Wet Adhesion Research Articles

A Dry Patch with In Situ Solid-to-Gel Transformation for All-in-One Skin Wound Care.

Hydrogel-based dressing materials offer significant potential in expediting skin wound healing. Nevertheless, they face several challenges: poor adhesion to wound tissues, difficulties in preservation under ambient conditions, and limited multifunctionality to support all wound healing stages. In this work, a dry patch is designed to address these persistent issues by featuring an in situ solid-to-gel transformation and Janus wet tissue adhesiveness. The HGP patch integrates a wet adhesive layer combining dopamine-conjugated hyaluronic acid (HD) and poly(acrylic acid) (PAA), a drug-loading layer comprising gelatin (Gel), and a nonadhesive gelation layer of poly(vinyl alcohol) (PVA) and sodium alginate (SA). This hierarchical structural design confers exceptional wound adhesion, hemostatic capabilities, and antibacterial and antioxidant activities, as well as immune regulatory properties. These attributes collectively support accelerated skin wound healing, particularly in cases complicated by bacterial infections. This research charts an approach to engineer hydrogel-based wound dressings through on-site hydrogel formation, thus advancing the treatment of wounds afflicted with complex infections.

Environment-tolerant, inherently conductive and self-adhesive gelatin-based supramolecular eutectogel for flexible sensor

Although hydrogels have attracted increasing attention in the stretchable devices, the low adhesion properties and poor environmental adaptation still seriously restrict their development and application. Herein, we focused on the interaction between polymer networks with disperse media and their resultant influence on gel performance, and constructed self-adhesive and environment-tolerant gelatin/polyacrylamide supramolecular-polymer double-network (Gelatin/PAM SP-DN) eutectogels using multiple supramolecular interactions between natural macromolecule and well-designed deep eutectic solvent (DES). The dual networks of Gelatin/PAM SP-DN eutectogels produced significant supramolecular forces with DES, including hydrogen bonding and electrostatic interaction, contributing to enhance the energy dissipation capacity. Additionally, the Gelatin-PAM SP-DN eutectogels were more prone to generate strong bonding force to various substrates, showcasing both in-situ and ex-situ adhesion performance, and even being used for wet and underwater adhesion. The eutectogels revealed excellent environmental tolerance to maintain excellent mechanical flexibility, conductivity and adhesion at high and low temperatures, ensuring the constructed sensor to sensitively and reliably perceive strain, pressure and human motions over a wide temperature range. Also, the eutectogel demonstrated great potential as a temperature sensor. This work opens up a new horizon in the design of multifunctional and environment-tolerant natural macromolecule-based gel materials for flexible electronics, human-machine interaction and health diagnosis.

Rapid preparation of bioadhesive hydrogels containing catechol moieties at room temperature with reproducible adhesion to wet tissues, antimicrobial, antioxidant capacity for noncompressive hemostasis.

In order to cope with the massive tissue bleeding caused by sudden trauma and the demand for bioengineering materials with adjustable wet adhesion properties, this study formed the first layer of network by adding galactomannan (GG) and collagen (Col) structure, and then use the Fe3+-urushiol (UH) redox system to activate free radicals to initiate the polymerization of acrylic acid (AA) to quickly form an interpenetrating double network hydrogel. The cis hydroxyl group in GG and the hydroxyl group of UH form dynamic covalent borate ester bonds with borate ions in the borax solution, and use their responsiveness to pH to control the catechol group to achieve controllable adhesion. UH and Fe3+ endowed the hydrogel with excellent antibacterial ability, while adding Col enhanced the mechanical properties of the hydrogel. The elastic modulus and toughness increased from 4.32 kPa and 92.9 kJ/m3 to 18.90 kPa and 264.54 kJ/m3. In addition, due to the joint action of UH and Col, the hydrogel dressing can achieve rapid hemostasis within 20 s. In short, this hydrogel dressing has good biocompatibility, inherent antibacterial ability, adjustable moist tissue adhesion properties and rapid hemostatic ability, and is expected to become a candidate for wound hemostasis dressing.

