Mechanotopography-Driven Design of Dispersible Nanofiber-Laden Hydrogel as a 3D Cell Culture Platform for Investigating Tissue Fibrosis

Abstract

Fibrosis is one of the most frequent occurrences during one's lifetime, identified by various physiological changes including, most notably, excessive deposition of extracellular matrix (ECM). Despite its physiological importance, it is still a significant challenge to conduct a systematic investigation of tissue fibrosis, mainly due to the lack of in vitro 3D tissue model that can accurately portray the characteristic features of fibrotic events. Herein, a hybrid hydrogel system incorporating dispersible nanofibers is developed to emulate highly collagenous deposits formed within a fibrotic tissue leading to altered mechanotopographical properties. Micrometer-length, aqueous-stable nanofibers consisting of crosslinked gelatin network embedded with graphene oxide (GO) or reduced graphene (rGO) are infused into hydrogel, resulting in controllable mechanotopographical properties while maintaining permeability sufficiently enough for various cellular activities. Ultimately, the ability to induce fibrotic behavior of fibroblasts cultured in these mechanotopography-controlled, nanofiber-laden hydrogels is investigated in detail.