Session: 16-01-01: Government Agency Student Poster Competition

Paper Number: 149915

149915 - Cad-Facilitated Optimization of a 3d Bioprinted Human Heart Model 

Introduction

The development of the human heart in embryo is a complex process susceptible to errors that can lead to congenital heart defects (CHDs). Leveraging computer aided design (CAD) and 3D bioprinting, we created a perfusable 3D human heart model at the linear heart tube stage (day 22). Cardiomyocytes (CMs) and endothelial cells (ECs) were differentiated from human induced pluripotent stem cells (hiPSCs) and cocultured in the 3D bioprinted human heart models to study cellular responses to microenvironmental factors, including flow hemodynamics. In this research, we utilize CAD design to optimize the fabrication and electrical conditioning of our 3D bioprinted human heart models. 

 

Significance and Innovation

In this study, the use of CAD design has enhanced the efficiency and accuracy at multiple experimental steps in engineering our 3D in vitro model. The versatility of CAD editing permits us to customize and faithfully mimic the microenvironment in early human heart development. Moreover, CAD design allows incorporation of both an external pacing system and a hemodynamic flow system in the same 3D in vitro platform. By applying electrical and mechanical stimulation to the cardiac tissue simultaneously, we can attempt to synchronize and improve cardiac function while studying the effect of microenvironmental factors (i.e. flow hemodynamics) in our model. With the multitude of additions made possible by CAD design, this project helps to build on the wide applications of 3D modeling in the engineering community.

 

Methods

An idealistic human linear heart tube model was designed by CAD and 3D bioprinted via digital light processing (DLP). Customized flipping boxes and perfusion housings were CAD designed and 3D printed using a Form3 resin printer to assist with uniform cellularization and controlled dynamic flow perfusion. Further, a noninvasive pacing system was tailor-designed and incorporated into our 3D culture platform to include electrical conditioning of the 3D human heart models. Cellular structure and interactions were visualized using immunohistochemistry (IHC). Contractile function of the heart models was assessed by video-based contractility analysis. 

 

Preliminary Results 

Flipping boxes with easy assembly and an open structure facilitated a controlled rotation of the 3D bioprinted human heart models during cell loading. Uniform cellularization was achieved and assisted the optimization of both lumen endothelialization and cardiac tissue compaction in the 3D heart models. Customized perfusion chamber system effectively allowed for the 3D bioprinted human heart models to sustain tissue fidelity and viability under dynamic flow for 1 week. Via the noninvasive pacing, contractile function changes were detected across human heart models.

 

Conclusions

The integration of CAD designs with our 3D bioprinted human heart models enables the optimization of model construction and electrical conditioning. The incorporation of a noninvasive pacing system shows the great promise of our 3D culture platform for cardiac contractile function evaluation and enhancement. By using assistive CAD and 3D printing in this study, we hope to improve the recapitulation of 3D microenvironment and cellular interactions, for the study of embryonic human heart development and CHDs.  

Presenting Author: Sarah Fineman Emory University

Presenting Author Biography: Sarah Fineman is currently working towards her B.S. in biology at Emory University. In her undergraduate education, Ms. Fineman’s research experience began in the Raj Lab, where she helped develop late stage modification techniques for the functionalization of bioactive peptides. More recently Ms. Fineman has pursued research in the Serpooshan Lab, where she works in projects utilizing a bioengineered iPSC-based, functional cardiovascular tissue model to study heart development and congenital heart defects. Ms. Fineman also works as a patient care specialist at Children’s Healthcare of Atlanta, and she is a member of the varsity track & field team at Emory University.

Authors:

Sarah Fineman Emory University
Linqi Jin Emory University and Georgia Institute of Technology
Vahid Serpooshan Emory University and Georgia Institute of Technology