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Wainwright, John Michael (2010) CARDIAC RECONSTRUCTION WITH ORGAN SPECIFIC EXTRACELLULAR MATRIX. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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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.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Wainwright, John
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairBadylak,
Committee MemberTobita, Kimimasakit3@pitt.eduKIT3
Committee MemberShroff, Sanjeevsshroff@pitt.eduSSHROFF
Committee MemberGilbert, Thomasgilberttw@upmc.eduTWGST5
Committee MemberWagner, Williamwagnerwr@upmc.eduWAGNER
Date: 30 September 2010
Date Type: Completion
Defense Date: 5 April 2010
Approval Date: 30 September 2010
Submission Date: 25 March 2010
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: biologic scaffold; cardiac reconstruction; congenital heart disease; extracellular matrix; heart failure; tissue engineering
Other ID:, etd-03252010-122914
Date Deposited: 10 Nov 2011 19:32
Last Modified: 19 Dec 2016 14:35


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