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Author Notes:

Vahid Serpooshan, Ph.D. 1760 Haygood Dr. NE, HSRB Bldg., Suite E480, Atlanta, GA 30322, USA, Phone: 404-712- 9717, Fax: 404-727-9873. Email: vahid.serpoosahan@bme.gatech.edu

Holly Bauser-Heaton, M.D., Ph.D. 1405 Clifton Rd NE, Atlanta, GA 30322, USA, Phone: 404-256-2593, Fax: 404-785-0998. Email: bauserh@kidsheart.com

We are grateful for the expert technical assistance and help provided by Sassan Hashemi and Timothy Slesnick. We would like to also acknowledge Dr. Alejandro Roldán-Alzate and his team at University of Wisconsin-Madison for providing the fetal human heart data, Dr. Bjarke Jensen at University of Amsterdam for providing the embryonic human heart data, and Alessandro Veneziani for his help in computational modeling.

Subject:

Research Funding:

This research was funded by the NIH grant number R00HL127295 and Emory University School of Medicine (Pediatric Research Alliance Pilot Grant and the Dean’s Imagine, Innovate and Impact (I3) Research Award).

This research was also funded in part by the Department of Biomedical Engineering and the College of Engineering at Georgia Institute of Technology and by R01HL144714 and R00HL138288 from the National Institutes of Health.

Keywords:

  • Science & Technology
  • Technology
  • Engineering, Biomedical
  • Nanoscience & Nanotechnology
  • Materials Science, Biomaterials
  • Engineering
  • Science & Technology - Other Topics
  • Materials Science
  • 3D bioprinting
  • cardiovascular modeling
  • developing human heart
  • embryonic heart
  • fetal left ventricle
  • linear heart tubes
  • IPSC-DERIVED CARDIOMYOCYTES
  • PLURIPOTENT STEM-CELLS
  • CARDIAC DEVELOPMENT
  • HYDRAULIC PERMEABILITY
  • BLOOD-FLOW
  • DISEASE
  • DIFFERENTIATION
  • REGENERATION
  • MECHANISMS
  • SCAFFOLDS

Patient-Specific 3D Bioprinted Models of Developing Human Heart

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Journal Title:

ADVANCED HEALTHCARE MATERIALS

Volume:

Volume 10, Number 15

Publisher:

, Pages e2001169-e2001169

Type of Work:

Article | Post-print: After Peer Review

Abstract:

The heart is the first organ to develop in the human embryo through a series of complex chronological processes, many of which critically rely on the interplay between cells and the dynamic microenvironment. Tight spatiotemporal regulation of these interactions is key in heart development and diseases. Due to suboptimal experimental models, however, little is known about the role of microenvironmental cues in the heart development. This study investigates the use of 3D bioprinting and perfusion bioreactor technologies to create bioartificial constructs that can serve as high-fidelity models of the developing human heart. Bioprinted hydrogel-based, anatomically accurate models of the human embryonic heart tube (e-HT, day 22) and fetal left ventricle (f-LV, week 33) are perfused and analyzed both computationally and experimentally using ultrasound and magnetic resonance imaging. Results demonstrate comparable flow hemodynamic patterns within the 3D space. We demonstrate endothelial cell growth and function within the bioprinted e-HT and f-LV constructs, which varied significantly in varying cardiac geometries and flow. This study introduces the first generation of anatomically accurate, 3D functional models of developing human heart. This platform enables precise tuning of microenvironmental factors, such as flow and geometry, thus allowing the study of normal developmental processes and underlying diseases.
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