Engineering protein microenvironments : integrin-binding ligands and neurotrophic cues for neural regeneration
Abstract/Contents
- Abstract
- Regenerative therapies for peripheral nerve injury have achieved significant success in neural regeneration by combining growth-permissive materials with anisotropic features to guide regenerating neurites across the injury gap. Despite their success in the peripheral nervous system, these strategies tend to neglect the neuron-level precision required for fully functional regeneration. Fortunately, studies of the developing peripheral nervous system have revealed a variety of innate molecular-level tools to promote outgrowth, guide axons toward targets of re-innervation, and stimulate re-myelination by glial cells. We have developed a class of customizable, protein-engineered microenvironments to study three aspects of the neural microenvironment involved in regeneration: cell-adhesive ligands in the Extracellular Matrix (ECM), soluble neurotrophic factors, and cell-cell contact. In particular, we demonstrated the ability of RGD ligand density in the ECM to enhance neurite outgrowth from Dorsal Root Ganglia. Furthermore, the strategic inclusion of Nerve Growth Factor in these microenvironments enhanced L1CAM-mediated interaction between Schwann cells and neurons, resulting in cooperative outgrowth between the two cell types. Microenvironments promoting both cell-cell and cell-matrix interactions resulted in better neural outgrowth than those that prioritized either one or the other. Finally, we incorporated a chemoattractive gradient of Nerve Growth Factor to induce directed outgrowth within 3-dimensional protein matrices. The density of cell-adhesive RGD ligands in the microenvironment impacted the ability of neurites to initiate outgrowth, progress through the matrix, and turn toward the chemoattractive source. These findings underscore the ability of orthogonal strategies to synergistically enhance neural regeneration, and the utility of protein-engineered microenvironments to apply those strategies.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2014 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Romano, Nicole Halley |
|---|---|
| Associated with | Stanford University, Department of Materials Science and Engineering. |
| Primary advisor | Heilshorn, Sarah |
| Thesis advisor | Heilshorn, Sarah |
| Thesis advisor | Dunn, Alexander Robert |
| Thesis advisor | Lee, Jin Hyung |
| Advisor | Dunn, Alexander Robert |
| Advisor | Lee, Jin Hyung |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Nicole Halley Romano. |
|---|---|
| Note | Submitted to the Department of Materials Science and Engineering. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2014. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2014 by Nicole Halley Romano
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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