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2016 ; 5
(1
): 72-83
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Biomimetic Culture Reactor for Whole-Lung Engineering
#MMPMID27088061
Raredon MS
; Rocco KA
; Gheorghe CP
; Sivarapatna A
; Ghaedi M
; Balestrini JL
; Raredon TL
; Calle EA
; Niklason LE
Biores Open Access
2016[]; 5
(1
): 72-83
PMID27088061
show ga
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.