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Current hyaluronic acid (HA) hydrogel systems often cause cytotoxicity to encapsulated cells and lack the adhesive property required for effective localization of transplanted cells in vivo. In addition, the injection of hydrogel into certain organs (e.g., liver, heart) induces tissue damage and hemorrhage. In this study, we describe a bioinspired, tissue-adhesive hydrogel that overcomes the limitations of current HA hydrogels through its improved biocompatibility and potential for minimally invasive cell transplantation. HA functionalized with an adhesive catecholamine motif of mussel foot protein forms HA-catechol (HA-CA) hydrogel via oxidative crosslinking. HA-CA hydrogel increases viability, reduces apoptosis, and enhances the function of two types of cells (human adipose-derived stem cells and hepatocytes) compared with a typical HA hydrogel crosslinked by photopolymerization. Due to the strong tissue adhesiveness of the HA-CA hydrogel, cells are easily and efficiently transplanted onto various tissues (e.g., liver and heart) without the need for injection. Stem cell therapy using the HA-CA hydrogel increases angiogenesis in vivo, leading to improved treatment of ischemic diseases. HA-CA hydrogel also improved hepatic functions of transplanted hepatocytes in vivo. Thus, this bioinspired, tissue-adhesive HA hydrogel can enhance the efficacy of minimally invasive cell therapy.

Adhesives play an important role in industrial fields such as electronics, architectures, energy plantation, and others. However, adhesives used for medical purpose are rather under-developed compared with those used in industry and consumer products. One key property required for medical adhesives is to maintain their adhesiveness in the presence of body fluid. Here, an entirely new class of medical adhesives called TAPE is reported; this is produced by intermolecular hydrogen bonding between a well-known polyphenol compound, tannic acid, and poly(ethylene glycol). The preparation method of TAPE is extremely easy, forming a few liters at once by just the simple mixing of the two compounds without any further chemical synthetic procedures. TAPE shows a 250% increase in adhesion strength compared with fibrin glue, and the adhesion is well maintained in aqueous environments. It is demonstrated that TAPE is an effective hemostatic material and a biodegradable patch for detecting gastroesophageal reflux disease in vivo. Widespread use of TAPE is anticipated in various medical and pharmaceutical applications such as muco-adhesives, drug depots, and others, because of its scalability, adhesion, and facile preparation.

DNA has emerged as a novel material in many areas of materials science due to its programmability. Especially, DNA hydrogels have been studied to incorporate new functions into gels. To date, only a few methods have been developed for fabricating DNA hydrogels, such as the use of complementary sequences or covalent bond. Herein, it is demonstrated that one of the most well-known plant-derived polyphenols, tannic acid (TA), can form a DNA hydrogel which is named TNA hydrogel (TA + DNA). TA plays a role as a “molecular glue” by a new mode of action reversibly connecting between phosphodiester bonds, which is different from the crosslinking utilizing complementary sequences. TA intrinsically degrades due to ester bonds connecting between pyrogallol groups, causing a degradable DNA hydrogel. Furthermore, TNA gel is multifunctional in that the gel is extensible upon pulling and adhesive to tissues because of the rich polyphenol groups in TA (ten phenols per TA). Unexpectedly, TNA gel exhibits superior in vivo hemostatic ability that can be useful for biomedical applications. This new DNA hydrogel preparation method represents a new technique for fabricating a large amount of DNA-based hemostatic hydrogel without chemically modifying DNA or requiring the crosslinking by complementary sequences.

In nature, a variety of functional water-insoluble organic materials are biologically synthesized in aqueous conditions without chemical additives and organic solvents. Insect cuticle, crustacean shells, and many others are representative examples. The insoluble materials are prepared by enzyme reactions and programmed self-assembly in water from water-soluble precursors. If the water-basis could be adapted, environment-friendly strategy developed in nature, many problems caused by the vast consumption of petroleum-based olefin materials could be solved or significantly attenuated. Here, the spontaneous formation of water-insoluble, biocompatible films from a water-soluble polymer is demonstrated without using any chemical additives and organic solvents. It is found that a water-soluble chitosan–catechol polymeric precursor is spontaneously self-converted to flexible water-insoluble thin film by simple dehydration. The preparation of mechanically robust, water-insoluble, flexible, transparent chitosan–catechol film is a completely unexpected result because most water-soluble polymers exist as powders when dehydrated. The film can be used as a bag similar to polyvinyl one and is multifunctional and biocompatible for drug delivery depots and tissue engineering applications.