The overall goal of the proposed work is to create a technology that permits the design and reliable creation of ordered in vitro neural networks. Essential elements of this technology are the ability to retard cell attachment and growth from background areas, to confine somata to desired positions, to control axonal extension so as to create an oriented network. Further, to permit input, output, and control over the network, we will superpose the neurons on electrode arrays for stimulation and recording. We will utilize microlithographic techniques, primarily microcontact printing, to control the patterns of biomolecules on planar culture surfaces in order to effect control of position of attachment and extension of neurons and glia. We hope that the work leads to basic science experimentation in the areas of neural development, learning and memory, and neural prosthetics.
The first aim i s to use stamped patterns of several proteins to control the development and position of axons vs. dendrites in culture, the direction of outgrowth of axons, and the positions of glia vs. neurons. This will demonstrate that the stamp technology is a novel means of understanding and testing how particular molecules influence attachment and growth of cells. This result will be an important step toward the creation of in vitro neural circuits with which one can investigate properties of the nervous system. The second specific aim is to combine the pattern technology with microelectrode array technology so that neural circuit electrical activity can be recorded and stimulated at many individual cells over long periods of time. This combined technology will contribute further to our understanding of basic neuroscience. It is hoped that the lessons learned in creating defined neural circuits will be applicable to neural prosthetics and spinal cord injury, where it is essential to control glial and neural and to guide regrowth of axons. The technology should be applicable to numerous testing paradigms, including clinical chemistry, where large numbers of replications of a variable number of tests needed to identify biological chemicals and their effects on cell cultures.
| Chang, John C; Brewer, Gregory J; Wheeler, Bruce C (2006) Neuronal network structuring induces greater neuronal activity through enhanced astroglial development. J Neural Eng 3:217-26 |
| Nam, Yoonkey; Chang, John C; Wheeler, Bruce C et al. (2004) Gold-coated microelectrode array with thiol linked self-assembled monolayers for engineering neuronal cultures. IEEE Trans Biomed Eng 51:158-65 |
| Chang, John C; Brewer, Gregory J; Wheeler, Bruce C (2003) A modified microstamping technique enhances polylysine transfer and neuronal cell patterning. Biomaterials 24:2863-70 |
| Branch, D W; Wheeler, B C; Brewer, G J et al. (2001) Long-term stability of grafted polyethylene glycol surfaces for use with microstamped substrates in neuronal cell culture. Biomaterials 22:1035-47 |
