Arginine-solubilized lipoic acid-induced ß-sheets of silk fibroin-strengthened hydrogel for postoperative rehabilitation of breast cancer.

Breast cancer is the most common cancer among women worldwide, and adjuvant radiotherapy (RT) following tumor removal is one of the most commonly used treatments for breast cancer. However, the high risk of tumor recurrence and inevitable radiation skin injury after RT remain fatal problems, seriously challenging the patient's postoperative rehabilitation. Herein, a multifunctional poly (lipoic acid)-based hydrogel is constructed through one-step heating the mixture of α-lipoic acid (LA)/arginine (Arg)/silk fibroin (SF), without introducing any non-natural molecules. The multiple synergistic interactions among LA, Arg, and SF not only enhance the solubilization of LA in aqueous systems but also stabilize poly(lipoic acid) through strong salt bridge hydrogen bonds and ionic hydrogen bonds. Intriguingly, the LA-based surfactant induced ß-sheet transformation of SF can further modulate the bulk strength of the hydrogel. Regulating the content of LA in hydrogels not only allows efficient control of hydrogel bioactivity but also enables the evolution of hydrogels from injectable forms to adhesive patches. Based on the different biological activities and forms of hydrogels, they can be implanted internally or applied externally on the mice's skin, achieving simultaneous prevention of tumor recurrence post-surgery and assistance in treating radiation-induced skin damage after radiotherapy.

Novel injectable adhesive hydrogel loaded with exosomes for holistic repair of hemophilic articular cartilage defect.

Hemophilic articular cartilage damage presents a significant challenge for surgeons, characterized by recurrent intraarticular bleeding, a severe inflammatory microenvironment, and limited self-repair capability of cartilage tissue. Currently, there is a lack of tissue engineering-based integrated therapies that address both early hemostasis, anti-inflammation, and long-lasting chondrogenesis for hemophilic articular cartilage defects. Herein, we developed an adhesive hydrogel using oxidized chondroitin sulfate and gelatin, loaded with exosomes derived from bone marrow stem cells (BMSCs) (Hydrogel-Exos). This hydrogel demonstrated favorable injectability, self-healing, biocompatibility, biodegradability, swelling, frictional and mechanical properties, providing a comprehensive approach to treating hemophilic articular cartilage defects. The adhesive hydrogel, featuring dynamic Schiff base bonds and hydrogen bonds, exhibited excellent wet tissue adhesiveness and hemostatic properties. In a pig model, the hydrogel could be smoothly injected into the knee joint cartilage defect site and gelled in situ under fluid-irrigated arthroscopic conditions. Our in vitro and in vivo experiments confirmed that the sustained release of exosomes yielded anti-inflammatory effects by modulating macrophage M2 polarization through the NF-κB pathway. This immunoregulatory effect, coupled with the extracellular matrix components provided by the adhesive hydrogel, enhanced chondrogenesis, promoted the cartilage repair and joint function restoration after hemophilic articular cartilage defects. In conclusion, our results highlight the significant application potential of Hydrogel-Exos for early hemostasis, immunoregulation, and long-term chondrogenesis in hemophilic patients with cartilage injuries. This innovative approach is well-suited for application during arthroscopic procedures, offering a promising solution for addressing the complex challenges associated with hemophilic articular cartilage damage.

Bioresponsive and transformable coacervate actuated by intestinal peristalsis for targeted treatment of intestinal bleeding and inflammation.

Developing an oral in situ-forming hydrogel that targets the inflamed intestine to suppress bleeding ulcers and alleviate intestinal inflammation is crucial for effectively treating ulcerative colitis (UC). Here, inspired by sandcastle worm adhesives, we proposed a water-immiscible coacervate (EMNs-gel) with a programmed coacervate-to-hydrogel transition at inflammatory sites composed of dopa-rich silk fibroin matrix containing embedded inflammation-responsive core-shell nanoparticles. Driven by intestinal peristalsis, the EMNs-gel can be actuated forward and immediately transform into a hydrogel once contacting with the inflamed intestine to yield strong tissue adhesion, resulting from matrix metalloproteinases (MMPs)-triggered release of Fe3+ from embedded nanoparticles and rearrangement of polymer network of EMNs-gel on inflamed intestine surfaces. Extensive in vitro experiments and in vivo UC models confirmed the preferential hydrogelation behavior of EMNs-gel to inflamed intestine surfaces, achieving highly effective hemostasis, and displaying an extended residence time ( > 48 h). This innovative EMNs-gel provides a non-invasive solution that accurately suppresses severe bleeding and improves intestinal homeostasis in UC, showcasing great potential for clinical applications.

