News

Engineering an endothelialized, endocrine NeoPancreas
Stacks Image 16043
Acta Biomaterialia accepted our latest paper on "Engineering an endothelialized, endocrine Neo-Pancreas: evaluation of islet functionality in an ex vivo model".

Islet-based recellularization of decellularized, repurposed rat livers may form a transplantable Neo-Pancreas. The aim of this study is the establishment of the necessary protocols, the evaluation of the organ structure and the analysis of the islet functionality ex vivo.
After perfusion-based decellularization of rat livers, matrices were repopulated with endothelial cells and mesenchymal stromal cells, incubated for 8 days in a perfusion chamber and finally repopulated on day 9 with intact rodent islets. Integrity and quality of re-endothelialization was assessed by histology and FITC-dextran perfusion assay. Functionality of the islets of Langerhans was determined on day 10 and day 12 via glucose stimulated insulin secretion.
Blood gas analysis variables confirmed the stability of the perfusion cultivation. Histological staining showed that cells formed a monolayer inside the intact vascular structure. These findings were confirmed by electron microscopy. Islets infused via the bile duct could histologically be found in the parenchymal space. Adequate insulin secretion after glucose stimulation after 1-day and 3-day cultivation verified islet viability and functionality after the repopulation process.
We provide the first proof-of-concept for the functionality of islets of Langerhans engrafted in a decellularized rat liver. Furthermore, a re-endothelialization step was implemented to provide implantability. This technique can serve as a bioengineered platform to generate implantable and functional endocrine Neo-Pancreases.

Authors are Hannah Everwien, Eriselda Keshi, Karl H. Hillebrandt, Barbara Ludwig, Marie Weinhart, Peter Tang, Anika S. Beierle, Hendrik Napierala, Joseph MGV Gassner, Nicolai Seiffert, Simon Moosburner, Dominik Geisel, Anja Reutzel-Selke, Benjamin Strücker, Johann Pratschke, Nils Haep, and Igor M. Sauer.
Stacks Image 16045
The Human Liver Matrisome
Stacks Image 16070
Biomaterials accepted our latest paper on „The Human Liver Matrisome – Proteomic Analysis of Native and Fibrotic Human Liver Extracellular Matrices for Organ Engineering Approaches“.

The production of biomaterials that endow significant morphogenic and microenvironmental cues for the constitution of cell integration and regeneration remains a key challenge in the successful implementation of functional organ replacements. Despite the vast development in the production of biological and architecturally native matrices, the complex compositions and pivotal figures by which the human matrisome mediates many of its essential functions are yet to be defined. Here we present a thorough analysis of the native human liver proteomic landscape using decellularization and defatting protocols to extract create extracellular matrix scaffolds of natural origin that can further be used in both bottom-up and top-down approaches in tissue engineering based organ replacements. Furthermore, by analyzing human liver extracellular matrices in different stages of fibrosis and cirrhosis, we have identified distinct attributes of these tissues that could potentially be exploited therapeutically and thus require further investigation. The general experimental pipeline presented in this study is applicable to any type of tissue and can be widely used for different approaches in regenerative medicine and in the construction of novel biomaterials for organ engineering approaches.

Authors are A. Daneshgar, O. Klein, G. Nebrich, M. Weinhart, P. Tang, A. Arnold, I. Ullah, J. Pohl, S. Moosburner, N. Raschzok, B. Strücker, M. Bahra, J. Pratschke, I.M. Sauer, and K.H. Hillebrandt. The authors acknowledge the support of the Cluster of Excellence Matters of Activity. Image Space Material funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany´s Excellence Strategy – EXC 2025.
Stacks Image 16072
Magnetic resonance elastography quantification of decellularized liver tissue
Stacks Image 16121
"Magnetic resonance elastography quantification of the solid-to-fluid transition of liver tissue due to decellularization" was published in the latest issue of the Journal of the Mechanical Behavior of Biomedical Materials.

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.

Authors are Hannah Everwien, Angela Ariza de Schellenberger, Nils Haep, Heiko Tzschätzsch, Johann Pratschke, Igor M. Sauer, Jürgen Braun, Karl H. Hillebrandt and Ingolf Sack.

J Mech Behav Biomed Mater. 2020 Apr;104:103640. doi: 10.1016/j.jmbbm.2020.103640. Epub 2020 Jan 14.
New book: Decellularized Extracellular Matrix: Characterization, Fabrication and Applications
Stacks Image 16136
The extracellular matrix (ECM) supports cells and regulates various cellular functions in our body. The native ECM promises to provide an excellent scaffold for regenerative medicine. In order to use the ECM as a scaffold in medicine, its cellular fractions need to be removed while retaining its structural and compositional properties. This process is called decellularization, and the resulting product is known as the decellularized extracellular matrix (dECM).
The book Decellularized Extracellular Matrix: Characterization, Fabrication and Applications (Editors: Tetsuji Yamaoka, Takashi Hoshiba) focuses on the sources of dECM and its preparation, characterization techniques, fabrication, and applications in regenerative medicine and biological studies. Using this book, the reader will gain a good foundation in the field of ECM decellularization complemented with a broad overview of dECM characterization, ranging from structural observation and compositional assessment to immune responses against dECM and applications, ranging from microfabrication and 3D-printing to the application of tissue-derived dECM in vascular grafts and corneal tissue engineering etc. The book closes with a section dedicated to cultured cell dECM, a complementary technique of tissue-derived dECM preparation, for application in tissue engineering and regenerative medicine, addressing its use in stem cell differentiation and how it can help in the study of the tumor microenvironment as well as in clinical trials of peripheral nerve regeneration.

E. Keshi, I.M. Sauer and K.H. Hillebrandt contributed the chapter "Engineering an endocrine Neo-Pancreas".

The print version of this book (Royal Society of Chemistry, ISBN 978-1-78801-467-0) is planned for release on 11 December 2019.
 Page 1 / 1 

Archive


Categories

Year

This website or its third-party tools use cookies, which are necessary to its functioning and required to achieve the purpose illustrated in the Disclaimer. By closing this banner, scrolling this page, clicking a link or continuing to browse otherwise, you agree to the use of cookies.