Regarding synthetic self-healing materials, as healing reactions occur at the molecular level, bond formation occurs when healing chemicals are nanometer distances apart. However, motility of healing chemicals in materials is quite limited, permitting only passive diffusion, which reduces the chance of bond formation. By contrast, biological-tissues exhibit significant high-performance self-healing, and cadherin-mediated cell−cell adhesion is a key mechanism in the healing process. This is because cells are capable of a certain level of motility and actively migrate to damage sites, thereby achieving cell−cell adhesion with high efficacy. Here, we report biological-tissue-inspired, self-healing hydrogels in which azide-modified living cells are covalently cross-linked with alkyne-modified alginate polymers via bioorthogonal reactions. As a proof-of-concept, we demonstrate their unique self-healing capabilities originating from cadherin-mediated adhesion between cells incorporated into the gels as mobile healing mechanism. This study provides an example of self-healing material incorporating living components into a synthetic material to promote self-healing.

Development of nanomaterials that surely transport functional biomacromolecules and bioactive synthetic compounds into the cell nucleus must be promising for the generation of nuclear‐targeting new technologies. However, the development of nuclear transporting nanomaterials thus still remains a significant challenge, because molecular transport between the cytoplasm and the nucleus of a eukaryotic cell is strictly regulated by the sole gateway through the nuclear envelope, the nuclear pore complexes (NPCs). Here, the rational design of novel artificial nuclear nanotransporters (NucPorters), inspired by importin, naturally occurring nuclear transporters is shown. The NucPorter is generated by simple molecular design: self‐assembly of amphiphilic polymers, where a few numbers of hydrophobic amino‐acid derivatives with phenyl groups are conjugated to negatively charged hydrophilic heparin. The NucPorter can mimic essential structural and chemical features of importin machinery to pass through the NPCs. Importantly, the NucPorter demonstrates remarkable rapid and high efficient nuclear transport in cultured cells, tissue/organ, and living mice. Moreover, the NucPorter successfully imports both enzymes and synthetic anticancer drugs into the nucleus while maintaining their bioactivity. Thus, the NucPorter provides a promising new route to generate innovative nuclear‐targeting medicines, diagnostics, cell imaging and engineering techniques, and drug delivery systems.

Currently, one of the major tendencies to be adopted for the design of hydrogel scaffolds in tissue engineering include that cells are loaded physically into the pores of 3D hydrogel networks. In this study, a drastic deviation from this tendency is proposed and developed a new type of hydrogel scaffold in which cells are covalently connected to 3D hydrogel networks via bioorthogonal click cross‐linking reactions of azide‐modified cells with alkyne‐modified polymers. The purpose of this study is to directly compare the utility of the covalent cell‐loading approach and the conventional physical cell‐loading approach as hydrogel scaffolds for in vivo tissue engineering. It is found that the proposed covalent cell‐loading approach significantly promotes tissue regeneration and functional recovery in vivo in comparison with the conventional physical cell‐loading approach. This is the first report demonstrating the importance of the covalent cell‐loading approach in tissue engineering. This covalent cell‐loading approach is applicable to a broad spectrum of mammalian cells, including stem cells. The present findings provide a promising new route to generate innovative hydrogel scaffolds for in vivo tissue engineering.

A novel technique to form a thin hydrogel barrier on aberrantly expressed sialic acid residues on cancer cell surfaces was developed.