Dihydromyricetin-loaded oxidized polysaccharide/L-arginine chitosan adhesive hydrogel promotes bone regeneration by regulating PI3K/AKT signaling pathway and MAPK signaling pathway.

Bone defects caused by trauma, infection and congenital diseases still face great challenges. Dihydromyricetin (DHM) is a kind of flavone extracted from Ampelopsis grossedentata, a traditional Chinese medicine. DHM can enhance the osteogenic differentiation of human bone marrow mesenchymal stem cells with the potential to promote bone regeneration. Hydrogel can be used as a carrier of DHM to promote bone regeneration due to its unique biochemical characteristics and three-dimensional structure. In this study, oxidized phellinus igniarius polysaccharides (OP) and L-arginine chitosan (CA) are used to develop hydrogel. The pore size and gel strength of the hydrogel can be changed by adjusting the oxidation degree of oxidized phellinus igniarius polysaccharides. The addition of DHM further reduce the pore size of the hydrogel (213 µm), increase the mechanical properties of the hydrogel, and increase the antioxidant and antibacterial activities of the hydrogel. The scavenging rate of DPPH are 72.30 ± 0.33 %, and the inhibition rate of E.coli and S.aureus are 93.12 ± 0.38 % and 94.49 ± 1.57 %, respectively. In addition, PCAD has good adhesion and biocompatibility, and its extract can effectively promote the osteogenic differentiation of MC3T3-E1 cells. Network pharmacology and molecular docking show that the promoting effect of DHM on osteogenesis may be achieved by activating the PI3K/AKT and MAPK signaling pathways. This is confirmed through in vitro cell experiments and in vivo animal experiments.

Mussel-inspired adhesive drug-loaded hydrogels for oral ulcers treatment.

Oral aphthous ulcers are common mucosal lesions that cause pain and discomfort. There are diverse biomaterials and drug treatments for oral ulcers used in both research and clinical settings. However, the complex oral environment often results in low adhesion and short drug retention times, which lead to poor drug availability and treatment outcomes. In this study, a mussel-inspired adhesive hydrogel was developed by grafting catechol onto hyaluronic acid (C-HA), and dopamine was added for oxidative pre-polymerization to form modified hyaluronic acid (M-HA), which remarkably increased the adhesion of the hydrogels. Then, M-HA was interpenetrated into the gelatin methacryloyl (GelMA) network. Chlorhexidine gluconate (CHG) was then incorporated into the hydrogel to enhance its availability and therapeutic effect through its sustained-release capability. The GelMA/M-HA hydrogel demonstrated strong adhesion to wet tissues, antibacterial and anti-inflammatory properties, and good biocompatibility. In both rat oral ulcers and infected wounds, the adhesive hydrogel significantly accelerated the healing of the ulcers and infected wounds. These results indicated that this adhesive hydrogel offers a promising new strategy for the treatment of oral ulcers in clinical practice. STATEMENT OF SIGNIFICANCE: Oral ulcers are a common and high-incidence mucosal condition that seriously affect people's daily lives, often making it difficult for patients to chew and speak. However, a dynamic oral environment with various types of bacteria influences drug availability and treatment effects in clinical settings. To address this challenge, an adhesive, mussel-inspired, drug-loaded hydrogel was constructed using natural macromolecules (hyaluronic acid and gelatin) with good biocompatibility. Chlorhexidine gluconate (CHG), with its broad-spectrum antibacterial activity, has been incorporated to synergistically promote oral ulcer healing. The splendid adhesion, antibacterial, and therapeutic effects of this hydrogel demonstrated a new strategy for treating oral ulcers.

