Vascularizations
Extracellular matrix. Experiments by Emile De Visscher, 2020. Credits and copyright: Experimental Surgery, Charité.
Many living organisms rely on vascularization to generate a flow of matter fundamental to sustaining life. This flow can be traced to various energy-driven processes underlying dynamic environments, both in living and non-living. To understand this functional entanglement, we strive to unravel the interplay of materials, structures, and processes of vascularization across scales, in experiments at the intersection of Regenerative Medicine, Architecture & Design, and the Humanities. Investigating vascularization as a key component of biological systems and its capacity to (re)grow or (re)use complex bioactive architectures will help in finding novel ways to reconstruct defects, as an interdisciplinary intervention in design, bioengineering, and surgery. We hereby pursue three goals: 1) to explore ways of (re)using plant vasculature as an »extended body« of environmental exchange in architecture and design. In this sense, the strand shares approaches with Architectural Yarns as Environmental Devices, 2) to bio-fabricate structurally well-defined 3D organs that contain an in vivo-like mammal vasculature to explore new methods for biomedical applications, and 3) to contribute to further theoretical inquiry in the Humanities, specifically in the Behavioral Matter strand. The experiments serve as case studies and conceptual frameworks for living/non-living entanglements, embodiment, and performativity.
1) Repurposing of plants for tissue engineering and active building materials
Plant tissues, such as leaves, roots, or flowers can be freed from their cellular material by a technique named decellularization, forming a scaffold that is subsequently reseeded with animal or human cells. This technique allows for the preservation of the native three-dimensional tissue structure and its vasculature. Although vegetal vascular systems differ significantly in their structure and compositions to those of mammals, the use of plant scaffolds may serve as a less invasive and safer approach to tissue engineering and may offer novel alternatives to current, ethically controversial practices of animal use. Through interdisciplinary, experimental methods that combine surgery, materials science, cultural history and theory, architecture and design, the project explores the practices of plant decellularization, and the surrounding sites, technologies, and architectures of plant growth and adaptation.
Human-plant encounters. Decellularized flower petals adhering to the human skin (left). Decellularized leaf with retained three-dimensional architecture and vascularization (right). Experiments by Assal Daneshgar, Maja Avnat and Iva Rešetar with Igor Sauer at the Experimental Surgery, Charité, 2023. Photography: Michelle Mantel. Copyright: Matters of Activity
2) Cells and their matrisome – dismantling and recomposing of components for the production of vascularized living tissues
The restoration of organ function remains a crucial aspect of surgical interventions – however, challenges persist in achieving complete recovery (restitutio ad integrum) after surgery. With the population aging and the impact of dietary and toxic factors on the rise, the importance of addressing these issues is escalating. Here, we focus is on revitalizing the function of cells, tissues, and organs through biological, bioartificial, or artificial support and replacement. This involves advancing and applying tissue engineering methods to promote endogenous and organ-specific regeneration processes. To achieve this, we focus on biological matrices by in-depth proteomic analyzes and investigate biomechanical properties. By shedding light on the complex interaction of cells and their surrounding microenvironmental niche – also known as the matrisome – we aim to bridge bottom-up and top-down bioengineering approaches from experimental design to clinical reality. Key techniques include de- and re-cellularization, as well as 3D tissue bioprinting. The central objective is the generation of an endocrine NeoIPancreas based on a vascularized, anastomosable tissue construct that provides a suitable habitat for human islets of Langerhans. We successfully established methods for the de- and recellularization of liver, pancreas, and larger vessels from pigs and rats. Upon successful recellularization and repurposing of decellularized rat livers into an insulin producing endocrine organ, the vitality of the islets of Langerhans and their physiological responses to glucose have been demonstrated ex vivo.
Concept of decellularization and subsequent recellularization of the matrisome with cells and further disintegration and use in biocompatible inks or cell-containing bioinks for 3D bioprinting. Copyright: Igor Sauer, Experimental Surgery, Charité.
3) Electron partial discharge to generate micro-vascular structures in biomaterials
Exploring alternative and unconventional ways to generate micro-vasculatures, Emile De Visscher used the behavior of electrons to carve self-optimized micro-networks. Inspired by Fulgurites, the glass structures created by a lightning discharge in sand, we have succeeded in using electrons to tunnel through materials on micrometer scales, using an electron accelerator at École Polytechnique in Palaiseau, FR, with help of the LSI lab. The principle is simple: a block of biocompatible material is exposed to a beam of electrons, which are captured in its structure. Once extracted from the electron accelerator, we then hit a nail connected to the terrestrial network. Instantly, all the electrons escape, creating vascular networks whose paths are optimized by the process itself. While the technique itself was known and already explored for other contexts and applications, we succeeded in finding a method to create transfusable continuous networks of micro-vasculatures in PLA bioplastic blocks, which have been analyzed at Freie Universität Berlin.
