Format

Send to

Choose Destination
Biores Open Access. 2016 Apr 1;5(1):72-83. doi: 10.1089/biores.2016.0006. eCollection 2016.

Biomimetic Culture Reactor for Whole-Lung Engineering.

Author information

1
Department of Biomedical Engineering, Yale University, New Haven, Connecticut.; Department of Anesthesia, Yale University, New Haven, Connecticut.; Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts.
2
Department of Biomedical Engineering, Yale University, New Haven, Connecticut.; Department of Anesthesia, Yale University, New Haven, Connecticut.
3
Department of Obstetrics, Gynecology, and Reproductive Services, Yale University , New Haven, Connecticut.
4
Department of Anesthesia, Yale University , New Haven, Connecticut.
5
Department of Anesthesia, Yale University, New Haven, Connecticut.; Department of Pathology, Yale University, New Haven, Connecticut.
6
Raredon Resources, Inc. , Northampton, Massachusetts.

Abstract

Decellularized organs are now established as promising scaffolds for whole-organ regeneration. For this work to reach therapeutic practice, techniques and apparatus are necessary for doing human-scale clinically applicable organ cultures. We have designed and constructed a bioreactor system capable of accommodating whole human or porcine lungs, and we describe in this study relevant technical details, means of assembly and operation, and validation. The reactor has an artificial diaphragm that mimics the conditions found in the chest cavity in vivo, driving hydraulically regulated negative pressure ventilation and custom-built pulsatile perfusion apparatus capable of driving pressure-regulated or volume-regulated vascular flow. Both forms of mechanical actuation can be tuned to match specific physiologic profiles. The organ is sealed in an elastic artificial pleura that mounts to a support architecture. This pleura reduces the fluid volume required for organ culture, maintains the organ's position during mechanical conditioning, and creates a sterile barrier allowing disassembly and maintenance outside of a biosafety cabinet. The combination of fluid suspension, negative-pressure ventilation, and physiologic perfusion allows the described system to provide a biomimetic mechanical environment not found in existing technologies and especially suited to whole-organ regeneration. In this study, we explain the design and operation of this apparatus and present data validating intended functions.

KEYWORDS:

bioprocessing; extracellular matrix; regeneration; tissue engineering

Supplemental Content

Full text links

Icon for Atypon Icon for PubMed Central
Loading ...
Support Center