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Pihlamagi, Ceren C. ; Pretzel, David ; Nölte, Peer ; Rezaei, Kourosh ; Schubert, Ulrich S. ; Brendel, Johannes C.:
Bio-Orthogonally Crosslinked Supramolecular Polymer Bottlebrush Hydrogels for Long-Term 3D Cell Culture.
In: Advanced Functional Materials.
Bd. 36
(2026)
Heft 40
.
- e22667.
ISSN 1616-3028
DOI: https://doi.org/10.1002/adfm.202522667
Angaben zu Projekten
| Projekttitel: |
Offizieller Projekttitel Projekt-ID Supramolekulare Polymerbürsten als Wirkstoffträgersysteme – Aufbau definierter und reaktiver Systeme 358263073 Nanostrukturierung reaktiver Polymere – Von funktionellen Wirkstoffträgern zu hierarchisch strukturierten, lebensähnlichen Systemen 517761335 SFB 1278: Polymerbasierte Nanopartikel-Bibliotheken für die Entwicklung zielgerichteter anti-inflammatorischer Strategien 316213987 Open Access Publizieren Ohne Angabe |
|---|---|
| Projektfinanzierung: |
Deutsche Forschungsgemeinschaft |
Abstract
The native extracellular matrix (ECM) comprises fibrous networks formed by supramolecular assembly of biomacromolecules, which provides cells mechanical support and bioactive cues. As synthetic mimics of ECM, hydrogels made of supramolecular motifs are prospective candidates resembling the fibrous nature of ECM and providing a versatile platform for further functionalization. As recently reported, poly(ethylene oxide) (PEO) modified benzenetrispeptide (BTP) motifs can self-assemble into supramolecular bottlebrush-like fibers and form biocompatible hydrogels when crosslinked. However, previous gelation methods are not suitable for 3D cell encapsulation. Herein, we introduce a bio-orthogonal, strain-promoted azide-alkyne cycloaddition (SPAAC) crosslinking strategy enabling a fast and selective coupling under cell-compatible conditions. The properties of the hydrogels can be tuned by fiber and crosslinking concentrations. Importantly, our design approach enables long-term (up to 10 days) 3D cell culture, although the system is intrinsically bioinert. Deep-learning-assisted image analysis reveals that the fiber content significantly influences cell viability and colony growth across multiple cell lines. Long-term live cell imaging indicates that colony formation occurs by division of single cells rather than the pre-gelation aggregation of individual cells. As a step toward employing BTP hydrogels as ECM mimics, these findings underscore the role of supramolecular design in directing the formation pathways of multicellular assemblies.