An adhesive hydrogel functionalized silica sphere for polar analytes separation and analysis.

In response to the challenges associated with the chromatographic separation of polar compounds, this study aims to devise a solution by introducing a novel stationary phase. Hydrogels, characterized by a three-dimensional network structure, have aroused wide attention owing to its functional designability, multiple interaction sites and good adhesion, etc. In this work, an adhesive hydrogel functionalized silica stationary phase (Sil@PVA/TA) was synthesized using physical coating technique. Due to the co-existence of hydroxyl and benzene ring in the hydrogel structure, the obtained composites materials exhibited excellent separation performance for various of compounds and excellent column efficiency up to 71385.6 plates/m for thymidine. Furthermore, the hydrogel functionalized silica demonstrated superior selectivity to bare silica, diol-column and NH2-column for the separation of various of polar molecules, including, nucleosides/bases, alkaloids, organic acids, antibiotics and amino acids. Notably, for alkaloids, which frequently encounter peak tailing issues, Sil@PVA/TA demonstrated superior peak shape compared with C18 column. In short, this study successfully synthesized a hydrogel functionalized silica stationary phase, offering a novel method for the separation and analysis of polar compounds.

Designing a Naturally Inspired Conductive Copolymer to Engineer Wearable Bioadhesives for Sensing Applications.

The design of adhesive and conductive soft hydrogels using biopolymers with tunable mechanical properties has received significant interest in the field of wearable sensors for detecting human motions. These hydrogels are primarily fabricated through the modification of biopolymers to introduce cross-linking sites, the conjugation of adhesive components, and the incorporation of conductive materials into the hydrogel network. The development of a multifunctional copolymer that integrates adhesive and conductive properties within a single polymer chain with suitable cross-linking sites eliminates the need for biopolymer modification and the addition of extra conductive and adhesive components. In this study, we synthesized a copolymer based on poly([2-(methacryloyloxy)ethyl] trimethylammonium chloride-co-dopamine methacrylamide) (p(METAC-DMA)) using a controlled radical polymerization, allowing for the efficient conjugation of both adhesive and conductive units within a single polymer chain. Subsequently, our multifunctional hydrogel named Gel-MD was fabricated by mixing the p(METAC-DMA) copolymer with non-modified gelatin in which cross-linking took place in an oxidative environment. We confirmed the biocompatibility of the Gel-MD hydrogel through in vitro studies using NIH 3T3 cells as well as in vivo subcutaneous implantation in rats. Furthermore, the Gel-MD hydrogel was effective and sensitive in detecting various human motions, making it a promising wearable sensor for health monitoring and diagnosis.

Study the effect of different concentrations of polydopamine as a secure and bioactive crosslinker on dual crosslinking of oxidized alginate and gelatin wound dressings.

Alginate hydrogels are commonly used in wound care due to their ability to maintain a moist environment, absorb fluids, and aid wound healing. However, their stability and mechanical properties can sometimes limit their effectiveness. This study explores a new approach by creating a dual network system of oxidized alginate and gelatin hydrogel crosslinked with polydopamine in a single step, with the goal of improving the mechanical properties of these hydrogels. The unique aspect of this research is the comprehensive examination of different polydopamine concentrations in dual crosslinking systems. First, alginate was modified with sodium periodate to create additional active groups on its backbone, and various polydopamine concentrations were then tested to assess their impact on the dual crosslinking network and hydrogel properties. The study involved a range of tests, including FTIR, H-NMR, SEM, gelation time, rheology, adhesion, antioxidant activity, swelling ratio, weight loss, drug release, and cell viability. The addition of polydopamine was found to enhance the crosslinking density (0.859 × 109 mol.cm-3). Additionally, the results indicated improvements in properties such as reduced weight loss, enhanced antioxidant and adhesive qualities, and better mechanical properties (2240 kPa). However, the optimal concentration of polydopamine must be determined to achieve the best properties for a wound dressing. Excessive polydopamine can increase the space between polymer chains, leading to a reduction in crosslinking density and storage modulus. Nevertheless, it can also increase the swelling ratio, degradation rate, pore size, porosity, antioxidant activity, and dopamine release. Therefore, identifying the optimal concentration for a functional hydrogel is crucial. Notably, the hydrogel containing 0.5 mg.mL-1 polydopamine exhibited outstanding cell viability (108 % on the third day), swelling capacity (480 %), storage modulus (2240 kPa), gelation time (3 min), antioxidant activity (42.27 %), and skin adherence (11 kPa), making it an optimal choice for advanced wound management. According to the findings, it is emphasized that the application of this particular hydrogel expedites wound healing, as indicated by wound closure and histological studies. ABBREVIATIONS.

