Preservation of micro-architecture and angiogenic potential in a pulmonary acellular matrix obtained using intermittent intra-tracheal flow of detergent enzymatic treatment

Panagiotis Maghsoudlou, Fanourios Georgiades, Athanasios Tyraskis, Giorgia Totonelli, Stavros P. Loukogeorgakis, Giuseppe Orlando, Panicos Shangaris, Peggy Lange, Jean Marie Delalande, Alan J. Burns, Angelo Cenedese, Neil J. Sebire, Mark Turmaine, Brogan N. Guest, John F. Alcorn, Anthony Atala, Martin A. Birchall, Martin J. Elliott, Simon Eaton, Agostino PierroThomas W. Gilbert, Paolo De Coppi

Research output: Contribution to journalArticle

43 Scopus citations

Abstract

Tissue engineering of autologous lung tissue aims to become a therapeutic alternative to transplantation. Efforts published so far in creating scaffolds have used harsh decellularization techniques that damage the extracellular matrix (ECM), deplete its components and take up to 5 weeks to perform. The aim of this study was to create a lung natural acellular scaffold using a method that will reduce the time of production and better preserve scaffold architecture and ECM components. Decellularization of rat lungs via the intratracheal route removed most of the nuclear material when compared to the other entry points. An intermittent inflation approach that mimics lung respiration yielded an acellular scaffold in a shorter time with an improved preservation of pulmonary micro-architecture. Electron microscopy demonstrated the maintenance of an intact alveolar network, with no evidence of collapse or tearing. Pulsatile dye injection via the vasculature indicated an intact capillary network in the scaffold. Morphometry analysis demonstrated a significant increase in alveolar fractional volume, with alveolar size analysis confirming that alveolar dimensions were maintained. Biomechanical testing of the scaffolds indicated an increase in resistance and elastance when compared to fresh lungs. Staining and quantification for ECM components showed a presence of collagen, elastin, GAG and laminin. The intratracheal intermittent decellularization methodology could be translated to sheep lungs, demonstrating a preservation of ECM components, alveolar and vascular architecture. Decellularization treatment and methodology preserves lung architecture and ECM whilst reducing the production time to 3h. Cell seeding and invivo experiments are necessary to proceed towards clinical translation.

Original languageEnglish (US)
Pages (from-to)6638-6648
Number of pages11
JournalBiomaterials
Volume34
Issue number28
DOIs
StatePublished - Sep 1 2013

Keywords

  • Angiogenesis
  • Decellularization
  • Extracellular matrix
  • Lung tissue engineering
  • Natural acellular scaffold

ASJC Scopus subject areas

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

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  • Cite this

    Maghsoudlou, P., Georgiades, F., Tyraskis, A., Totonelli, G., Loukogeorgakis, S. P., Orlando, G., Shangaris, P., Lange, P., Delalande, J. M., Burns, A. J., Cenedese, A., Sebire, N. J., Turmaine, M., Guest, B. N., Alcorn, J. F., Atala, A., Birchall, M. A., Elliott, M. J., Eaton, S., ... De Coppi, P. (2013). Preservation of micro-architecture and angiogenic potential in a pulmonary acellular matrix obtained using intermittent intra-tracheal flow of detergent enzymatic treatment. Biomaterials, 34(28), 6638-6648. https://doi.org/10.1016/j.biomaterials.2013.05.015