To be successful a tissue engineered small diameter blood vessel must be non-immunogenic, non-thrombogenic, have mechanical properties similar to native vessel and be vasoactive. The vascular media is responsible for the mechanical properties and the vasoactivity of the vessel. The collagen hydrogel approach has been long used and has many advantages, but has not yet achieved the mechanical integrity needed for implantation. No collagen-based tissue engineered vascular media has been shown to be vasoactive using culture techniques required to achieve the cell numbers needed to make a vascular graft. To study collagen synthesis, two model systems were used. Cells were seeded on top of an adsorbed collagen I or fibrin layer. Alternatively the cells were encapsulated in a collagen or fibrin hydrogel. Collagen I, decorin and biglycan synthesis was affected by both matrix type and presentation. After two weeks in culture the smooth muscle cells produce more type I collagen in the collagen based hydrogels then in the fibrin hydrogels and was used for further studies. The collagen based tissue engineered vascular media produced a consistent vasoactive response between two and eight weeks of culture. The smooth muscle cells have functional endothelin, kinin, adrenergic, serotonergic and purinergic receptors. The application of cyclic strain improves both the tissue strength and the contractile response. Use of transforming growth factor-β improved tissue strength, but reduced the contractile response. Transforming growth factor- β actually promoted a more contractile cell phenotype, but a stronger contractile force was required to overcome the thick compact collagen hydrogel and elicit a measurable contraction. This work adds to what is known about collagen-based tissue engineered vascular medias by identifying means of improving not only strength but vasoactivity. The trade-offs found between these two important characteristics are relevant to all tissue engineered medias.
| Identifer | oai:union.ndltd.org:GATECH/oai:smartech.gatech.edu:1853/28241 |
| Date | 06 April 2009 |
| Creators | Schutte, Stacey C. |
| Publisher | Georgia Institute of Technology |
| Source Sets | Georgia Tech Electronic Thesis and Dissertation Archive |
| Detected Language | English |
| Type | Dissertation |
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