Date of Award

2017

Document Type

Open Access Dissertation

Degree Name

Doctor of Philosophy in Chemical Engineering (PhD)

Administrative Home Department

Department of Chemical Engineering

Advisor 1

Michael Mullins

Advisor 2

Feng Zhao

Committee Member 1

Caryn Heldt

Committee Member 2

Jeremy Goldman

Abstract

A suitable tissue scaffold to support and assist in the repair of damaged tissues or cells is important for success in clinical trials and for injury recovery. Electrospinning can create a variety of polymer nanofibers and microfibers, and is being widely used to produce experimental tissue scaffolds for neural applications. This dissertation examines various approaches by which electrospinning is being used for neural tissue engineering applications for the repair of injuries to the central nervous system (CNS) and the peripheral nervous system (PNS). Due to the poor regeneration of neural tissues in the event of injury, tissue scaffolds are being used to promote the recovery and restoration of neural function. Next generation scaffolds using bioactive materials, conductive polymers, and coaxial fiber structures are now being developed to improve the recovery of motor functions in in vivo studies. This dissertation includes fabrication techniques, the results of neural cell cultures performed both in vivo and in vitro on electrospun fiber scaffolds, examines barriers to full functional recovery, and future directions for electrospinning and neural tissue engineering.

Aligned, free-standing fiber scaffolds using poly-L-lactic acid (PLLA) were developed as an in vitro model to study cell interaction on free-standing fiber scaffolds in vivo. Stages were designed to allow for the formation of free-standing fiber scaffolds that were not supported by an underlying surface. Fibers were spun across the columns of the stages to produce free-standing fiber scaffolds. The scaffolds were then used for in vitro cell culture using chick dorsal root ganglia (DRG). Fiber scaffolds were also spun on a flat substrate and used for in vitro cell studies for comparison. The axonal outgrowth observed for DRG cells cultured on free-standing fiber scaffolds was comparable to those grown on fibers with an underlying surface, indicating that cells follow the alignment of fibers even without an underlying support.

Electrospinning coaxial fibers is a more complex application of electrospinning techniques that has been explored here as a method of creating a core-sheath fiber structure to act as a scaffold across glial scar tissue present in spinal cord injuries (SCIs). Here, we looked at altering the basic electrospinning set-up to spin core-sheath fibers. The core was spun with a conductive polymer, poly(3,4-ethyelenedixoythiophene): poly(styrene sulfonate) (PEDOT:PSS) and the sheath was spun PLLA to create coaxial fibers with a conductive core and an insulating sheath. A conductive polymer was used so that electrical stimulation could be applied along the fibers during cell culture to examine if the additional external stimulation would further assist in axonal outgrowth when combined with the topographical cues of the fiber scaffolds. This allows for the combination of electrical stimulation with the topographical guidance provided by aligned fiber scaffolds to improve axonal outgrowth and functional recovery in vivo.

Available for download on Thursday, March 01, 2018

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