(691b) Dynamically Responsive Acellular Living Hydrogels

Engineering dynamically responsive hydrogels that emulate the mechanical and biological properties of tissues may enable living soft materials. Most native mammalian tissues consist of non-living extracellular matrices (ECM) and living cell ensembles. As a key building block of mammalian tissues, ECM stiffen under shear deformation and undergo cell-imparted healing upon damage, features that are vital for cell function and tissue survival. Developing multifunctional living hydrogels with dynamic ECM mechanics and self-healing properties remains an ongoing challenge. Inspired by the dynamic mechanical responsiveness of three-dimensional (3D) ECM networks, we engineered an acellular nanocomposite living hydrogels (LivGels), comprising a network-forming semi-flexible biopolymer and bifunctional hairy nanoparticle linkers (nLinker). We showed, for the first time, that the nLinker, bearing semi-flexible aldehyde- and carboxylate-modified cellulose chains attached to rigid cellulose nanocrystals converts static hydrogels to ECM-like analogues via ionic and dynamic covalent hydrazone bonds. The network formation in polymer-nlinker inclusions was tunable via varying nLinker or calcium ions (Ca²⁺)-enriched nLinker concentrations. The non-linear stiffening index (from ~ 0.09 to ~ 0.9), critical stress (from ~ 7 to ~ 290 Pa), and storage modulus (from ~ 30 to ~ 1700 Pa) of LivGels were engineered within the biological window, independent of the matrix biopolymer concentration. The strain-stiffening LivGels underwent prompt recovery under cyclic low (1%)-high (500%) strains. Overall, this work presents a novel bio-based nanotechnology for engineering acellular hydrogels that mimic ECM, which may enable transformative functional materials which would otherwise be impossible to accomplish without living components and extreme conditions.