Adhesive Hydrogel Research Articles

Application of polymer adhesive hydrogel in wound healing

As the global adhesive industry continues to grow, researchers are discovering that polymer adhesives are playing an increasing role in the medical field, polymer adhesives have attracted more and more attention from the medical industry due to their unique advantages, such as hydrogels, have gradually appeared, which can effectively help wound healing. Most of the hydrogels have good biocompatibility and water absorption, and have the advantages of controllable structure, adjustable performance and easy degradation. Compared with traditional wound healing methods, hydrogels effectively reduce additional trauma and leakage and allow for greater tissue integration. This paper reviews the types of polymeric adhesive hydrogels and examples of some of them being artificially modified to be applied to the field of wound healing. Analyzes their mechanism of action and the advantages and shortcomings of their clinical applications, and finally looks into the potential functions and clinical efficacy of hydrogels in the future.

Correction to “Injectable Adhesive Hydrogel as Photothermal‐Derived Antigen Reservoir for Enhanced Anti‐Tumor Immunity”

Correction to “Injectable Adhesive Hydrogel as Photothermal‐Derived Antigen Reservoir for Enhanced Anti‐Tumor Immunity”

Stretchable, self-healing, adhesive and anti-freezing ionic conductive cellulose-based hydrogels for flexible supercapacitors and sensors

Stretchable, self-healing, adhesive and anti-freezing ionic conductive cellulose-based hydrogels for flexible supercapacitors and sensors

Gene Therapy for Inflammatory Cascade in Intrauterine Injury with Engineered Extracellular Vesicles Hybrid Snail Mucus-enhanced Adhesive Hydrogels.

Early hyper-inflammation caused by intrauterine injury triggered subsequent intrauterine adhesion (IUA). STAT1-mediated M1 macrophages are confirmed to secrete pro-inflammatory cytokines to accelerate inflammatory cascade and IUA formation by multi-omics analysis and experimental verification. However, clinically used hyaluronic acid (HA) hydrogels are prone to slip out of injury sites due to poor bio-adhesion properties. Therefore, there are still challenges in applying hydrogels for M1 macrophage intervention in IUA treatment. Herein, an engineered extracellular vesicles (EVs) hybrid snail mucus (SM)-enhanced adhesive hydrogels to improve bio-adhesion property is fabricated and M1 macrophage intervention through targeting delivery and STAT1 silencing is achieved. First, inspired by the high bio-adhesion capacity of SM, SM and gelatin methacrylate (GelMA) solution are mixed to construct GelMA/SM (GS) hydrogel. Then, folic acid-modified extracellular vesicles (FA-EVs) are synthesized for targeting the delivery of STAT1-siRNA. Upon injection of FA-EVs hybrid GS hydrogel into the uterine cavity, a protective hydrogel layer forms on the surface of injury sites and sustains the release of STAT1-siRNA-loaded FA-EVs to curtail M1 macrophages generation through inhibiting STAT1 phosphorylation, resulting in reduction of myofibroblasts activation and collagen deposition. In addition, the pregnancy rate and the number of fetuses in rats treated with this hydrogel were much higher than those in other groups, suggesting that the hydrogel could promote functional endometrial regeneration and restore fertility. Overall, this study presents a promising strategy for employing FA-EVs hybrid adhesive hydrogel with superior bio-adhesion properties and M1 macrophage targeting delivery for IUA treatment and uterus recovery.

Cohesion Regulation of Polyphenol Cross‐Linked Hydrogel Adhesives: From Intrinsic Cross‐Link to Designs of Temporal Responsiveness

AbstractPolyphenol hydrogels have found widespread application in wound healing, bone repair, drug delivery, and biosensors due to their robust wet adhesion, high ductility, and excellent self‐healing ability. However, these hydrogels often exhibit low intrinsic cohesion, which limits their overall adhesive strength. Enhancing cohesion is critical for improving both the adhesion and mechanical properties of the hydrogels, thereby expanding their utility in biomedical fields. This review begins by exploring strategies to enhance the cohesion of polyphenol hydrogel adhesives, detailing modifications that act individually or synergistically. The importance of temporally regulating cohesion is emphasized to accommodate various applications and environmental conditions. Finally, this paper discusses remaining challenges in cohesion regulation and outlines prospects for future research. It is hoped that this comprehensive review will provide new insights into the development of advanced polyphenolic hydrogel adhesives and contribute to the design of “smart adhesives” for increasingly complex needs in biomedical applications.

