A synthetic hydrogel niche reveals the interplay of matrix adhesion and mechanics in human epiblast model development

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Yanuar Dwi Putra Limasale - , Max Bergmann Center of Biomaterials Dresden (Author)
  • Passant Atallah - , Max Bergmann Center of Biomaterials Dresden (Author)
  • Andrea Meinhardt - , Max Bergmann Center of Biomaterials Dresden (Author)
  • Ayham Frra - , Max Bergmann Center of Biomaterials Dresden (Author)
  • Aukha Stoppa - , Max Bergmann Center of Biomaterials Dresden (Author)
  • Manfred F. Maitz - , Max Bergmann Center of Biomaterials Dresden (Author)
  • Jens Friedrichs - , Max Bergmann Center of Biomaterials Dresden (Author)
  • Uwe Freudenberg - , Max Bergmann Center of Biomaterials Dresden (Author)
  • Carsten Werner - , Center for Regenerative Therapies Dresden, Clusters of Excellence PoL: Physics of Life, Chair of Biofunctional Polymer Materials, Max Bergmann Center of Biomaterials Dresden (Author)

Abstract

Investigating the role of physical and adhesive matrix cues in human peri -implantation development is hampered by insufficiently defined culture systems, limiting mechanistic understanding. Here, we use a rationally designed matrix metalloproteinase (MMP)-cleavable glycosaminoglycan-based hydrogel system with orthogonally tunable stiffness and adhesiveness to systematically dissect the exogenous control of epiblast morphogenesis in an induced pluripotent stem cell (iPSC)-based model system. A Design of Experiments (DoE) approach reveals that matrix adhesiveness is the primary factor governing iPSC survival, outweighing the influence of stiffness. We further reveal that adhesive ligand presentation, matrix stiffness, and prolonged Rho-associated protein kinase (ROCK) inhibition cooperatively drive the self-organization of iPSCs into lumenized structures with apicobasal polarity. The resulting epiblast models maintain pluripotency and trilineage differentiation potential. Importantly, pluripotency maintenance and morphogenetic competence are partially decoupled, with matrix properties more strongly influencing morphogenesis than pluripotency among viable cells. In sum, our work establishes a defined platform to decouple the interplay of matrix mechanics and adhesion, revealing how their coordination with intracellular signaling controls early epiblast development and providing design principles for engineering synthetic microenvironments that recapitulate developmental processes.

Details

Original languageEnglish
Pages (from-to)269-281
Number of pages13
JournalMaterials today
Volume92
Early online date18 Dec 2025
Publication statusPublished - Jan 2026
Peer-reviewedYes

External IDs

ORCID /0000-0003-0189-3448/work/201621565

Keywords

Keywords

  • Epiblast morphogenesis, Glycosaminoglycans, Hydrogels, Induced pluripotent stem cells, Lumenogenesis, Matrix stiffness, ROCK inhibition