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Dissertation
Development of a multi-functional construct for central nervous system repair
Doctor of Philosophy (Ph.D.), Drexel University
Aug 2008
DOI:
https://doi.org/10.17918/etd-2906
Abstract
Engineered tissue strategies for central nervous system (CNS) repair have the potential for localizing treatment using a wide variety of cells and/or growth factors. However, these strategies are often limited by their ability to address only one aspect of the injury. Here we report the development of an alginate construct that acts as a multifunctional tissue scaffold for CNS repair, and as a localized growth factor delivery vehicle. Initially the effect of alginate constructs on the model mouse neuroblastoma (NB2a) cell line was studied. NB2a attachment and differentiation patterns were observed on the surface of alginate constructs. These results were then used in order to demonstrate the ability of these constructs to support neural progenitor cell (NPC) attachment, preserve viability, and initiate lineage differentiation of cultured NPCs. Three different hydrogel constructs were evaluated and it was found that alginate optimally supported NPC attachment and viability. In addition, a laminin-111 surface coating of alginate enhanced NPC attachment and migration. It was also demonstrated that encapsulation of fibroblasts over expressing mitogens (NT-3 or BDNF) promoted unique NPC differentiation profiles while directing the phenotypical lineage of the cells. Moreover, the encapsulation of these growth factor producing fibroblasts within the alginate construct reduced the severity of injury when implanted in vivo. A final test of the construct showed that alginate constructs seeded with NPCs allowed for migration and integration of lineage restricted cells into the surrounding injured tissue, while directing phenotypical differentiation and influencing the injury environment.
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Details
- Title
- Development of a multi-functional construct for central nervous system repair
- Creators
- Mihir S. Shanbhag - DU
- Contributors
- Margaret A. Wheatley (Advisor) - Drexel University (1970-)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems (1997-2026); Drexel University
- Other Identifier
- 2906; 991014632332404721