Remlinger, Nathaniel
(2013)
Engineering contractile myocardial tissue using extracellular matrix scaffolds.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
There is currently an overwhelming need for functional replacement of diseased or damaged cardiac tissue. Biologic based scaffolds are an attractive tissue engineering approach to cardiac repair because they avoid sensitization associated with homograft materials and theoretically possess the potential for growth in similar patterns as surrounding native tissue. A strategy that has been investigated previously is the use of cardiomyocytes seeded onto collagen based scaffolds in order to engineer a contractile tissue. However, in order for this approach to be effective, the cardiomyocytes must be aligned and maintain contractility after seeding onto biologic scaffolds. UBM collagen fiber organization and cyclic mechanical stretch have each been shown to induce cell alignment while maintaining normal cell phenotype. In theory, a combination of these methods should yield a contractile tissue that may perform well when used to reconstruct myocardial tissue.
It was previously shown that a cardiac-derived ECM patch provides beneficial effects when compared to synthetic cardiac patch materials. Acellular UBM and C-ECM patches were directly compared in the present work as scaffolds to repair a full thickness defect in the RVOT of rats. By 16 weeks, only the UBM patches had degraded and were replaced with areas of new muscle tissue, which was in direct contrast to the integration response observed with C-ECM patches. Next, UBM scaffolds were seeded with cardiomyocytes and cyclically stretched in vitro. Cells preferentially aligned in the direction of stretch, showed intracellular free calcium transients, expressed contractile cardiac markers, and were visibly contractile. Cell-seeded UBM patches possessed the ability to repair the RVOT of rats and support the infiltration of cells. Cardiomyocyte seeded patches were also able to develop an endothelial lining and integrate into the surrounding native tissue. In addition, stretched scaffolds appeared to show preliminary indications of communication with the surrounding native tissue. Future studies are necessary to investigate translation to a clinically applicable model, but the methods described herein show that contractile tissue can be generated from ECM scaffolds and may also aid in functional restoration to myocardial tissue when used as a cardiac patch material.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
| Title | Member | Email Address | Pitt Username | ORCID |
|---|
| Committee Chair | Gilbert, Thomas | | | | | Committee CoChair | Wearden, Peter | | | | | Committee Member | Shroff, Sanjeev G | | | | | Committee Member | Soto-Gutierrez, Alejandro | | | | | Committee Member | Tobita, Kimimasa | kit3@pitt.edu | KIT3 | | | Committee Member | Wagner, William | | | |
|
| Date: |
25 September 2013 |
| Date Type: |
Publication |
| Defense Date: |
18 June 2013 |
| Approval Date: |
25 September 2013 |
| Submission Date: |
23 July 2013 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Number of Pages: |
180 |
| 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: |
Tissue Engineering, Regenerative Medicine, Extracellular Matrix, Cardiac Repair, Urinary Bladder Matrix |
| Date Deposited: |
25 Sep 2013 13:41 |
| Last Modified: |
15 Nov 2016 14:14 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/19426 |
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