is greatly decreased or even eliminated. For instance, the widely used cyanoacrylate adhesives exhibit strong adhesion in air, but when applied in water environment, they are hardened quickly to form a layer of stiff plastics, eventually resulting in the loss of adhesion. [9] The commercially available epoxy resins [10] and polyurethanes [11] are reported to demonstrate strong underwater adhesion, but long time of curing is usually required. Recently, host-guest chemistry strategy was reportedly employed to prepare underwater adhesives; however, the substrate surface needs to be modified in advance. [5,12] In addition, electrostatic and hydrophobic interactions were also proved to contribute to enhanced underwater adhesion, but the adhesion strength was relatively poor. [13,14] In nature, many organisms, such as mussels, barnacles, and castle worms, have evolved an unparalleled mechanism to perfectly tackle the underwater adhesion problem. [15][16][17] The finding of universality of catechol chemistry for wet adhesion has provided a valuable biomimetic source to develop diverse adhesives for use in aqueous environments. However, several problems, such as the complexity of administration, release of harmful organic solvents, [18,19] long-term curing, [2] need for oxidant addition, [20,21] and low adhesion strength, [18,22] may hamper the actual applications of these bioinspired adhesives. Although numerous dopamine-based adhesives have been reported and shown to bond various material surfaces, strong adhesion in water and particularly blood environment, remains nonexistent so far.Increasing studies on bioadhesives secreted by molluscs and insects have suggested that liquid coacervation plays a critical role in achieving underwater adhesion. [13] In this process, phase separation and concurrently increased hydrophobicity induced by coacervation can dispel the hydrated water on the interface, leading to much enhanced interaction of adhesive groups with the adherent and thus stable underwater adhesion. Up to date, several complex coacervate adhesives with linear structure have been reported, but the occurrence of those coacervations in water needs external triggers, such as temperature, [13] pH, [20,23] and iron strength. [24] Compared to linear counterparts, hyperbranched polymer (HBP) has a unique highly branched Despite recent advance in bioinspired adhesives, achieving strong adhesion and sealing hemostasis in aqueous and blood environments is challenging. A hyperbranched polymer (HBP) with a hydrophobic backbone and hydrophilic adhesive catechol side branches is designed and synthesized based on Michael addition reaction of multi-vinyl monomers with dopamine.It is demonstrated that upon contacting water, the hydrophobic chains selfaggregate to form coacervates quickly, displacing water molecules on the adherent surface to trigger increased exposure of catechol groups and thus rapidly strong adhesion to diverse materials from low surface energy to high energy in various environments, such as deionized water, sea ...

Despite rapid development of adhesive hydrogels, the typical double-sided adhesives fail to adhere to wet tissues and concurrently prevent postoperative tissue adhesion, thus severely limiting their applications in repair of internal tissues. Herein, a negatively charged carboxyl-containing hydrogel is gradiently, electrostatically complexed with a cationic oligosaccharide by a one-sided dipping method to form a novel Janus hydrogel wet adhesive whose two-side faces demonstrate strikingly distinct adhesive and nonadhesive properties. The lightly complexed surface demonstrates instant robust adhesion to various wet biological tissues even under water since the phase separation induced by electrostatic complexation increases the hydrophobicity and water drainage capacity. Intriguingly, the highly complexed surface is non-adhesive due to complete neutralization of carboxyls in the hydrogels. The Janus hydrogel can be used to replace traditional sutures to treat gastric perforation of rabbits. Animal experiment outcomes reveal that one side of the Janus hydrogel is firmly glued to the stomach tissue, and other side facing outward can efficiently prevent the postoperative adhesion. Molecular simulation elucidates the importance for selecting cationic polymer species. It is believed that gradient polyelectrolyte complexation establish a new direction to create Janus adhesives for internal tissue/organ repair and simultaneous prevention of post-operative adhesion.

Over the past decade, tissue-engineering strategies, mainly involving injectable hydrogels and epicardial biomaterial patches, have been pursued to treat myocardial infarction. However, only limited therapeutic efficacy is achieved with a single means. Here, a combined therapy approach is proposed, that is, the coadministration of a conductive hydrogel patch and injectable hydrogel to the infarcted myocardium. The self-adhesive conductive hydrogel patch is fabricated based on Fe3+-induced ionic coordination between dopamine–gelatin (GelDA) conjugates and dopamine-functionalized polypyrrole (DA–PPy), which form a homogeneous network. The injectable and cleavable hydrogel is formed in situ via a Schiff base reaction between oxidized sodium hyaluronic acid (HA-CHO) and hydrazided hyaluronic acid (HHA). Compared with a single-mode system, injecting the HA-CHO/HHA hydrogel intramyocardially followed by painting a conductive GelDA/DA–PPy hydrogel patch on the heart surface results in a more pronounced improvement of the cardiac function in terms of echocardiographical, histological, and angiogenic outcomes.

