Expanding the matrix space – modulating growth factor signals by cell instructive GAG-peptide hydrogels with customizable viscoelastic properties

This project developed a predictive strategy to engineer multicomponent hydrogels that mimic key features of the extracellular matrix (ECM). We combined self‑assembling peptides with sulfated glycosaminoglycans (GAGs) which bind and present growth factors. By systematically varying the peptide sequence (aromaticity and charge) and GAG sulfation, we established rules that link molecular design to how the materials assemble, how stiff they are, and how they dissipate stress—properties that strongly affect cells. A notable discovery is that sufficiently sulfated GAGs can drive a “coil‑to‑β‑sheet” transition in weakly assembling peptides, acting as an assembly cofactor to trigger gelation and expand the tunable design space. The resulting hydrogels cover a broad, tissue‑relevant stiffness range and exhibit rapid, ECM‑like stress relaxation. We applied these materials to human hematopoietic stem cells (HSCs), which are essential for transplantation but difficult to expand outside the body. Using Design of Experiments (DoE) and regression modeling, we identified net negative matrix charge and an optimal heparin content as critical for homogeneous gels and robust HSC survival and expansion. The optimized formulation maintained primitive stem cell subsets and functional colony‑forming potential. This work provides a materials‑by‑design framework to program peptide–GAG interfaces for regenerative medicine, with potential applications in stem cell culture, organoids, and protein delivery. Zusammenfassung auf Deutsch: