Author ORCID Identifier
0000-0002-2654-0473
Document Type
Dissertation
Date of Award
12-31-2022
Degree Name
Doctor of Philosophy in Chemical Engineering - (Ph.D.)
Department
Chemical and Materials Engineering
First Advisor
Murat Guvendiren
Second Advisor
Edward L. Dreyzin
Third Advisor
Xiaoyang Xu
Fourth Advisor
Kathleen McEnnis
Fifth Advisor
Sophie Astrof
Abstract
Heart disease is one of the leading causes of death in the world. With a growing demand for in vitro cardiac models that can recapitulate the complex physiology of the cardiac tissue, there is a desire to create novel therapies and treatments. However, due to a lack of fundamental understanding of the heart's inflammatory response to myocardial infarction, the development of new therapies is both time consuming and costly. In this work, a novel approach to fabricating a dynamic hydrogel cardiac platform is reported. This platform better mimics the dynamic changes occurring in the native cardiac tissue microenvironment during cardiac disease. These dynamic changes include the alteration of the cellular alignment and increase of the tissue stiffness (fibrosis). The feasibility of the model is demonstrated by using human cardiac fibroblasts (hCFs), human cardiomyocytes (hCMs), and induced pluripotent stem cell derived cardiomyocytes (iPSC-CMs).
In Chapter 1, a detailed literature review is given describing the impact of heart disease and summarizing the major design considerations for engineering heart tissue. The currently available and state-of-the-art biomaterial platforms, including micromolded structures, 3-dimensional (3D) structures, porous scaffolds, electrospun scaffolds, bioprinted constructs, and lab-on-a-chip devices are then viewed through a critical lens and evaluated based on their advances to tissue development and current limitations. In Chapter 2, the importance of alignment during cell culture is highlighted, along with the approach to control substrate architecture. This is then related to cell alignment to demonstrate how the patterns can be applied spatially or as a gradient across the surface. In Chapter 3, the importance of substrate stiffness is highlighted, and the novel approach for creating a cardiac platform with similar properties to native tissue is presented in more detail. This approach better replicates cardiac tissue through both stiffness and alignment. Described therein is a method for synthesizing a hydrogel with tunable stiffness and using them to coat the previously patterned substrates discussed in Chapter 2. A quantification of surface topography, hydrogel stiffness, cellular morphology, and protein expression is then presented using iPSC-CMs. In vitro studies were conducted to confirm functionality, using these cells. In Chapter 4, future studies are proposed, where a dynamically complex system is created to study how changes in stiffness and alignment take effect in real time during culture. Preliminary results are presented, confirming the high cell viability and activity during these cultures. Future plans for studying how cells react to stiffening during culture as well as at the boundaries of stiffened hydrogels are discussed. This platform is to be validated as a potential model for long-term disease modeling studies.
Recommended Citation
House, Andrew, "A novel biomaterial platform for cardiac tissue engineering" (2022). Dissertations. 1870.
https://digitalcommons.njit.edu/dissertations/1870
