Three-dimensional scaffolds of acellular human and porcine lungs for high throughput studies of lung disease and regeneration

Darcy E. Wagner, Nicholas R. Bonenfant, Dino Sokocevic, Michael J. DeSarno, Zachary D. Borg, Charles S. Parsons, Elice M. Brooks, Joseph J. Platz, Zain I. Khalpey, David M. Hoganson, Bin Deng, Ying W. Lam, Rachael A. Oldinski, Takamaru Ashikaga, Daniel J. Weiss

Research output: Contribution to journalArticle

80 Scopus citations

Abstract

Acellular scaffolds from complex whole organs such as lung are being increasingly studied for ex vivo organ generation and for in vitro studies of cell-extracellular matrix interactions. We have established effective methods for efficient de and recellularization of large animal and human lungs including techniques which allow multiple small segments (~1-3 cm3) to be excised that retain 3-dimensional lung structure. Coupled with the use of a synthetic pleural coating, cells can be selectively physiologically inoculated via preserved vascular and airway conduits. Inoculated segments can be further sliced for high throughput studies. Further, we demonstrate thermography as a powerful noninvasive technique for monitoring perfusion decellularization and for evaluating preservation of vascular and airway networks following human and porcine lung decellularization. Collectively, these techniques are a significant step forward as they allow high throughput in vitro studies from a single lung or lobe in a more biologically relevant, three-dimensional acellular scaffold.

Original languageEnglish (US)
Pages (from-to)2664-2679
Number of pages16
JournalBiomaterials
Volume35
Issue number9
DOIs
StatePublished - Mar 1 2014

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Keywords

  • Acellular matrix
  • Endothelial cell
  • Epithelial cell
  • Extracellular matrix (ECM)
  • Human lung fibroblast
  • Mesenchymal stem cell

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

Cite this

Wagner, D. E., Bonenfant, N. R., Sokocevic, D., DeSarno, M. J., Borg, Z. D., Parsons, C. S., Brooks, E. M., Platz, J. J., Khalpey, Z. I., Hoganson, D. M., Deng, B., Lam, Y. W., Oldinski, R. A., Ashikaga, T., & Weiss, D. J. (2014). Three-dimensional scaffolds of acellular human and porcine lungs for high throughput studies of lung disease and regeneration. Biomaterials, 35(9), 2664-2679. https://doi.org/10.1016/j.biomaterials.2013.11.078