A high-strength, environmental-friendly, and multifunctional soy protein adhesive inspired by biomineralization

Soy protein is an economical and eco-friendly adhesive material that offers significant potential for the development of bio-based adhesives. However, they have poor water resistance, low bonding strength, mold-susceptibility, and deterioration, which are serious challenges to the widespread application of soy protein adhesives in plywood. This work was inspired by the biomineralization phenomenon and the preparation of a novel soy protein adhesive (SPI-RGT-AgNPs). The SPI-RGT-AgNPs adhesive exhibited excellent viscosity, residual rate, and moisture absorption performance compared with the original soy protein isolate (SPI) adhesive, with an increase from 37° (SPI) to 81° (SPI-10RGT-10AgNPs) in water contact angle testing. The dry and wet adhesion strengths reached 2.49MPa and 1.43MPa, 193% and 117% higher than SPI adhesive, respectively. Molecular docking simulations were used to verify that the introduction of modifiers significantly improved the stability and crosslinking strength of the adhesive. The best ratio of the SPI-RGT-AgNP adhesive was confirmed using the response surface methodology (RSM). Simultaneously, SPI-RGT-AgNPs adhesive also showed excellent anti-mildew and anti-microbial efficiencies to Escherichia coli (98.18%) and Staphylococcus aureus (99.33%). In addition, a life-cycle assessment was used to explore the pollution emissions from the adhesives. As compared to formaldehyde-based adhesives, the SPI-RGT-AgNP adhesive had lower energy consumption and pollution emissions. Therefore, this study prepared a novel high-strength and multifunctional soy protein adhesive, guiding the production of multifunctional and green adhesives.

External Bleeding and Advanced Biomacromolecules for Hemostasis.

Hemorrhage is a significant medical problem that has been an active area of research over the past few decades. The human body has a complex response to bleeding that leads to blood clot formation and hemostasis. Many biomaterials based on various biomacromolecules have been developed to either accelerate or improve the body's natural response to bleeding. This review examines the mechanisms of hemostasis, types of bleeding, and the in vitro or in vivo models and techniques used to study bleeding and hemostatic materials. It provides a detailed overview of the diverse hemostatic materials, including those that are highly absorbent, wet adhesives, and those that accelerate the biochemical cascade of blood clotting. These materials are currently marketed, under preclinical testing, or being researched. In exploring the latest advancements in hemostatic technologies, this paper highlights the potential of these materials to significantly improve bleeding control in clinical and emergency situations.

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.

Ionically assembled hemostatic powders with rapid self-gelation, strong acid resistance, and on-demand removability for upper gastrointestinal bleeding.

Upper gastrointestinal bleeding (UGIB) is bleeding in the upper part of the gastrointestinal tract with an acidic and dynamic environment that limits the application of conventional hemostatic materials. This study focuses on the development of N-[(2-hydroxy-3-trimethylammonium) propyl] chitosan chloride/phytic acid (HTCC/PA, HP) powders with fast hemostatic capability and strong acid resistance, for potential applications in managing UGIB. Upon contact with liquids within 5 seconds, HP powders rapidly transform into hydrogels, forming ionic networks through electrostatic interactions. The ionic crosslinking process facilitates the HP powders with high blood absorption (3.4 times of self-weight), sufficient tissue adhesion (5.2 and 6.1 kPa on porcine skin and stomach, respectively), and hemostasis (within 15 seconds for in vitro clotting). Interestingly, the PA imparts the HP powders with strong acid resistance (69.8% mass remaining after 10 days of incubation at pH 1) and on-demand removable sealing while HTCC contributes to fast hemostasis and good wet adhesion. Moreover, the HP powders show good biocompatibility and promote wound healing. Therefore, these characteristics highlight the promising clinical potential of HP powders for effectively managing UGIB.

Assessing bonding and debonding properties of Evotherm modified bitumen with natural aggregates using surface free energy approach

ABSTRACT An incongruous pairing of aggregates and bitumen can result in early pavement failures such as stripping, raveling, and fatigue cracking. Surface free energy (SFE) assessments of aggregates and bitumen offer a means to evaluate the compatibility of the aggregate-bitumen system. It is important to emphasise that the SFE of both bitumen and aggregates significantly influences the determination of a compatible aggregate-bitumen combination. In this study, the moisture damage resistance of unmodified bitumen types (VG20, VG40) and modified bitumen types (PMB40, CRMB60) incorporating chemical-based warm mix asphalt (WMA) additives, specifically Evotherm, was investigated. The SFE approach was utilised to gain insights into their performance. In the laboratory, the static contact angle and SFE parameters of both unmodified and modified bitumen, with and without Evotherm, were determined using the Sessile drop method. Five different aggregate types were employed to calculate SFE performance parameters. Subsequently, the SFE performance parameter of forty combinations of aggregates and bitumen was calculated. As part of the assessment of moisture damage resistance, the compatibility ratio (CR) parameter was estimated using the dry adhesion energy, bitumen cohesion energy, wet adhesion energy, and wettability of different combinations of bitumen with aggregates. From the result, Evotherm addition to base bitumen (excluding VG20) significantly improved CR across various aggregates. Notable increases were observed for VG40, PMB40, and CRMB60 after Evotherm addition, with improvements of 66.67%, 48.48%, and 64.54% respectively for basalt aggregate. PMB40+EM with basalt aggregate exhibited the highest CR and Tensile Strength Ratio (TSR), suggesting superior moisture damage resistance compared to other bitumen combinations.

