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A Tissue Engineering Platform to Investigate Effects of Finite Deformation on Extracellular Matrix Production and Mechanical Properties

Stella, John (2012) A Tissue Engineering Platform to Investigate Effects of Finite Deformation on Extracellular Matrix Production and Mechanical Properties. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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It is estimated that more than 85,000 prosthetic heart valves are implanted annually in the US and ~275,000 worldwide. Although current heart valve replacements have extended the lives of many patients, there is to date still no ideal alternative. Pediatric applications, in particular, pose unique problems because current valve replacement options are unable to accommodate somatic growth of the patient. Since its inception, the tissue engineering paradigm has garnered widespread attention as a means to recapitulate native tissue structure, composition, and mechanical function in a controlled and reproducible manner by combining engineering and life science principles. Before fully functioning tissue surrogates can be developed for clinical use, many complex biological, chemical and mechanical aspects of native tissues must be addressed. Furthermore, contemporary literature lacks a consolidated approach, instead, presenting a wide variety of scaffold materials, cell sources, and mechanical conditioning regimes in efforts to restore native tissue function. These challenges coupled with the paucity of structurally based, finite deformation framework constitutive models hinders our understanding of engineered tissues and their ability to perform as tissue surrogates.
The focus of this dissertation is to elucidate the effects of large deformation mechanical stimuli on the development of engineered leaflet tissues. With our ability to incorporate viable cells distributed throughout the scaffold via concurrent electrospraying and electrospinning of poly (ester urethane) urea (PEUU) fiber scaffolds, we are provided a unique, controllable platform to: (1) characterize the mechanical behavior of electrospun PEUU and cellular response to global deformation, (2) assess our ability to create functional cell integrated surrogates via dynamic culture, and (3) develop a generalized finite deformation framework than can be used to gain an understanding of how the evolving extracellular matrix phase contributes to the construct gross mechanical behavior. We contend that much can be learned about the mechanical modulation of functional tissue from electrospun PEUU scaffolds since they capture aspects of native tissue microstructure and exhibit the ability to endure large deformations while recovering completely. It is our hope that these studies will guide the emergence of new materials and processing methods to develop functional pulmonary valve (PV) tissue surrogates which serve a predominantly biomechanical function.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Stella, Johnjas122@pitt.eduJAS122
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairSacks, Michael
Committee MemberSanjeev , Shroff G. sshroff@pitt.eduSSHROFF
Committee MemberWagner, William R. wagnerwr@upmc.eduWAGNER
Committee MemberRobertson, Anne M.rbertson@pitt.eduRBERTSON
Committee MemberKeller, Bradley B.
Date: 2 February 2012
Date Type: Publication
Defense Date: 9 September 2011
Approval Date: 2 February 2012
Submission Date: 16 November 2011
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Number of Pages: 296
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, extracellular matrix, finite deformation, mechanical stimuli
Date Deposited: 02 Feb 2012 15:25
Last Modified: 19 Dec 2016 14:38


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