Nano-enabled dynamically responsive living acellular hydrogels†

As a key building block of mammalian tissues, extracellular matrices (ECMs) stiffen under shear deformation and undergo cell-imparted healing after damage, features that regulate cell fate, communication, and survival. The shear-stiffening behavior is attributed to semi-flexible biopolymeric ECM networks. Inspired by the mechanical behavior of ECMs, we develop acellular nanocomposite living hydrogels (LivGels), comprising network-forming biopolymers and anisotropic hairy nanoparticle linkers that mimic the dynamic mechanical properties of living counterparts. We show that a bifunctional dynamic linker nanoparticle (nLinker), bearing semi-flexible aldehyde- and carboxylate-modified cellulose chains attached to rigid cellulose nanocrystals converts bulk hydrogels to ECM-like analogues via ionic and dynamic covalent hydrazone bonds. The nLinker not only enables the manipulation of nonlinear mechanics and stiffness within the biological window, but also imparts self-healing to the LivGels. This work is a step forward in designing living acellular soft materials with complex dynamic properties using bio-based nanotechnology.