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An ideal adhesive hydrogel must possess high adhesion to the native tissue, biocompatibility, eligible biodegradability, and good mechanical compliance with the substrate tissues. We constructed an interpenetrating double-network hydrogel containing polysaccharides (alginate and dextran) and nanosized spherical dendrimer by both physical and chemical crosslinking, thus endowing the hydrogel with a broad range of mechanical properties, adhesive properties, and biological functions. The double-network hydrogel has moderate pore sizes and swelling properties. The chelation of calcium ions significantly enhances the tensile and compressive properties. The incorporation of dendrimer improves both the mechanical and adhesive properties. This multicomponent interpenetrating network hydrogel has excellent biocompatibility, tunable mechanical and adhesive properties, and satisfied multi-functions to meet the complex requirements of wound healing and tissue engineering. The hydrogel exhibits promising corneal adhesion capabilities in vitro, potentially supplanting the need for sutures in corneal stromal surgery and mitigating the risks associated with donor corneal damage and graft rejection during corneal transplantation. This novel polysaccharide and dendrimer hydrogel also shows good results in sutureless keratoplasty, with high efficiency and reliability. Based on the clinical requirements for tissue bonding and wound closure, the hydrogel provides insight into solving the mechanical properties and adhesive strength of tissue adhesives., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Monodisperse nanoparticles of biodegradable polyhydroxyalkanoates (PHAs) polymers, copolymers of 3-hydroxybutyrate (3HB) and 4-hydroxybutyrate (4HB), are synthesized using a membrane-assisted emulsion encapsulation and evaporation process for biomedical resorbable adhesives. The precise control over the diameter of these PHA particles, ranging from 100 nm to 8 μm, is achieved by adjusting the diameter of emulsion or the PHA concentration. Mechanical properties of the particles can be tailored based on the 3HB to 4HB ratio and molecular weight, primarily influenced by the level of crystallinity. These monodisperse PHA particles in solution serve as adhesives for hydrogel systems, specifically those based on poly(N, N-dimethylacrylamide) (PDMA). Semi-crystalline PHA nanoparticles exhibit stronger adhesion energy than their amorphous counterparts. Due to their self-adhesiveness, adhesion energy increases even when those PHA nanoparticles form multilayers between hydrogels. Furthermore, as they degrade and are resorbed into the body, the PHA nanoparticles demonstrate efficacy in in vivo wound closure, underscoring their considerable impact on biomedical applications., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Gi-Ra Yi reports financial support was provided by CJ CheilJedang Corp. Gi-Ra Yi has patent pending to POSTECH, CJ Cheiljedang Corp. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Timely and effective interventions after tracheal mucosal injury are lack in clinical practices, which elevate the risks of airway infection, tracheal cartilage deterioration, and even asphyxiated death. Herein, we proposed a biomaterial-based strategy for the repair of injured tracheal mucosal based on a copper hydrogen phosphate nanosheets (CuHP NSs) functionalized commercial hydrogel (polyethylene glycol disuccinimidyl succinate-human serum albumin, PH). Such CuHP/PH hydrogel achieved favorable injectability, stable gelation, and excellent adhesiveness within the tracheal lumen. Moreover, CuHP NSs within the CuHP/PH hydrogel effectively stimulate the proliferation and migration of endothelial/epithelial cells, enhancing angiogenesis and demonstrating excellent tissue regenerative potential. Additionally, it exhibited significant inhibitory effects on both bacteria and bacterial biofilms. More importantly, when injected injured site of tracheal mucosa under fiberoptic bronchoscopy guidance, our results demonstrated CuHP/PH hydrogel adhered tightly to the tracheal mucosa. The therapeutic effects of the CuHP/PH hydrogel were further confirmed, which significantly improved survival rates, vascular and mucosal regeneration, reduced occurrences of intraluminal infections, tracheal stenosis, and cartilage damage complications. This research presents an initial proposition outlining a strategy employing biomaterials to mitigate tracheal mucosal injury, offering novel perspectives on the treatment of mucosal injuries and other tracheal diseases., (© 2024. The Author(s).)

Chitosan bio-adhesives bond strongly with various biological tissues, such as skin, mucosa, and internal organs. Their adhesive ability arises from amino acid and hydroxyl groups in chitosan, facilitating interactions with tissue surfaces through chemical (ionic, covalent, and hydrogen) and physical (chain entanglement) bonding. As non-toxic, biodegradable, and biocompatible materials, chitosan bio-adhesives are a safe option for medical therapies. They are particularly suitable for drug delivery, wound healing, and tissue regeneration. In this review, we address chitosan-based bio-adhesives and the mechanisms associated with them. We also discuss different chitosan composite-based bio-adhesives and their biomedical applications in wound healing, drug delivery, hemostasis, and tissue regeneration. Finally, challenges and future perspectives for the clinical use of chitosan-based bio-adhesives are discussed.

Traditional adhesive hydrogels perform well in tissue adhesion but they fail to prevent postoperative tissue adhesion. To address this challenge, a biodegradable Janus adhesive hydrogel (J-AH) was designed and fabricated by the assembly of three different functional layers including anti-adhesive layer, reinforceable layer, and wet tissue adhesive layer. Each layer of J-AH serves a specific function: the top zwitterionic polymeric anti-adhesive layer shows superior resistance to cell/protein and tissue adhesion; the middle poly(vinyl alcohol)/tannic acid reinforceable matrix layer endows the hydrogel with good mechanical toughness of ∼2.700 MJ/m 3 ; the bottom poly(acrylic acid)/polyethyleneimine adhesive layer imparts tough adhesion (∼382.93 J/m 2 of interfacial toughness) to wet tissues. In the rat liver and femoral injury models, J-AH could firmly adhere to the bleeding tissues to seal the wounds and exhibit impressive hemostatic efficiency. Moreover, in the in vivo adhesion/anti-adhesion assay of J-AH between the defected cecum and peritoneal walls, the top anti-adhesive layer can effectively inhibit undesired postoperative abdominal adhesion and inflammatory reaction. Therefore, this research may present a new strategy for the design of advanced bio-absorbable Janus adhesive hydrogels with multi-functions including tissue adhesion, anti-postoperative adhesion and biodegradation. STATEMENT OF SIGNIFICANCE: Despite many adhesive hydrogels with tough tissue adhesion capability have been reported, their proclivity for undesired postoperative adhesion remains a serious problem. The postoperative adhesion may lead to major complications and even endanger the lives of patients. The injectable hydrogels can cover the irregular wound and suppress the formation of postoperative adhesion. However, due to the lack of adhesive properties with tissue, it is difficult for the hydrogels to maintain on the wound surface, resulting in poor anti-postoperative adhesion effect. Herein, we design a Janus adhesive hydrogel (J-AH). J-AH integrates together robust wet tissue adhesion and anti-postoperative adhesion. Therefore, this research may present a new strategy for the design of advanced bio-absorbable Janus adhesive hydrogels., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

The development of tissue adhesives with good biocompatibility and potent antimicrobial properties is crucial for addressing the high incidence of surgical site infections in emergency and clinical settings. Herein, an injectable hydrogel adhesive composed of chitosan biguanidine (CSG), oxidized dextran (ODex) and tannin (TA) was synthesized primarily through Schiff-base reactions, hydrogen bonding, and electrostatic interactions. TA was introduced into the CSG/ODex hydrogel to prepare a physicochemically double cross-linked hydrogel. The hydrogel formulation incorporating 2 wt% TA (CSG/ODex-TA2) exhibited rapid gelation, moderate mechanical properties, good tissue adhesion, and sustained release behavior of TA. Both in vitro and in vivo studies demonstrated that CSG/ODex-TA2 showed significantly enhanced adhesion and antibacterial effectiveness compared to the CSG/ODex hydrogel and commercial fibrin glue. Leveraging the positive charge of CSG, the CSG/ODex-TA2 hydrogel demonstrated a strong contact antibacterial effect, while the sustained release of TA provided diffusion antibacterial capabilities. By integrating contact and diffusion antibacterial mechanisms into the hydrogel, a promising approach was developed to boost antibacterial efficiency and accelerate the healing of wounds infected with methicillin-resistant Staphylococcus aureus (MRSA). The CSG/ODex-TA2 hydrogel has excellent biocompatibility, hemostatic properties, and antibacterial capabilities, making it a promising candidate for improving in vivo wound care and combating bacterial infections., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Commitment to the 3Rs principle (Replacement, Reduction, and Refinement) led to the development of a cell-based system to measure buccal bioadhesion in vitro and replace the use of porcine buccal and esophageal tissues (PBT and PET, respectively). Additionally, the aim is to bridge the gap in knowledge regarding the bioadhesion properties of PBT and PET. The in vitro models are based on the human buccal epithelial cell line-TR146 without ("Model I") or with ("Model II") 5% (w/v) mucous layer. The in vitro setup also provides a method to evaluate the bioadhesion between two soft materials. Standard bioadhesive hydrogels (alginate, chitosan, and gelatin) are used to test and compare the results from the in vitro models to the ex vivo tissues. The ex vivo and in vitro models show increased bioadhesion as the applied force and contact time increases. Furthermore, Model I exhibits bioadhesion values-of alginate, chitosan, and gelatin-comparable to those obtained with PBT. It is also found that contact time and applied force similarly affect PBT and PET bioadhesion, while PET exhibits greater values. In conclusion, Model I can replace PBT for measuring bioadhesion and be incorporated into the experimental design of bioadhesive DDS, thus minimizing animal tissue usage., (© 2024 The Author(s). Small published by Wiley‐VCH GmbH.)