Partial discharge in PMMA blocks, conducted at LSI Lab, École Polytechnique, with support from EMIR research network. Part of the Vascularization experiments of Emile De Visscher, 2020. Copyright: Palta Studio.
Dr. med. Assal Daneshgar (Experimental Surgery, Charité Universitätsmedizin Berlin)
Späth-Arboretum der Humboldt-Universität zu Berlin, Thomas Janßen (Repurposing Plants project)
The MoA research group Adaptive Fibrous Materials, Max Planck Institute of Colloids and Interfaces, Michaela Eder (Repurposing Plants project)
Weinhart Group, Freie Universität Berlin, Institut für Chemie und Biochemie, Organische Chemie (Matrisome project and Electron Partial Discharge project)
LSI Lab, École Polytechnique (Electron Partial Discharge project)
Engineering an endothelialized, endocrine Neo-Pancreas: Evaluation of islet functionality in an ex vivo model
Hannah Everwien, Eriselda Keshi, Karl H. Hillebrandt, Barbara Ludwig, Marie Weinhart, Peter Tang, Anika S. Beierle, Hendrik Napierala, Joseph M.G.V. Gassner, Nicolai Seiffert, Simon Moosburner, Dominik Geisel, Anja Reutzel-Selke, Benjamin Strücker, Johann Pratschke, Nils Haep, Igor M. Sauer
Acta Biomater. 2020 Nov:117:213-225. doi: 10.1016/j.actbio.2020.09.022. Epub 2020 Sep 16.
The human liver matrisome – Proteomic analysis of native and fibrotic human liver extracellular matrices for organ engineering approaches
Assal Daneshgar, Oliver Klein, Grit Nebrich, Marie Weinhart, Peter Tang, Alexander Arnold, Imran Ullah, Julian Pohl, Simon Moosburner, Nathanael Raschzok, Benjamin Strücker, Marcus Bahra, Johann Pratschke, Igor M. Sauer, Karl H. Hillebrandt
Biomaterials. 2020 Oct:257:120247. doi: 10.1016/j.biomaterials.2020.120247. Epub 2020 Jul 24.
Proteomic analysis of decellularized mice liver and kidney extracellular matrices
Anna-Maria Diedrich, Assal Daneshgar, Peter Tang, Oliver Klein, Annika Mohr, Olachi A. Onwuegbuchulam, Sabine von Rueden, Kerstin Menck, Annalen Bleckmann, Mazen A. Juratli, Felix Becker, Igor M. Sauer, Karl H. Hillebrandt, Andreas Pascher, Benjamin Struecker
J Biol Eng. 2024 Feb 22;18(1):17. doi: 10.1186/s13036-024-00413-8.
Papain-based solubilization of decellularized extracellular matrix for the preparation of bioactive, thermosensitive pregels
Ahed Almalla, Laura Elomaa, Leïla Bechtella, Assal Daneshgar, Prabhu Yavvari, Zeinab Mahfouz, Peter Tang, Beate Koksch, Igor M. Sauer, Kevin Pagel, Karl H. Hillebrandt, Marie Weinhart
Biomacromolecules. 2023 Dec 11;24(12):5620-5637. doi: 10.1021/acs.biomac.3c00602. Epub 2023 Nov 27.
Bioactive photocrosslinkable resin solely based on refined decellularized small intestine submucosa for vat photopolymerization of in vitro tissue mimics
Laura Elomaa, Lorenz Gerbeth, Ahed Almalla, Nora Fribiczer, Assal Daneshgar, Peter Tang, Karl H. Hillebrandt, Sebastian Seiffert, Igor M. Sauer, Britta Siegmund, Marie Weinhart
Additive Manufacturing. 2023, Volume 64, 103439. doi.org/10.1016/j.addma.2023.103439.
Rise of tissue- and species-specific 3D bioprinting based on decellularized extracellular matrix-derived bioinks and bioresins
Laura Elomaa, Ahed Almalla, Eriselda Keshi, Karl H. Hillebrandt, Igor M. Sauer, Marie Weinhart
Biomater Biosyst. 2023 Nov 7:12:100084. doi: 10.1016/j.bbiosy.2023.100084. eCollection 2023 Dec.
