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Neural pathfinding on uni- and multidirectional photopolymerized micropatterns.

Tuft BW, Xu L, White SP, Seline AE, Erwood AM, Hansen MR, Guymon CA - ACS Appl Mater Interfaces (2014)

Bottom Line: SGN neurites orient randomly on unpatterned photopolymer controls, align and consistently track unidirectional patterns, and are substantially influenced by, but do not consistently track, multidirectional turning cues.Neurite lengths are 20% shorter on multidirectional substrates compared to unidirectional patterns while neurite branching and microfeature crossing events are significantly higher.Developing methods to understand neural pathfinding and to guide de novo neurite growth to specific stimulatory elements will enable design of innovative biomaterials that improve functional outcomes of devices that interface with the nervous system.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemical and Biochemical Engineering, University of Iowa , Iowa City, Iowa 52242, United States, United States.

ABSTRACT
Overcoming signal resolution barriers of neural prostheses, such as the commercially available cochlear impant (CI) or the developing retinal implant, will likely require spatial control of regenerative neural elements. To rationally design materials that direct nerve growth, it is first necessary to determine pathfinding behavior of de novo neurite growth from prosthesis-relevant cells such as spiral ganglion neurons (SGNs) in the inner ear. Accordingly, in this work, repeating 90° turns were fabricated as multidirectional micropatterns to determine SGN neurite turning capability and pathfinding. Unidirectional micropatterns and unpatterned substrates are used as comparisons. Spiral ganglion Schwann cell alignment (SGSC) is also examined on each surface type. Micropatterns are fabricated using the spatial reaction control inherent to photopolymerization with photomasks that have either parallel line spacing gratings for unidirectional patterns or repeating 90° angle steps for multidirectional patterns. Feature depth is controlled by modulating UV exposure time by shuttering the light source at given time increments. Substrate topography is characterized by white light interferometry and scanning electron microscopy (SEM). Both pattern types exhibit features that are 25 μm in width and 7.4 ± 0.7 μm in depth. SGN neurites orient randomly on unpatterned photopolymer controls, align and consistently track unidirectional patterns, and are substantially influenced by, but do not consistently track, multidirectional turning cues. Neurite lengths are 20% shorter on multidirectional substrates compared to unidirectional patterns while neurite branching and microfeature crossing events are significantly higher. For both pattern types, the majority of the neurite length is located in depressed surface features. Developing methods to understand neural pathfinding and to guide de novo neurite growth to specific stimulatory elements will enable design of innovative biomaterials that improve functional outcomes of devices that interface with the nervous system.

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Number of turnsper SGN neurite on substrates with varied topography. SGN neuritesturned significantly more on unpatterned surfaces compared to patternedsubstrates and on patterns that change direction compared to unidirectionalmorphologies (*p < 0.05, ANOVA).
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fig8: Number of turnsper SGN neurite on substrates with varied topography. SGN neuritesturned significantly more on unpatterned surfaces compared to patternedsubstrates and on patterns that change direction compared to unidirectionalmorphologies (*p < 0.05, ANOVA).

Mentions: The number of turns per neurite in response to topographic guidancecues was measured as a final comparison of SGN neurite pathfindingability on uni- and multidirectional patterns and on unpatterned controls(Figure 8). Turns are defined as a 10°change in direction over three consecutive 10 μm length neuritesegments relative to the previous three segments. Ultimately, thecapacity to guide regenerative neurite growth to spatially specificstimulating elements will require strong adherence to engineered guidancecues and may include precision turning at specific points. SGN neuritesturn over five times more on unpatterned substrates compared to unidirectionalmicropatterns. They also turn significantly more on unpatterned substratescompared to neurites on repeating angle features. The high degreeof turning on unpatterned platforms supports the observation thatneurite growth is random on unpatterned controls and results in multipleinstances of neural growth cone direction change and, thus, turningpoints for any given neurite (Figure 5).