Corneal injuries play a significant role in global visual impairment, underscoring the demand for innovative biomaterials with specific attributes such as adhesion, cohesion, and regenerative potential. In this study, we have developed a biocompatible bioadhesive for corneal reconstruction. Derived from Collagen type I, naturally present in human corneal stromal tissue, the bioadhesive was cross-linked with modified polyethylene glycol diacrylate (PEGDA-DOPA), rendering it curable through visible light exposure and exhibiting superior adhesion to biological tissues even in wet conditions. The physicochemical characteristics of the proposed bioadhesive were customized by manipulating the concentration of its precursor polymers and adjusting the duration of photocrosslinking. To identify the optimal sample with maximum adhesion, mechanical strength, and biocompatibility, characterization tests were conducted. The optimal specimen, consisting of 30 % (w/v) PEGDA-DOPA and cured with visible light for 5 min, exhibited commendable adhesive strength of 783.6 kPa and shear strength of 53.7 kPa, surpassing that of commercialized eye adhesives.Additionally, biocompatibility test results indicated a notably high survival rate (>100 %) of keratocytes seeded on the hydrogel adhesive after 7 days of incubation. Consequently, this designed bioadhesive, characterized by high adhesion strength, robust mechanical strength, and excellent biocompatibility, is anticipated to enhance the spontaneous repair process of damaged corneal stromal tissue., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier B.V.)

Gauze or bandages are commonly used to effectively control bleeding during trauma and surgery. However, conventional treatment methods can sometimes lead to secondary damages. In recent years, there has been increased interest in developing adhesive hemostatic hydrogels as a safer alternative for achieving hemostasis. Methylcellulose (MC) is a well-known thermo-sensitive polymer with excellent biocompatibility that is capable of forming a hydrogel through physical crosslinking owing to its inherent thermo-reversible properties. However, the poor mechanical properties of the MC hydrogel comprising a single crosslinked network (SN) limit its application as a hemostatic material. To address this issue, we incorporated a chitosan-gallol (CS-GA) conjugate, which has the ability to form chemical crosslinks through self-crosslinking reactions under specific pH conditions, into the MC hydrogel to reinforce the MC hydrogel network. The resulting MC/CS-GA hydrogel with a dual-crosslinked network (DN), involving both physical and chemical crosslinks, exhibited synergistic effects of the two types of crosslinks. Thus, compared with those of the SN hydrogel, the composite DN hydrogel exhibited significantly enhanced mechanical strength and tissue adhesive properties. Moreover, the DN hydrogel presented excellent biological activity in vitro. Additionally, in rat hepatic hemorrhage models, the DN hydrogel exhibited high hemostatic efficiency, showcasing its multifunctional capabilities., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

As an alternative to tissue adhesives, photochemical tissue bonding is investigated for advanced wound healing. However, these techniques suffer from relatively slow wound healing with bleeding and bacterial infections. Here, the versatile attributes of afterglow luminescent particles (ALPs) embedded in dopamine-modified hyaluronic acid (HA-DOPA) patches for accelerated wound healing are presented. ALPs enhance the viscoelastic properties of the patches, and the photoluminescence and afterglow luminescence of ALPs maximize singlet oxygen generation and collagen fibrillogenesis for effective healing in the infected wounds. The patches are optimized to achieve the strong and rapid adhesion in the wound sites. In addition, the swelling and shrinking properties of adhesive patches contribute to a nonlinear behavior in the wound recovery, playing an important role as a strain-programmed patch. The protective patch prevents secondary infection and skin adhesion, and the patch seamlessly detaches during wound healing, enabling efficient residue clearance. In vitro, in vivo, and ex vivo model tests confirm the biocompatibility, antibacterial effect, hemostatic capability, and collagen restructuring for the accelerated wound healing. Taken together, this research collectively demonstrates the feasibility of HA-DOPA/ALP patches as a versatile and promoting solution for advanced accelerated wound healing, particularly in scenarios involving bleeding and bacterial infections., (© 2024 Wiley‐VCH GmbH.)

Hydrogel bioadhesives have emerged as a promising alternative to wound dressings for chronic wound management. However, many existing bioadhesives do not meet the functional requirements for efficient wound management through dynamically mechanical modulation, due to the reduced wound contractibility, frequent wound recurrence, incapability to actively adapt to external microenvironment variation, especially for those gradually-expanded chronic wounds. Here, a self-growing hydrogel bioadhesive (sGHB) patch that exhibits instant adhesion to biological tissues but also a gradual increase in mechanical strength and interfacial adhesive strength within a 120-h application is presented. The gradually increased mechanics of the sGHB patch could effectively mitigate the stress concentration at the wound edge, and also resist the wound expansion at various stages, thus mechanically contracting the chronic wounds in a programmable manner. The self-growing hydrogel patch demonstrated enhanced wound healing efficacy in a mouse diabetic wound model, by regulating the inflammatory response, promoting the faster re-epithelialization and angiogenesis through mechanical modulation. Such kind of self-growing hydrogel bioadhesives have potential clinical utility for a variety of wound management where dynamic mechanical modulation is indispensable., (© 2024 Wiley‐VCH GmbH.)

Cartilage repair remains a major challenge in human orthopedic medicine, necessitating the application of innovative strategies to overcome existing technical and clinical limitations. Adhesive hydrogels have emerged as promising candidates for cartilage repair promotion and tissue engineering, offering key advantages such as enhanced tissue integration and therapeutic potential. This comprehensive review navigates the landscape of adhesive hydrogels in cartilage repair, discussing identified challenges, shortcomings of current treatment options, and unique advantages of adhesive hydrogel products and scaffolds. While emphasizing the critical need for in situ lateral integration with surrounding tissues, we dissect current limitations and outline future perspectives for hydrogel scaffolds in cartilage repair. Moreover, we examine the clinical translation pathway and regulatory considerations specific to adhesive hydrogels. Overall, this review synthesizes the existing insights and knowledge gaps and highlights directions for future research regarding adhesive hydrogel-based devices in advancing cartilage tissue engineering.

The development of multifunctional wound adhesives is critical in clinical settings due to the scarcity of dressings with effective adhesive properties while protecting against infection by drug-resistant bacteria. Polysaccharide and gelatin-based hydrogels, known for their biocompatibility and bioactivity, assist in wound healing. This study introduces a multifunctional bioadhesive hydrogel developed through dynamic covalent bonding and light-triggered covalent bonding, comprising oxidized hyaluronic acid, methacrylated gelatin, and the bacteriocin recently discovered by our lab, named jileicin (JC). The adhesion strength of the hydrogel, measured at 180 kPa, was 4.35 times higher than that of the fibrin glue. Furthermore, the hydrogel demonstrated robust platelet adhesion, procoagulant activity, and outstanding hemostatic properties in a mouse liver injury model. Incorporating JC significantly enhanced the phagocytosis and bactericidal capabilities of the macrophages. This immunomodulatory function on host cells, coupled with its potent bacterial membrane-disrupting ability, makes JC an effective killer against methicillin-resistant Staphylococcus aureus . In wound repair experiments on diabetic mice with infected full-thickness skin defects, the hydrogel treatment group showed a notable reduction in bacterial load, accelerated M2-type macrophage polarization, diminished inflammation, and hastened wound healing. Owing to its outstanding biocompatibility, antibacterial activity, and controlled adhesion, this hydrogel presents a promising therapeutic option for treating infected skin wounds.