Injectable bioadhesive hydrogel as a local nanomedicine depot for targeted regulation of inflammation and ferroptosis in rheumatoid arthritis.

Medicine intervention is the major clinical treatment used to relieve the symptoms and delay the progression of rheumatoid arthritis (RA), but is limited by its poor targeted delivery and short therapeutic duration. Herein, we developed an injectable and bioadhesive gelatin-based (Gel) hydrogel as a local depot of leonurine (Leon)-loaded and folate-functionalized polydopamine (FA-PDA@Leon) nanoparticles for anti-inflammation and chondroprotection in RA. The nanoparticles could protect Leon and facilitate its entry into the M1 phenotype macrophage for intracellular delivery of Leon, while the hydrogel tightly adhered to the tissues in the joint cavity and prolonged the retention of FA-PDA@Leon nanoparticles, thus achieving higher availability and therapeutic efficiency of Leon. In vitro and in vivo experiments demonstrated that the Gel/FA-PDA@Leon hydrogel could strongly suppress the inflammatory response by down-regulating the JAK2/STAT3 signaling pathway in macrophages and protect the chondrocytes from ferritinophagy/ferroptosis. This contributed to maintaining the structural integrity of articular cartilage and accelerating the joint functional recovery. This work provides an effective and convenient strategy to achieve higher bioavailability and long-lasting therapeutic duration of medicine intervention in arthritis diseases.

Epidermal growth factor-loaded, dehydrated physical microgel-formed adhesive hydrogel enables integrated care of wet wounds.

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.

Engineered Regenerative and Adhesive Hydrogel for Concurrent Sealing and Healing of Enterocutaneous Fistulas.

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.

An injectable adhesive hydrogel for photothermal ablation and antitumor immune activation against bacteria-associated oral squamous cell carcinoma.

Pathogenic bacteria are closely associated with the occurrence, development and metastasis of oral squamous cell carcinoma (OSCC). Antibacterial therapy has been considered an enhancement strategy to suppress bacteria-associated tumors and promote anti-tumor immune responses. Herein, we developed an injectable adhesive hydrogel, PNIPAM/DL@TIR, for the in situ photothermal ablation and robust stimulation of antitumor immunity against OSCC colonized by Porphyromonas gingivalis (Pg), one of the major oral pathogenic bacteria. PNIPAM/DL@TIR, composed of poly(N-isopropylacrylamide), demethylated lignin, and TAT peptide-conjugated IR820, was prepared using a simple dissolve-dry-swell solvent exchange method. Upon 808 nm laser irradiation, PNIPAM/DL@TIR exerted photothermal effects to ablate Pg-colonized OSCC and generate dual tumor and bacterial antigens. Owing to its large number of catechol groups, PNIPAM/DL@TIR efficiently captured these antigens to form an in situ antigen repository, thereby eliciting robust and durable antitumor immune responses. Proteomic analysis revealed that the captured antigens comprised both tumor neoantigens and bacterial antigens. The catechol groups endowed PNIPAM/DL@TIR with antioxidant activity, which was also conducive to stimulating antitumor immunity. Altogether, this study develops an injectable adhesive hydrogel and provides a combination strategy for treating bacteria-associated OSCC. STATEMENT OF SIGNIFICANCE: In this study, we developed an injectable adhesive hydrogel, PNIPAM/DL@TIR, for in situ photothermal ablation and robust stimulation of antitumor immunity against OSCC colonized by Porphyromonas gingivalis, one of the major oral pathogenic bacteria. PNIPAM/DL@TIR, which consists of poly(N-isopropylacrylamide), demethylated lignin, and TAT peptide-conjugated IR820 exhibited outstanding photothermal performance. Owing to the presence of catechol groups, PNIPAM/DL@TIR has good bioadhesive properties and can capture protein antigens to form in situ antigen repository, thus initiating robust and long-term antitumor immune responses. In addition, PNIPAM/DL@TIR exhibited strong antioxidant activity that is favorable for promoting antitumor immunity. In the mouse model of OSCC with bacterial infection, PNIPAM/DL@TIR not only ablated the primary tumors upon NIR laser irradiation, but also induced tumor and bacterial vaccination in situ to suppress distant tumors and lung metastasis.

