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 Pierro; Thomas W. Gilbert; Paolo De Coppi

doi:10.1016/j.biomaterials.2013.05.015

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^*

^*Corresponding author for this work

Women & Children's Health

Research output: Contribution to journal › Article › peer-review

64 Citations (Scopus)

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 language	English
Pages (from-to)	6638-6648
Number of pages	11
Journal	Biomaterials
Volume	34
Issue number	28
DOIs	https://doi.org/10.1016/j.biomaterials.2013.05.015
Publication status	Published - 1 Sept 2013

Keywords

Angiogenesis
Decellularization
Extracellular matrix
Lung tissue engineering
Natural acellular scaffold

Access to Document

10.1016/j.biomaterials.2013.05.015

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

@article{f9dc1ca8c1884b10891e095779e6d50d,

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

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.",

keywords = "Angiogenesis, Decellularization, Extracellular matrix, Lung tissue engineering, Natural acellular scaffold",

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

year = "2013",

month = sep,

day = "1",

doi = "10.1016/j.biomaterials.2013.05.015",

language = "English",

volume = "34",

pages = "6638--6648",

journal = "Biomaterials",

issn = "0142-9612",

publisher = "Elsevier BV",

number = "28",

}

Maghsoudlou, P, Georgiades, F, Tyraskis, A, Totonelli, G, Loukogeorgakis, SP, Orlando, G, Shangaris, P, Lange, P, Delalande, JM, Burns, AJ, Cenedese, A, Sebire, NJ, Turmaine, M, Guest, BN, Alcorn, JF, Atala, A, Birchall, MA, Elliott, MJ, Eaton, S, Pierro, A, Gilbert, TW & 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, vol. 34, no. 28, pp. 6638-6648. https://doi.org/10.1016/j.biomaterials.2013.05.015

Preservation of micro-architecture and angiogenic potential in a pulmonary acellular matrix obtained using intermittent intra-tracheal flow of detergent enzymatic treatment. / Maghsoudlou, Panagiotis; Georgiades, Fanourios; Tyraskis, Athanasios et al.
In: Biomaterials, Vol. 34, No. 28, 01.09.2013, p. 6638-6648.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Preservation of micro-architecture and angiogenic potential in a pulmonary acellular matrix obtained using intermittent intra-tracheal flow of detergent enzymatic treatment

AU - Maghsoudlou, Panagiotis

AU - Georgiades, Fanourios

AU - Tyraskis, Athanasios

AU - Totonelli, Giorgia

AU - Loukogeorgakis, Stavros P.

AU - Orlando, Giuseppe

AU - Shangaris, Panicos

AU - Lange, Peggy

AU - Delalande, Jean Marie

AU - Burns, Alan J.

AU - Cenedese, Angelo

AU - Sebire, Neil J.

AU - Turmaine, Mark

AU - Guest, Brogan N.

AU - Alcorn, John F.

AU - Atala, Anthony

AU - Birchall, Martin A.

AU - Elliott, Martin J.

AU - Eaton, Simon

AU - Pierro, Agostino

AU - Gilbert, Thomas W.

AU - De Coppi, Paolo

PY - 2013/9/1

Y1 - 2013/9/1

N2 - 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.

AB - 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.

KW - Angiogenesis

KW - Decellularization

KW - Extracellular matrix

KW - Lung tissue engineering

KW - Natural acellular scaffold

UR - http://www.scopus.com/inward/record.url?scp=84879463145&partnerID=8YFLogxK

U2 - 10.1016/j.biomaterials.2013.05.015

DO - 10.1016/j.biomaterials.2013.05.015

M3 - Article

C2 - 23727263

AN - SCOPUS:84879463145

SN - 0142-9612

VL - 34

SP - 6638

EP - 6648

JO - Biomaterials

JF - Biomaterials

IS - 28

ER -

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

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this