Leibniz-Institut für Polymerforschung Dresden e. V.

Glycosaminoglycan-based hydrogels are developed for the sustained administration of soluble signaling molecules (cytokines, chemokines, growth factors, drugs) utilizing extracellular matrix-derived binding principles. The polymer networks are prepared by a theory-driven design concept using variable building blocks and crosslinking strategies to afford independently tunable elasticity, degradability, signal molecule affinity, cell adhesiveness in ways to respond to cell-based or external triggers (enzyme activity, temperature, light or pH). Being used to embed cells, applied via injection to form in situ, and micro-processed by microfluidics, micromolding, cryogelation and printing techniques, customized hydrogel variants enable a broad range of new therapeutic concepts.

Seth, P., Friedrichs, J., Limasale, Y. D. P., Fertala, N., Freudenberg, U., Zhang, Y., Lampel, A., Werner, C. Interpenetrating polymer network hydrogels with tunable viscoelasticity and proteolytic cleavability to direct stem cells in vitro. Advanced Healthcare Materials 2402656 (2024).

Limasale, Y. D. P., Fusenig, M., Samulowitz, M., Atallah, P. M., Sievers, J., Dennison, N., Freudenberg, U., Friedrichs, J., Werner, C. Glycosaminoglycan concentration and sulfation patterns of biohybrid polymer matrices direct microvascular network formation and stability. Advanced Functional Materials 34, 2411475 (2024).

Freudenberg, U., Atallah, P., Sommer, J.-U., Werner, C., Ballauff, M. Analysis of the binding of cytokines to highly charged polymer networks.  Macromolecular Bioscience 23, 2200561 (2023).

Sievers, J., Zimmermann, R., Friedrichs, J., Pette, D., Limasale, Y. D. P., Werner, C., Welzel, P. B. Customizing biohybrid cryogels to serve as ready-to-use delivery systems of signaling proteins Biomaterials 278, 121170 (2021).

Decellularized extracellular matrices (ECM) derived from tissue, organs or cell cultures are prepared to faithfully reproduce specific cellular microenvironments in vitro. Macromolecular crowding conditions as well as customized decellularization and processing/re-assembly protocols are developed and applied to tune structural and compositional features of fibrillar biopolymer matrix types.

Magno V., Werner C. Tissue-derived decellularized materials for biomedical applications. in: Handbook of the Extracellular Matrix: Biologically-Derived Materials / F. R. Maia, J. M. Oliveira, R. L. Reis (Eds.). Cham: Springer, 841-873; ISBN: 978-3-031-56362-1 (2024).

Martínez-Vidal, L., Magno, V., Welzel, P. B., Friedrichs, J., Bornhäuser, M., Werner, C. Combining cryogel architecture and macromolecular crowding-enhanced extracellular matrix cues to mimic the bone marrow niche. Macromolecular Chemistry and Physics 224, 2200348 (2023).

Magno V., Friedrichs J., Weber H.M., Prewitz M.C., Tsurkan M.V., Werner C. Macromolecular crowding for tailoring tissue-derived fibrillated matrices. Acta Biomaterialia 55, 109-119 (2017).

Kräter M., Jacobi A., Otto O., Tietze S., Müller K., Biehain U., Palm U., Zinna V., Wobus M., Chavakis T., Werner C., Bornhäuser M. Bone marrow niche-mimetics modulate HSPC function via integrin signaling. Scientific Reports 7, 2549 (2017).

Cell-instructive polymer matrices offer unprecedented options to reproduce tissue development, homeostasis and regeneration as well as pathologic scenarios based on 3D co- or organoid cultures in vitro. By adjusting the hydrogel’s degradability and stiffness, and decorating it with selected adhesive peptides to mimic the native ECM environment the polymer matrices can be adapted towards each cellular need. Sulfated glycosaminoglycans (GAGs) possess the unique ability to modulate morphogen gradients in vitro, thereby directing cell morphogenesis and growth leading to the formation of 3D vascular and renal tubular networks as well as the reconstruction of tissue-specific (bone marrow) stem cell niches. Multiphasic and graded materials made out of the GAG-containing hydrogels are being applied in combinatorial approaches aiming at guiding 3D organoid growth, such as kidney or cancer organoids.

Kühn, S., Magno, V., Zimmermann, R., Limasale, Y. D. P., Atallah, P. M., Stoppa, A., Männel, M. J., Thiele, J., Friedrichs, J., Freudenberg, U., Werner, C. Microgels with electrostatically controlled molecular affinity to direct morphogenesis. Advanced Materials 2409731 (2024).

Dennison, N. R., Fusenig, M., Grönnert, L., Maitz, M. F., Ramirez Martinez, M. A., Wobus, M., Freudenberg, U., Bornhäuser, M., Friedrichs, J., Westenskow, P. D., Werner, C. Precision culture scaling to establish high-throughput vasculogenesis models. Advanced Healthcare Materials 13, 2400388 (2024).

Sievers, J., Mahajan, V., Welzel, P.B., Werner, C., Taubenberger, A. Precision hydrogels for the study of cancer cell mechanobiology. Advanced Healtchare Materials 12, 2202514 (2023).

Magno V., Meinhardt A., Werner C. Polymer hydrogels to guide organotypic and organoid cultures.  Advanced Functional Materials 30, 2000097 (2020).

Husman D., Welzel P. B., Vogler S., Bray L., Träber N., Friedrichs J., Körber V., Tsurkan M.V., Freudenberg U., Thiele J., Werner C. Multiphasic microgel-in-gel materials to recapitulate cellular mesoenvironments in vitro. Biomaterials Science 1, 101-108 (2020).