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, log in via an institution to check access.
Similar content being viewed by others
References
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
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
Berg JM, Tymoczko JL, Stryer L (2002) Biochemistry. W H Freeman, New York
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Authors and Affiliations
Contributions
All authors contributed to the present work.
Corresponding author
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
About this article
Cite this article
Carter, N., Towne, J. & Neivandt, D.J. Finite element analysis of glucose diffusivity in cellulose nanofibril peripheral nerve conduits. Cellulose 28, 2791–2803 (2021). https://doi.org/10.1007/s10570-021-03724-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10570-021-03724-x