Adhesive Hydrogel Research Articles

Adaptive Opto-Thermal-Hydrodynamic Manipulation and Polymerization (AOTHMAP) for 4D Colloidal Patterning.

Precision colloidal patterning holds great promise in constructing customizable micro/nanostructures and functional frameworks, which showcases significant application values across various fields, from intelligent manufacturing to optoelectronic integration and biofabrication. Here, a direct 4D patterning method via adaptive opto-thermal-hydrodynamic manipulation and polymerization (AOTHMAP) with single-particle resolution is reported. This approach utilizes a single laser beam to automatically transport, position, and immobilize colloidal particles through the adaptive utilization of light-induced hydrodynamic force, optical force, and photothermal polymerization. The AOTHMAP enables precise 1D, 2D, and 3D patterning of colloidal particles of varying sizes and materials, facilitating the construction of customizable microstructures with complex shapes. Furthermore, by harnessing the pH-responsive properties of hydrogel adhesives, the AOTHMAP further enables 4D patterning by dynamic alteration of patterned structures through shrinkage, restructuring, and cloaking. Notably, the AOTHMAP also enables biological patterning of functional bio-structures such as bio-micromotors. The AOTHMAP offers a simple and efficient strategy for colloidal patterning with high versatility and flexibility, which holds great promises for the construction of functional colloidal microstructures in intelligent manufacturing, as well as optoelectronic integration and biofabrication.

Adhesive, Stretchable, and Photothermal Antibacterial Hydrogel Dressings for Wound Healing of Infected Skin Burn at Joints.

Dressings for infectious skin burn wounds at joints should have therapeutic functions as well as high tissue-adhesion, stretching, and self-healing properties. This makes it difficult for most hydrogel dressings to simultaneously meet the above-mentioned requirements. In this study, poly(vinyl alcohol), anhydrous sodium borax, epigallocatechin gallate, and copper chloride were used to prepare a hydrogel dressing (PBEC) for the infected burn wound healing at joints. The PBEC hydrogel can adhere to a variety of substrates, has a stretching capacity, and quickly self-healing after being damaged. Additionally, the PBEC hydrogel has the properties of reactive oxygen species scavenging, photothermal sterilization, hemostatic ability, and biocompatibility. Finally, the hydrogel could accelerate the process of wound healing in vivo, especially with the assistance of near-infrared radiation. Therefore, the hydrogel dressing shows great potential for clinical application in the healing of infected burn wounds at joints.

Bioadhesive First-Aid Patch with Rapid Hemostasis and High Toughness Designed for Sutureless Sealing of Acute Bleeding Wounds.

The global military and civilian sectors express widespread concern over the significant hemorrhage associated with various acute wounds. Such bleedings lead to numerous casualties in military confrontations, traffic accidents, and surgical injuries. Consequently, the rapid control of the bleedings, particularly for extensive and pressurized wounds, is crucial in first-aid situations. In this work, a double-layered bioadhesive patch that combines a superabsorbent adhesive hydrogel with a highly tough antibacterial polyurethane film, which is called as Bio-Patch, is proposed. The Bio-Patch demonstrates superior mechanical strength and forms robust bioadhesion to acute bleeding wounds. Furthermore, the Bio-Patch enables protecting against external Gram-negative and Gram-positive bacteria. Thanks to the double-layered structures having synergistic functions of stable barrier and robust adhesion, the Bio-Patch provides optimal wound sealing (burst strength exceeding 310mmHg) both in vitro and in vivo. It also demonstrates superior hemostatic effects (less than 30 s) in vivo. This offers promising opportunities for rapid control of extensive and pressurized hemorrhage in first-aid clinical scenarios.

