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Thermoresponsive, Shear-Thinning Supramolecular Hydrogels from Peptide-Polymer Conjugates for Bioinspired 3D Cell Culture

Huntington, B. M.; Dresel, J. A.; Schweitzer, M.; Furst, E. M.; Besenius, P.; Kloxin, A. M.

2026-09-09 bioengineering
10.64898/2026.09.04.749227 bioRxiv
Show abstract

Physically assembled, supramolecular hydrogels often are formed by weak bonds, producing useful viscoelastic properties that are reminiscent of soft tissues within the human body yet presenting challenges in stability under physiological conditions. In this work, we establish an approach for creating self-assembling, supramolecular hydrogels based on a peptide-polymer conjugate (PPC) as a three-dimensional (3D) cell culture platform. The viscoelastic properties of these hydrogels, including thermoresponsiveness and shear-thinning, were measured using rheometry. Building on these observations, we then developed a method for the encapsulation and culture of human wound healing cells, fibroblasts, within the PPC hydrogels, observing both excellent cell viability and material stability over time. The modulation of stiffness by temperature variation and the reversible nature of these hydrogels imparts unique properties for both cell encapsulation and harvesting and offers potential for a variety of biomedical applications, from 3D cell culture systems to therapeutic delivery.

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