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ArtHep - Hepatocytes-Like Microreactors for Liver Tissue Engineering

The global epidemics of obesity and diabetes type 2 lead to higher abundancy of medical conditions like non-alcoholic fatty liver disease causing an increase in liver failure and demand for liver transplants. The shortage of donor organs and the insufficient success in tissue engineering to ex vivo grow complex organs like the liver is a global medical challenge. 

ArtHep targets the assembly of hepatic-like tissue, consisting of biological and synthetic entities, mimicking the core structure elements and key functions of the liver. ArtHep comprises an entirely new concept in liver regeneration with multi-angled core impact: i) cell mimics are expected to reduce the pressure to obtain donor cells, ii) the integrated biocatalytic subunits are destined to take over tasks of the damaged liver slowing down the progress of liver damage, and iii) the matching micro-environment in the bioprinted tissue is anticipated to facilitate the connection between the transplant and the liver.

Success criteria of ArtHep include i) engineering enzyme-mimics, which can perform core biocatalytic conversions similar to the liver, ii) the assembly of biocatalytic active subunits and iii) their encapsulation in cell-like carriers (microreactors), which have mechanical properties that match the liver tissue and that have a camouflaging coating to mimic the surface cues of liver tissue-relevant cells. Finally, matured bioprinted liver-lobules consisting of microreactors and live cells need to connect to liver tissue when transplanted into rats.

ArtHep Team

PhD Students: 

Jarvi Spanjers

Isabella Westensee

Stefan Pendlmayr

Paula De Dios Andres

Lazaros Primpas

Post Docs: 

Dr. Xiaomin Qian

Dr. Noga Gal

Dr. Edit Brodszkij

Dr. Olav Vestrheim

BSc/MSc/Project Students:

Dobroslawa Lewicka (Project student)

Cecilie Ryberg Jensen (BSc thesis)

Catarina Cavalheiro Fernandes (Project and MSc thesis)

Steffen Friis Holleufer (BSc thesis)

Publications

Distinct Network Morphologies from In Situ Polymerization of Microtubules in Giant Polymer-Lipid Hybrid Vesicles, P. De Dios Andres, M. Akter, C. Ryberg, B. Städler, A. P. Liu, ADV. BIOLOGY 2025, early view

Cell Membrane Vesicle Camouflaged Artificial Cells, P. De Dios Andres, S. Pendlmayr, N. Gal, C. Abild Meyer, C. Ryberg, O. Vestrheim, N. A. Kalacas, F. Demir, M. M. Rinschen, K. Haupt, R. P. Mookerjee, B. Städler, ADV. FUNCT. MATER. 2025, early view

Construction of Liposome‐Based Extracellular Artificial Organelles on Individual Living Cells, S. Yang, W. Youn, H. Bin Rheem, S. Yeong Han, N. Kim, S. Han, P. Schattling, B. Städler, I. S. Choi, ANGEW. CHEM. INT. ED. 2025, 64, e202415823

Engineered Lipids for Intracellular Reactive Oxygen Species Scavenging in Steatotic Hepatocytes, I. N. Westensee, P. de Dios Andres, E. Brodszkij, P.-L. Descours, D. Perez-Rodriguez, A. Spinazzola, R. Prosad Mookerjee, B. Städler, SMALL, 2024, 20, 2400816

Advances in Block Copolymer-Phospholipid Hybrid Vesicles: From Physical-Chemical Properties to Applications, E. Brodszkij, B. Städler, CHEM. SCI., 2024, 15, 10724-10744

Poly(Sitosterol)-Based Hydrophobic Blocks in Amphiphilic Block Copolymers for the Assembly of Hybrid Vesicles, E. Brodszkij, C. Ryberg, J. A. Lyons, D. Wilkens Juhl, N. Chr. Nielsen, N. I. Sigalas, A. V. Lyulin, J. Skov Pedersen, B. Städler, SMALL, 2024, 20, 2401934

Light-Activated 3D Printed Fish-Like Actuator, S. Pendlmayr, M. A. Ramos-Docampo, D. H. Bento, E. Brodszkij, D. Wilkens Juhl, N. Chr. Nielsen, B. Städler, J. APPL. POLYM. SCI., 2024, 141, e55746

From Single-Compartment Artificial Cells to Tissue-Like Materials, I. N. Westensee, P. de Dios Andres, B. Städler*, ADV. MATER. TECHNOL., 2024, 9, 2301804

Artificial Cells And HepG2 Cells in 3D Bioprinted Arrangements, I. N. Westensee, L. Paffen, S. Pendlmayr, P. de Dios Andres, M. A. Ramos Docampo, B. Städler, ADV. HEALTHCARE MATER., 2024, 13, 2303699

Antioxidant Microgels Support Peroxide-Challenged Hepatic Cells, I. N. Westensee, K. L. Thomsen, R. P. Mookerjee, B. Städler, ADV. BIOLOGY, 2024, e2300547-e2300547

Artificial Cells Eavesdropping on HepG2 Cells, I. Westensee, B. Städler, INTERFACE FOCUS, 2023, 13, 202300078

