Mechanostructure and composition of highly reproducible decellularized liver matrices

Mattei, Giorgio; Patria, Valentina Di; Tirella, Annalisa; Alaimo, Alessandro; Elia, Giuliano; Corti, Angelo; Paolicchi, Aldo; Ahluwalia, Arti

doi:10.1016/j.actbio.2013.10.023

Cited by 70 publications

(82 citation statements)

References 26 publications

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“…Their results are consistent with those recently published by Lu et al [80], who report that freezing affects the mechanical properties of bovine liver tissue but not those of porcine liver. Although the data are in agreement with those of Mattei et al [22], the variability between different reports attests to the difficulty in standardising liver sample and testing variables.…”

Section: Testing Temperature and Sample Freezingsupporting

confidence: 81%

Sample, testing and analysis variables affecting liver mechanical properties: A review

Mattei

Ahluwalia

2016

Acta Biomaterialia

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Section: Testing Temperature and Sample Freezingsupporting

confidence: 81%

Sample, testing and analysis variables affecting liver mechanical properties: A review

Mattei

Ahluwalia

2016

Acta Biomaterialia

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“…Generally speaking, the efficiency of an immersion and agitation protocol may vary according to the agitation intensity, detergent type, immersion time, and, most importantly, the thickness and density of the tissue being decellularized. In the case of liver tissue, satisfactory results can only be achieved using slices or discs of no more than 5 mm in thickness [Lang et al, 2011;Mattei et al, 2014].…”

Section: Decellularization Techniquesmentioning

confidence: 99%

Recent Advances in Decellularization and Recellularization for Tissue-Engineered Liver Grafts

Wang

Nicolas²,

Chen³

et al. 2016

Cells Tissues Organs

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Liver transplantation from deceased or living human donors remains the only proven option for patients with end-stage liver disease. However, the shortage of donor organs is a significant clinical concern that has led to the pursuit of tissue-engineered liver grafts generated from decellularized liver extracellular matrix and functional cells. Investigative efforts on optimizing both liver decellularization and recellularization protocols have been made in recent decades. In the current review, we briefly summarize these advances, including the generation of high-quality liver extracellular matrix scaffolds, evaluation criteria for quality control, modification of matrix for enhanced properties, and reseeding strategies. These efforts to optimize the methods of decellularization and recellularization lay the groundwork towards generating a transplantable, human-sized liver graft for the treatment of patients with severe liver disease.

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“…In translational studies, large animals such as pigs and sheep are preferred [25,26,27,28,29,30,31,32]. The use of pigs as organ donors is discussed controversially because of the immunological barrier due to the expression of galactose-1,3-alpha-galactose in porcine organs which may lead to hyperacute rejection of the repopulated organ.…”

Section: Source Of Organs For Liver Engineeringmentioning

confidence: 99%

“…A commonly used molecular biological method to determine cell removal is the quantification of the DNA content of the acellular scaffold (fig. 3) [14,15,17,19,20,21,27,29,39]. Crapo et al [40] suggested defining a DNA content below 50 ng dsDNA/mg tissue (dry weight) and a fragment length below 200 bp as quality criteria.…”

Section: Quality Assessment Of Decellularizationmentioning

confidence: 99%

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Bioengineered Livers: A New Tool for Drug Testing and a Promising Solution to Meet the Growing Demand for Donor Organs

et al. 2016

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Background: Organ engineering is a new innovative strategy to cope with two problems: the need for physiological models for pharmacological research and donor organs for transplantation. A functional scaffold is generated from explanted organs by removing all cells (decellularization) by perfusing the organ with ionic or nonionic detergents via the vascular system. Subsequently the acellular scaffold is reseeded with organ-specific cells (repopulation) to generate a functional organ. Summary: This review gives an overview of the state of the art describing the decellularization process, the subsequent quality assessment, the repopulation techniques and the functional assessment. It emphasizes the use of scaffolds as matrix for culturing human liver cells for drug testing. Further, it highlights the techniques for transplanting these engineered scaffolds in allogeneic or xenogeneic animals in order to test their biocompatibility and use as organ grafts. Key Messages: The first issue is the so-called decellularization, which is best explored and resulted in a multitude of different protocols. The most promising approach seems to be the combination of pulsatile perfusion of the liver with Triton X-100 and SDS via hepatic artery and portal vein. Widely accepted parameters of quality control include the quantitative assessment of the DNA content and the visualization of eventually remaining nuclei confirmed by HE staining. Investigations regarding the composition of the extracellular matrix focused on histological determination of laminin, collagen, fibronectin and elastin and remained qualitatively. Repopulation is the second issue which is addressed. Selection of the most suitable cell type is a highly controversial topic. Currently, the highest potential is seen for progenitor and stem cells. Cells are infused into the scaffold and cultured under static conditions or in a bioreactor allowing dynamic perfusion of the scaffold. The quality of repopulation is mainly assessed by routine histology and basic functional assays. These promising results prompted to consider the use of a liver scaffold repopulated with human cells for pharmacological research. Transplantation of the (repopulated) scaffold is the third topic which is not yet widely addressed. Few studies report the heterotopic transplantation of repopulated liver tissue without vascular anastomosis. Even fewer studies deal with the heterotopic transplantation of a scaffold or a repopulated liver lobe. However, observation time was still limited to hours, and long-term graft survival has not been reported yet. These exciting results emphasize the potential of this new and promising strategy to create physiological models for pharmacological research and to generate liver grafts for the transplant community to treat organ failure. However, the scientific need for further development in the field of liver engineering is still tremendous.

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Mechanostructure and composition of highly reproducible decellularized liver matrices

Cited by 70 publications

References 26 publications

Sample, testing and analysis variables affecting liver mechanical properties: A review

Sample, testing and analysis variables affecting liver mechanical properties: A review

Recent Advances in Decellularization and Recellularization for Tissue-Engineered Liver Grafts

Bioengineered Livers: A New Tool for Drug Testing and a Promising Solution to Meet the Growing Demand for Donor Organs

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