Ink-based textile electrodes for wearable functional electrical stimulation: A proof-of-concept study to evaluate comfort and efficacy.

BACKGROUND: Functional Electrical Stimulation (FES) represents a promising technique for promoting functional recovery in individuals with neuromuscular diseases. Traditionally, current pulses are delivered through self-adhesive hydrogel Ag/AgCl electrodes, which allow a good contact with the skin, are easy-to-use and have a moderate cost. However, skin adherence decreases after a few uses and skin irritations can originate. Recently, textile electrodes have become an attractive alternative as they assure increased durability, easy integration into clothes and can be conveniently cleaned, improving the wearability of FES. However, as various manufacture processes were attempted, their clear validation is lacking. This proof-of-concept study proposes a novel set of ink-based printed textile electrodes and compares them to adhesive hydrogel electrodes in terms of impedance, stimulation performance and perceived comfort. METHODS: The skin-electrode impedance was evaluated for both types of electrodes under different conditions. These electrodes were then used to deliver FES to the Rectus Femoris of 14 healthy subjects to induce its contraction in both isometric and dynamic conditions. This allowed to compare the two types of electrodes in terms of sensory, motor, maximum and pain thresholds, FES-induced range of motion during dynamic tests, FES-induced torque during isometric tests and perceived stimulation comfort. RESULTS: No statistically significant differences were found both in terms of stimulation performance (Wilcoxon test) and comfort (Generalized Linear Mixed Model). CONCLUSION: The results showed that the proposed ink-based printed textile electrodes can be effectively used as alternative to hydrogel ones. Further experiments are needed to evaluate their durability and their response to sterilizability and stretching tests.

Nanocomposite hyaluronic acid adhesive hydrogel with controllable drug release for bone regeneration.

Hyaluronic acid (HA) hydrogels have arisen as candidate materials to simulate the extracellular matrix and restore the functions of both cartilage and hard bones. However, integration of bone tissue adhesion and long-term osteogenic properties in one hydrogel is often ignored. Herein, a strategy to construct nanocomposite hydrogel with host tissue adhesive properties, enhanced mechanical strength, improved stability and osteogenic effects was developed. Simvastatin (SIM) was firstly incorporated into zeolitic imidazolate framework-8 (ZIF-8) and surface decoration with hydroxyapatite was realized to obtain SIM loaded and hydroxyapatite modified ZIF-8 particles (SP). As the inorganic strengthening component, SP could further cross-link the mixture of dopamine-hyaluronic acid (dHA) and tannic (TA) via coordination interaction to fabricate the hybrid adhesive hydrogel (dHA/TA/SP). Sufficient phenolic groups endowed dHA/TA/SP with excellent tissue adhesion and antibacterial properties, while incorporation of SP significantly improved the mechanical strength and stability of hydrogel. Further, due to the multiple protective effects of ZIF-8 and hydrogel, SIM was sustainably released from dHA/TA/SP. Together with the active Zn2+ and Ca2+, the expressions of ALP, OCN and RUNX2 were upregulated, and the mineralization was also promoted. With significant osteogenic effect in vitro and in vivo, this nanocomposite adhesive hydrogel holds great potential for bone defects repair.

Bionic double-crosslinked hydrogel of poly (γ-glutamic acid)/poly (N-(2-hydroxyethyl) acrylamide) with ultrafast gelling process and ultrahigh burst pressure for emergency rescue.

