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4D Biofabrication of Magnetically Augmented Callus Assembloid Implants Enables Rapid Endochondral Ossification via Activation of Mechanosensitive Pathways
https://orcid.org/0000-0002-1800-534X
https://orcid.org/0000-0003-2275-3348
https://orcid.org/0000-0003-2541-8983
https://orcid.org/0009-0009-7752-8608
https://orcid.org/0000-0003-4811-3787
https://orcid.org/0000-0002-9602-4933
https://orcid.org/0000-0003-3903-2678
https://orcid.org/0000-0003-4633-2724
https://orcid.org/0000-0003-1700-1053
https://orcid.org/0000-0001-7187-5128
https://orcid.org/0000-0002-7687-4498
https://orcid.org/0000-0001-8753-781X
https://orcid.org/0000-0001-7424-5543
https://orcid.org/0000-0002-4754-5492
AbstractThe use of magnetic‐driven strategies for non‐contact manipulation of engineered living modules opens up new possibilities for tissue engineering. The integration of magnetic nanoparticles (MNPs) with cartilaginous microtissues enables model‐driven 4D bottom‐up biofabrication of remotely actuated assembloids, providing unique properties to mechanoresponsive tissues, particularly skeletal constructs. However, for clinical use, the long‐term effects of magnetic stimulation on phenotype and in vivo functionality need further exploration. Magnetic‐driven biofabrication includes both rapid processes, such as guided microtissue assembly, and slower biological processes, like extracellular matrix secretion. This work explores the interplay between magnetic fields and MNP‐loaded cartilaginous microtissues through mathematical modeling and experimental approaches, investigating long‐term stimulation effects on ECM maturation and chondrogenic hypertrophy. Transcriptomic analysis reveal that magnetic stimulation activated mechanosensitive pathways and catabolic processes, driving accelerated cartilage‐to‐bone transitions via endochondral ossification, outcomes not observed in non‐stimulated controls. This study paves the way for pre‐programmed, remotely actuated skeletal assembloids with superior bone‐forming capacity for regenerating challenging bone fractures.
4D Biofabrication of Magnetically Augmented Callus Assembloid Implants Enables Rapid Endochondral Ossification via Activation of Mechanosensitive Pathways
https://orcid.org/0000-0002-1800-534X
https://orcid.org/0000-0003-2275-3348
https://orcid.org/0000-0003-2541-8983
https://orcid.org/0009-0009-7752-8608
https://orcid.org/0000-0003-4811-3787
https://orcid.org/0000-0002-9602-4933
https://orcid.org/0000-0003-3903-2678
https://orcid.org/0000-0003-4633-2724
https://orcid.org/0000-0003-1700-1053
https://orcid.org/0000-0001-7187-5128
https://orcid.org/0000-0002-7687-4498
https://orcid.org/0000-0001-8753-781X
https://orcid.org/0000-0001-7424-5543
https://orcid.org/0000-0002-4754-5492
AbstractThe use of magnetic‐driven strategies for non‐contact manipulation of engineered living modules opens up new possibilities for tissue engineering. The integration of magnetic nanoparticles (MNPs) with cartilaginous microtissues enables model‐driven 4D bottom‐up biofabrication of remotely actuated assembloids, providing unique properties to mechanoresponsive tissues, particularly skeletal constructs. However, for clinical use, the long‐term effects of magnetic stimulation on phenotype and in vivo functionality need further exploration. Magnetic‐driven biofabrication includes both rapid processes, such as guided microtissue assembly, and slower biological processes, like extracellular matrix secretion. This work explores the interplay between magnetic fields and MNP‐loaded cartilaginous microtissues through mathematical modeling and experimental approaches, investigating long‐term stimulation effects on ECM maturation and chondrogenic hypertrophy. Transcriptomic analysis reveal that magnetic stimulation activated mechanosensitive pathways and catabolic processes, driving accelerated cartilage‐to‐bone transitions via endochondral ossification, outcomes not observed in non‐stimulated controls. This study paves the way for pre‐programmed, remotely actuated skeletal assembloids with superior bone‐forming capacity for regenerating challenging bone fractures.
4D Biofabrication of Magnetically Augmented Callus Assembloid Implants Enables Rapid Endochondral Ossification via Activation of Mechanosensitive Pathways
https://orcid.org/0000-0002-1800-534X
https://orcid.org/0000-0003-2275-3348
https://orcid.org/0000-0003-2541-8983
https://orcid.org/0009-0009-7752-8608
https://orcid.org/0000-0003-4811-3787
https://orcid.org/0000-0002-9602-4933
https://orcid.org/0000-0003-3903-2678
https://orcid.org/0000-0003-4633-2724
https://orcid.org/0000-0003-1700-1053
https://orcid.org/0000-0001-7187-5128
https://orcid.org/0000-0002-7687-4498
https://orcid.org/0000-0001-8753-781X
https://orcid.org/0000-0001-7424-5543
https://orcid.org/0000-0002-4754-5492
AbstractThe use of magnetic‐driven strategies for non‐contact manipulation of engineered living modules opens up new possibilities for tissue engineering. The integration of magnetic nanoparticles (MNPs) with cartilaginous microtissues enables model‐driven 4D bottom‐up biofabrication of remotely actuated assembloids, providing unique properties to mechanoresponsive tissues, particularly skeletal constructs. However, for clinical use, the long‐term effects of magnetic stimulation on phenotype and in vivo functionality need further exploration. Magnetic‐driven biofabrication includes both rapid processes, such as guided microtissue assembly, and slower biological processes, like extracellular matrix secretion. This work explores the interplay between magnetic fields and MNP‐loaded cartilaginous microtissues through mathematical modeling and experimental approaches, investigating long‐term stimulation effects on ECM maturation and chondrogenic hypertrophy. Transcriptomic analysis reveal that magnetic stimulation activated mechanosensitive pathways and catabolic processes, driving accelerated cartilage‐to‐bone transitions via endochondral ossification, outcomes not observed in non‐stimulated controls. This study paves the way for pre‐programmed, remotely actuated skeletal assembloids with superior bone‐forming capacity for regenerating challenging bone fractures.
4D Biofabrication of Magnetically Augmented Callus Assembloid Implants Enables Rapid Endochondral Ossification via Activation of Mechanosensitive Pathways
Advanced Science
Ioannidis, Konstantinos (author) / Dimopoulos, Andreas (author) / Decoene, Isaak (author) / Guilliams, Maya (author) / Svitina, Hanna (author) / Storozhuk, Liudmyla (author) / de Oliveira‐Silva, Rodrigo (author) / Basov, Sergey (author) / Thanh, Nguyen Thi Kim (author) / Mourdikoudis, Stefanos (author)
2025-02-25
Article (Journal)
Electronic Resource
English