Many features of extracellular matrices, e.g., self-healing, adhesiveness, viscoelasticity, and conductivity, are associated with the intricate networks composed of many different covalent and non-covalent chemical bonds. Whereas a reductionism approach would have the limitation to fully recapitulate various biological properties with simple chemical structures, mimicking such sophisticated networks by incorporating many different functional groups in a macromolecular system is synthetically challenging. Herein, we propose a strategy of convergent synthesis of complex polymer networks to produce biomimetic electroconductive liquid metal hydrogels. Four precursors could be individually synthesized in one to two reaction steps and characterized, then assembled to form hydrogel adhesives. The convergent synthesis allows us to combine materials of different natures to generate matrices with high adhesive strength, enhanced electroconductivity, good cytocompatibility in vitro and high biocompatibility in vivo. The reversible networks exhibit self-healing and shear-thinning properties, thus allowing for 3D printing and minimally invasive injection for in vivo experiments.

Synthetic conductive biopolymers have gained increasing interest in tissue engineering, as they can provide a chemically defined electroconductive and biomimetic microenvironment for cells. In addition to low cytotoxicity and high biocompatibility, injectability and adhesiveness are important for many biomedical applications but have proven to be very challenging. Recent results show that fascinating material properties can be realized with a bioinspired hybrid network, especially through the synergy between irreversible covalent crosslinking and reversible noncovalent self‐assembly. Herein, a polysaccharide‐based conductive hydrogel crosslinked through noncovalent and reversible covalent reactions is reported. The hybrid material exhibits rheological properties associated with dynamic networks such as self‐healing and stress relaxation. Moreover, through fine‐tuning the network dynamics by varying covalent/noncovalent crosslinking content and incorporating electroconductive polymers, the resulting materials exhibit electroconductivity and reliable adhesive strength, at a similar range to that of clinically used fibrin glue. The conductive soft adhesives exhibit high cytocompatibility in 2D/3D cell cultures and can promote myogenic differentiation of myoblast cells. The heparin‐containing electroconductive adhesive shows high biocompatibility in immunocompetent mice, both for topical application and as injectable materials. The materials could have utilities in many biomedical applications, especially in the area of cardiovascular diseases and wound dressing.

Conductive hydrogels (CHs) are emerging as a promising and well‐utilized platform for 3D cell culture and tissue engineering to incorporate electron signals as biorelevant physical cues. In conventional covalently crosslinked conductive hydrogels, the network dynamics (e.g., stress relaxation, shear shining, and self‐healing) required for complex cellular functions and many biomedical utilities (e.g., injection) cannot be easily realized. In contrast, dynamic conductive hydrogels (DCHs) are fabricated by dynamic and reversible crosslinks. By allowing for the breaking and reforming of the reversible linkages, DCHs can provide dynamic environments for cellular functions while maintaining matrix integrity. These dynamic materials can mimic some properties of native tissues, making them well‐suited for several biotechnological and medical applications. An overview of the design, synthesis, and engineering of DCHs is presented in this review, focusing on the different dynamic crosslinking mechanisms of DCHs and their biomedical applications.

DNA origami nanostructures are versatile substrates for the single‐molecule investigation of biomolecular interactions as they enable the display of molecular species in complex arrangements. Herein, the fundamental limitations of this approach are explored by displaying pairs of small‐molecule ligands of the protein trypsin on DNA origami substrates and adjusting their ligand–ligand spacing with subnanometer precision. Bidentate binding of trypsin to the ligand pairs is investigated by atomic force microscopy (AFM), microscale thermophoresis (MST), and molecular dynamics simulations. Bidentate trypsin binding is strongly affected by the distance of the ligand pairs and the accessibility of the protein's binding pockets. MST cannot resolve the differences in bidentate trypsin binding because of the nonspecific binding of trypsin to the DNA origami substrates, rendering the AFM‐based single‐molecule detection of binding events superior to ensemble measurements. Finally, even monodentate binding to a single ligand may be affected by subnanometer variations in its position, highlighting the importance of local microenvironments that vary even over molecular distances. While this single‐molecule approach can provide viable information on the effects of ligand arrangements on bidentate protein binding, in‐depth investigations into the nature of local microenvironments will be required to exploit its full potential.