Tissue adhesion of hydrogels plays an important role in wound healing, which can improve the efficiency of wound treatment, stop bleeding, facilitate tissue growth and wound closure. However, most non-covalent crosslinked hydrogels have weak tissue adhesion and rheological properties. Furthermore, it remains a challenge to synthesize a fully physically crosslinked hydrogel with good rheological properties without compromising its tissue adhesion strength. In this paper, a physically crosslinked hydrogel was developed from a mixture of chitosan and pullulan in different polymer volume ratios using aqueous NaOH. Fourier transform infrared spectroscopy, scanning electron microscopy, thermal analysis, rheological and lap shear tests were used to evaluate the influence of polymer volume ratios on the rheological, and tissue adhesive properties of the hydrogels. It was found that the hydrogels possessed high tissue adhesive strength ranging from 18.0 ± 0.90 to 49.0 ± 2.45 kPa and good storage moduli up to 5.157 ± 1.062 kPa. Gentamicin was incorporated into this polymer matrix and the release profile was investigated. The ratio of chitosan and pullulan to obtain hydrogels with optimum viscoelastic and tissue adhesive properties was identified to be CS/PUL 2:1. These results indicated that the synthesized hydrogels can be potential materials for biomedical applications such as medical adhesives and wound dressings., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Development of bioadhesives that can be facilely delivered by endoscope and exhibit instant and robust adhesion with gastric tissues to promote gastric ulcer healing remains challenging. In this study, an advanced bioadhesive is prepared through free radical polymerization of ionized N-acryloyl phenylalanine (iAPA) and N-[tris (hydroxymethyl) methyl] acrylamide (THMA). The precursory polymer solution exhibits low viscosity with the capability for endoscope delivery, and the hydrophilic-hydrophobic transition of iAPA upon exposure to gastric acid can trigger gelation through phenyl groups assisted multiple hydrogen bonds formation and repel water molecules on tissue surface to establish favorable environment for interfacial interactions between THMA and functional groups on tissues. The in-situ formed hydrogel features excellent stability in acid environment (14 days) and exhibits firm wet adhesion to gastric tissue (33.4 kPa), which can efficiently protect the wound from the stimulation of gastric acid and pepsin. In vivo studies reveal that the bioadhesive can accelerate the healing of ulcers by inhibiting inflammation and promoting capillary formation in the acetic acid-induced gastric ulcer model in rats. Our work may provide an effective solution for the treatment of gastric ulcers clinically., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Wounds often necessitate the use of instructive biomaterials to facilitate effective healing. Yet, consistently filling the wound and retaining the material in place presents notable challenges. Here, we develop a new class of injectable tissue adhesives by leveraging the dynamic crosslinking chemistry of Schiff base reactions. These adhesives demonstrate outstanding mechanical properties, especially in regard to stretchability and self-healing capacity, and biodegradability. Furthermore, they also form robust adhesion to biological tissues. Their therapeutic potential was evaluated in a rodent model of volumetric muscle loss (VML). Ultrasound imaging confirmed that the adhesives remained within the wound site, effectively filled the void, and degraded at a rate comparable to the healing process. Histological analysis indicated that the adhesives facilitated muscle fiber and blood vessel formation, and induced anti-inflammatory macrophages. Notably, the injured muscles of mice treated with the adhesives displayed increased weight and higher force generation than the control groups. This approach to adhesive design paves the way for the next generation of medical adhesives in tissue repair., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:David Mooney reports financial support was provided by National Institutes of Health. David Mooney, Sungmin Nam, Junzhe Lou have patent pending to the adhesive materials. David J. Mooney, Sungmin Nam, and Junzhe Lou are inventors on patent applications on the adhesive materials utilized in this study. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Over the past few decades, there have been advancements in the development of high-performance tissue adhesives as alternatives to traditional sutures and staples for rapid and effective wound closure post-surgery. While tissue adhesives offer advantages such as ease of use, short application time, and minimal tissue damage, they also face challenges related to biocompatibility, biodegradability, and adhesive strength. In this study, L-lysine diisocyanate (LDI) and trimethylolpropane (TMP) were utilized as the primary raw materials to produce a prepolymer terminated with NCO, resulting in the development of a new biocompatible polyurethane tissue adhesive (TMP-LDI). Additionally, SiO 2 nanoparticles were incorporated into the prepolymer, significantly enhancing the adhesive strength of the TMP-LDI tissue adhesive through the "nanobridging effect," achieving a strength of 170.4 kPa. Furthermore, the SiO 2 /TMP-LDI tissue adhesive exhibited satisfactory temperature change during curing and degradation performance. In vitro and in vivo studies demonstrated that SiO 2 /TMP-LDI exhibited good biocompatibility, efficient hemostasis, antimicrobial properties, and the ability to promote wound healing. This research presents a novel approach for the development of tissue adhesives with superior adhesive performance., (© 2024 Wiley Periodicals LLC.)

Wound closure in surgeries is traditionally achieved using invasive methods such as sutures and staples. Adhesion-based wound closure methods such as tissue adhesives, sealants, and hemostats are slowly replacing these methods due to their ease of application. Although several chemistries have been developed and used commercially for wound closure, there is still a need for better tissue adhesives from the point of view of toxicity, wet-adhesion strength, and long-term bonding. Catechol chemistry has shown great promise in developing wet-set adhesives that meet these criteria. Herein, we have studied the biocompatibility of a catechol-based copolymer adhesive, poly([dopamine methacrylamide]-co-[methyl methacrylate]-co-[poly(ethylene glycol) methyl ether methacrylate]) or poly(catechol-MMA-OEG), which is soluble in water. The adhesive was injected subcutaneously in a mouse model on its own and in combination with a sodium periodate crosslinker. After 72 h, 4 weeks, and 12 weeks, the mice were euthanized and subjected to histopathological analysis. Both adhesives were present and still palpable at the end of 12 weeks. The moderate inflammation observed for the poly(catechol-MMA-OEG) cohort at 72 h had reduced to mild inflammation at the end of 12 weeks. However, the moderate inflammatory response observed for the poly(catechol-MMA-OEG) + crosslinker cohort at 72 h had not subsided at 12 weeks., (© 2024 The Author(s). Journal of Biomedical Materials Research Part A published by Wiley Periodicals LLC.)

Polymer adhesives play an important role in many medical, consumer, and industrial products. Polymers of α-lipoic acid (αLA) have the potential to fulfill the need for versatile and environmentally friendly adhesives, but their performance is plagued by spontaneous depolymerization. We report a family of stabilized αLA polymer adhesives that can be tailored for a variety of medical or nonmedical uses and sustainably sourced and recycled in a closed-loop manner. Minor changes in monomer composition afforded a pressure-sensitive adhesive that functions well in dry and wet conditions, as well as a structural adhesive with strength equivalent to that of conventional epoxies. αLA surgical superglue successfully sealed murine amniotic sac ruptures, increasing fetal survival from 0 to 100%.

The impressive adhesive capacity of marine mussels has inspired various fascinating designs in biomedical fields. Mussel-inspired injectable adhesive hydrogels, as a type of promising mussel-inspired material, have attracted much attention due to their minimally invasive property and desirable functions provided by mussel-inspired components. In recent decades, various mussel-inspired injectable adhesive hydrogels have been designed and widely applied in numerous biomedical fields. The rational incorporation of mussel-inspired catechol groups endows the injectable hydrogels with the potential to exhibit many properties, including tissue adhesiveness and self-healing, antimicrobial, and antioxidant capabilities, broadening the applications of injectable hydrogels in biomedical fields. In this review, we first give a brief introduction to the adhesion mechanism of mussels and the characteristics of injectable hydrogels. Further, the typical design strategies of mussel-inspired injectable adhesive hydrogels are summarized. The methodologies for integrating catechol groups into polymers and the crosslinking methods of mussel-inspired hydrogels are discussed in this section. In addition, we systematically overview recent mussel-inspired injectable adhesive hydrogels for biomedical applications, with a focus on how the unique properties of these hydrogels benefit their applications in these fields. The challenges and perspectives of mussel-inspired injectable hydrogels are discussed in the last section. This review may provide new inspiration for the design of novel bioinspired injectable hydrogels and facilitate their application in various biomedical fields.