Paintable, Fast Gelation, Highly Adhesive Hydrogels for High-fidelity Electrophysiological Monitoring Wirelessly.

High-fidelity wireless electrophysiological monitoring is essential for ambulatory healthcare applications. Soft solid-like hydrogels have received significant attention as epidermal electrodes because of their tissue-like mechanical properties and high biocompatibility. However, it is challenging to develop a hydrogel electrode that provides robust contact and high adhesiveness with glabrous skin and hairy scalp for high-fidelity, continuous electrophysiological signal detection. Here, a paintable, fast gelation, highly adhesive, and conductive hydrogel is engineered for high-fidelity wireless electrophysiological monitoring. The hydrogel, consisting of gelatin, gallic acid, sodium citrate, lithium chloride, glycerol, and Tris-HCl buffer solution exhibits a reversible thermal phase transition capability, which endows it with the attributes of on-skin applicability and fast in situ gelation with 15 s, thereby addressing the aforementioned limitations. The introduction of gallic acid enhances the adhesive properties of the hydrogel, facilitating secure electrode attachment to the skin or hairy scalp. To accentuate the potential applications in at-home electrophysiological health monitoring, the hydrogel electrodes are demonstrated for high-fidelity electrocardiogram recording for one hour during various daily activities, as well as in simultaneous electroencephalogram and electrocardiogram recording during a 30 min nap.

Preventing postsurgical colorectal cancer relapse: A hemostatic hydrogel loaded with METTL3 inhibitor for CAR-NK cell therapy

Colorectal cancer (CRC) recurrence post-surgery remains a major challenge. While Chimeric Antigen Receptor (CAR)-engineered natural killer (NK) cells hold immense therapeutic potential, their intratumoral infiltration ability remains limited, hampering efficacy. Building upon prior research suggesting that chemokines like C-X-C motif chemokine ligand 9 (CXCL9) and C-X-C motif chemokine ligand 10 (CXCL10) recruit CAR-NK cells, we hypothesized that tumor cell m6A methylation, regulated by Methyltransferase-like 3 (METTL3), influences chemokine secretion. This study aims to elucidate the underlying mechanisms and improve METTL3 inhibition efficiency. We designed an adhesive hemostasis hydrogel loaded with STM2457, a METTL3 inhibitor, aimed at sustained release in the acidic tumor microenvironment. In vitro, the hydrogel promoted CAR-NK cell recruitment and tumor killing via sustained METTL3 inhibition. The hydrogel's Schiff base bonds further enabled intestinal adhesion and hemostasis in an incomplete tumor resection model of CRC. Combining the hydrogel with CAR-NK cell therapy significantly reduced CRC recurrence in vivo. Overall, our study reveals the crucial role of METTL3 in CRC recurrence and proposes a promising, multimodal strategy using STM2457-loaded hydrogel and CAR-NK cells for enhanced therapeutic efficacy.

Responsively aggregatable nanochelator-mediated antiangiogenesis to enhance interventional therapies for liver cancer

Transarterial chemoembolization (TACE) requires the complete embolization of tumor vessels. However, after embolization, tumor hypoxia and angiogenesis increase, and copper ions (Cu2+) play a key role in the regulation of angiogenesis. Decreasing the undesirable release of Cu2+ into serum and tumor tissues is a major challenge in the use of TACE. In this study, we constructed an adhesive injectable thermosensitive hydrogel (poly(N-isopropylacrylamide-codopamine methacrylamide), PND) loaded with a small Cu chelator (SO-N) for use in synergistic tumor embolization; this agent is called PNDS. SO-N chelates Cu2+ in a highly selective manner and can effectively consume the biocopper that is involved in angiogenesis. In addition, the adhesive thermosensitive hydrogel rapidly formed a gel in situ, which further inhibited the local blood ny to the tumor and accelerated ischemic necrosis. Moreover, the ability of PNDS to efficiently chelate Cu2+ and inhibit angiogenesis was investigated in vitro. Our in vivo experiments demonstrated that PNDS can promote tumor necrosis, reduce tumor Cu2+ levels, inhibit angiogenesis and tumor metastasis, and greatly prolong rabbit survival. This study is the first to show elevated serum Cu2+ levels in liver cancer patients with TACE failure/refractoriness; PNDS provides a promising approach for improving the efficacy of TACE for liver cancer by regulating Cu homeostasis.