Adhesive hydrogels are promising to be explored as biomedical sealants, hemostatic agents, and glues in promoting wound healing and tissue regeneration. However, it is challenging to engineer a hydrogel combining instant robust adhesion and high strength. Herein, a high‐strength instantly self‐adhesive organic–inorganic hybrid (OIH) hydrogel by a one‐pot radical polymerization of N‐acryloyl 2‐glycine (ACG), biocompatible glycine derivative vinyl monomer with addition of hydroxyapatite (HAp), naturally occurring mineral is designed and fabricated. The hydrogen bonding from side chain of poly(N‐acryloyl 2‐glycine) (PACG), carboxyl‐Ca2+ ionic crosslinking together with PACG chain‐HAp physical interactions contribute to automatic self‐repairing high mechanical properties. Importantly, this OIH hydrogel exhibits robust adhesion to diverse substrates, presumably due to synergistic interactions of carboxyl with the substrate surface and the enhanced contact of PACG chains to adherent surfaces facilitated by HAp nanoparticles. Remarkably, the PACG‐HAp OIH hydrogels can instantly self‐adhere to the soft tissues with adhesion strength of 105 kPa, and anastomose the broken intestines, meanwhile promoting wound healing and stopping bleeding. The OIH hydrogel is autolytic in the body without eliciting inflammatory reaction. Further, the ready‐to‐use PACG‐HAp adhesive hydrogel can be properly stored for a long time. This novel hydrogel will find an appealing application as a new adhesive for emergency self‐rescue.

The supramolecular polymer hydrogels feature self-healability, adjustable mechanical strength, and thermoplasticity, which are derived from the formation of supramolecular physical interactions in the hydrogel networks, such as H-bonding interactions, [6] host-guest interactions, [7] metal-ligand coordination interactions, [8] hydrophobic interactions, [9] multiple combined interactions. [10] Among them, H-bonds are generally weak noncovalent bonds, ubiquitous in biomolecules, but their synergistic interactions can reach a strength of the covalent bond; thus it is commonly utilized in designing supramolecular tough hydrogels. [11] Our previous study suggested that supramolecular polymer hydrogels based on single amide H-bonding interaction were unstable in water, [12] because the competitive solvation of H-bond donor and acceptor in polar solvents weakens its strengthening effect. [13] Inspired by the hydrogen-bonded clusters in the secondary structure of proteins, we constructed a supramolecular poly(N-acryloyl glycinamide) (PNAGA) hydrogel whose dual amide motifs in the side chain contributed to high strengths and outstanding antiswelling ability due to strong shielding of the hydrogen-bonded microdomains from water molecule attack. [12] By utilizing Type II photoinitiated self-condensing vinyl polymerization of N-acryloyl glycinamide (NAGA), the resultant hyperbranched PNAGA hydrogels demonstrated superior mechanical performances to those of linear PNAGA counterparts owing to the higher cross-linking density of H-bonds. [14] In addition, the H-bonding interactions of dual amide motifs could also be modulated by copolymerizing other monomers, [15][16][17][18] thus achieving the versatile hydrogels with mechanical properties spanning from high strength to soft injectability, which show promising applications as 3D printed osteochondral regeneration scaffold, [16] artificial vitreous body, [17] and postoperative antiadhesion barrier. [18] Our recent study revealed that only introducing one methyl group to the double bond of NAGA could lead to a considerable decrease in mechanical strengths and an increase in room temperature autonomous self-healability of the poly(N-methacryloyl glycinamide) hydrogels (MNAGA), which was resulted from the perturbation of one methyl substitution to H-bonds. [19] The intermolecular H-bonding density heavily influences the gelation and rheological behavior of hydrogen-bonded supramolecular polymer hydrogels, thus offering a delicate pathway to tailor their physicochemical properties for meeting a specific biomedical application. Herein, one methylene spacer between two amides in the side chain of N-acryloyl glycinamide (NAGA) is introduced to generate a variant monomer, N-acryloyl alaninamide (NAAA). Polymerization of NAAA in aqueous solution affords an unprecedented ultrasoft and highly swollen supramolecular polymer hydrogel due to weakened H-bonds caused by an extra methylene spacer, which is verified by variabletemperature Fourier transform infrared (FTIR) spectroscopy and s...