Design and Synthesis of an Artificial Pulmonary Pleura for High Throughput Studies in Acellular Human Lungs.
Whole organ decellularization of complex organs, such as lungs, presents a unique opportunity for use of acellular scaffolds forex vivotissue engineering or for studying cell-extracellular matrix interactionsex vivo. A growing body of literature investigating decellularizing and recellularizing rodent lungs has provided important proof of concept models and rodent lungs are readily available for high throughput studies. In contrast, comparable progress in large animal and human lungs has been impeded owing to more limited availability and difficulties in handling larger tissue. While the use of smaller segments of acellular large animal or human lungs would maximize usage from a single lung, excision of small acellular segments compromises the integrity of the pleural layer, leaving the terminal ends of blood vessels and airways exposed. We have developed a novel pleural coating using non-toxic ionically crosslinked alginate or photocrosslinked methacrylated alginate which can be applied to excised acellular lung segments, permits inflation of small segments, and significantly enhances retention of cells inoculated through cannulated airways or blood vessels. Further, photocrosslinking methacrylated alginate, using eosin Y and triethanolamine at 530 nm wavelength, results in a mechanically stable pleural coating that permits effective cyclic 3-dimensional stretch, i.e., mechanical ventilation, of individual segments.
Department of Medicine, University of Vermont, 226 Health Sciences Research Facility Center, Burlington, VT 05405 USA.
Darcy E
DE
Wagner
College of Engineering and Mathematical Sciences, University of Vermont, 109 Votey Hall, Burlington, VT 05405 USA.
Spencer L
SL
Fenn
Department of Medicine, University of Vermont, 226 Health Sciences Research Facility Center, Burlington, VT 05405 USA.
Nicholas R
NR
Bonenfant
Department of Medicine, University of Vermont, 226 Health Sciences Research Facility Center, Burlington, VT 05405 USA.
Elliot R
ER
Marks
Department of Medicine, University of Vermont, 226 Health Sciences Research Facility Center, Burlington, VT 05405 USA.
Zachary
Z
Borg
Department of Medicine, University of Vermont, 226 Health Sciences Research Facility Center, Burlington, VT 05405 USA.
Patrick
P
Saunders
College of Engineering and Mathematical Sciences, University of Vermont, 109 Votey Hall, Burlington, VT 05405 USA.
Rachael A
RA
Floreani
Department of Medicine, University of Vermont, 226 Health Sciences Research Facility Center, Burlington, VT 05405 USA.
Daniel J
DJ
Weiss
Alginate; Artificial pleura; Decellularization; Lung; Ventilation