Date of Award

12-2011

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Legacy Department

Mechanical Engineering

Advisor

Huang, Yong

Committee Member

Huang , Yong

Committee Member

Coutris , Nicole

Committee Member

Brown , Philip J.

Committee Member

Li , Gang

Committee Member

Miller , Richard

Abstract

Nerve injury is a general but intractable disease in traumatic injuries, leading to a significant reduction of functions in the nervous system. Extensive efforts are made on nerve injury rehabilitation. Since the appropriate connections between neurons and their targets are necessary, guiding axonal outgrowth is an essential step for neuron outgrowth in nervous system development, functioning, and regeneration. Besides the direct surgical nerve connection, an artificial means of guiding nerve regeneration called nerve conduits is widely applied in nerve injury rehabilitation. The main function of nerve conduits is to bridge the nerve gap, to help regenerating axons across damaged regions and guide them to appropriate targets. Recently, polymeric hollow fiber membranes (HFMs) have been studied as a potential nerve conduit for nerve regeneration and repair. In order to further improve the efficiency of HFMs, micropatterns such as aligned grooves are usually introduced on the inner surface of HFMs as an effective topographical guidance cue.
The goal of this study is to fabricate HFMs with aligned grooves on the inner surface and understand their effect on nerve regeneration and repair. Consequently, there is a need, first, to carefully design the fabrication process of HFMs introducing aligned grooves on inner surface and understand the groove formation mechanism; second, to better understand the role of defined grooves on the inner surface of HFMs as topographical guidance cues promoting axonal outgrowth.
The grooved HFMs were fabricated by means of a phase inversion-based spinning technique with a smooth and annular spinneret by carefully controlling the fabrication conditions. The effects of different operating conditions were experimentally studied, and the fabricated HFMs were also characterized. In order to explain the formation of grooves on the HFM inner surface, two different instability mechanisms were introduced: a hydrodynamic or Marangoni instability and an elastic or buckling instability. The results obtained between the experimental and the theoretical studies were compared in terms of the number of grooves under different operating conditions. Then, the fabricated HFMs with textured inner surface were used as nerve conduits. The effect of the geometry of the grooved inner surface on the axonal outgrowth was studied. A numerical model describing the motion and deformation of an axon moving on the grooved HMF inner surface was developed to study the effect of substrate geometry on axonal outgrowth.
This work developed the first theoretical model for the groove formation mechanism during the HFM fabrication. In this model, the Marangoni instability was first used to investigate the onset of instability in the HFM fabrication, and the buckling of instability magnification was also studied. This work also presented the numerical simulation of axonal outgrowth on a three-dimensional substrate, where the influence of the substrate geometry was taken into account. The work covered by this thesis will help to fabricate nerve conduits for better nerve regeneration and repair.

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