Medical adhesives have been used for wound closure with many advantages over sutures, but the wet environment in the human body poses a big challenge for its application. The currently used dry double-sided tape (DST) can remove the water barrier by water absorption, but its over-swelling makes it difficult to achieve long-term adhesion. In this study, a dry double-sided tape post-treated with tannic acid (DST-TA) was developed. A double network adhesive composed of polyacrylic acid and gelatin was first prepared by free radical photocrosslinking, and was post-treated in acidic (pH = 2) tannic acid solution. Tannic acid was immobilized in the DST through the catecholyl group, which could form hydrogen bonds with the DST, or react with the amino group on the gelatin by oxidizing to quinone. In vivo and in vitro studies demonstrated that DST-TA had significantly higher swelling resistance and tensile strength than DST. The introduced catecholyl group could reduce over-swelling of the DST, and improve short-term and long-term adhesion in a wet environment. We also demonstrated that the DST-TA had good hemocompatibility, biodegradability, and no cytotoxicity, offering a potential option for long-term medical adhesive in a wet environment.

The development of bioadhesives with strong adhesion and on-demand adhesion-detachment behavior is still critically important and challenging for facilitating painless and damage-free removal in clinical applications. In this work, for the first time, we report the easy fabrication of novel polyurethane-urea (PUU)-based bioadhesives with thermoresponsive on-demand adhesion and detachment behavior. The PUU copolymer was synthesized by a simple copolymerization of low-molecular-weight, hydrophilic, and biocompatible poly(ethylene glycol), glyceryl monolaurate (GML, a special chain extender with a long side hydrophobic alkyl group), and isophorone diisocyanate (IPDI). Here, GML was expected to not only adjust the temperature-dependent adhesion behavior but also act as an internal plasticizer. By simple adjustment of the water content, the adhesion strength of the 15 wt % water-containing PUU film toward porcine skin is as high as 55 kPa with an adhesion energy of 128 J/m 2 at 37 °C. The adhesion strength dramatically decreases to only 3 kPa at 10 °C, exhibiting switching efficiency as high as 0.95. Furthermore, the present PUU-based adhesive also shows good on-demand underwater adhesion and detachment with a cell viability close to 100%. We propose that biomaterial research fields, especially novel PUU/polyurethane (PU)-based functional materials and bioadhesives, could benefit from such a novel thermoresponsive copolymer with outstanding mechanical and functional performances and an easy synthesis and scaled-up process as described in this article.

Vocal fold (VF) scarring, a complex problem in laryngology, results from injury and inflammation of the layered architecture of the VFs. The resultant voice hoarseness, for which successful therapeutic options are currently limited, affects the patient's quality of life. A promising strategy to reverse this disorder is the use of antifibrotic drugs. The present study proposes a novel microbead-embedded injectable hydrogel that can sustain the release of the anti-fibrotic drug pirfenidone (PFD) for vocal fold scarring. Microbeads were developed using sodium alginate and gelatin, which were further embedded into a biomimetic and tissue adhesive gellan gum (GG) hydrogel. The microbead-embedded hydrogel exhibited improved injectability, viscoelasticity, tissue adhesiveness, degradability, and swelling compared to the hydrogel without beads. Additionally, the bead-embedded hydrogel could sustain the release of the PFD for a week. In vitro studies showed that the drug-loaded hydrogel could reduce the migration and proliferation of fibroblast cells in a dose-dependent manner. In summary, this study demonstrates the potential of a PFD-loaded injectable hydrogel with enhanced viscoelastic and tissue-adhesive properties for vocal fold scarring applications.

Epidural adhesion or epidural fibrosis is the major reason for postoperative pain, which remains a clinically challenging problem. Current physical barriers fail to provide a satisfactory therapeutic outcome mainly due to their lack of adhesion, inability to prevent fluid leakage, and exhibiting limited antioxidant properties. Herein, we fabricated a cysteine-modified bioadhesive (SECAgel) with improved sealing and antioxidant properties for epidural adhesion prevention, inspired by the organism's antioxidant systems. The resulting SECAgel showed good injectability and in situ adhesion ability, effectively covering every corner of the irregular wound. Besides, it possessed efficient sealing properties (395.2 mmHg), effectively stopping blood leakage in the rabbit carotid artery transection model. The antioxidant experiments demonstrated that the SECAgel effectively scavenged various radicals and saved the cells from oxidative stress. Two animal models were used to show that the SECAgel effectively inhibited adhesion in both situations with and without cerebrospinal fluid leakage. The RNA sequencing analysis showed that SECAgel treatment effectively inhibited the expression of key genes related to adhesion development, inflammatory response, and oxidative stress. The SECAgel, together with good biocompatibility, can be a good candidate for preventing epidural adhesion in the clinic.

Intervertebral disc (IVD) herniation is a leading cause of disability and lower back pain, causing enormous socioeconomic burdens. The standard of care for disc herniation is nucleotomy, which alleviates pain but does not repair the annulus fibrosus (AF) defect nor recover the biomechanical function of the disc. Existing bioadhesives for AF repair are limited by insufficient adhesion and significant mechanical and geometrical mismatch with the AF tissue, resulting in the recurrence of protrusion or detachment of bioadhesives. Here, we report a composite hydrogel sealant constructed from a composite of a three-dimensional (3D)-printed thermoplastic polyurethane (TPU) mesh and tough hydrogel. We tailored the fiber angle and volume fraction of the TPU mesh design to match the angle-ply structure and mechanical properties of native AF. Also, we proposed and tested three types of geometrical design of the composite hydrogel sealant to match the defect shape and size. Our results show that the sealant could mimic native AF in terms of the elastic modulus, flexural modulus, and fracture toughness and form strong adhesion with the human AF tissue. The bovine IVD tests show the effectiveness of the composite hydrogel sealant for AF repair and biomechanics recovery and for preventing herniation with its heightened stiffness and superior adhesion. By harnessing the combined capabilities of 3D printing and bioadhesives, these composite hydrogel sealants demonstrate promising potential for diverse applications in tissue repair and regeneration.

In addressing the intricate challenges of enterocutaneous fistula (ECF) treatment, such as internal bleeding, effluent leakage, inflammation, and infection, our research is dedicated to introducing a regenerative adhesive hydrogel that can seal and expedite the healing process. A double syringe setup was utilized, with dopagelatin and platelet-rich plasma (PRP) in one syringe and Laponite and sodium periodate in another. The hydrogel begins to cross-link immediately after passing through a mixing tip and exhibits tissue adhesive properties. Results demonstrated that PRP deposits within the pores of the cross-linked hydrogel and releases sustainably, enhancing its regenerative capabilities. The addition of PRP further improved the mechanical properties and slowed down the degradation of the hydrogel. Furthermore, the hydrogel demonstrated cytocompatibility, hemostatic properties, and time-dependent macrophage M1 to M2 phase transition, suggesting the anti-inflammatory response of the material. In an in vitro bench test simulating high-pressure fistula conditions, the hydrogel effectively occluded pressures up to 300 mmHg. In conclusion, this innovative hydrogel holds promise for ECF treatment and diverse fistula cases, marking a significant advancement in its therapeutic approaches.

