaler P (2014) Sugar for the brain: the role of glucose in physiological and pathological brain function. Trends Neurosci 36(10):587–597. https://doi.org/10.1016/j.tins.2013.07.001.Sugar

    Article  Google Scholar 

  20. Moor BK, Haefeli M, Bouaicha S, Nagy L (2010) Results after delayed axillary nerve reconstruction with interposition of sural nerve grafts. J Shoulder Elbow Surg 19(3):461–466. https://doi.org/10.1016/j.jse.2009.07.011

    Article  PubMed  Google Scholar 

  21. Niu X, Liu Y, Fang G, Huang C, Rojas OJ, Pan H (2018) Highly transparent, strong, and flexible films with modified cellulose nanofiber bearing UV shielding property. Biomacromol 19(12):4565–4575. https://doi.org/10.1021/acs.biomac.8b01252

    CAS  Article  Google Scholar 

  22. Sibson NR, Mason GF, Behar KL, Rothman DL, Shulman RG (1998) Mapping glutamatergic activity: stoichiometric coupling of brain glucose metabolism and neurotransmitter glutamate cycling. NeuroImage 7(4):316–21. https://doi.org/10.1016/s1053-8119(18)31120-0

    Article  Google Scholar 

  23. Stecker MM, Stevenson M (2014) Effect of glucose concentration on peripheral nerve and its response to anoxia. Muscle Nerve 49(3):370–377. https://doi.org/10.1002/mus.23917

    CAS  Article  PubMed  Google Scholar 

  24. Suhaimi H, Wang S, Das DB (2015) Glucose diffusivity in cell culture medium. Chem Eng J 269:323–327. https://doi.org/10.1016/j.cej.2015.01.130

    CAS  Article  Google Scholar 

  25. Suhaimi H, Wang S, Thornton T, Das DB (2015) On glucose diffusivity of tissue engineering membranes and scaffolds. Chem Eng Sci 126:244–256. https://doi.org/10.1016/j.ces.2014.12.029

    CAS  Article  Google Scholar 

  26. Takagi H, Asano A (2008) Effects of processing conditions on flexural properties of cellulose nanofiber reinforced ‘green’ composites. Compos A Appl Sci Manuf 39(4):685–689. https://doi.org/10.1016/j.compositesa.2007.08.019

    CAS  Article  Google Scholar 

  27. Taras JS, Nanavati V, Steelman P (2005) Nerve conduits. J Hand Ther 18(2):191–197. https://doi.org/10.1197/j.jht.2005.02.012

    Article  PubMed  Google Scholar 

  28. Thennadil SN, Rennert JL, Wenzel BJ, Hazen KH, Ruchti TL, Block MB (2001) Comparison of glucose concentration in interstitial fluid, and capillary and venous blood during rapid changes in blood glucose levels. Diabet Technol Therapeut 3(3):357–365. https://doi.org/10.1089/15209150152607132

    CAS  Article  Google Scholar 

  29. Tirosh A, Shai I, Rudich A (2006) Normal fasting plasma glucose levels and type 2 diabetes in young men. N Engl J Med 354(1):87–88. https://doi.org/10.1056/NEJMc052984

    Article  Google Scholar 

  30. Xue Y, Mou Z, Xiao H (2017) Nanocellulose as a sustainable biomass material: structure, properties, present status and future prospects in biomedical applications. Nanoscale 9(39):14758–14781. https://doi.org/10.1039/c7nr04994c

    CAS  Article  PubMed  Google Scholar 

Download references

Funding

This research was funded by a National Science Foundation award “Explore It! Building the Next Generation of Sustainable Forest Bioproduct Researchers”, NSF REU Award 1757529 in conjunction with the University of Maine Graduate School of Biomedical Science and Engineering, National Institute of Health T32 award “Transdisciplinary predoctoral training in biomedical science and engineering” Award #5T32GM132006-02.

Author information

Affiliations

Authors

Contributions

All authors contributed to the present work.

Corresponding author

Correspondence to David J. Neivandt.

Ethics declarations

Conflict of interest

Not applicable.

Data availability  (data transparency)

Available upon request.

Code availability (software application or custom code)

Available upon request.

Additional information

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

Verify currency and authenticity via CrossMark

Cite this article

Carter, N., Towne, J. & Neivandt, D.J. Finite element analysis of glucose diffusivity in cellulose nanofibril peripheral nerve conduits. Cellulose (2021). https://doi.org/10.1007/s10570-021-03724-x

Download citation

Keywords

  • Cellulose nanofiber
  • Neural conduits
  • Glucose diffusion
  • Finite element analysis