3D anisotropic scaffolds for spinal cord regeneration

Joana P.M. Sousa (a)(b)(c)* , Sara C. Santos (b) , Catarina A. Custódio (b) , Emmanuel Stratakis (c) , João F. Mano (b)and Paula A.A.P. Marques (a)

(a) - TEMA, Department of Mechanical Engineering, University of Aveiro; (b) - CICECO, Department of Chemistry, University of Aveiro; (c) – Institute of Electronic Structure and Laser (IESL), Foundation for Research and Technology-Hellas (FORTH) (a) and (b) Aveiro, Portugal; (c) Heraklion, Greece *joanapmsousa@ua.pt

Abstract — Spinal cord injury is defined as a damage to the spinal cord that causes changes in its function and can mean permanent loss of functionality at the sensory and motor level affecting, for example, locomotion, breathing, heart rate, sexual function and bowel and bladder control, resulting in psychological and social consequences devastating for patients worldwide [1].

Currently, there is no treatment capable of fully restore spinal cord physiology, and patients’ well-being is ensured by palliative and rehabilitation approaches. In this regard, neural tissue engineering offers an opportunity to associate cells, biomolecules, biomaterials and microfabrication techniques to reconnect the two stumps of the injury [2]. Considering tissue organization, the core of spinal cord - grey matter - consists mainly of randomly distributed nerve cell bodies, myelinic fibres and glial cells, while the periphery is composed of aligned motor and sensory axon tracts - white matter – that are responsible for the conduction of neural information through electrical impulses. A lesion to the spinal cord may result in tissue disruption, loss of blood supply, death of neural cells and scar formation [3] Particularly, the damage to the white matter has been shown to prevent axon extension across the injured area blocking the restoration of the neuronal network [4]. To overcome this inhibitory environment, some tissue engineering approaches are specifically focused on mimicking the white matter alignment via the design of 3D anisotropic scaffolds. Those scaffolds can be divided in three major categories according to their micro/nanostructure: vertically aligned fibres, vertically aligned pores and multichannel scaffolds.

Here, we summarize and discuss the features, fabrication techniques, and reported impacts on spinal cord regeneration of each category and present our own strategies for the fabrication of 3D scaffolds to promote aligned tissue regrowth between the proximal and distal ends of the injury.

Agreement, through the European Regional Development Fund; and European Horizon 2020 - FET OPEN Program under Grant No. 829060 (“NeuroStimSpinal”; URL: www. neurostimspinal.eu/"). JPMS thanks to FCT for the PhD grant SFRH/BD/144579/2019.

TOPIC 2) Technologies for the Wellbeing a. Multiscale Technologies and Devices for

Medicine, Environment & Energy

REFERENCES

[1] Ahuja, C. S.; Wilson, J. R.; Nori, S.; Kotter, M. R. N.; Druschel, C.; Curt, A.; Fehlings, M. G., “Traumatic Spinal Cord Injury”, Nat. Rev. Dis. Prim., vol. 3, pp. 1-21, 2017.

[2] Führmann, T.; Anandakumaran, P. N.; Shoichet, M. S., “Combinatorial Therapies After Spinal Cord Injury: How Can Biomaterials Help?”, Adv. Healthc. Mater., vol. 6, pp. 1-21, 2017.

[3]

Holmes, D., S50-S51, 2017. “Repairing the Neural Highway”, Nature, vol. 552,

[4] Pettigrew, D. B.; Shockley, K. P.; Crutcher, K. A., “Disruption of Spinal Cord White Matter and Sciatic Nerve Geometry Inhibits Axonal Growth in Vitro in the Absence of Glial Scarring”, BMC Neuroscience., vol. 2, 2001.

Keywords — Spinal cord injury; Tissue Engineering; Scaffold; Anisotropic

ACKNOWLEGEMENTS

This work is supported by the projects: UIDB/00481/2020 and UIDP/00481/2020 - FCT - Fundação para a Ciencia e a Tecnologia; CENTRO-01-0145-FEDER022083 - Centro Portugal Regional Operational Program (Centro2020), under the PORTUGAL 2020 Partnership