Development of a Bioengineering Strategy to Promote Functional Repair Following Traumatic Peripheral Nervous System Injury
Final Report Abstract
The goal of the project was to develop and assess a nanofibre-based tissue engineering strategy for the repair of traumatically injured peripheral nervous system (PNS). At the time of requesting funding, the only CE and FDA approved artificial devices that were available for repairing injury-induced gaps in the PNS were simple hollow conduits. Major milestones that were successfully achieved during the project: 1. Modification of the electrospinning process to collect individual 2D arrays of highly orientated polycaprolactone (PCL) nanofibres that were suspended in air. 2. Sequential stacking of the PCL nanofibre arrays to form a 3D structure of highly orientated nanofibres with a defined spacing between arrays and demonstration of maintained nanofibre orientation and array spacing following embedding in 3D fibrin hydrogel. 3. In vitro determination of the cell-substrate interactions of purified populations of Schwann cells within the non-orientated, functionalised environment of the fibrin hydrogel and the significant influence embedded arrays of orientated nanofibres. 4. Development of the spinal cord organotypic slice preparation as a simple and cost effect means of studying motor axon interactions with 3D bioengineered substrates. 5. Development of a strategy for incorporating the 3D fibrin hydrogel/nanofibre arrays into hollow type-I collagen nerve conduits (generously provided by the French bioenterprise Biom’UP) and its implantation into an experimental, 15mm gap model of peripheral nerve injury in the adult rat sciatic nerve. 6. Demonstration of the biocompatibility and integration of the implanted scaffold with the host peripheral nerve tissues. 7. Behavioural, electrophysiological and morphological evaluation of the extent of tissue repair and functional recovery supported by the implanted 3D fibrin/nanofibre array-containing conduit. Experimental groups being: (I) lesion plus autografted sciatic nerve, (II) lesion and no repair, (III) implantation of Schwann cell seeded 3D fibrin/nanofibre array-containing conduit, (IV) implantation of non-seeded 3D fibrin/nanofibre array-containing conduit, (V) implantation of the empty type-I collagen conduit.
Publications
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(2012). Electrospinning of Nanofibres for Repair of the Injured Peripheral Nervous System. In: Nanomedicine and the Nervous System. Ed. Preedy VR. Science Publishers, New Hampshire USA
Hodde D, Gerardo-Nava JL, Deumens R, Mey J, Brook GA
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(2014) Grundleges zu Degeneration und Regeneration von Nerven. In Nervenchirurgie - Trauma, Tumor, Kompression. Eds Kretschmer, Antoniadis, Assmus pp 1-10. Springer-Verlag Berlin Heidelberg. ISBN 978-3-642-36894-3
Brook GA, Hodde D, Kretschmer T
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(2014) Spinal cord organotypic slice cultures for the study of regenerating motor axon interactions with 3D scaffolds. Biomaterials. 35:4288- 4296
Gerardo-Nava J, Hodde D, Katona I, Bozkurt A, Grehl T, Steinbusch HW, Weis J, Brook GA
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(2014). Assessing motor outcome and functional recovery following nerve injury. Methods Mol Biol. 1162:179-88
Deumens R, Marinangeli C, Bozkurt A, Brook GA
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Characterisation of cell-substrate interactions between Schwann cells and three-dimensional fibrin hydrogels containing orientated nanofibre topographical cues. European Journal of Neuroscience EJN Volume 43, Issue 3, Special Issue: PERIPHERAL NERVE REGENERATION, February 2016, Pages 376-387
Hodde D, Gerardo-Nava JL, Wöhlk V, Weinandy S, Jockenhövel S, Kriebel A, Haktan Altinova, Harry W. M. Steinbusch, Möller M, Weis J, Mey J, Brook GA