Development of low-molecular-weight polysaccharide-based wound dressings for full-thickness cutaneous wound healing via coacervate formation

The development of polysaccharide-based wound dressings that are easy to prepare, adhere to tissue, adapt to diverse shapes and exhibit tunable mechanical properties holds significant clinical interest. This study introduced a simple spontaneous liquid-liquid phase separation technique employing low-molecular-weight and high polyion concentration of chitosan (CS) and hyaluronic acid (HA) to fabricate CS/HA coacervates. Upon increasing the molecular weight of chitosan from 7 kDa to 250 kDa, a transition in the CS/HA coacervates from liquid-like state to an elastic liquid and eventually to a solid-like state was observed. The resulting CS/HA coacervates demonstrated robust water resistance and adhesion to skin tissue. Notably, the molecular weight of chitosan significantly influenced the mechanical properties and hydration levels of the CS/HA coacervates. Moreover, in vivo studies using a full-thickness cutaneous defect model revealed that the CS/HA coacervates, prepared using 100 kDa chitosan, markedly accelerate wound healing. The coacervates' ease of preparation, wet adhesion, heterogeneous structure, suitability for irregularly shaped wounds, and exceptional wound healing promotion of the coacervates qualify them as an optimal wound dressing.

Black Phosphorus Nanosheets-Loaded Mussel-Inspired Hydrogel with Wet Adhesion, Photothermal Antimicrobial, and In Situ Remineralization Capabilities for Caries Prevention.

The main features of early caries are the massive colonization of cariogenic bacteria and demineralization of tooth enamel by the acids that they produce. Owing to the lack of effective treatments, the development of anticaries therapeutics with both antimicrobial and remineralizing properties is urgently required. Black phosphorus nanosheets (BPNs) are ideal therapeutics for the treatment of early caries because they can mediate photothermal antibacterial activity and subsequently promote remineralization by generating PO4 3-. However, the dynamic and wet environment of the oral cavity prevents the long-term adhesion of BPNs to the tooth surface. In this study, using catechol-modified chitosan and PLGA-PEG-PLGA as raw materials, a mussel-inspired versatile hydrogel, BP@CP5, is presented that can be used to physically load BPNs. BP@CP5 has exceptional injectability and can firmly adhere to tooth surfaces for up to 24h. Upon irradiation, BP@CP5 can quickly eliminate ≈99% of Streptococcus mutans and Streptococcus sanguinis; furthermore, the PO4 3- generated via degradation also promotes rapid remineralization of enamel slabs. Importantly, the vivo rodent caries modeling results further confirm the excellent caries-prevention properties of BP@CP5. This study demonstrates that BP@CP5 is a promising anticaries material for caries management.

A bio-inspired Janus hydrogel patch facilitates oral ulcer repair by combining prolonged wet adhesion and lubrication

Oral ulcers, the most common type of mucosal lesion, are both highly prevalent and prone to recurrence. In the persistently moist environment of the oral cavity, current therapeutic patches face challenges such as short adhesion time, disruption by food particles and bacteria, and oral movements. To address these challenges, we develop a Janus patch, named ANSB, inspired by the multi-layered and asymmetric structure of natural mucosa, featuring a long-lasting adhesive layer and a lubricating layer. By eliminating the salivary barrier and leveraging covalent crosslinking between tissue surface amine groups and N-hydroxysuccinimide ester (NHS), the adhesive layer—composed of gelatin and acrylic acid—achieves rapid (≤ 30 s), strong (≥ 45 kPa), and durable (≥ 8 h) adhesion to wet buccal tissues. Furthermore, the efficient lubricating effect (COF = 0.02 ± 0.003) provided by zwitterions renders the lubricating layer of ANSB highly similar to natural mucosal tissue, effectively preventing bacterial invasion, secondary damage, and unintended adhesion. Additionally, the strong interlayer bonding and complementary mechanical properties are confirmed, resulting in a unified performance characterized by rapid wet adhesion, hydration lubrication, and enhanced mechanical strength. Importantly, ANSB treatment demonstrates a long-term protective barrier and superior therapeutic effects in rat oral ulcers, inhibiting pseudomembrane formation and accelerating tissue regeneration without causing secondary damage. Consequently, this distinctive Janus patch, characterized by prolonged adhesion, efficient lubrication, and simple preparation, holds significant potential for clinical oral ulcer treatment. Statement of SignificanceOral ulcers, with healing impeded by secondary injury and bacterial invasion due to the absence of protective barriers, are highly prevalent and recurrent. However, sustaining therapeutic materials and physical barriers in the highly dynamic and moist oral environment poses a considerable challenge. In this study, a Janus patch (ANSB) that integrated a soft wet adhesive layer and a tough lubricating layer was developed to reconstruct a new protective barrier thus preventing external stimuli such as secondary damage and bacterial infiltration. This innovative patch with high therapeutic potential for oral ulcers may offer a new way for ulcer treatment based on barrier protection.