Injectable adhesive hydrogels combining rapid gelling with robust adhesion to wet tissues are highly required for fast hemostasis in surgical and major trauma scenarios. Inspired by the cross-linking mechanism of mussel adhesion proteins, we developed a bionic double-crosslinked (BDC) hydrogel of poly (γ-glutamic acid) (PGA)/poly (N-(2-hydroxyethyl) acrylamide) (PHEA) fabricated through a combination of photo-initiated radical polymerization and hydrogen bonding cross-linking. The BDC hydrogel exhibited an ultrafast gelling process within 1 s. Its maximum adhesion strength to wet porcine skin reached 254.5 kPa (9 times higher than that of cyanoacrylate (CA) glue) and could withstand an ultrahigh burst pressure of 626.4 mmHg (24 times higher than that of CA glue). Notably, the BDC hydrogel could stop bleeding within 10 s from a rat liver incision 10 mm long and 5 mm deep. The wound treated with the BDC hydrogel healed faster than the control groups, underlining the potential for emergency rescue and wound care scenarios.

Mussel-Inspired Self-Adhesive and Tough Hydrogels for Effectively Cooling Solar Cells and Thermoelectric Generators.

Adhesive hydrogel-based evaporative cooling, which necessitates no electricity input, holds promise for reducing energy consumption in thermal management. Herein, inspired by the surface attachment of mussel adhesive proteins via abundant dynamic covalent bonds and noncovalent interactions, we propose a facile strategy to fabricate a self-adhesive cooling hydrogel (Li-AA-TA-PAM) using a copolymer of acrylamide (AM) and acrylic acid (AA) as the primary framework. The monomers formed hydrogen bonds between their carboxyl and amide groups, while tannic acid (TA), rich in catechol groups, enhances the adhesion of the hydrogel through hydrogen bonding. The hydrogel demonstrated strong adhesion to various material surfaces, including plastic, ceramic, glass, and metal. Even under high-speed rotation, it still maintains robust adhesion. The adhesion strength of the Li-AA-TA-PAM hydrogel to aluminum foil reached an impressive value of 296.875 kPa. Interestingly, the excellent contact caused by robust adhesion accelerates heat transfer, resulting in a rapid cooling performance, which mimics the perspiration of mammals. Lithium bromide (LiBr) with hydroactively sorptive sites is introduced to enhance sorption kinetics, thereby extending the effective cooling period. Consequently, the operation temperature of commercial polycrystalline silicon solar cells was reduced by 16 °C under an illumination of 1 kW m-2, and the corresponding efficiency of energy conversion was increased by 1.14%, thereby enhancing the output properties and life span of solar cells. The strategy demonstrates the potential for refrigeration applications using viscous gels.

A Solvent Exchange Induced Robust Wet Adhesive Hydrogels to Treat Solid Tumor Through Synchronous Ethanol Ablation and Chemotherapy.

The treatment of tumors in developing countries, especially those with poor medical conditions, remains a significant challenge. Herein, a novel solvent-exchange strategy to prepare adhesive hydrogels for the concurrent treatment of tumors through synchronous ethanol ablation and local chemotherapy is reported. First, a poly (gallic acid-lipoic acid) (PGL) ethanol gel is prepared that can undergo solvent exchange with water to form a hydrogel in situ. PGL ethanol gel deposited on the wet tissue can form a hydrogel in situ to effectively repel interfacial water and establish a tight contact between the hydrogel and tissue. Additionally, the functional groups between the hydrogels and tissues can form covalent and non-covalent bonds, resulting in robust adhesion. Furthermore, this PGL ethanol gel demonstrates exceptional capacity to effectively load antitumor drugs, allowing for controlled and sustained release of the drugs locally and sustainably both in vitro and in vivo. In addition, the PGL ethanol gel can combine ethanol ablation and local chemotherapy to enhance the antitumor efficacy in vitro and in vivo. The PGL ethanol gel-derived hydrogel shows robust wet bioadhesion, drug loading, sustained release, good biocompatibility and biodegradability, easy preparation and usage, and cost-effectiveness, which make it a promising bioadhesive for diverse biomedical applications.

