Neural Tissue Engineering
Jennifer Recknor, Erin Jones, Carlos Ariza
Our work in this thrust has focused on using a combination of physical, chemical and biological cues at the cellular level to enable directed and accelerated growth of neurons to facilitate regeneration in the peripheral nervous systems. More recently, we have been investigating the use of these approaches in the central nervous system and also in the use of these specific cues in understanding the growth and differentiation mechanisms of adult neural progenitor cells.
Micropatterned Biodegradable Polymers for Peripheral Nerve Regeneration: Directional nerve growth is important for regeneration. We are using micro/nanopatterned biodegradable polymer substrates to simulate in vivo conditions during peripheral nerve regeneration. Our approach involves utilizing a combination of physical, chemical and biological cues on biodegradable polymer substrates to enhance guided peripheral nerve regeneration. When simultaneously combining the physical effects of the microgrooves, the chemical influence of the laminin and biological enhancements from the Schwann cells, the synergistic effects caused the axons to grow along the direction of the grooves at an accelerated rate. The microgrooved substrates with physical, chemical and biological cues were inserted into conduits and implanted at the site of sciatic nerve transections in rats. The results showed that the functional regeneration of the sciatic nerve was significantly enhanced compared to conventional entubulization strategies. |
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Effect of Micropatterning and Soluble Cues on Neural Stem Cell Differentiation: We are extending the approaches used for peripheral nerve regeneration to the central nervous system, specifically optic nerve regeneration, using a combination of astrocytes and adult neuronal stem cells on micropatterned substrates. Another aspect of the project is to answer a fundamental question in biology as to how the development of the elaborately organized mammalian brain is orchestrated. To develop a better understanding of the movement and differentiation of adult neural stem cells (NSCs) in vivo, we are collaborating with mathematicians and biochemists to develop a mathematical model, and use a cell culture system involving controlled patterns of extracellular matrix proteins on micropatterned substrates to provide quantitative data for the model. Our recent work has showed that physical cues in the form of micropatterned substrates, in synergy with other cues, preferentially cause NSCs to adopt a neuronal fate as opposed to cells grown on smooth substrates. Our approach provides exquisite spatial microcontrol of cell growth on these substrates. |
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Publications |
• Recknor, J., Sakaguchi, D., and Mallapragada, S.K., “Growth and Differentiation of Neural Progenitor Cells on Micropatterned Polymer Substrates”, Biomaterials , 27 , 4098-4108 (2006). |
Reprint |
• Recknor, J. and Mallapragada, S.K., “Polymers for Nerve Regeneration” in “ Handbook of Tissue Engineering ”, CRC Press (in press). |
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• Recknor, J. B., Sakaguchi, D., and Mallapragada, S.K., “Growth and Differentiation of Astrocytes and Neural Progenitor Cells on Micropatterned Polymer Films”, Annals. N. Y. Acad. Sci ., 1049 , 24-7 (2005 ). |
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• Mallapragada, S. K., and Konety, B., “Biodegradable Nerve Grafts – Physiologically and Environmentally Friendly? J. Urology , 173 , 8-9 (2005). |
Reprint |
• Rutkowski, G., Miller, C.A. , Jeftinija, S., and Mallapragada, S.K., “Synergistic Effects of Micropatterned Biodegradable Conduits and Schwann Cells on Sciatic Nerve Regeneration”, J. Neural. Eng. , 1 , 151-157 (2004). |
Reprint |
• Recknor, J. B., Sakaguchi, D., and Mallapragada, S. K. “Oriented Astroglial Growth on Micropatterned Polymer Substrates”, Biomaterials , 25 , 2753-67 (2004). |
Reprint |
• Mallapragada, S. K. and Recknor, J.B., “Polymeric Materials for Nerve Regeneration”, in Adv. Chem. Eng. , 29 , 47-74 (2004). |
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• Miller, C. A., Jeftinija, S., and Mallapragada, S. K., “Synergistic Effects of Physical and Chemical Guidance Cues on Neurite Alignment and Outgrowth on Biodegradable Polymer Substrates” Tissue Eng . , 8 (3), 367-378 (2002). |
Reprint |
• Rutkowski, G., and Mallapragada, S.K., “Microfabrication (nerve repair)”, in 2002 Yearbook of Science and Technology, McGraw Hill, 221-223 (2002). |
Reprint |
• Miller, C. A., Rutkowski, G., Witt, A., Shanks, H., and Mallapragada, S. K., “Micropatterned Polymer Substrates for Guided Schwann Cell Growth In Vitro ”, Biomaterials , 22 , 1263-1269 (2001). |
Reprint |
| • Rutkowski, G., Miller, C.A. , and Mallapragada, S.K., “Fabrication of Polymer Scaffolds: Solvent Casting”, in Methods of Tissue Engineering , Atala, A., and Lanza, R., (Eds.), Chap. 58, pp. 681-686, Academic Press, San Diego , CA (2001) |