pH-Responsive Reversible Granular Hydrogels Based on Metal-Binding Mussel-Inspired Peptides.

Taking advantage of their thixotropic behavior, microporosity, and modular properties, granular hydrogels formed from jammed hydrogel microparticles have emerged as an exciting class of soft, injectable materials useful for numerous applications, ranging from the production of biomedical scaffolds for tissue repair to the therapeutic delivery of drugs and cells. Recently, the annealing of hydrogel microparticles in situ to yield a porous bulk scaffold has shown numerous benefits in regenerative medicine, including tissue-repair applications. Current annealing techniques, however, mainly rely either on covalent connections, which produce static scaffolds, or transient supramolecular interactions, which produce dynamic but mechanically weak hydrogels. To address these limitations, we developed microgels functionalized with peptides inspired by the histidine-rich cross-linking domains of marine mussel byssus proteins. Functionalized microgels can reversibly aggregate in situ via metal coordination cross-linking to form microporous, self-healing, and resilient scaffolds at physiological conditions by inclusion of minimal amounts of zinc ions at basic pH. Aggregated granular hydrogels can subsequently be dissociated in the presence of a metal chelator or under acidic conditions. Based on the demonstrated cytocompatibility of these annealed granular hydrogel scaffolds, we believe that these materials could be developed toward applications in regenerative medicine and tissue engineering.

Small Molecule-Templated DNA Hydrogel with Record Stiffness Integrates and Releases DNA Nanostructures and Gene Silencing Nucleic Acids.

Deoxyribonucleic acid (DNA) hydrogels are a unique class of programmable, biocompatible materials able to respond to complex stimuli, making them valuable in drug delivery, analyte detection, cell growth, and shape-memory materials. However, unmodified DNA hydrogels in the literature are very soft, rarely reaching a storage modulus of 103  Pa, and they lack functionality, limiting their applications. Here, a DNA/small-molecule motif to create stiff hydrogels from unmodified DNA, reaching 105  Pa in storage modulus is used. The motif consists of an interaction between polyadenine and cyanuric acid-which has 3-thymine like faces-into multimicrometer supramolecular fibers. The mechanical properties of these hydrogels are readily tuned, they are self-healing and thixotropic. They integrate a high density of small, nontoxic molecules, and are functionalized simply by varying the molecule sidechain. They respond to three independent stimuli, including a small molecule stimulus. These stimuli are used to integrate and release DNA wireframe and DNA origami nanostructures within the hydrogel. The hydrogel is applied as an injectable delivery vector, releasing an antisense oligonucleotide in cells, and increasing its gene silencing efficacy. This work provides tunable, stimuli-responsive, exceptionally stiff all-DNA hydrogels from simple sequences, extending these materials' capabilities.