The incorporation of growth factor and chondroitinase ABC into an electrospun scaffold to promote axon regrowth following spinal cord injury.
Spinal cord injury results in tissue necrosis in and around the lesion site, commonly leading to the formation of a fluid-filled cyst. This pathological end point represents a physical gap that impedes axonal regeneration. To overcome the obstacle of the cavity, we have explored the extent to which axonal substrates can be bioengineered through electrospinning, a process that uses an electrical field to produce fine fibres of synthetic or biological molecules. Recently, we demonstrated the potential of electrospinning to generate an aligned matrix that can influence the directionality and growth of axons. Here, we show that this matrix can be supplemented with nerve growth factor and chondroitinase ABC to provide trophic support and neutralize glial-derived inhibitory proteins. Moreover, we show how air-gap electrospinning can be used to generate a cylindrical matrix that matches the shape of the cord. Upon implantation in a completely transected rat spinal cord, matrices supplemented with NGF and chondroitinase ABC promote significant functional recovery. An examination of these matrices post-implantation shows that electrospun aligned monofilaments induce a more robust cellular infiltration than unaligned monofilaments. Further, a vascular network is generated in these matrices, with some endothelial cells using the electrospun fibres as a growth substrate. The presence of axons within these implanted matrices demonstrates that they facilitate axon regeneration following spinal cord injury. Collectively, these results demonstrate the potential of electrospinning to generate an aligned substrate that can provide trophic support, directional guidance cues and regeneration-inhibitory neutralizing compounds to regenerating axons following spinal cord injury. Copyright © 2016 John Wiley & Sons, Ltd.
Department of Anatomy and Neurobiology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA, USA.
Raymond J
RJ
Colello
Department of Anatomy and Neurobiology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA, USA.
Woon N
WN
Chow
Department of Anatomy and Neurobiology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA, USA.
John W
JW
Bigbee
Department of Anatomy and Neurobiology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA, USA.
Charles
C
Lin
Department of Anatomy and Neurobiology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA, USA.
Dustin
D
Dalton
Department of Anatomy and Neurobiology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA, USA.
Damien
D
Brown
Department of Anatomy and Neurobiology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA, USA.
Balendu Shekhar
BS
Jha
Department of Neurosurgery, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA, USA.
Bruce E
BE
Mathern
Department of Neurosurgery, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA, USA.
Kangmin D
KD
Lee
Department of Anatomy and Neurobiology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA, USA.
David G
DG
Simpson
D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000473:pathology; D019765:Chondroitin ABC Lyase / Q000737:chemistry / Q000494:pharmacology; D020932:Nerve Growth Factor / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D058630:Spinal Cord Regeneration / Q000187:drug effects*; D054457:Tissue Scaffolds / Q000737:chemistry*
D020932:Nerve Growth Factor; D019765:Chondroitin ABC Lyase
alginate; angiogenesis; axon regeneration; electrospinning; matrix; polydioxinone; spinal cord injury