Alpha-Tocopherol-Infused Flexible Liposomal Nanocomposite Pressure-Sensitive Adhesive: Enhancing Skin Permeation of Retinaldehyde

Retinaldehyde (RAL), or retinal, is a vitamin A derivative that is widely used for several skin conditions. However, it is light sensitive and has low water solubility, limiting its efficiency in transdermal delivery. This study developed a novel delivery system for retinal (RAL) using flexible liposomes (FLPs) infused with α-tocopherol succinate (α-TS) to improve stability, and enhance skin permeability. The RAL-FLPs were embedded in pressure-sensitive adhesive (PSA) hydrogels, creating a delivery platform that supports prolonged skin residence and efficient permeation of RAL. The stability and skin permeation as well as human skin irritation and adhesion capabilities were assessed to determine the formulation’s safety and efficacy. Our findings suggested that the addition of α-TS could improve liposomal stability and RAL chemical stability. Moreover, the skin permeation and fluorescence microscopic-based studies suggested that the addition of α-TS could enhance skin permeability of RAL through hair follicles. The RAL-FLP was embedded in PSA hydrogels fabricated from 25% GantrezTM S-97 (GT) and 1% hyaluronic acid (Hya) with aluminum as a crosslinker. The PSA hydrogel exhibited desirable peeling and tacking strengths. The developed hydrogels also demonstrated greater skin deposition of RAL compared with its aqueous formulation. Additionally, the RAL-FLP-embedded PSA hydrogels showed no skin irritation and maintained better adhesion for up to 24 h compared to commercial patches. Hence, the developed hydrogels could serve as a beneficial platform for delivering RAL in treating skin conditions.

Mechanism and Performance Evaluation of a Strain Sensor Made from a Composite Hydrogel Containing Conductive Fibers of Thermoplastic Polyurethane and Polyvinyl Alcohol.

Monitoring human physiological conditions using flexible, stretchable strain sensors is an effective approach to prevent and treat critical illnesses, emergencies, and infectious diseases. However, achieving ultralow detection limits, high sensitivity, and a wide detection range in a cost-effective manner is challenging. In this study, a strain sensor was developed by embedding an adhesive hydrogel composed of polyvinyl alcohol, starch, and glutaraldehyde into conductive fibers made from thermoplastic polyurethane. By leveraging the high sensitivity of the conductive fibers and the wide detection range of the hydrogel, a robust dual-layer continuous conductive network was formed through their synergistic interaction. Tensile strength tests and other assessments indicated that the sensitivity of the sensor increased from a gauge factor of 49.32 (for fiber-based sensors) to 74.18, while the detection range expanded from 250 to 400%. Furthermore, the sensor demonstrated a low detection limit (0.6%), fast response and recovery times (80 ms/120 ms), and durability exceeding 800 cycles. Tests on pulse monitoring, joint movement, and voice recognition confirmed the significant applicability of the sensor for real-time monitoring of various physiological activities throughout a human's life. This study aims to provide technical support for the development of flexible wearable systems.

An Adhesive Hydrogel Technology for Enhanced Cartilage Repair: A Preliminary Proof of Concept.

