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J Mech Behav Biomed Mater. 2020 Apr;104:103640. doi: 10.1016/j.jmbbm.2020.103640. Epub 2020 Jan 14.

Magnetic resonance elastography quantification of the solid-to-fluid transition of liver tissue due to decellularization.

Author information

1
Department of Surgery, CCM|CVK, Charité - Universitätsmedizin Berlin, Germany; Berlin Institute of Health (BIH), Berlin, Germany.
2
Department of Radiology, Charité - Universitätsmedizin Berlin, Germany.
3
Department of Surgery, CCM|CVK, Charité - Universitätsmedizin Berlin, Germany.
4
Institute of Medical Informatics, Charité - Universitätsmedizin Berlin, Germany.
5
Department of Surgery, CCM|CVK, Charité - Universitätsmedizin Berlin, Germany; BIH Charité Clinician Scientist Program, Berlin Institute of Health (BIH), Berlin, Germany.
6
Department of Radiology, Charité - Universitätsmedizin Berlin, Germany. Electronic address: ingolf.sack@charite.de.

Abstract

Maintenance of tissue extracellular matrix (ECM) and its biomechanical properties for tissue engineering is one of the substantial challenges in the field of decellularization and recellularization. Preservation of the organ-specific biomatrix is crucial for successful recellularization to support cell survival, proliferation, and functionality. However, understanding ECM properties with and without its inhabiting cells as well as the transition between the two states lacks appropriate test methods capable of quantifying bulk viscoelastic parameters in soft tissues. We used compact magnetic resonance elastography (MRE) with 400, 500, and 600 Hz driving frequency to investigate rat liver specimens for quantification of viscoelastic property changes resulting from decellularization. Tissue structures in native and decellularized livers were characterized by collagen and elastin quantification, histological analysis, and scanning electron microscopy. Decellularization did not affect the integrity of microanatomy and structural composition of liver ECM but was found to be associated with increases in the relative amounts of collagen by 83-fold (37.4 ± 17.5 vs. 0.5 ± 0.01 μg/mg, p = 0.0002) and elastin by approx. 3-fold (404.1 ± 139.6 vs. 151.0 ± 132.3 μg/mg, p = 0.0046). Decellularization reduced storage modulus by approx. 9-fold (from 4.9 ± 0.8 kPa to 0.5 ± 0.5 kPa, p < 0.0001) and loss modulus by approx. 7-fold (3.6 kPa to 0.5 kPa, p < 0.0001), indicating a marked loss of global tissue rigidity as well as a property shift from solid towards more fluid tissue behavior (p = 0.0097). Our results suggest that the rigidity of liver tissue is largely determined by cellular components, which are replaced by fluid-filled spaces when cells are removed. This leads to an overall increase in tissue fluidity and a viscous drag within the relatively sparse remaining ECM. Compact MRE is an excellent tool for quantifying the mechanical properties of decellularized biological tissue and a promising candidate for useful applications in tissue engineering.

KEYWORDS:

Decellularization; Liver; Tabletop magnetic resonance elastography; Tissue fluidity; Transplantation

Conflict of interest statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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