Biocompatible Ink Optimization Enables Functional Volumetric Bioprinting With Xolography
Abstract
Abstract Xolography is a novel linear volumetric manufacturing technique that offers unparalleled precision and speed. Yet, its application to bioprinting remains limited due to insufficient understanding of biocompatibility constraints. Here, this work establishes fundamental design principles for cell‐compatible Xolography bioinks by dissecting the effects of extracellular pH, osmolality, and lysosomotropic stress on cell viability and function. By systematically studying the tolerances for these parameters, this work defines a framework for bioink formulations that enables fast, support‐free fabrication of complex designs with maintained cell viability and function as validated in different murine and human cell lines, primary human cells and induced pluripotent stem cell (iPSC)‐derived cells. These results show that, unlike triethanolamine, BisTris indeed can function as a fully biocompatible co‐initiator enabling cell viability beyond 90% as well as uncompromised metabolic activity and differentiation performance when used in a tightly controlled formulation, contrasting previous reports. This work showcases the biomedical potential of the formulation by achieving fibroblast‐driven extracellular matrix (ECM) formation, endothelial sprouting from pre‐vascularized spheroids, and maintenance of an iPSC‐derived hepatocyte differentiation phenotype within Xolography‐printed constructs. These advancements transform Xolography into a powerful and foremost reliable bioprinting platform for fabrication of complex, cell‐laden structures for versatile applications in tissue engineering, organ‐on‐a‐chip models, and regenerative medicine.
Article Details
Authors (18)
Erik Brauer
Center for the Science of Materials Berlin (CSMB) and Department of Chemistry Humboldt University 12489 Berlin Germany
Aiste Balciunaite
Soft Robotics Laboratory Department of Mechanical and Process Engineering ETH Zurich Tannenstrasse 3 Zurich 8092 Switzerland
Matthias R. Kollert
Berlin Institute of Health at Charité – Universitätsmedizin Berlin Julius Wolff Institute – Center for Musculoskeletal Biomechanics and Regeneration 13353 Berlin Germany
Julian Weihs
Department of Pediatrics Division of Gastroenterology Nephrology and Metabolic Medicine Charité – Universitätsmedizin Berlin 13353 Berlin Germany
Raphael S. Knecht
Berlin Institute of Health at Charité – Universitätsmedizin Berlin Julius Wolff Institute – Center for Musculoskeletal Biomechanics and Regeneration 13353 Berlin Germany
Rose Behncke
Berlin Institute of Health at Charité – Universitätsmedizin Berlin BIH Center for Regenerative Therapies (BCRT) 13353 Berlin Germany
Susanna Quach
Department of Pediatrics Division of Gastroenterology Nephrology and Metabolic Medicine Charité – Universitätsmedizin Berlin 13353 Berlin Germany
Niklas Felix König
xolo GmbH 12489 Berlin Germany
Asia Badolato
Soft Robotics Laboratory Department of Mechanical and Process Engineering ETH Zurich Tannenstrasse 3 Zurich 8092 Switzerland
Stella Monestier
Regenerative Medicine Division Institute for Translational Research (IRT) Faculty of Biomedical Sciences Università della Svizzera italiana and Ente Ospedaliero Cantonale Via Chiesa 5 6900 Bellinzona Switzerland
Simone Bersini
Regenerative Medicine Division Institute for Translational Research (IRT) Faculty of Biomedical Sciences Università della Svizzera italiana and Ente Ospedaliero Cantonale Via Chiesa 5 6900 Bellinzona Switzerland
Matteo Moretti
Miriam Filippi
Soft Robotics Laboratory Department of Mechanical and Process Engineering ETH Zurich Tannenstrasse 3 Zurich 8092 Switzerland
René Hägerling
Berlin Institute of Health at Charité – Universitätsmedizin Berlin BIH Center for Regenerative Therapies (BCRT) 13353 Berlin Germany
Milad Rezvani
Berlin Institute of Health at Charité – Universitätsmedizin Berlin BIH Center for Regenerative Therapies (BCRT) 13353 Berlin Germany
Stefan Hecht
Department of Chemistry and Center for the Science of Materials Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
Ansgar Petersen
Berlin Institute of Health at Charité – Universitätsmedizin Berlin Julius Wolff Institute – Center for Musculoskeletal Biomechanics and Regeneration 13353 Berlin Germany
Robert K. Katzschmann
Soft Robotics Laboratory Department of Mechanical and Process Engineering ETH Zurich Tannenstrasse 3 Zurich 8092 Switzerland