The key to saving lives is to achieve instant and effective sealing hemostasis in the event of emergency bleeding. Herein, a plant oil-based EMTA/Zn 2+ bioadhesive is prepared by a facile reaction of epoxidized soybean oil (ESO) with methacrylic acid (MAA) and tannic acid (TA), followed by the addition of zinc ions for coordination with TA. The EMTA/Zn 2+ bioadhesive can be rapidly cured in situ at the wound site through photo-cross-linking under ultraviolet (UV) light-emitting diode (LED) irradiation within 30 s, achieving ultrastrong wet-tissue adhesion performance of 92.4 and 51.8 kPa to porcine skin and aortic skin after 7 days underwater, respectively. Especially, the EMTA/Zn 2+ bioadhesive exhibits outstanding sealing performance in vitro with the high burst pressure of 525 mmHg (70 kPa) and 337.5 mmHg (45 kPa) to porcine skin and aortic skin, respectively. Moreover, the EMTA/Zn 2+ bioadhesive not only has outstanding hemocompatibility and good biodegradability but also exhibits excellent cytocompatibility and antibacterial properties. Notably, the EMTA/Zn 2+ bioadhesive has remarkable instant sealing hemostatic ability for hemorrhaging liver in vivo . Therefore, the prepared plant oil-based EMTA/Zn 2+ bioadhesive can serve as a charming alternative candidate for instant sealing hemostasis in clinical applications, especially in traumatic internal organs and arterial bleeding.

Endoscopic submucosal dissection (ESD) is the gold-standard surgical procedure for superficial esophageal cancer. A significant and challenging complication of this technique is post-ESD esophageal stricture. In this study, the feasibility of endoscopic catheter delivery of bioadhesive to esophageal lesions in a porcine model was tested. Injectable bioadhesive was composed of oxidized dextran (ODA) and chitosan hydrochloride (CS), its physicochemical properties, injectability, antibacterial activity, and cytocompatibility were investigated before in vivo test. ODA-CS bioadhesive was delivered to the wound bed of the esophageal tissue using a custom-made catheter device after ESD in a porcine model. Our results show that the ODA-CS bioadhesive is of good injectability, tissue adhesive strength, antibacterial capacity, and blood compatibility. In vivo delivery was achieved by endoscopic spraying of ODA and CS in separate catheters fixed on the endoscopic probe. ODA and CS can be mixed well to allow in situ bioadhesive formation and firmly adhere to the esophageal wound surface. After two weeks, the bioadhesive maintained structural integrity and adhered to the surface of esophageal wounds. However, histological analysis reveals that the ODA-CS bioadhesive did not show improvement in attenuating inflammatory response after ESD. This pilot study demonstrates the feasibility of ODA-CS bioadhesive for shielding esophageal wounds after ESD, whereas efforts need to improve its anti-inflammatory activity to reduce fibrosis for stricture prevention., (© 2024 IOP Publishing Ltd.)

Uncontrolled bleeding and wound infections following severe trauma pose significant challenges for existing tissue adhesives, primarily due to their weak wet adhesion, slow adhesion formation, cytotoxicity concerns, and lack of antibacterial properties. Herein, an injectable hydrogel (denoted as ES gel) with rapid, robust adhesive sealing and inherent antibacterial activity based on ε-polylysine and a poly(ethylene glycol) derivative is developed. The engineered hydrogel exhibits rapid gelation behavior, high mechanical strength, strong adhesion to various tissues, and can sustain an ultrahigh burst pressure of 450 mmHg. It also presents excellent biocompatibility, biodegradability, antibacterial properties, and on-demand removability. Significantly improved hemostatic efficacy of ES gel compared to fibrin glue is demonstrated using various injury models in rats and rabbits. Remarkably, the adhesive hydrogel can effectively halt lethal non-compressible hemorrhages in visceral organs (liver, spleen, and heart) and femoral artery injury models in fully anticoagulated pigs. Furthermore, the hydrogel outperforms commercial products in sutureless wound closure and repair in the rat liver defect, skin incision, and infected full-thickness skin wound models. Overall, this study highlights the promising clinical applications of ES gel for managing uncontrolled hemorrhage, sutureless wound closure, and infected wound repair., (© 2024 Wiley‐VCH GmbH.)

Myocardial infarction (MI) is a significant cardiovascular disease that restricts blood flow, resulting in massive cell death and leading to stiff and noncontractile fibrotic scar tissue formation. Recently, sustained oxygen release in the MI area has shown regeneration ability; however, improving its therapeutic efficiency for regenerative medicine remains challenging. Here, a combinatorial strategy for cardiac repair by developing cardioprotective and oxygenating hybrid hydrogels that locally sustain the release of stromal cell-derived factor-1 alpha (SDF) and oxygen for simultaneous activation of neovascularization at the infarct area is presented. A sustained release of oxygen and SDF from injectable, mechanically robust, and tissue-adhesive silk-based hybrid hydrogels is achieved. Enhanced endothelialization under normoxia and anoxia is observed. Furthermore, there is a marked improvement in vascularization that leads to an increment in cardiomyocyte survival by ≈30% and a reduction of the fibrotic scar formation in an MI animal rodent model. Improved left ventricular systolic and diastolic functions by ≈10% and 20%, respectively, with a ≈25% higher ejection fraction on day 7 are also observed. Therefore, local delivery of therapeutic oxygenating and cardioprotective hydrogels demonstrates beneficial effects on cardiac functional recovery for reparative therapy., (© 2024 Wiley‐VCH GmbH.)

Integrated wound care, a sequential process of promoting wound hemostasis, sealing, and healing, is of great clinical significance. However, the wet environment of wounds poses formidable challenges for integrated care. Herein, we developed an epidermal growth factor (EGF)-loaded, dehydrated physical microgel (DPM)-formed adhesive hydrogel for the integrated care of wet wounds. The DPMs were designed using the rational combination of hygroscopicity and reversible crosslinking of physical hydrogels. Unlike regular bioadhesives, which consider interfacial water as a barrier to adhesion, DPMs utilize water to form desirable adhesive structures. The hygroscopicity allowed the DPMs to absorb interfacial water and subsequently, the interfacial adhesion was realized by the interactions between tissue and DPMs. The reversible crosslinks further enabled DPMs to integrate into hydrogels (DPM-Gels), thus achieving wet adhesion. Importantly, the water-absorbing gelation mode of DPMs enabled facile loading of biologically active EGF to promote wound healing. We demonstrated that the DPM-Gels possessed wet tissue adhesive performance, with about 40 times the wet adhesive strength of fibrin glue and about 4 times the burst pressure of human blood pressure. Upon application at the injury site, the EGF-loaded DPM-Gels sequentially promoted efficient wound hemostasis, stable sealing, and quick healing, achieving integrated care of wet wounds., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Tissue adhesives and sealants offer promising alternatives to traditional wound closure methods, but the existing trade-off between biocompatibility and strength is still a challenge. The current study explores the potential of a gelatin-alginate-based hydrogel, cross-linked with a carbodiimide, and loaded with two functional fillers, the hemostatic agent kaolin and cellulose fibres, to improve the hydrogel's mechanical strength and hemostatic properties for use as a sealant. The effect of the formulation parameters on the mechanical and physical properties was studied, as well as the biocompatibility and microstructure. The incorporation of the two functional fillers resulted in a dual micro-composite structure, with uniform dispersion of both fillers within the hydrogel, and excellent adhesion between the fillers and the hydrogel matrix. This enabled to strongly increase the sealing ability and the tensile strength and modulus of the hydrogel. The fibres' contribution to the enhanced mechanical properties is more dominant than that of kaolin. A combined synergistic effect of both fillers resulted in enhanced sealing ability (247%), tensile strength (400%), and Young's modulus (437%), compared to the unloaded hydrogel formulation. While the incorporation of kaolin almost did not affect the physical properties of the hydrogel, the incorporation of the fibres strongly increased the viscosity and decreased the gelation time and swelling degree. The cytotoxicity tests indicated that all studied formulations exhibited high cell viability. Hence, the studied new dual micro-composite hydrogels may be suitable for medical sealing applications, especially when it is needed to get a high sealing effect within a short time. The desired hemostatic effect is obtained due to kaolin incorporation without affecting the physical properties of the sealant. Understanding the effects of the formulation parameters on the hydrogel's properties enables the fitting of optimal formulations for various medical sealing applications., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Integrated wound care through sequentially promoting hemostasis, sealing, and healing holds great promise in clinical practice. However, it remains challenging for regular bioadhesives to achieve integrated care of dynamic wounds due to the difficulties in adapting to dynamic mechanical and wet wound environments. Herein, we reported a type of dehydrated, physical double crosslinked microgels (DPDMs) which were capable of in situ forming highly stretchable, compressible and tissue-adhesive hydrogels for integrated care of dynamic wounds. The DPDMs were designed by the rational integration of the reversible crosslinks and double crosslinks into micronized gels. The reversible physical crosslinks enabled the DPDMs to integrate together, and the double crosslinked characteristics further strengthen the formed macroscopical networks (DPDM-Gels). We demonstrated that the DPDM-Gels simultaneously possess outstanding tensile (∼940 kJ/m 3 ) and compressive (∼270 kJ/m 3 ) toughness, commercial bioadhesives-comparable tissue-adhesive strength, together with stable performance under hundreds of deformations. In vivo results further revealed that the DPDM-Gels could effectively stop bleeding in various bleeding models, even in an actual dynamic environment, and enable the integrated care of dynamic skin wounds. On the basis of the remarkable mechanical and appropriate adhesive properties, together with impressive integrated care capacities, the DPDM-Gels may provide a new approach for the smart care of dynamic wounds. STATEMENT OF SIGNIFICANCE: Integrated care of dynamic wounds holds great significance in clinical practice. However, the dynamic and wet wound environments pose great challenges for existing hydrogels to achieve it. This work developed robust adhesive hydrogels for integrated care of dynamic wounds by designing dehydrated, physical double crosslinked microgels (DPDMs). The reversible and double crosslinks enabled DPDMs to integrate into macroscopic hydrogels with high mechanical properties, appropriate adhesive strength and stable performance under hundreds of external deformations. Upon application at the injury site, DPDM-Gels efficiently stopped bleeding, even in an actual dynamic environment and showed effectiveness in integrated care of dynamic wounds. With the fascinating properties, DPDMs may become an effective tool for smart wound care., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

