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Jäkel, A.C.* ; Truong, D.J.J. ; Simmel, F.C.*

Genetic manipulation of mammalian cells in microphysiological hydrogels.

Adv. Sci., DOI: 10.1002/advs.202505474:e05474 (2025)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Engineering functional 3D tissue constructs is essential for developing advanced organ-like systems, with applications ranging from fundamental biological research to drug testing. The generation of complex multicellular structures requires the integration of external geometric and mechanical cues with the ability to activate genetic programs that regulate and stimulate cellular self-organization. Here, it is demonstrated that gelatin methacryloyl (GelMA) hydrogels serve as effective matrices for 3D cell culture, supporting both in situ genetic manipulation and cell growth. HEK293T cells embedded in GelMA remained viable and proliferated over 16 days, forming clusters within the matrix. Efficient gene delivery is achieved in the 3D hydrogel environment using both plasmid DNA and mRNA as gene vectors. Furthermore, in situ prime editing is applied to induce permanent genetic modifications in embedded cells. To achieve spatially confined gene expression, gel-embedded channels are introduced that allowed localized stimulation via doxycycline perfusion through a Tet-On system. These findings demonstrate the feasibility of integrating gene delivery, inducible expression, and spatial control within GelMA-based hydrogels, establishing a versatile framework for engineered 3D cell systems with programmable genetic activity.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter 3d Cell Culture ; Genome Editing ; Hydrogels ; Tissue Engineering ; Transfection ; Vascular Channels; Thick; Tetracyclines; Transfection
Sprache englisch
Veröffentlichungsjahr 2025
HGF-Berichtsjahr 2025
ISSN (print) / ISBN 2198-3844
e-ISSN 2198-3844
Zeitschrift Advanced science
Quellenangaben Band: , Heft: , Seiten: , Artikelnummer: e05474 Supplement: ,
Verlag Wiley
Verlagsort Weinheim
Begutachtungsstatus Peer reviewed
Institut(e) Insitute of Synthetic Biomedicine (ISBM)
POF Topic(s) 30205 - Bioengineering and Digital Health
Forschungsfeld(er) Enabling and Novel Technologies
PSP-Element(e) G-509300-001
Förderungen Bayrisches Staatsministerium für Forschung und Kunst : ONE MUNICH Multiscale Biofabrication
Federal Ministry of Education and Research
Scopus ID 105010166526
PubMed ID 40632898
Erfassungsdatum 2025-07-18