Editorial for the Special Issue ‘Synthetic Biology and Biomimicry', A. N. Zelikin, E. S. Andersen, B. Städler, SMALL, 2023, 19, 2301160

Astrocytes in Paper Chips and Their Interaction with Hybrid Vesicles, Cathrine Abild Meyer, Paula De Dios Andres, Edit Brodszkij, Isabella N Westensee, Joseph Lyons, Sandra H. Vaz, Brigitte Städler, ADV. BIOLOGY, 2023, 7, 2200209

On the Assembly of Zwitterionic Block Copolymers with Phospholipids, Jarvi M. Spanjers, Edit Brodszkij, Noga Gal, Jan Skov Pedersen, Brigitte Städler,  EUR. POLYM. J., 2022, 180, 111612

Membrane Composition of Polymer/Lipid Hybrid Vesicles, Edit Brodszkij, Isabella Nymann Westensee, Steffen Friis Holleufer, Carina  Ade, Paula De Dios Andres, Jan Skov Pedersen, Brigitte Städler, APPL. MATER. TODAY, 2022, 29, 101549

Manganese Dioxide Nanosheet-Containing Reactors as Antioxidant Support for Neuroblastoma Cells, Oksana K. Savchak, Nanying Wang, Miguel  A. Ramos-Docampo, Paula de Dios Andres, Ana M. Sebastião, F. F. Ribeiro, Adam Armada-Moreira, Brigitte Städler, Sandra H. Vaz, J. MATER. CHEM. B, 2022, 10, 4672-4683

Nitric Oxide Producing Artificial Enzymes based on Metalloporphyrins, Xiaomin Qian, Miguel A.Ramos-Docampo, Carine Ade, Edit Brodszkij, Isabella N.Westensee, and Brigitte Städler, MATER. TODAY CHEM. 2022, 23, 100743

Polymer Micelles vs Polymer–Lipid Hybrid Vesicles: A Comparison Using RAW 264.7 Cells, Carina Ade, Xiaomin Qian, Edit Brodszkij, Paula De Dios Andres, Järvi Spanjers, Isabella N. Westensee, Brigitte Städler, BIOMACROMOLECULES, 2022, 23, 1052–1064

Enzyme Mimic Facilitated Artificial Cell to Mammalian Cell Signal Transfer, Xiaomin Qian, Isabella Nymann Westensee, Catarina Cavalheiro Fernandes, Brigitte Städler, ANGEW. CHEM. INT. ED. 2021, 133, 18852-18859

Mitochondria Encapsulation in Hydrogel-Based Artificial Cells as ATP Producing Subunits, Isabella Nymann Westensee, Edit Brodszkij, Xiaomin Qian, Thaís Floriano Marcelino, Konstantinos Lefkimmiatis, Brigitte Städler, SMALL, 2021, 17, 2007959

Cell Mimicry as a Bottom‐Up Strategy for Hierarchical Engineering of Nature‐Inspired Entities, Xiaomin Qian, Isabella Nymann Westensee, Edit Brodszkij, Brigitte Städler, WIREs NANOMEDICINE AND NANOBIOTECHNOLOGY, 2021, 13, e1683  

Cell Membrane Coated Particles, Järvi M. Spanjers,  Brigitte Städler,  ADV. BIOSYSTEMS, 2020, doi: 10.1002/adbi.202000174

Artificial Biology: Molecular Design and Cell Mimicry (Editorial), Alexander Zelikin,  Brigitte Städler, SMALL, 2020, 16, 2003442

Polymer–Lipid Hybrid Vesicles and Their Interaction with HepG2 Cells, Edit Brodszkij, Isabella N. Westensee, Mathias Bertelsen, Noga Gal, Thomas Boesen, Brigitte Städler, SMALL, 2020, 16, 1906493

Interaction of pH-Responsive Polyanions with Phospholipid Membranes, Edit Brodszkij, Martin Hviid, Carina Ade,  Philipp Schattling, Moritz Burmeister, Sven Szilagyi, Noga Gal, Chuntao Zhu, Xiaojun Han, Brigitte Städler, POLYM. CHEM. 2019, 10, 5992 - 5997

Hybrid Vesicles as Intracellular Reactive Oxygen Species and Nitric Oxide Generators, Yan Zhang, Noga Gal,  Fabian Itel, Isabella Westensee, Edit Brodszkij, Daniel Mayer, Steffen Spenger, Miquel Castellote-Borrell, Thomas Boesen, Seyed R Tabaei, Fredrik Höök,  Brigitte Städler, NANOSCALE, 2019, 11, 11530 - 11541  

Small Organic Catalase Mimic Encapsulated in Micellar Artificial Organelles as Reactive Oxygen Species Scavengers, Carina Ade, Edit Brodszkij, Bo Thingholm, Noga Gal, Fabian Itel, Essi Taipaleenmäki, Martin Juul Hviid, Philipp S. Schattling, Brigitte Städler, ACS APPL. POLY. MATER, 2019, 1, 1532 - 1539