Surgical reconstruction of congenital heart defects is often limited by the non-resorbable material used to approximate normal anatomy. In contrast, non-crosslinked extracellular matrix (ECM) biologic scaffold materials have been used for tissue reconstruction of multiple organs and are replaced by host tissue. Preparation of whole organ ECM by vascular perfusion can maintain much of the native three-dimensional (3D) structure, strength, and tissue specific composition. A 3D Cardiac-ECM (C-ECM) biologic scaffold material would logically have structural and functional advantages over materials such as Dacron™ for myocardial repair, but the in vivo remodeling characteristics of C-ECM have not been investigated to date. Intact porcine and rat hearts were decellularized through retrograde aortic perfusion to create a 3D C-ECM biologic scaffold material. C-ECM biochemical and structural composition were evaluated. C-ECM was not different in cell survival assays from a standard ECM material, urinary bladder matrix (UBM), and supported cardiomyocytes in both 2D and 3D culture. Finally, a porcine C-ECM or Dacron™ patch was used to reconstruct a full thickness right ventricular outflow tract (RVOT) defect in a rat model with a primary endpoint of 16 wk The Dacron patch was encapsulated by dense fibrous tissue and showed little cellular infiltration. Echocardiographic analysis showed that the Dacron patched heart had dilated right ventricular minimum and maximum dimensions at 16 wk compared to pre-surgery baseline values. The C-ECM patch remodeled into dense, cellular connective tissue including: collagen, endothelium, smooth muscle, and small islands of cardiomyocytes. The C-ECM patch showed no ventricular dimensional or functional differences to baseline values at either the 4 or 16 wk time point. The porcine and rat heart can be efficiently decellularized using perfusion in less than 10 hours. The potential benefit of the 2D and 3D C-ECM was shown to support cardiomyocytes with an organized sarcomere structure. The C-ECM patch was associated with better function and histomorphology compared to the Dacron™ patch in this rat model of RVOT reconstruction. While there is much work to be done, the methodology described herein provides a useful step to fully realizing a functional cardiac patch.
| Identifer | oai:union.ndltd.org:PITT/oai:PITTETD:etd-03252010-122914 |
| Date | 30 September 2010 |
| Creators | Wainwright, John Michael |
| Contributors | Stephen Badylak, Thomas Gilbert, Sanjeev Shroff, William Wagner, Kimimasa Tobita |
| 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-03252010-122914/ |
| 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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