Knee cartilage has limited natural healing capacity, complicating the development of effective treatment plans. Current non-cell-based therapies (e.g., microfracture) result in poor repair cartilage mechanical properties, low durability, and suboptimal tissue integration. Advanced treatments, such as autologous chondrocyte implantation, face challenges including cell leakage and inhomogeneous distribution. Successful cell therapy relies on prolonged retention of therapeutic biologicals at the implantation site, yet the optimal integration of implanted material into the surrounding healthy tissue remains an unmet need. This study evaluated the effectiveness of a newly developed photo-curable adhesive hydrogel for cartilage repair, focusing on adhesion properties, integration performance, and ability to support tissue regeneration. The proposed hydrogel design exhibited significant adhesion strength, outperforming commercial adhesives such as fibrin-based glues. An in vivo goat model was used to evaluate the hydrogels' adhesion properties and long-term integration into full-thickness cartilage defects over six months. Results showed that cell-free hydrogel-treated defects achieved superior integration with surrounding tissue and enhanced cartilage repair, with notable lateral integration. In vitro results further demonstrated high cell viability, robust matrix production, and successful cell encapsulation within the hydrogel matrix. These findings highlight the potential of adhesive hydrogel formulations to improve the efficacy of cell-based therapies, offering a potentially superior treatment for knee cartilage defects.

Mussel-inspired thermo-switchable underwater adhesive based on a Janus hydrogel

On-demand underwater adhesives with excellent adhesive and gentle detachment properties enable stable connections to various biomedical devices and biointerfaces and avoid the risk of harmful tissue damage upon detachment. Herein, we present a Janus hydrogel adhesive that can reversibly switch its adhesion strength, which is controlled by temperature, using a thermoresponsive polymer and mussel-inspired molecules. This thermoswitchable adhesive (TSA) hydrogel displays both strong adhesion and gentle detachment with an over 1000-fold gap in underwater adhesion strength onto glass, titanium, aluminum, and Teflon substrates when exposed to temperatures above and below the lower critical solution temperature (LCST). The adhesion switch is possibly caused by the change in toughness of the TSA hydrogels with temperature because the Janus hydrogel possesses gradient crosslinked structures. Moreover, the lowermost surface is sufficiently soft to gently detach from the substrate below the LCST. The electrode-integrated hydrogel remains on human skin, and electrical signals are continuous over 10 min above the LCST. In contrast, commercially available hydrogel electrodes quickly swell and detach from the skin. The thermoswitchability of the TSA hydrogel, with its robust adhesion and gentle detachment, offers significant potential for biomedical applications characterized by minimally invasive procedures.

A rapid and robust organ repair polyacrylamide/alginate adhesive hydrogel mediated via interfacial adhesion-trigger molecules.

Adhesive hydrogels have been widely explored as tissue adhesives for wound sealing and repair. However, developing adhesive hydrogels with simple preparation techniques and strong adhesion to internal organs in a short time remains a challenge. In this study, we developed a strategy for robust and rapid tissue adhesion of internal organ sealing and repair by an interfacial adhesion-molecule triggered hydrogel system. In this system, polyphenol molecules act as adhesion-trigger reagents to achieve fast and strong adhesion of polyacrylamide/alginate hydrogels on the surface of wound tissue by rapidly forming abundant hydrogen bonds at the interface. The adhesion energy is significantly enhanced by 45 times under the mediation of polyphenol adhesion-trigger molecules, resulting in a robust (> 600Jm-2) tissue adhesion in just 30s. This interfacial adhesion system demonstrates good biocompatibility, strong sealing performance on multiple organs (porcine heart, lung, stomach, and intestine), and excellent repair properties in gastric perforation wounds of rabbits in vivo. Moreover, immunocytochemical and transcriptomic analyses reveal that this interfacial adhesion system significantly promotes vascular regeneration and inhibits inflammatory responses during wound repairing. The proposed hydrogel provides a facile strategy for rapid and robust tissue adhesion, and shows potential applications in organ sealing and repair.

