Integrated Electrical Conditioning and Dynamic Flow Perfusion for 3D Bioprinted Developing Human Heart Models Restricted; Files Only

Abstract

The development of the human heart in embryos is a complex process susceptible to errors resulting in congenital heart defects (CHDs). Our research focuses on a CHD called Hypoplastic Left Heart Syndrome (HLHS), which has profound long-term complications despite postnatal surgical interventions. However, research remains limited on the factors that contribute to HLHS. Due to the limitations of studying in vivo embryonic human hearts, a perfusable 3D human heart model at linear heart tube stage (day 22) was created by computer aided design (CAD) and 3D bioprinting. Cardiomyocytes (CMs) were differentiated from human induced pluripotent stem cells (hiPSCs) and cultured in the 3D bioprinted heart models for studying cellular responses to the microenvironmental factor of flow hemodynamics and chronic external electrical conditioning. By increasing the microenvironmental accuracy for the embryonic heart model, our research works to uncover the factors that contribute to HLHS. In this study, an integrated platform will be developed to allow for both electrical conditioning and dynamic flow perfusion of the 3D bioprinted heart models for assessing their effects on cardiac function and maturation.

Table of Contents

Chapter 1: Background, Inspiration, and Approach 1

Embryonic Human Heart Development: Linear Heart Tube Stage 1

Hemodynamic and Mechanical Factors in Embryonic Human Heart Development 2

Congenital Heart Defects & Hypoplastic Left Heart Syndrome 4

Biomimetic Embryonic Human Heart Model for Perfusion 6

External Electrical Conditioning in Biomimetic Embryonic Human Heart Model 7

Biomimetic Embryonic Human Heart Model Incorporates HLHS Genetics, Perfusion, and Pacing 8

Chapter 2: Evaluating the Effect of Flow Perfusion on Developing Cardiomyocytes 10

Design Optimization of the Perfusion Platform 10

Experimental Results from Perfusion Study 12

Chapter 3: External Pacing as a Factor to Enhance Cardiomyocyte Maturation 14

Designing a Pacing Platform 14

Creating a Customized 6-well Plate 16

Experimental Timeline and Planning for Perfusion-Pacing Experiment 20

Set up for the Perfusion and Pacing Experiment 21

Obtaining Videos for Contractility Analysis 23

Experimental Results and Discussion 25

Discussion and Future Directions 34

Supplementary Information 36

Materials and Methods 36

Bibliography 38

About this Honors Thesis

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School	Emory College
Department	Biology
Degree	B.S.
Submission	Honors Thesis
Language	English
Research Field	Health Sciences, Human Development Biology, Anatomy Engineering, Biomedical
关键词	cardiac tissue engineering 3D bioprinting congenital heart defects electric stimulation cardiomyocytes
Committee Chair / Thesis Advisor	Serpooshan, Vahid , Emory University
Committee Members	O'Toole, Kate , Emory University Eisen, Arri , Emory University

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