Link to the University of Pittsburgh Homepage
Link to the University Library System Homepage Link to the Contact Us Form

Coupled Theoretical and Experimental Methods to Understand Growth and Remodeling of In Situ Engineered Vascular Grafts in Young and Aged Hosts

Gade, Piyusha (2019) Coupled Theoretical and Experimental Methods to Understand Growth and Remodeling of In Situ Engineered Vascular Grafts in Young and Aged Hosts. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

[img] PDF
Submitted Version
Restricted to University of Pittsburgh users only until 10 September 2020.

Download (9MB) | Request a Copy

Abstract

In 1975, Rodbard introduced the concept of mechanical homeostasis; that arteries have an inherent capacity to maintain homeostatic stress states by altering their morphology through a negative feedback mechanism in response to mechanical loads. More recently, this capacity has been leveraged to develop acellular, in situ tissue-engineered vascular grafts (iTEVGs) which promote host growth and remodeling (G&R) to develop new arteries (neoarteries) in the tissue's functional site (in situ). These grafts offer a much-needed option to address the lack of viable autologous conduits, difficulties in scaling traditional tissue engineered grafts, and the rising demand for bypass grafting in an aging population. One such acellular, poly (glycerol sebacate) (PGS) iTEVG developed by Wang et al. has demonstrated in situ mature elastin and collagen formation in young hosts. However, the trial and error nature of graft design, coupled with the lack of knowledge of fundamental mechanisms guiding neoarterial G&R impedes efforts to translate these successes across age and species.
In this work, we take a coupled theoretical and experimental approach to understanding salient mechanisms guiding neoartery formation in young and aged hosts. We developed a mathematical model of graft degradation based on in vitro assessment of enzymatic degradation. Next, we translated successful neoartery development from a rat aorta to the substantially smaller, rat carotid artery. We determined that after three-months of remodeling, the neoartery has similar mechanical properties to those of the clinical gold standard, vein graft. We then successfully translated the iTEVG to an aged murine carotid model and assessed differences in mechanical, microstructural, and biological stages of neoarterial G&R in young versus aged hosts over the course of six months. Subsequently, a constrained mixture model-based G&R tool was developed, informed with these experimental data, and used to predict long-term neoarterial G&R response in both age groups. Finally, we identified a common mode of adverse remodeling in neoarteries - rupture and calcification. Motivated by these results, we developed new techniques to analyze calcification in a parallel, model system exhibiting similar modes of adverse remodeling - cerebral aneurysms. These results provide insights for future work developing strategies necessary to optimally design iTEVGs.


Share

Citation/Export:
Social Networking:
Share |

Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Gade, Piyushapsg16@pitt.edupsg160000-0002-7991-5873
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Thesis AdvisorRobertson, Anneanne.robertson@pitt.edurbertson0000-0002-5063-4293
Committee MemberAbramowitch, Stevesdast9@pitt.edusdast9
Committee MemberSigal, Iansigalia@upmc.edusigalia
Committee MemberMaiti, Spandanspm54@pitt.eduspm54
Committee MemberWang, Yadongyw839@cornell.edu
Date: 10 September 2019
Date Type: Publication
Defense Date: 8 July 2019
Approval Date: 10 September 2019
Submission Date: 10 July 2019
Access Restriction: 1 year -- Restrict access to University of Pittsburgh for a period of 1 year.
Number of Pages: 265
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: vascular grafts, continuum mechanics, modeling
Date Deposited: 10 Sep 2019 16:13
Last Modified: 10 Sep 2019 16:13
URI: http://d-scholarship.pitt.edu/id/eprint/37078

Metrics

Monthly Views for the past 3 years

Plum Analytics


Actions (login required)

View Item View Item