In this study, we developed a tissue-adhesive and long-term antibacterial hydrogel consisting of protamine (PRTM) grafted carboxymethyl chitosan (CMC) (PCMC), catechol groups modified CMC (DCMC), and oxidized hyaluronic acid (OHA), named DCMC-OHA-PCMC. According to the antibacterial experiments, the PCMC-treated groups showed obvious and long-lasting inhibition zones against E. coli (and S. aureus), and the corresponding diameters varied from 10.1 mm (and 15.3 mm) on day 1 to 9.8 mm (and 15.3 mm) on day 7. The DCMC-OHA-PCMC hydrogel treated groups also exhibited durable antibacterial ability against E. coli (and S. aureus), and the antibacterial rates changed from 99.3 ± 0.21 % (and 99.6 ± 0.36 %) on day 1 to 76.2 ± 1.74 % (and 84.2 ± 1.11 %) on day 5. Apart from good mechanical and tissue adhesion properties, the hydrogel had excellent hemostatic ability mainly because of the grafted positive-charged PRTM. As the animal assay results showed, the hydrogel was conducive to promoting the deposition of new collagen (0.84 ± 0.03), the regeneration of epidermis (98.91 ± 6.99 μm) and wound closure in the process of wound repairing. In conclusion, the presented outcomes underline the prospective potential of the multifunctional CMC-based hydrogel for applications in wound dressings., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Stimuli-responsive adhesives with on-demand adhesion capabilities are highly advantageous for facilitating wound healing. However, the triggering conditions of stimuli-responsive adhesives are cumbersome, even though some of them are detrimental to the adhesive and adjacent natural tissues. Herein, a novel stimuli-responsive adhesive called shear-stiffening adhesive (SSA) has been created by constructing a poly(diborosiloxane)-based silicone network for the first time, and SSA exhibits a rate-responsive adhesion behavior. Furthermore, we introduced bactericidal factors (PVP-I) into SSA and applied it as a wound dressing to promote the healing of infected wounds. Impressively, the wound dressing not only has excellent biocompatibility and long-term antibacterial properties but also performs well in accelerating wound healing. Therefore, this study provides a new strategy for the synthesis of intelligent adhesives with force rate response, which simplifies the triggering conditions by the force rate. Thus, SSA has great potential to be applied in wound management as an intelligent bioadhesive with on-demand adhesion performance.

Solid particles placed at the interface between hydrogels and biological tissues can create an adhesive joint through the adsorption of macromolecules onto their surfaces. Here, we investigated how this adhesion by particle bridging depends on the wetting of tissue surfaces and on the heterogeneities in tissue composition. Ex vivo peeling experiments were performed using poly(ethylene glycol) films coated with aggregates of silica nanoparticles deposited on the internal tissues of porcine liver. We show that the adhesion produced by particle bridging is altered by the presence of fluid wetting the tissue-hydrogel interface. For both uncoated and coated films, a transition from lubricated to adhesive contact was observed when all the interfacial fluid was drained. The presence of a silica nanoparticle coating shifted the transition towards more hydrated conditions and significantly enhanced adhesion in the adhesive regime. After 5 min of contact, the adhesion energy achieved on liver parenchyma with the coated films (7.7 ± 1.9 J m -2 ) was more than twice that of the uncoated films (3.2 ± 0.3 J m -2 ) or with a surgical cyanoacrylate glue (2.9 ± 1.9 J m -2 ). Microscopic observations during and after peeling revealed different detachment processes through either particle detachment or cohesive fracture in the tissue. These mechanisms could be directly related to the microanatomy of the liver parenchyma. The effects of both interfacial wetting and tissue composition on adhesion may provide guidelines to tailor the design of tissue adhesives using particle bridging.

Emergency prehospital wound closure and hemorrhage control are the first priorities for life-saving. Majority of bioadhesives form bonds with tissues through irreversible cross-linking, and the remobilization of misalignment may cause severe secondary damage to tissues. Therefore, developing an adhesive that can quickly and tolerably adhere to traumatized dynamic tissue or organ surfaces in emergency situations is a major challenge. Inspired by the structure of human serum albumin (HSA), a branched polymer with multitentacled sulfhydryl is synthesized, then, an instant and fault-tolerant tough wet-tissue adhesion (IFA) hydrogel is prepared. Adhesive application time is just 5 s (interfacial toughness of ≈580 J m -2 ), and favorable tissue-adhesion is maintained after ten cycles. IFA hydrogel shows unchangeable adhesive performance after 1 month of storage based on the internal oxidation-reduction mechanism. It not only can efficiently seal various organs but also achieves effective hemostasis in models of the rat femoral artery and rabbit-ear artery. This work also proposes an effective strategy for controllable adhesion, enabling the production of asymmetric adhesives with on-demand detachment. Importantly, IFA hydrogel has sound antioxidation, antibacterial property, hemocompatibility, and cytocompatibility. Hence, the HSA-inspired bioadhesive emerges as a promising first-aid supply for human-machine interface-based health management and non-invasive wound closure., (© 2024 Wiley‐VCH GmbH.)

Novel adhesives for biological tissues offer an advanced surgical approach. Here, the authors report the development and application of solid-state adhesives consisting of porous hydroxyapatite (HAp) biocompatible ceramics as novel internal organ retractors. The operational principles of the porous solid-state adhesives are experimentally established in terms of water migration from biological soft tissues into the pores of the adhesives, and their performance is evaluated on several soft tissues with different hydration states. As an example of practical medical utility, HAp adhesive devices demonstrate the holding ability of porcine livers and on-demand detachability in vivo, showing great potential as internal organ retractors in laparoscopic surgery., (© 2024 The Authors. Advanced Healthcare Materials published by Wiley‐VCH GmbH.)

