Wet Adhesion Research Articles

Adhesive hydrogel releases protocatechualdehyde-Fe3+ complex to promote three healing stages for accelerated therapy of oral ulcers

Oral ulcers can significantly reduce the life quality of patients and even lead to malignant transformations. Local treatments using topical agents are often ineffective because of the wet and dynamic environment of the oral cavity. Current clinical treatments for oral ulcers, such as corticosteroids, have limitations and side effects for long-term usage. Here, we develop adhesive hydrogel patches (AHPs) that effectively promote the healing of oral ulcers in a rat model. The AHPs are comprised of the quaternary ammonium salt of chitosan, aldehyde-functionalized hyaluronic acid, and a tridentate complex of protocatechualdehyde and Fe3+ (PF). The AHPs exhibit tunable mechanical properties, self-healing ability, and wet adhesion on the oral mucosa. Through controlling the formula of the AHPs, PF released from the AHPs in a temporal manner. We further show that the AHPs have good biocompatibility and the capability to heal oral ulcers rapidly. Both in vitro and in vivo experiments indicate that the PF released from AHPs facilitated ulcer healing by suppressing inflammation, promoting macrophage polarization, enhancing cell proliferation, and inducing epithelial-mesenchymal transition involving inflammation, proliferation, and maturation stages. This study provides insights into the healing of oral ulcers and presents an effective therapeutic biomaterial for the treatment of oral ulcers. STATEMENT OF SIGNIFICANCE: By addressing the challenges associated with current clinical treatments for oral ulcers, the development of adhesive hydrogel patches (AHPs) presents an effective approach. These AHPs possess unique properties, such as tunable mechanical characteristics, self-healing ability, and strong adhesion to the mucosa. Through controlled release of protocatechualdehyde-Fe3+ complex, the AHPs facilitate the healing process by suppressing inflammation, promoting cell proliferation, and inducing epithelial-mesenchymal transition. The study not only provides valuable insights into the healing mechanisms of oral ulcers but also introduces a promising therapeutic biomaterial. This work holds significant scientific interest and demonstrates the potential to greatly improve the treatment outcomes and quality of life for individuals suffering from oral ulcers.

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.

Dough-Kneading-Inspired Design of an Adhesive Cardiac Patch to Attenuate Cardiac Fibrosis and Improve Cardiac Function via Regulating Glycometabolism.

Recently, hydrogel adhesive patches have been explored for treating myocardial infarction. However, achieving secure adhesion onto the wet beating heart and local regulation of pathological microenvironment remains challenging. Herein, a dough-kneading-inspired design of hydrogel adhesive cardiac patch is reported, aiming to improve the strength of prevalent powder-formed patch and retain wet adhesion. In mimicking the polysaccharide and protein components of natural flour, methacrylated polyglutamic acid (PGAMA) is electrostatically interacted with hydroxypropyl chitosan (HPCS) to form PGAMA/HPCS coacervate hydrogel. The PGAMA/HPCS hydrogel is freeze-dried and ground into powders, which are further rehydrated with two aqueous solutions of functional drug, 3-acrylamido phenylboronic acid (APBA)/rutin (Rt) complexes for protecting the myocardium from advanced glycation end product (AGEs) injury by reactive oxygen species (ROS) -responsive Rt release, and hypoxanthine-loaded methacrylated hyaluronic acid (HAMA) nanogels for enhancing macrophage targeting ability to regulate glycometabolism for combating inflammation. The rehydrated powders bearing APBA/Rt complexes and HAMA-hypoxanthine nanogels are repeatedly kneaded into a dough-like gel, which is further subjected to thermal-initiated crosslinking to form a stabilized and sticky patch. This biofunctional patch is applied onto the rats' infarcted myocardium, and the outcomes at 28 days post-surgery indicate efficient restoration of cardiac functions and attenuation of cardiac fibrosis.