Biomimetic poly(thioctic acid)-based bioadhesive hydrogels for wet adhesion, expeditious hemostasis and enhanced wound healing

The bioadhesive hydrogels have been viewed as promising substitutes for surgical sutures in wound closure. However, current bioadhesives face challenges such as weak wet adhesion and hemostatic performance, which hinder their wider clinical application. In this study, a novel poly(thioctic acid)Li+/caffeic acid-grafted sericin (CAS) (PTALi-CAS) supramolecular hydrogel was prepared using facile one-pot method. Among the PTALi-CAS hydrogels with varying CAS content, the PTALi-7%CAS hydrogels exhibited the highest adhesion strength (32.02 ± 2.28 kPa) and could adhere on surfaces of various organs in moist environments. It is noteworthy that the microstructure of the PTALi-7%CAS hydrogels after stretching closely resemble those of mussel byssal adhesion proteins. Additionally, the PTALi-7%CAS hydrogels exhibited rapid hemostatic properties in rat hemorrhage models and significantly accelerated the wound healing in rat skin incision experiments. Therefore, this study proposes a promising approach for developing a versatile hydrogel to aid in healing traumatic wounds.

Cellulose-based dual-crosslinked hydrogels with strong wet adhesion and benign on-demand detachment

Cellulose-based dual-crosslinked hydrogels with strong wet adhesion and benign on-demand detachment

Functionalized Amyloid‐Like Protein Nanofilm‐Mediated Synergistic Disulfidptosis and Photodynamic Therapy for Preventing Postoperative Recurrence of Colorectal Cancer

Colorectal cancer (CRC) has a postoperative recurrence rate of up to 50%. Local treatment at the surgical site offers a new strategy to prevent recurrence, minimizing systemic side effects. However, these treatments often face issues like poor stability, insufficient targeting, and significant local side effects. Research shows glucose starvation can induce disulfidptosis, a novel cell death pathway, in CRC cells, suitable for precise intervention in residual tumor cells postsurgery. This study develops a biocompatible 2D therapeutic platform using amyloid‐like protein nanofilm technology for precise local synergistic intervention in disulfidptosis and photodynamic therapy (PDT) after CRC surgery. The nanofilm boasts excellent drug‐loading capacity, enzyme activity retention, ultrathin dimensions, wet adhesion, and biocompatibility. A model simulating incomplete tumor resection post‐CRC surgery shows that the GCI@nanofilm effectively inhibits recurrence through an enzyme‐catalyzed cascade reaction inducing disulfidptosis and synergizing with PDT. In summary, GCI@nanofilm overcomes multiple challenges in local postsurgical intervention, providing a foundation for precise and efficient treatment of residual tumors.

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.

Hagfish-inspired hydrogel for root caries: A multifunctional approach including immediate protection, antimicrobial phototherapy, and remineralization