Structure regulation of oxidized soybean cellulose nanocrystals/poly-acrylamide hydrogel and its application potential in wound dressing

The development of functional dressings based on natural polysaccharide-based hydrogels remains a great challenge, and the specific roles of gel composition and drug-controlled release mechanisms were unclear. In this study, oxidized soybean cellulose nanocrystals (CNCs)/poly-acrylamide (PAM) hydrogel was prepared. The proportion of CNCs, crosslinkers, and water in the system was regulated to fine-tune the rheological performances, texture properties, transparency, and micro-network structures of CNCs/PAM hydrogel, and further explored its application potential in the field of wound dressings. It was found that CNCs improved the rigidity and adhesion of hydrogels, crosslinkers improved the network density, and water promoted the softening and fluidity of hydrogels. The effective filling of CNCs in the composite hydrogel was verified by FTIR, XRD, and NMR. Furthermore, the pH responsiveness and drug-loading potential of the smart hydrogel were tested by swelling and drug-controlled release experiments, elucidating drug-release dynamic mechanisms during the wound healing process. The inhibition zones (>7 mm) of gram-positive/negative bacteria and cell viability (>100 %) assay showed satisfactory biocompatibility, as the hydrogel effectively accelerated wound healing in a wound model. These results elucidated the regulation mechanism of the structures of CNCs/PAM hydrogel and revealed the application potential of CNCs/PAM hydrogel in wound dressings.

An adhesive, highly stretchable and low-hysteresis alginate-based conductive hydrogel strain sensing system for motion capture

A strain sensor stands as an indispensable tool for capturing intricate motions in various applications, ranging from human motion monitoring to electronic skin and soft robotics. However, existing strain sensors still face difficulties in simultaneously achieving superior sensing performance sufficing for practical applications like high stretchability and low hysteresis, as well as seamless device fabrication like desirable interfacial adhesion and system-level integration. Herein, we develop a highly stretchable and low-hysteresis strain sensor with adhesive poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS)/polyacrylamide (PAAm)‑sodium alginate (SA) composite hydrogel, allowing the successful construction of a wireless motion capture sensing system that can provide precise data collection within a large deformation range. The resultant composite hydrogel displays favorable interfacial adhesion and robust mechanical stability, and the fabricated strain sensor demonstrates a wide working strain range (up to 500 %) with high sensitivity (gauge factor = 11) and ultra-low hysteresis (1.52 %), outperforming previous PEDOT-based hydrogel strain sensors. Enabled by the intriguing material properties and high sensing performance, we further demonstrate the fabrication and integration of a wireless motion capture sensing system for diverse applications like human motion monitoring, gesture recognition, and interactive communication.

A selective frequency damping and Janus adhesive hydrogel as bioelectronic interfaces for clinical trials

Maintaining stillness is essential for accurate bioelectrical signal acquisition, but dynamic noise from breathing remains unavoidable. Isotropic adhesives are often used as bioelectronic interfaces to ensure signal fidelity, but they can leave irreversible residues, compromising device accuracy. We propose a hydrogel with selective frequency damping and asymmetric adhesion as a bioelectronic interface. This hydrogel mitigates dynamic noise from breathing, with a damping effect in the breathing frequency range 60 times greater than at other frequencies. It also exhibits an asymmetric adhesion difference of up to 537 times, preventing residues. By homogenizing ion distribution, extending Debye length, and densifying the electric field, the hydrogel ensures stable signal transmission over 10,000 cycles. Additionally, it can non-invasively diagnose otitis media with higher sensitivity than invasive probes and has been effective in clinical polysomnography monitoring, aiding in the diagnosis of obstructive sleep apnea.

Polyphenol-Mediated Adhesive and Anti-Inflammatory Double-Network Hydrogels for Repairing Postoperative Intervertebral Disc Defects.

Hydrogels have garnered tremendous attention for their applications in the repair of intervertebral disk (IVD) degeneration and postoperative IVD defects. However, it is still challenging to develop a hydrogel fulfilling the requirements for high mechanical properties, adhesive capability, biocompatibility, antibacterial properties, and anti-inflammatory performance. Herein, we report a multifunctional double-network (DN) hydrogel composed of physically cross-linked carboxymethyl chitosan (CMCS) and tannic acid (TA) networks as well as chemically cross-linked acrylamide (AM) networks, which integrates the properties of high strength, adhesion, biocompatibility, antimicrobial activity, and anti-inflammation for the repair of postoperative IVD defects. The treatment with CMCS/TA/PAM DN hydrogels can significantly decrease the levels of inflammatory cytokines and degeneration-related factors and upregulated collagen type II alpha 1. In addition, the hydrogels can effectively seal the annulus fibrosus defect, prevent nucleus pulposus degeneration, retain IVD height, and restore the biomechanical properties of the disc to some extent. This polyphenol-mediated DN hydrogel is promising for sealing IVD defects and preventing herniation after lumbar discectomy.

