A 3D Human Bone and Bone Marrow‐on‐a‐Chip Model for In Vitro Bone Remodeling and Immune Cell Maintenance
Source abstract
Abstract
ABSTRACT We developed a human Bone‐on‐a‐Chip (BOAC) model that integrates autologous primary immune and bone cells on native human bone substrates within a xeno‐free, perfused environment. In contrast to existing models, which focus primarily on hematopoietic or stromal compartments, our system recapitulates key aspects of functional bone remodeling and enables the maintenance of mature immune cells (up to 42 days), with preserved functional responsiveness at defined time points during culture. Dynamic flow and sequential cell seeding facilitated osteoclast‐mediated resorption, osteoblast‐driven matrix formation, and the maintenance of donor‐specific immune profiles over extended culture periods. The balance between bone cell activity and immune cell persistence was further optimized by controlled temperature modulation. The BOAC model preserves key features of bone and bone marrow physiology, including extracellular matrix formation, soluble factor signaling, and cellular heterogeneity. The bone scaffold provides a physiologically relevant 3D architecture derived from decellularized human trabecular bone. Single‐nucleus RNA sequencing confirmed the presence of major donor‐specific immune and bone cell populations. This 3D human in vitro system provides a robust platform for translational research and personalized medicine.
Source: crossref · Quality: baseline
Research context
OpenAlex topics: 3D Printing in Biomedical Research · Bone Tissue Engineering Materials · Bone Metabolism and Diseases
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
BIH‐Center for Regenerative Therapies Berlin Institute of Health at Charité‐Universitätsmedizin Berlin Berlin Germany
Julius Wolff Institute Berlin Institute of Health at Charité‐Universitätsmedizin Berlin Berlin Germany
Technische Universität Berlin Berlin Germany
Institute of Medical Biochemistry Medical University Innsbruck Austria
Institute of Human Genetics Universitätsklinikum Schleswig‐Holstein (UKSH) University of Lübeck and University of Kiel Lübeck Germany
Xploraytion GmbH Berlin Germany
Freie Universität Berlin Berlin Germany
Wyss Institute for Biologically Inspired Engineering Harvard University Boston Massachusetts USA
Center for Orthopaedics Trauma Surgery and Rehabilitation Medicine University Medicine Greifswald Greifswald Germany
TissUse GmbH Berlin Germany
Institute for Medical Genetics and Human Genetics Charité – Universitätsmedizin Berlin Berlin Germany
Max Planck Institute for Molecular Genetics Berlin Germany
Institute of Human Genetics University Medical Center Göttingen Göttingen Germany
Center for Musculoskeletal Surgery Charité‐Universitätsmedizin Berlin Berlin Germany
Human Molecular Genetics Group Max Planck Institute for Molecular Genetics Berlin Germany
DZHK e.V. (German Center for Cardiovascular Research) Partner Site Hamburg/Kiel/Lübeck Germany
Funding
European Health and Digital Executive Agency
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