A grape seed protein-tannic acid powder to transform various non-adhesive hydrogels into adhesive gels.

Realizing adhesion between wet materials remains challenging because of the interfacial water. Current strategies depend on complicated surface modifications, resulting in limited functions. Herein, a facile strategy based on the powder of grape seed protein and tannic acid (GSP-TA) was reported to endow various non-adhesive hydrogels adhesion without chemical modifications for both hydrogels and adherents. The GSP-TA powder has the capability to absorb interfacial water, form an adhesive layer on the hydrogel surface, diffusion into the underneath hydrogel matrix, and establish the initial adhesion within 5 s. By forming multiple non-covalent interactions between powders and substrates, the GSP-TA powder served as an efficient surface treating agent, enabling robust adhesion to solid substrates (wood, cardboard, glass, iron, and rubber) and wet tissues (pigskin, muscle, liver and heart). The adhesive strength for wood, cardboard, glass, iron, and rubber was 145.92 ± 5.93, 123.93 ± 15.98, 66.24 ± 7.67, 98.22 ± 4.13, and 80.83 ± 7.48 kPa, respectively. Because of reversible interactions, the adhesion was also repeatable. Due to the merits of grape seed protein and plant polyphenol, it could be completely degraded within 11 days. Bearing several merits, this strategy has promising applications in wound patches, tissue repair, and sensors.

Bioinspired wet adhesive carboxymethyl cellulose-based hydrogel with rapid shape adaptability and antioxidant activity for diabetic wound repair.

Currently, adhesive hydrogels have shown promising effect in chronic diabetic wound repair. However, there are issues and challenges in treating diabetic wounds due to inadequate wet adhesion, unable to fill irregular and deep wounds, and oxidative stress. Herein, a mussel-inspired naturally hydrogel dressing with rapid shape adaptability, wet adhesion and antioxidant abilities for irregular, deep and frequently movement diabetic wounds repair was constructed by comprising catechol modified carboxymethyl cellulose (CMC-DA) and tannic acid. Benefiting from the reversible hydrogen bonding, the resulting hydrogels exhibited injectability, remarkable self-healing ability, rapid shape adaptability and strong tissue adhesion (45.9 kPa), thereby contributing to self-adaptive irregular-shaped wounds or moving joint parts. Especially, the adhesion strength of the hydrogel on wet tissue still remained at 14.9 kPa. Besides, the hydrogels could be easily detached from the skin by ice-cooling that avoided secondary damage caused by dressing change. Remarkably, the hydrogels possessed excellent antioxidant, satisfactory biocompatibility, efficient hemostasis and antibacterial properties. The in vivo evaluation further demonstrated that the hydrogel possessed considerable wound-healing promotion effect by regulating diabetic microenvironment, attributed to that the hydrogel could significantly reduce inflammatory response, alleviate oxidative stress and regulate neovascularization. Overall, this biosafe adhesive hydrogel had great potentials for diabetic wound management.

Nature-Inspired Gelatin-Based Adhesive Hydrogel: A Rapid and User-Friendly Solution for Hemostatic Applications.

Conventional hemostatic agents face challenges in achieving rapid hemostasis and effective tissue repair due to limited hemostatic scenarios, suboptimal efficacy, and inadequate adhesion to wet tissues. Drawing inspiration from nature-sourced materials, a gelatin-based adhesive hydrogel (AOT)  is designed, easily prepared and quick to form, driven by Schiff base and multiple hydrogen bonds for applications in arterial and liver bleeding models. AOT exhibits exceptional adhesion to wet tissues (48.67 ± 0.16 kPa) and displays superior hemostatic properties with reduced blood loss and hemostatic time compared to other hydrogels and conventional hemostatic materials. Moreover, AOT exhibits good biocompatibility and biodegradability. In summary, this easily prepared adhesive hydrogel has the potential to supplant traditional hemostatic agents, offering a novel approach to achieve swift sealing of hemostasis and facilitate wound healing and repair in broader application scenarios, owing to its unique advantages.