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Mechanisms of Extracellular Matrix Scaffold Remodeling

Gilbert, Thomas Wayne (2007) Mechanisms of Extracellular Matrix Scaffold Remodeling. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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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), á-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.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Gilbert, Thomas Waynegilberttw@upmc.eduTWGST5
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairBadylak, Stephen Fbadylaks@upmc.eduSFB8
Committee MemberWang, James H-Cwanghc@pitt.eduWANGHC
Committee MemberSacks, Michael
Committee MemberWoo, Savio L-Yslyw@pitt.eduSLYW
Committee MemberBraunhut, Susan
Date: 31 January 2007
Date Type: Completion
Defense Date: 20 October 2006
Approval Date: 31 January 2007
Submission Date: 27 September 2006
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Institution: University of Pittsburgh
Schools and Programs: Swanson School of Engineering > Bioengineering
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: animal studies; extracellular matrix; mechanical loading; tissue engineering; gene expression; wound healing
Other ID:, etd-09272006-122207
Date Deposited: 10 Nov 2011 20:02
Last Modified: 19 Dec 2016 14:37


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