Nanofibers and hydrogel composite patch with sandwich structure for prevention post-operative abdominal adhesion

Abdominal adhesions have a high incidence after surgery due to fibrosis and inflammation resulting in damaged tissues caused by trauma, bleeding, infection, foreign body stimulation. The adhesions introduced persistent chronic pain because of attachment and traction seriously affects physical health patients. Recent years, various kinds of membrances, hydrogel, nanofibers were developed to inhibit post-operative abdominal adhesion by physical isolation or drug treatment. However, the integration of physical isolation and pharmaceutical therapy in one platform still has some challenges. For example, the anti-swelling property of hydrogel is not good, membrane is easy prone to displacement. Herein, we developed a nanofiber-hydrogel composite patch (FHCP) with sandwich structure providing effectively anti swelling property and wet adhesion performance. Meanwhile, the nanofiber-hydrogel composite patch achieved combining excellent physical isolation and drug treatment, the sandwich structure of patch provided hierarchical drug release drugs release, and then made the patch realized excellent anti-inflammatory, tissue regeneration, and preventing post-operative abdominal adhesion. Our results showed that the prepared patch has better effects on anti-inflammation, effectively suppressing post-operative adhesion in the abdominal cavity. Therefore, we believe that our nanofiber-hydrogel composite patch has broad clinical application prospects.

Natural Polymer-Polyphenol Bioadhesive Coacervate with Stable Wet Adhesion, Antibacterial Activity, and On-Demand Detachment.

Medical adhesives are emerging as an important clinical tool as adjuvants for sutures and staples in wound closure and healing and in the achievement of hemostasis. However, clinical adhesives combining cytocompatibility, as well as strong and stable adhesion in physiological conditions, are still in demand. Herein, a mussel-inspired strategy is explored to produce adhesive coacervates using tannic acid (TA) and methacrylate pullulan (PUL-MA). TA|PUL-MA coacervates mainly comprise van der Waals forces and hydrophobic interactions. The methacrylic groups in the PUL backbone increase the number of interactions in the adhesives matrix, resulting in enhanced cohesion and adhesion strength (72.7 Jm-2), compared to the non-methacrylated coacervate. The adhesive properties are kept in physiologic-mimetic solutions (72.8 Jm-2) for 72h. The photopolymerization of TA|PUL-MA enables the on-demand detachment of the adhesive. The poor cytocompatibility associated with the use of phenolic groups is here circumvented by mixing reactive oxygen species-degrading enzyme in the adhesive coacervate. This addition does not hamper the adhesive character of the materials, nor their anti-microbial or hemostatic properties. This affordable and straightforward methodology, together with the tailorable adhesivity even in wet environments, high cytocompatibility, and anti-bacterial activity, enables foresee TA|PUL-MA as a promising ready-to-use bioadhesive for biomedical applications.

Wet adhesion on rough surfaces: A JKR model with thermodynamic considerations

Understanding wet adhesion is vital for advancing technologies such as underwater robotics, aquatic microsystems, and sweat-interfaced devices. It involves the formation of a liquid bridge with a meniscus between two solid surfaces. This phenomenon has a significant impact on surface adhesion, particularly in relation to roughness. Determining the profile of this liquid bridge is critical for accurately characterizing wet adhesion. In this paper, we propose a JKR mechanical model combined with a thermodynamic approach to investigate adhesive contact between a spherical indenter and an axisymmetric wavy surface in a wetting environment. The numerical solution for the pull-off force is obtained by considering parameters such as waviness, roughness, liquid volume, and liquid surface energy. The theoretical findings validated by experimental results provide insights into wet adhesion mechanisms on rough surfaces.

The effect of crystallographic orientation of α-Al2O3 on the wetting behavior and adhesion characteristics of aluminum droplets

To solve the problem of adhesion of aluminum fluid to the inner wall of the vacuum ladle in the aluminum electrolysis industry, molecular dynamics simulation is performed to research the wetting behavior of Al droplets on the surfaces of the α-Al2O3 substrates C (0001), M ( 11ˉ00 ), and R ( 11ˉ02 ) at 1073 K. Meanwhile, the adhesion characteristics of the Al droplet are evaluated by the potential of the mean force (PMF) for the separation of the Al droplets from different surfaces of the α-Al2O3 substrate. The results show that the wetting behavior of Al droplets on the α-Al2O3 substrate is influenced by the different crystallographic orientations. The diffusion of Al droplets in the x-o-y plane of the substrate exhibits isotropic. The PMF and the interfacial potential energy reveal that the magnitude of the adhesion work in the solid-liquid separation of Al droplets from α-Al2O3 substrates follows the order C (0001) > R ( 11ˉ02 ) > M ( 11ˉ00 ). These findings characterize the wetting properties and adhesion behavior of Al droplets on an atomic scale and provide a theoretical basis for the selection of materials for the inner wall of the vacuum ladle.