Neural pathfinding on uni- and multidirectional photopolymerized micropatterns.

Tuft BW, Xu L, White SP, Seline AE, Erwood AM, Hansen MR, Guymon CA - ACS Appl Mater Interfaces (2014)

Number of turnsper SGN neurite on substrates with varied topography. SGN neuritesturned significantly more on unpatterned surfaces compared to patternedsubstrates and on patterns that change direction compared to unidirectionalmorphologies (*p < 0.05, ANOVA).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4215840&req=5

fig8: Number of turnsper SGN neurite on substrates with varied topography. SGN neuritesturned significantly more on unpatterned surfaces compared to patternedsubstrates and on patterns that change direction compared to unidirectionalmorphologies (*p < 0.05, ANOVA).
Mentions: The number of turns per neurite in response to topographic guidancecues was measured as a final comparison of SGN neurite pathfindingability on uni- and multidirectional patterns and on unpatterned controls(Figure 8). Turns are defined as a 10°change in direction over three consecutive 10 μm length neuritesegments relative to the previous three segments. Ultimately, thecapacity to guide regenerative neurite growth to spatially specificstimulating elements will require strong adherence to engineered guidancecues and may include precision turning at specific points. SGN neuritesturn over five times more on unpatterned substrates compared to unidirectionalmicropatterns. They also turn significantly more on unpatterned substratescompared to neurites on repeating angle features. The high degreeof turning on unpatterned platforms supports the observation thatneurite growth is random on unpatterned controls and results in multipleinstances of neural growth cone direction change and, thus, turningpoints for any given neurite (Figure 5).

Bottom Line: SGN neurites orient randomly on unpatterned photopolymer controls, align and consistently track unidirectional patterns, and are substantially influenced by, but do not consistently track, multidirectional turning cues.Neurite lengths are 20% shorter on multidirectional substrates compared to unidirectional patterns while neurite branching and microfeature crossing events are significantly higher.Developing methods to understand neural pathfinding and to guide de novo neurite growth to specific stimulatory elements will enable design of innovative biomaterials that improve functional outcomes of devices that interface with the nervous system.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemical and Biochemical Engineering, University of Iowa , Iowa City, Iowa 52242, United States, United States.

ABSTRACT
Overcoming signal resolution barriers of neural prostheses, such as the commercially available cochlear impant (CI) or the developing retinal implant, will likely require spatial control of regenerative neural elements. To rationally design materials that direct nerve growth, it is first necessary to determine pathfinding behavior of de novo neurite growth from prosthesis-relevant cells such as spiral ganglion neurons (SGNs) in the inner ear. Accordingly, in this work, repeating 90° turns were fabricated as multidirectional micropatterns to determine SGN neurite turning capability and pathfinding. Unidirectional micropatterns and unpatterned substrates are used as comparisons. Spiral ganglion Schwann cell alignment (SGSC) is also examined on each surface type. Micropatterns are fabricated using the spatial reaction control inherent to photopolymerization with photomasks that have either parallel line spacing gratings for unidirectional patterns or repeating 90° angle steps for multidirectional patterns. Feature depth is controlled by modulating UV exposure time by shuttering the light source at given time increments. Substrate topography is characterized by white light interferometry and scanning electron microscopy (SEM). Both pattern types exhibit features that are 25 μm in width and 7.4 ± 0.7 μm in depth. SGN neurites orient randomly on unpatterned photopolymer controls, align and consistently track unidirectional patterns, and are substantially influenced by, but do not consistently track, multidirectional turning cues. Neurite lengths are 20% shorter on multidirectional substrates compared to unidirectional patterns while neurite branching and microfeature crossing events are significantly higher. For both pattern types, the majority of the neurite length is located in depressed surface features. Developing methods to understand neural pathfinding and to guide de novo neurite growth to specific stimulatory elements will enable design of innovative biomaterials that improve functional outcomes of devices that interface with the nervous system.

Show MeSH
Related in: MedlinePlus