Root caries is the main cause of oral pain and tooth loss in the elderly. Protecting root lesions from environmental disturbances, resisting pathogens, and facilitating remineralization over time are essential for addressing root caries, but are challenging due to the irregular root surface and the complex oral environment. Hagfish secretes slime when facing danger, which converts into gels upon contact with seawater, suffocating the predators. Inspired by hagfish's defense mechanism, a fluid-hydrogel conversion strategy is proposed to establish a mechanical self-regulating multifunctional platform for root caries treatment. The fluid system (silk fibroin-tannic acid-black phosphorene-urea, ST-BP-U), in which urea disrupts the hydrogen bonds between silk fibroin and tannic acid, can easily spread on the irregular root surface and permeate into dentinal tubules. Upon contact with the surrounding water, urea diffuses, prompting the hydrogel re-formation and creating intimate attachments with micromechanical inlay locks. Meanwhile, BP increases the crosslinking of the re-formed hydrogel network, resulting in reinforced cohesion for robust wet adhesion to the tooth root. This process establishes a structured platform for effective antimicrobial phototherapy and dentin remineralization promotion. This water-responsive fluid-hydrogel conversion system adapts to the irregular root surface in the dynamic wet environment, holding promise for addressing root caries. Statement of significanceRoot caries bring a heavy burden to the aging society, but the irregular root surface and dynamic moist oral environment always hinder non-surgical therapeutic effects. Here, we propose a water-responsive fluid-hydrogel conversion strategy aimed at mechanical self-regulation on the irregular and wet root interface to construct a functional structural platform. The liquid system (ST-BP-U) that prebreak intermolecular hydrogen bonds can easily spread on irregular surfaces and dentin tubules. When encountering water, hydrogen bonds re-form, and BP increases the crosslinking of the hydrogel formed in situ. Based on this firm wet-adhesion platform, it provides powerful phototherapy effects and promotes dentin remineralization. This fluid-hydrogel conversion system turns the disadvantages of wet environment into advantages, offering a promising strategy for root caries.

A Janus hydrogel that enables wet tissue adhesion and resists abdominal adhesions

Hydrogels have indeed achieved significant advancements, yet their clinical translation has been hampered by their inherent limitations in wet adhesion properties. Furthermore, the design of adhesive hydrogels that can resist postoperative adhesions remains an intricate challenge. In this study, we introduce a Janus hydrogel (JGP) that offers a novel approach to address these challenges. The JGP hydrogel has two asymmetrical sides, consisting of an adhesion layer (AL) and an anti-adhesion layer (AAL). Specifically, the AL incorporates three key components: N-[tris(hydroxymethyl)methyl]acrylamide (THMA), acrylic acid (AAc), and the acrylic acid N-hydroxysuccinimide ester (AAc-NHS). By drying the AL, it has a rapid water absorption capability. The abundance of hydroxyl and carboxyl groups in the AL enables the formation of robust hydrogen bonds with tissues, thereby achieving superior adhesive properties. Additionally, the synergistic effect of THMA's tridentate hydrogen bonding and the covalent bonding formed by AAc-NHS with tissue ensures long-lasting wet adhesion. To realize the anti-adhesion function, one side of the AL was immersed in a solution of [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide (SBMA), which undergoes crosslinking to form the AAL. A comprehensive series of tests have confirmed that the JGP hydrogel exhibits exceptional mechanical properties, efficient and enduring adhesion, excellent biocompatibility, and degradability. Moreover, it possesses remarkable hemostatic properties and robust anti-abdominal adhesion characteristics.

A tough Janus poly(vinyl alcohol)-based hydrogel for wound closure and anti postoperative adhesion

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/m3; the bottom poly(acrylic acid)/polyethyleneimine adhesive layer imparts tough adhesion (∼382.93 J/m2 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 significanceDespite 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.

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.

A hemoadhican-based sponge with anti-heparin interference for treating uncontrollable massive hemorrhage

Hemoadhican (HD) is an exopolysaccharide with a branched structure that has been reported for its high hemostatic ability. In this study, a HD-based hemostatic sponge was prepared through ultrasonic dissolution and freeze-drying without using any cross-linking agent. The sponge could spontaneously cross-link using hydrogen bonds to form adhesive mud within 3 s upon contact with blood. This sponge-mud mixture adhered tightly to the wound tissue, forming a pressure-resistant physical barrier that captures and locks in blood cells and platelets. Simultaneously, the hydrophobic methyl groups of HD sponges repel blood inwardly, effectively sealing the wound. The brush-like structure of HD molecules was suspected to penetrate wet tissues through topological entanglement, thereby enhancing wet adhesion. Compared with gauze and gelatin sponges, HD sponges achieved more effective hemostasis in animal models using rat and rabbit femoral arteries. In particular, HD sponges showed excellent hemostasis in heparin-induced hemorrhage models in mice and pigs. The in vivo experiment demonstrated the excellent biosafety of the HD sponge. Conclusively, the HD sponge is a safe and efficient rapid hemostatic material that is expected to become an alternative material for clinical hemostatic procedures.