Toward a 3D printed perfusable islet embedding structure: technical notes and preliminary results
Eriselda Keshi, Peter Tang, Tobias Lam, Simon Moosburner, Luna Haderer, Anja Reutzel-Selke, Lutz Kloke, Johann Pratschke, Igor M. Sauer, Karl H. Hillebrandt
Tissue Eng Part C Methods. 2023 Oct;29(10):469-478. doi: 10.1089/ten.TEC.2023.0045.
Development and systematic evaluation of decellularization protocols in different application models for diaphragmatic tissue engineering
Marco N. Andreas, Agnes K. Boehm, Peter Tang, Simon Moosburner, Oliver Klein, Assal Daneshgar, Joseph M.G.V. Gaßner, Nathanael Raschzok, Luna Haderer, Dag Wulsten, Jens-Carsten Rückert , Simone Spuler, Johann Pratschke, Igor M. Sauer, Karl H. Hillebrandt
Biomater Adv. 2023 Oct:153:213493. doi: 10.1016/j.bioadv.2023.213493. Epub 2023 Jun 5.
Tissue engineering for the diaphragm and its various therapeutic possibilities – A systematic review
Agnes K. Boehm, Karl H. Hillebrandt, Tomasz Dziodzio, Felix Krenzien, Jens Neudecker, Simone Spuler, Johann Pratschke, Igor M. Sauer, Marco N. Andreas
Advanced Therapeutics. August 2022, Volume5, Issue 8. doi.org/10.1002/adtp.
Surface modification of decellularized bovine carotid arteries with human vascular cells significantly reduces their thrombogenicity
Eriselda Keshi, Peter Tang, Marie Weinhart, Hannah Everwien, Simon Moosburner, Nicolai Seiffert, Michael Lommel, Ulrich Kertzscher, Brigitta Globke, Anja Reutzel-Selke, Benjamin Strücker , Johann Pratschke, Igor M. Sauer, Nils Haep, Karl H. Hillebrandt
J Biol Eng. 2021 Nov 24;15(1):26. doi: 10.1186/s13036-021-00277-2.
Development of GelMA/PCL and dECM/PCL resins for 3D printing of acellular in vitro tissue scaffolds by stereolithography
Laura Elomaa, Eriselda Keshi, Igor Maximilian Sauer, Marie Weinhart
Mater Sci Eng C Mater Biol Appl. 2020 Jul:112:110958. doi: 10.1016/j.msec.2020.110958. Epub 2020 Apr 12.
Teburu – Open source 3D printable bioreactor for tissue slices as dynamic three-dimensional cell culture models
Assal Daneshgar, Peter Tang, Christopher Remde, Michael Lommel, Simon Moosburner, Ulrich Kertzscher, Oliver Klein, Marie Weinhart, Johann Pratschke, Igor M. Sauer, Karl H. Hillebrandt
Artif Organs. 2019 Oct;43(10):1035-1041. doi: 10.1111/aor.13518. Epub 2019 Jul 17.
Strategies based on organ decellularization and recellularization
Karl H. Hillebrandt, Hannah Everwien, Niels Haep, Eriselda Keshi, Johann Pratschke, Igor M. Sauer
Transpl Int. 2019 Jun;32(6):571-585. doi: 10.1111/tri.13462.
Biocompatible Radiations: Designing for the Living
Emile De Visscher. In Léa Perraudin, Clemens Winkler, Claudia Mareis and Matthias Held (eds), Material Trajectories – Designing with Care?, Lüneburg, Meson Press, 2024, pp. 123-134.
The Round Table On the Fabrication of Organs: Vascular Structures, Medical Needs and Critical Speculations took place on January 12th, 2023 at Kunstgewerbemuseum Berlin.
The exhibition Design Lab #13: Material Legacies at Kunstgewerbemuseum Berlin (Nov. 3rd, 2022 – Feb. 26th, 2023) explored contingencies and ruptures between traditional crafts and the most recent developments at the crossroads of material research, design, engineering, and architecture.
The symposium Times of Waste – Handling Matter took place on June 17th&18th, 2021 and provided a platform to discuss the engagement with (waste) material and bridged between theoretical studies and a response/able, careful way of handling materiality in sciences, arts, and collections.
The workshop »Decellularizing Plants« was carried out at the Charité, Experimental Surgery in October 2023, by Maja Avnat (Design, Cultural History and Theory), Assal Daneshgar (Surgery) and Iva Rešetar (Architecture), and Igor Sauer (Surgery).