Document Type

Dissertation

Date of Degree

Summer 2014

Degree Name

PhD (Doctor of Philosophy)

Degree In

Chemical and Biochemical Engineering

First Advisor

C. Allan Guymon

Abstract

Neural prosthetics are used to replace or substantially augment remaining motor and sensory functions of neural pathways that were lost or damaged due to physical trauma, disease, or genetics. However, due to poor spatial signal resolution, neural prostheses fail to recapitulate the intimate, precise interactions inherent to neural networks. Designing materials and interfaces that direct de novo nerve growth to spatially specific stimulating elements is, therefore, a promising method to enhance signal specificity and performance of prostheses such as the successful cochlear implant (CI) and the developing retinal implant.

In this work, the spatial and temporal reaction control inherent to photopolymerization was used to develop methods to generate micro and nanopatterned materials that direct neurite growth from prosthesis relevant neurons. In particular, neurite growth and directionality has been investigated in response to physical, mechanical, and chemical cues on photopolymerized surfaces. Spiral ganglion neurons (SGNs) serve as the primary neuronal model as they are the principal target for CI stimulation. The objective of the research is to rationally design materials that spatially direct neurite growth and to translate fundamental understanding of nerve cell-material interactions into methods of nerve regeneration that improve neural prosthetic performance.

A rapid, single-step photopolymerization method was developed to fabricate micro and nanopatterned physical cues on methacrylate surfaces by selectively blocking light with photomasks. Feature height is readily tuned by modulating parameters of the photopolymerizaiton including initiator concentration and species, light intensity, separation distance from the photomask, and radiation exposure time. Alignment of neural elements increases significantly with increasing feature amplitude and constant periodicity, as well as with decreasing periodicity and constant amplitude. SGN neurite alignment strongly correlates with the maximum feature slope. Neurite alignment is compared on unpatterned, unidirectional, and multidirectional photopolymerized micropatterns.

The effect of substrate rigidity on neurite alignment to physical cues was determined by maintaining equivalent pattern microfeatures, afforded by the reaction control of photopolymerization, while concomitantly altering the composition of several copolymer platforms to tune matrix stiffness. For each platform, neurite alignment to unidirectional patterns increases with increasing substrate rigidity. Interestingly, SGN neurites respond to material stiffness cues that are orders of magnitude higher (GPa) than what is typically ascribed to neural environments (kPa).

Finally, neurite behavior at bioactive borders of various adhesion modulating molecules was evaluated on micropatterned materials to determine which cues took precedence in establishing neurite directionality. At low microfeatures aspect ratios, neurites align to the pattern direction but are then caused to turn and repel from or turn and align to bioactive borders. Conversely, physical cues dominate neurite path-finding as pattern feature slope increases, i.e. aspect ratio of sloping photopolymerized features increases, causing neurites to readily cross bioactive borders. The photopolymerization method developed in this work to generate micro and nanopatterned materials serves as an additional surface engineering tool that enables investigation of cell-material interactions including directed de novo neurite growth. The results of this interdisciplinary effort contribute substantially to polymer neural regeneration technology and will lead to development of advanced biomaterials that improve neural prosthetic tissue integration and performance by spatially directing nerve growth.

Keywords

Cochlear Implant, Neural Prosthetic, Neurite, Pattern, Photopolymerization, Topography

Pages

xxvi, 324 pages

Bibliography

Includes bibliographical references (pages 293-324).

Comments

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Copyright

Copyright 2014 Bradley William Tuft

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