Scaffolds composed of extracellular matrix (ECM) and derived from various species and various organs have been shown to promote constructive, site-specific tissue remodeling in pre-clinical studies and clinical use, including musculoskeletal, urogenital, dermal, cardiovascular, and neural applications. Despite extensive study, the mechanisms of the remodeling process are still not thoroughly understood. The goals of this dissertation were to elucidate the role of mechanical loading in the remodeling of ECM scaffolds and the role of bone marrow derived cells in the remodeling process.
To better understand the role of mechanical loading on the remodeling of an ECM scaffold, an ECM scaffold derived from the porcine small intestinal submucosa (SIS-ECM) was seeded with fibroblasts and subjected to a variety of magnitudes and frequencies of cyclic strain using a custom designed Cyclic Stretching Tissue Culture system. The magnitudes of stretch were based on a study of the collagen fiber kinematics of the SIS-ECM under uniaxial and biaxial loading conditions. The cyclic loading experiments showed that mechanical loading led to expression of matrix related genes that was consistent with a constructive remodeling response with increased expression of collagen type I (Col I), รก-smooth muscle actin (SMA), and tenascin-C (TN-C), as well as decreased expression of collagen type III (Col III).
It was also found that bone marrow cells were recruited to the site of ECM remodeling and that the cells remained at the site of remodeling for 16 weeks after implantation, unlike an autologous tendon repair. Furthermore, it was found that the bone marrow derived cells did not express the hematopoietic marker CD45, but did express Col I, Col III, and SMA. The cells did not show the same expression pattern as normal tendon fibroblast (Col I+, TN-C+), suggesting that the cells differentiated towards a myofibroblastic cell as opposed to a normal fibroblast. The results of this study show that an ECM scaffold recruits a bone marrow derived mesenchymal progenitor to the site of remodeling, and that those cells differentiate into site specific tissue as a result of mechanical and biochemical cues.
| Identifer | oai:union.ndltd.org:PITT/oai:PITTETD:etd-09272006-122207 |
| Date | 31 January 2007 |
| Creators | Gilbert, Thomas Wayne |
| Contributors | Stephen F. Badylak, Michael S. Sacks, James H-C. Wang, Savio L-Y. Woo, Susan J. Braunhut |
| 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-09272006-122207/ |
| Rights | unrestricted, 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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