The powerful adhesion systems of marine organisms have inspired the development of artificial protein-based bioadhesives. However, achieving robust wet adhesion using artificial bioadhesives remains technically challenging because the key element of liquid-liquid phase separation (LLPS)-driven complex coacervation in natural adhesion systems is often ignored. In this study, mimicking the complex coacervation phenomenon of marine organisms, an artificial protein-based adhesive hydrogel (SFG hydrogel) was developed by adopting the LLPS-mediated coacervation of the natural protein silk fibroin (SF) and the anionic surfactant sodium dodecylbenzene sulfonate (SDBS). The assembled SF/SDBS complex coacervate enabled precise spatial positioning and easy self-adjustable deposition on irregular substrate surfaces, allowing for tight contact. Spontaneous liquid-to-solid maturation promoted the phase transition of the SF/SDBS complex coacervate to form the SFG hydrogel in situ, enhancing its bulk cohesiveness and interfacial adhesion. The formed SFG hydrogel exhibited intrinsic advantages as a new type of artificial protein-based adhesive, including good biocompatibility, robust wet adhesion, rapid blood-clotting capacity, and easy operation. In vitro and in vivo experiments demonstrated that the SFG hydrogel not only achieved instant and effective hemostatic sealing of tissue injuries but also promoted wound healing and tissue regeneration, thus advancing its clinical applications. STATEMENT OF SIGNIFICANCE: Marine mussels utilize the liquid-liquid phase separation (LLPS) strategy to induce the supramolecular assembly of mussel foot proteins, which plays a critical role in strong underwater adhesion of mussel foot proteins. Herein, an artificial protein-based adhesive hydrogel (named SFG hydrogel) was reported by adopting the LLPS-mediated coacervation of natural protein silk fibroin (SF) and anionic surfactant sodium dodecylbenzene sulfonate (SDBS). The assembled SFG hydrogel enabled the precise spatial positioning and easy self-adjustable deposition on substrate surfaces with irregularities, allowing tight interfacial adhesion and cohesiveness. The SFG hydrogel not only achieved instant and effective hemostatic sealing of tissue injuries but also promoted wound healing and tissue regeneration, exhibiting intrinsic advantages as a new type of artificial protein-based bioadhesives., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Median sternotomy surgery stands as one of the prevailing strategies in cardiac surgery. In this study, the cutting-edge bone adhesive is designed, inspired by the impressive adhesive properties found in mussels and sandcastle worms. This work has created an osteogenic nanocomposite coacervate adhesive by integrating a cellulose-polyphosphodopamide interpenetrating network, quaternized chitosan, and zinc, gallium-doped hydroxyapatite nanoparticles. This adhesive is characterized by robust catechol-metal coordination which effectively adheres to both hard and soft tissues with a maximum adhesive strength of 900 ± 38 kPa on the sheep sternum bone, surpassing that of commercial bone adhesives. The release of zinc and gallium cations from nanocomposite adhesives and quaternized chitosan matrix imparts remarkable antibacterial properties and promotes rapid blood coagulation, in vitro and ex vivo. It is also proved that this nanocomposite adhesive exhibits significant in vitro bioactivity, stable degradability, biocompatibility, and osteogenic ability. Furthermore, the capacity of nanocomposite coacervate to adhere to bone tissue and support osteogenesis contributes to the successful healing of a sternum bone defect in a rabbit model in vivo. In summary, these nanocomposite coacervate adhesives with promising characteristics are expected to provide solutions to clinical issues faced during median sternotomy surgery., (© 2024 Wiley‐VCH GmbH.)

Management of infections at ocular injury often requires prolonged and high dose of antibiotic, which is associated with challenges of antibiotic resistance and bacterial biofilm formation. Tissue glues are commonly used for repairing ocular tissue defects and tissue regeneration, but they are ineffective in curing infection. There is a critical need for antibacterial ocular bio-adhesives capable of both curing infection and aiding wound closure. Herein, we present the development of an imine crosslinked N-(2-hydroxypropyl)-3-trimethylammonium chitosan chloride (HTCC)‑silver chloride nanocomposites (QAm 1 -Ag x ) and poly-dextran aldehyde (PDA) based bactericidal sealant (BacSeal). BacSeal exhibited potent bactericidal activity against a broad spectrum of bacteria including their planktonic and stationary phase within a short duration of 4 h. BacSeal effectively reduced biofilm-embedded MRSA and Pseudomonas aeruginosa by ∼99.99 %. In ex-vivo human cornea infection model, BacSeal displayed ∼99 % reduction of ocular infection. Furthermore, the hydrogel exhibited excellent sealing properties by maintaining ocular pressure up to 75 mm-Hg when applied to human corneal trauma. Cytotoxicity assessment and hydrogel-treated human cornea with a retained tissue structure, indicate its non-toxic nature. Collectively, BacSeal represents a promising candidate for the development of an ocular sealant that can effectively mitigate infections and may assist in tissue regeneration by sealing ocular wounds., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Patients with open abdominal (OA) wounds have a mortality risk of up to 30%, and the resulting disabilities would have profound effects on patients. Here, we present a novel double-sided adhesive tape developed for the management of OA wounds. The tape features an asymmetrical structure and employs an acellular dermal matrix (ADM) with asymmetric wettability as a scaffold. It is constructed by integrating a tissue-adhesive hydrogel composed of polydopamine (pDA), quaternary ammonium chitosan (QCS), and acrylic acid cross-linking onto the bottom side of the ADM. Following surface modification with pDA, the ADM would exhibit characteristics resistant to bacterial adhesion. Furthermore, the presence of a developed hydrogel ensures that the tape not only possesses tissue adhesiveness and noninvasive peelability but also effectively mitigates damage caused by oxidative stress. Besides, the ADM inherits the strength of the skin, imparting high burst pressure tolerance to the tape. Based on these remarkable attributes, we demonstrate that this double-sided (D-S) tape facilitates the repair of OA wounds, mitigates damage to exposed intestinal tubes, and reduces the risk of intestinal fistulae and complications. Additionally, the D-S tape is equally applicable to treating other abdominal injuries, such as gastric perforations. It effectively seals the perforation, promotes injury repair, and prevents the formation of postoperative adhesions. These notable features indicate that the presented double-sided tape holds significant potential value in the biomedical field.

Intestine damage is an acute abdominal disease that usually requires emergency sealing. However, traditional surgical suture not only causes secondary damage to the injured tissue, but also results in adhesion with other tissues in the abdominal cavity. To this end, a thermally reversible injectable gelatin-based hydrogel adhesive (GTPC) is constructed by introducing transglutaminase (TGase) and proanthocyanidins (PCs) into a gelatin system. By reducing the catalytic activity of TGase, the density of covalent and hydrogen bond crosslinking in the hydrogel can be regulated to tune the sol-gel transition temperature of gelatin-based hydrogels above the physiological temperature (42 °C) without introducing any synthetic small molecules. The GTPC hydrogel exhibits good tissue adhesion, antioxidant, and antibacterial properties, which can effectively seal damaged intestinal tissues and regulate the microenvironment of the damaged site, promoting tissue repair and regeneration. Intriguingly, temperature-induced hydrogen bond disruption and reformation confer the hydrogel with asymmetric adhesion properties, preventing tissue adhesion when applied in vivo . Animal experiment outcomes reveal that the GTPC hydrogel can seal the damaged intestinal tissue firmly, accelerate tissue healing, and efficiently prevent postoperative adhesion.

Achieving underwater adhesion possesses a significant challenge, primarily due to the presence of interfacial water, which restricts the potential applications of adhesives. In this study, we present a straightforward and environmentally friendly one-pot approach for synthesizing a solvent-free supramolecular TPFe bioadhesive composed of thioctic acid, proanthocyanidins, and FeCl 3 . The bioadhesive exhibits excellent biocompatibility and photothermal antibacterial properties and demonstrates effective adhesion on various substrates in both wet and dry environments. Importantly, the adhesive strength of this bioadhesive on steel exceeds 1.2 MPa and that on porcine skin exceeds 100 kPa, which is greater than the adhesive strength of most reported bioadhesives. In addition, the bioadhesive exhibits the ability to effectively halt bleeding, close wounds promptly, and promote wound healing in the rat skin wound model. Therefore, the TPFe bioadhesive has potential as a medical bioadhesive for halting bleeding quickly and promoting wound healing in the biomedical field. This study provides a new idea for the development of bioadhesives with firm wet adhesion.

Injectable bioadhesives are attractive for managing gastric ulcers through minimally invasive procedures. However, the formidable challenge is to develop bioadhesives that exhibit high injectability, rapidly adhere to lesion tissues with fast gelation, provide reliable protection in the harsh gastric environment, and simultaneously ensure stringent standards of biocompatibility. Here, a natural bioadhesive with tunable cohesion is developed based on the facile and controllable gelation between silk fibroin and tannic acid. By incorporating a hydrogen bond disruptor (urea or guanidine hydrochloride), the inherent network within the bioadhesive is disturbed, inducing a transition to a fluidic state for smooth injection (injection force <5 N). Upon injection, the fluidic bioadhesive thoroughly wets tissues, while the rapid diffusion of the disruptor triggers instantaneous in situ gelation. This orchestrated process fosters the formed bioadhesive with durable wet tissue affinity and mechanical properties that harmonize with gastric tissues, thereby bestowing long-lasting protection for ulcer healing, as evidenced through in vitro and in vivo verification. Moreover, it can be conveniently stored (≥3 m) postdehydration. This work presents a promising strategy for designing highly injectable bioadhesives utilizing natural feedstocks, avoiding any safety risks associated with synthetic materials or nonphysiological gelation conditions, and offering the potential for minimally invasive application., (© 2024 Wiley‐VCH GmbH.)

