title: Inhomogeneity of local stiffness in the extracellular matrix scaffold of fibrotic mouse lungs.
abstract: Lung disease models are useful to study how cell engraftment, proliferation and differentiation are modulated in lung bioengineering. The aim of this work was to characterize the local stiffness of decellularized lungs in aged and fibrotic mice. Mice (2- and 24-month old; 14 of each) with lung fibrosis (N=20) and healthy controls (N=8) were euthanized after 11 days of intratracheal bleomycin (fibrosis) or saline (controls) infusion. The lungs were excised, decellularized by a conventional detergent-based (sodium-dodecyl sulfate) procedure and slices of the acellular lungs were prepared to measure the local stiffness by means of atomic force microscopy. The local stiffness of the different sites in acellular fibrotic lungs was very inhomogeneous within the lung and increased according to the degree of the structural fibrotic lesion. Local stiffness of the acellular lungs did not show statistically significant differences caused by age. The group of mice most affected by fibrosis exhibited local stiffness that were ~2-fold higher than in the control mice: from 27.2±1.64 to 64.8±7.1kPa in the alveolar septa, from 56.6±4.6 to 99.9±11.7kPa in the visceral pleura, from 41.1±8.0 to 105.2±13.6kPa in the tunica adventitia, and from 79.3±7.2 to 146.6±28.8kPa in the tunica intima. Since acellular lungs from mice with bleomycin-induced fibrosis present considerable micromechanical inhomogeneity, this model can be a useful tool to better investigate how different degrees of extracellular matrix lesion modulate cell fate in the process of organ bioengineering from decellularized lungs.
authors.affiliation: Unitat de Biofísica i Bioenginyeria, Facultat de Medicina, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Melo
authors.affiliation: Dorothy P. & Richard P. Simmons Center for Interstitial Lung Disease, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: Nayra
authors.initials: N
authors.lastname: Cárdenes
authors.affiliation: Unitat de Biofísica i Bioenginyeria, Facultat de Medicina, Universitat de Barcelona, Barcelona, Spain; CIBER de Enfermedades Respiratorias, Bunyola, Spain; Institut Investigacions Biomediques August Pi Sunyer, Barcelona, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Garreta
authors.affiliation: Unitat de Biofísica i Bioenginyeria, Facultat de Medicina, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Tomas
authors.initials: T
authors.lastname: Luque
authors.affiliation: Dorothy P. & Richard P. Simmons Center for Interstitial Lung Disease, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; McGowan Institute for Regenerative Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: Mauricio
authors.initials: M
authors.lastname: Rojas
authors.affiliation: Unitat de Biofísica i Bioenginyeria, Facultat de Medicina, Universitat de Barcelona, Barcelona, Spain; CIBER de Enfermedades Respiratorias, Bunyola, Spain; Institut de Bioenginyeria de Catalunya, Barcelona, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Navajas
authors.affiliation: Unitat de Biofísica i Bioenginyeria, Facultat de Medicina, Universitat de Barcelona, Barcelona, Spain; CIBER de Enfermedades Respiratorias, Bunyola, Spain; Institut Investigacions Biomediques August Pi Sunyer, Barcelona, Spain. Electronic address: rfarre@ub.edu.
authors.forename: Ramon
authors.initials: R
authors.lastname: Farré
mesh_terms: D000375:Aging / Q000473:pathology; D000818:Animals; D001696:Biomechanical Phenomena; D001761:Bleomycin / Q000009:adverse effects; D003094:Collagen / Q000378:metabolism; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D005355:Fibrosis; D008168:Lung / Q000187:drug effects / Q000473:pathology*; D055595:Mechanical Phenomena; D051379:Mice; D008810:Mice, Inbred C57BL; D054457:Tissue Scaffolds
chemical_list: D001761:Bleomycin; D003094:Collagen
keywords: Ageing; Atomic force microscopy; Decellularization; Lung fibrosis; Tissue engineering