Most approaches to tissue engineering and regenerative medicine include a scaffold component. The scaffold material could be synthetic or natural and may be intended simply as a delivery vehicle for cells or growth factors or as an integral component of an engineered tissue or organ. Regardless of the type of material used, the scaffold must be cell friendly and promote host cell attachment, proliferation, migration, differentiation, and eventual three-dimensional tissue organization. Biologic scaffolds composed of extracellular matrix have shown minimal scar tissue formation with constructive remodeling of the damaged or missing tissue structures in a variety of clinical and pre-clinical applications. However, ECM scaffolds are typically characterized by a two-dimensional sheet and are limited to the mechanical and material properties inherent to the tissue from which it was derived.
A soluble form of ECM scaffold would expand the clinical utility of ECM by allowing the delivery of the scaffold via minimally invasive methods to the site of interest. The present work describes the enzymatic digestion of an ECM scaffold derived from the porcine urinary bladder (urinary bladder matrix or UBM). UBM was successfully digested with pepsin and papain under different conditions. The enzymatically digested UBM showed chemotactic and mitogenic properties towards progenitor cells while inhibition was found toward endothelial cells. In addition, pepsin digested UBM was able to re-polymerize into a gel form. The present study investigated the in vitro cell growth of different cell types on the surface of the gels and measured the rheological properties of the UBM gel.
Synthetic scaffold materials are an alternative to naturally derived ECM scaffolds. However, synthetic materials lack the bioactivity and beneficial host tissue response characteristic of ECM-derived scaffolds and often result in fibrous encapsulation when implanted in vivo. Poly(ester-urethane)urea (PEUU) is a biodegradable polymer that can be manufactured into an elastomeric scaffold by electro-spinning techniques with an ultrastructural morphology similar to the ECM. The present work successfully combined the soluble form of the UBM with the PEUU to create hybrid scaffolds. The in vitro characterization of the scaffolds and the in vivo response are described. Hybrid scaffolds showed a change in the host tissue response and higher degradation rates in vivo in a subcutaneous location when compared to the polymer alone. Finally, the potential use of the PEUU and a PEUU/UBM hybrid scaffold as a left ventricular patch in a canine model is discussed.
| Identifer | oai:union.ndltd.org:PITT/oai:PITTETD:etd-05062008-142335 |
| Date | 22 September 2008 |
| Creators | Freytes, Donald Osvaldo |
| Contributors | Dr. David A. Vorp, Dr. Peter D. Wearden, Dr. Stephen F. Badylak, Dr. William R. Wagner |
| Publisher | University of Pittsburgh |
| Source Sets | University of Pittsburgh |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.pitt.edu/ETD/available/etd-05062008-142335/ |
| Rights | restricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to University of Pittsburgh or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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