Multifunctional hydrogels loaded with tellurium nanozyme for spinal cord injury repair

Spinal cord injury (SCI) results in severe neurological deficits due to disrupted neural pathways. While the spinal cord possesses limited self-repair capabilities, recent advancements in hydrogel-based therapies have shown promise. Polyphenol-based hydrogels, known for their neuroprotective properties, offer a suitable microenvironment for neural regeneration. In this study, a novel poly(lipoic acid)/poly(dopamine) adhesive hydrogel was developed as a versatile platform for delivering therapeutic agents. This hydrogel was loaded with methylcobalamin, a neurotrophic factor, and tellurium nanoenzymes, potent antioxidants. The nanoenzymes effectively mitigated oxidative stress and inflammation, while methylcobalamin promoted nerve regeneration. The combined therapeutic effects of the nanoenzymatic hydrogel demonstrated significant efficacy in repairing spinal cord injuries, highlighting its potential as a promising strategy for treating this debilitating condition.

Antibacterial carboxymethyl chitosan hydrogel loaded with antioxidant cascade enzymatic system for immunoregulating the diabetic wound microenvironment

Diabetic wound healing faces several complex challenges, such as hypoxia, oxidative stress, and bacterial infections, which severely inhibit the wound-healing process. Herein, a quaternary ammonium salt-crosslinked carboxymethyl chitosan hydrogel (TPC) with excellent antioxidant and antibacterial properties was developed to immunoregulate the diabetic wound microenvironment. The TPC hydrogel was prepared by first mixing carboxymethyl chitosan (CMCS) and protocatechualdehyde (PA), followed by the addition of a quaternary ammonium cross-linker (TSPBA) and a superoxide dismutase (SOD)–catalase (CAT) cascade system. The immobilized SOD and CAT retained their activity, continuously converting endogenous ·O2− and H2O2 to O2 and H2O. PA also provided the TPC hydrogel excellent oxygen and nitrogen radical scavenging capacity. The quaternary ammonium groups in TSPBA significantly enhanced the inherent antibacterial ability of CMCS-based hydrogels. In diabetic wound-healing experiments, this porous and adhesive TPC hydrogel effectively closed wounds and regenerated skin tissue, resulting in shorter wound edges, thicker granulation, and higher collagen deposition levels compared with other groups. The TPC hydrogel also promoted macrophage polarization toward the M2 phenotype, accelerating wound healing by upregulating IL-10 expression, downregulating IL-6 expression, and enhancing angiogenesis. These results demonstrate the great potential of TPC hydrogel as a promising therapeutic dressing for treating diabetic wounds.

An integrally formed Janus supramolecular bio-gel with intelligent adhesion for multifunctional healthcare

Despite the rapid development of Janus adhesive hydrogels, most of them still entail complex fabrication processes and have the inherent flaws, such as fragility and instability, thereby restricting their biomedical applications. In this study, a novel Janus bio-gel with strong mechanical and intelligent adhesion functions is facilely fabricated through a gravity-driven settlement strategy, employing poly-cyclodextrin microspheres (PCDMs). This strategy takes advantage of the sedimentation behavior of PCDMs with various diameters to establish structural disparities on both sides of the Janus bio-gel, thereby resolving multiple predicaments including the tedious synthesis steps and poor bonding of multilayer hydrogels. Owing to the multiple dynamic interactions between polymers and PCDMs, the Janus supramolecular bio-gel demonstrates outstanding mechanical toughness (1.97 MJ/m3) and elongation rate (≈800 %). More attractively, the resulting Janus bio-gel exhibits remarkable adhesiveness (316.4 J/m2 for interfacial toughness) and adhesive differences that are exceed 50 times between the two surfaces. Furthermore, the Janus supramolecular bio-gel also has excellent antibacterial properties, biocompatibility, environmental stability, and multiple monitoring functions, accelerating wound stably healing and monitoring physiologic parameters on the skin. This strategy provides a straightforward and promising approach to directly achieve multifunctional integration for smart health management.

Thermostimulated shrinking and adhesive hydrogel dressing for treating chronic diabetic wounds

Thermostimulated shrinking and adhesive hydrogel dressing for treating chronic diabetic wounds

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.

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.