Self-healing, adhesive, antibacterial, and biocompatible hydrogel dressings using sialic acid substituted chitosan and oxidized pullulan with incorporation of epigallocatechin gallate

The development of innovative therapeutic strategies is highly desired for wound regeneration. In this study, sialic acid substituted chitosan (CS-SA) was reacted with oxidized pullulan (OPL) via Schiff base links to obtain functional CS-SA/OPL hydrogels, into which the polyphenol epigallocatechin gallate (EGCG) was in situ incorporated. The prepared hydrogels exhibited interconnected porous structure and good water absorption ability (over 37 g/g). Furthermore, the CS-SA/OPL hydrogels performed excellent self-healing and adhesive properties. With the incorporation of EGCG, the antibacterial effects against E. coli and S. aureus, as well as antioxidative activity, were significantly improved. In addition, in vitro L-929 cell experiments confirmed that cell viability and cell immigration could be significantly improved with the incorporation of EGCG in CS-SA/OPL hydrogels. Based on the above results, hydrogels possess a promising potential as wound dressings in wound healing applications.

Dynamic Adhesive Fibers for Remote Capturing of Objects

AbstractB. mori silk has been extensively utilized to create Regenerated Silk Fibroin solutions (RSF) for a wide range of technological applications, including tissue engineering, drug delivery, biomaterials, and adhesives. In this study, an RSF‐dopamine (DA) composite is introduced that yields easily deployable hydrogel fibers possessing adhesive properties that can be released on demand to capture and retrieve loads from a distance. The RSF‐DA serves as an artificial dope, combining the functional attributes of silk fibroin (i.e., hydrogel formation) and dopamine (i.e., adhesion) to instantly generate adjustable hydrogel fibers displaying a sticky behavior. The mechanical strength and adhesive characteristics of this material are assessed using tensile and lap‐shear tests. Furthermore, the possibility of tuning these properties is demonstrated by adding chitosan (Ch) and borate ions (BB), leading to remarkable mechanical and adhesive performances up to 107 MPa and 280 kPa, respectively, which allows the retrieval of objects from the ejected structure. This process can be finely tuned to achieve a controlled fabrication of instantaneously formed adhesive hydrogel fibers for manifold applications, mimicking living organisms’ ability to eject tunable adhesive functional threads.

Bioinspired Asymmetric-Adhesion Janus Hydrogel Patch Regulating by Zwitterionic Polymers for Wet Tissues Adhesion and Postoperative Adhesion Prevention.

Asymmetrically adhesive hydrogel patch with robust wet tissue adhesion simultaneously anti-postoperative adhesion is essential for clinical applications in internal soft-tissue repair and postoperative anti-adhesion. Herein, inspired by the lubricative role of serosa and the underwater adhesion mechanism of mussels, an asymmetrically adhesive hydrogel Janus patch is developed with adhesion layer (AL) and anti-adhesion layer (anti-AL) through an in situ step-by-step polymerization process in the mold. The AL exhibits excellent adhesion to internal soft-tissues. In contrast, the anti-AL demonstrated ultralow fouling property against protein and fibroblasts, which hinders the early and advanced stages of development of the adhesion. Moreover, the Janus patch simultaneously promotes tissue regeneration via ROS clearance capability of catechol moieties in the AL. Results from in vivo experiments with rabbits and rats demonstrate that the AL strongly adheres to traumatized tissue, while the anti-AL surface demonstrate efficacy in preventing of post-abdominal surgery adhesions in contrast to clinical patches. Considering the advantages in terms of therapeutic efficacy and off the shelf, the Janus patch developed in this work presents a promise for preventing postoperative adhesions and promoting regeneration of internal tissue defects.