Controlling 3D Contractility via Engineered Fibrous Hydrogel Composites

ABSTRACT Complex and dynamic mechanobiological crosstalk occurs between cells and their extracellular matrix (ECM) to support contraction, a process required for tissue morphogenesis and wound healing. In vitro models can be used to study this crosstalk by mimicking the ECM (collagen fibers within a ground substance) using controlled environments and defined mechanics. While useful, most in vitro models utilize poorly‐defined natural hydrogels that lack independent control over hydrogel properties and contraction tunability. Here, a fully‐defined hydrogel composite is introduced consisting of fragmented synthetic fibers (a collagen fiber mimic) that, when embedded within a synthetic hydrogel (a ground substance mimic), supports cell‐mediated traction‐based contraction in a manner similar to traditional collagen gels. Tuning this composite material by modulating fragmented fiber density and length and embedding hydrogel density and crosslinking enables control over contraction. Cells cultured within contraction‐permissive constructs support microtissue cell alignment and local densification of fiber fragments, while culture in contraction‐resistant composites (greater embedding hydrogel crosslinking) do not. This innovative composite material expands our ability to interrogate the complex cell‐ECM interplay during tissue morphogenesis.