In transdermal drug delivery system (TDDS) patches, achieving prolonged adhesion, high drug loading, and rapid drug release simultaneously presented a significant challenge. In this study, a PHT-SP-Cu 2+ adhesive was synthesized using polyethylene glycol (PEG), hexamethylene diisocyanate (HDI), trimethylolpropane (TMP), and silk protein (SP) as functional monomers which were combined with Cu 2+ to improve the adhesion, drug loading, and drug release of the patch. The structure of the adhesion chains and the formation of Cu 2+ -p-π conjugated network in PHT-SP-Cu 2+ were characterized and elucidated using different characterization methods including FT-IR, 13 C NMR, XPS, SEM imaging and thermodynamic evaluation. The formulation of pressure-sensitive adhesive (PSA) was optimized through comprehensive research on adhesion, mechanics, rheology, and surface energy. The formulation of 3 wt.% SP and 3 wt.% Cu 2+ provided superior adhesion properties compared to commercial standards. Subsequently, the peel strength of PHT-SP-Cu 2+ was 7.6 times higher than that of the commercially available adhesive DURO-TAK® 87-4098 in the porcine skin peel test. The adhesion test on human skin confirmed that PHT-SP-Cu 2+ could adhere to the human body for more than six days. Moreover, the drug loading, in vitro release test and skin permeation test were investigated using ketoprofen as a model drug, and the results showed that PHT-SP-Cu 2+ had the efficacy of improving drug compatibility, promoting drug release and enhancing skin permeation as a TDDS. Among them, the drug loading of PHT-SP-Cu 2+ was increased by 6.25-fold compared with PHT, and in the in vivo pharmacokinetic analysis, the AUC was similarly increased by 19.22-fold. The mechanism of α-helix facilitated drug release was demonstrated by Flori-Hawkins interaction parameters, molecular dynamics simulations and FT-IR. Biosafety evaluations highlighted the superior skin cytocompatibility and safety of PHT-SP-Cu 2+ for transdermal applications. These results would contribute to the development of TDDS patch adhesives with outstanding adhesion, drug loading and release efficiency. STATEMENT OF SIGNIFICANCE: A new adhesive, PHT-SP-Cu 2+ , was created for transdermal drug delivery patches. Polyethylene glycol, hexamethylene diisocyanate, trimethylolpropane, silk protein, and Cu 2+ were used in synthesis. Characterization techniques confirmed the structure and Cu 2+ -p-π conjugated networks. Optimal formulation included 3 wt.% SP and 3 wt.% Cu 2+ , exhibiting superior adhesion. PHT-SP-Cu 2+ showed 7.6 times higher peel strength than DURO-TAK® 87-4098 on porcine skin and adhered to human skin for over six days. It demonstrated a 6.25-fold increase in drug loading compared to PHT, with 19.22-fold higher AUC in vivo studies. α-helix facilitated drug release, proven by various analyses. PHT-SP-Cu 2+ showed excellent cytocompatibility and safety for transdermal applications. This study contributes to developing efficient TDDS patches., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interest. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Hydrogels incorporating natural biopolymer and adhesive substances have extensively been used to develop bioactive drugs and to design cells encapsulating sturdy structure for biomedical applications. However, the conjugation of the adhesive in most hydrogels is insufficient to maintain long-lasting biocompatibility inadequate to accelerate internal organ tissue repair in the essential native cellular microenvironment. The current work elaborates the synthesis of charged choline-catechol ionic liquid (BIL) adhesive and a hydrogel with an electronegative atom rich polyphenol (PU)-laden gelatinmethacryloyl (GelMA) to improve the structural bioactivities for in vivo tracheal repair by inducing swift crosslinking along with durable mechanical and tissue adhesive properties. It was observed that bioactive BIL and PU exhibited potent antioxidant (IC 50 % of 7.91 μg/mL and 24.55 μg/mL) and antibacterial activity against E. coli, P. aeruginosa and S. aureus. The novel integration of photocurable GelMA-BIL-PU revealed outstanding mechanical strength, biodegradability and sustained drug release. The in vitro study showed exceptional cell migration and proliferation in HBECs, while in vivo investigation of the GelMA-BIL-PU hydrogel on a rat's tracheal model revealed remarkable tracheal reconstruction, concurrently reducing tissue inflammation. Furthermore, the optimized GelMA-BIL-PU injectable adhesive bioink blend demonstrated superior MSCs migration and proliferation, which could be a strong candidate for developing stem cell-rich biomaterials to address multiple organ defects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Carbene-based bioadhesives have favourable attributes for tissue adhesion, including non-specific bonding to wet and dry tissues, but suffer from relatively weak fracture strength after photocuring. Light irradiation of carbene-precursor (diazirine) also creates inert side products that are absent under thermal activation. Herein, a dual activation method combines light irradiation at elevated temperatures for the evaluation of diazirine depletion and effects on cohesive properties. A customized photo/thermal-rheometer evaluates viscoelastic properties, correlated to the kinetics of carbene:diazoalkane ratios via 19 F NMR). The latter exploits the sensitive -CF 3 functional group to determine joule-based light/temperature kinetics on trifluoroaryl diazirine consumption. The combination of heat and photoactivation produced bioadhesives that are 3× tougher compared to control. Dual thermal/light irradiation may be a strategy to improve viscoelastic dissipation and toughness of photo-activated adhesive resins., (© 2024 The Authors. Advanced Healthcare Materials published by Wiley‐VCH GmbH.)

Naturally occurring internal bleeding, such as in stomach ulcers, and complications following interventions, such as polyp resection post-colonoscopy, may result in delayed (5-7 days) post-operative adverse events-such as bleeding, intestinal wall perforation, and leakage. Current solutions for controlling intra- and post-procedural complications are limited in effectiveness. Hemostatic powders only provide a temporary solution due to their short-term adhesion to GI mucosal tissues (less than 48 h). In this study, a sprayable adhesive hydrogel for facile application and sustained adhesion to GI lesions is developed using clinically available endoscopes. Upon spraying, the biomaterial (based on polyethyleneimine-modified Pluronic micelles precursor and oxidized dextran) instantly gels upon contact with the tissue, forming an adhesive shield. In vitro and in vivo studies in guinea pigs, rabbits, and pig models confirm the safety and efficacy of this biomaterial in colonic and acidic stomach lesions. The authors' findings highlight that this family of hydrogels ensures prolonged tissue protection (3-7 days), facilitates wound healing, and minimizes the risk of delayed complications. Overall, this technology offers a readily adoptable approach for gastrointestinal wound management., (© 2024 The Authors. Advanced Materials published by Wiley‐VCH GmbH.)

Suture pull-through is a clinical problem in meniscus repair surgery due to the sharp leading edge of sutures. Several tissue adhesives have been developed as an alternative to traditional suturing; however, there is still no suitable tissue adhesive specific for meniscus repair treatment due to unsatisfactory biosafety, biodegradable, sterilizable, and tissue-bonding characteristics. In this study, we used a tissue adhesive composed of chitosan hydrochloride reacted with oxidative periodate-oxidized dextran (ChitHCl-DDA) combined with a chitosan-based hydrogel and oxidative dextran to attach to the meniscus. We conducted viscoelastic tests, viscosity tests, lap shear stress tests, Fourier transform infrared (FTIR) spectroscopy, swelling ratio tests, and degradation behavior tests to characterize these materials. An MTT assay, alcian blue staining, migration assay, cell behavior observations, and protein expression tests were used to understand cell viability and responses. Moreover, ex vivo and in vivo tests were used to analyze tissue regeneration and biocompatibility of the ChitHCl-DDA tissue adhesive. Our results revealed that the ChitHCl-DDA tissue adhesive provided excellent tissue adhesive strength, cell viability, and cell responses. This tissue adhesive has great potential for torn meniscus tissue repair and regeneration., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)