Highly Resilient Noncovalently Associated Hydrogel Adhesives for Wound Sealing Patch.

The development of hydrogel adhesives with high mechanical resilience and toughness remains a challenging task. Hydrogels must exhibit high mechanical resilience to withstand the inevitable movement of the human body while simultaneously demonstrating strong wet tissue adhesion and appropriate toughness to hold and seal damaged tissues; However, tissue adhesion, toughness, and mechanical resilience are typically negatively correlated. Therefore, this paper proposes a highly resilient double-network (DN) hydrogel wound-sealing patch that exhibits a well-balanced combination of tissue adhesion, toughness, and mechanical resilience. The DN structure is formed by introducing covalently and non-covalently crosslinkable dopamine-modified crosslinkers and physically interactable linear poly(vinyl imidazole) (PVI). The resulting hydrogel adhesive exhibits high toughness and mechanical resilience due to the presence of a DN involving reversible physical intermolecular interactions such as hydrogen bonds, hydrophobic associations, cation-π interactions, π-π interactions, and chain entanglements. Moreover, the hydrogel adhesive achieves strong wet tissue adhesion through the polar hydroxyl groups of dopamine and the amine group of PVI. These mechanical attributes allow the proposed adhesive to effectively seal damaged tissues and promote wound healing by maintaining a moist environment.

Picking food by robot hand with tree-frog like pad in various wet conditions

Achieving stability with less squeeze in picking up wet-soft objects is still challenging for robots. To accomplish this challenge, preventing slippage between robotic grippers and an object is crucial. We used micropatterned pads on robotic grippers to enhance wet adhesion when picking up food items. This paper examines the role of micropattern interfaces in preventing slippage by experimental evaluations, in which soft robotic grippers picked up and released food samples such as tofu, quail egg, coffee jelly, konjac, and jelly under various wet conditions. A micropatterned pad, inspired by the toe pad of a tree-frog, comprises a large number of squared cells that are separated by channels. Normal pads without any micropattern were also made for comparison. Experimental results showed the micropatterned pad required less squeeze force than that of the normal pads, resulting in less deformation of a grasped object such as a piece of tofu. The potential of the micropatterned pad to prevent slippage between a robotic gripper and a fragile deformable object in various wet conditions without a complicated control method was demonstrated, thereby promising wider robotic applications in the food, service, and medical industries.

Wet environment-induced adhesion and softening of coenzyme-based polymer elastic patch for treating periodontitis

Periodontitis, a common chronic inflammatory disease caused by pathogenic bacteria, can be treated with diverse biomaterials by loading drugs, cytokines or proteins. However, these biomaterials often show unsatisfactory therapeutic efficiency due to their poor adhesion, short residence time in the wet and dynamic oral cavity and emerging drug resistance. Here we report a wet-responsive methacrylated gelatin (GelMA)-stabilized co-enzyme polymer poly(α-lipoic acid) (PolyLA)-based elastic patch with water-induced adhesion and softening features. In PolyLA-GelMA, the multiple covalent and hydrogen-bonding crosslinking between PolyLA and GelMA prevent PolyLA depolymerization and slow down the dissociation of PolyLA in water, allowing durable adhesion to oral periodontal tissue and continuous release of LA-based bioactive small molecule in periodontitis wound without resorting external drugs. Compared with the undifferentiated adhesion behavior of traditional adhesives, this wet-responsive patch demonstrates a favorable periodontal pocket insertion ability due to its non-adhesion and rigidity in dry environment. In vitro studies reveal that PolyLA-GelMA patch exhibits satisfactory wet tissue adhesion, antibacterial, blood compatibility and ROS scavenging abilities. In the model of rat periodontitis, the PolyLA-GelMA patch inhibits alveolar bone resorption and accelerates the periodontitis healing by regulating the inflammatory microenvironment. This biomacromolecule-stabilized coenzyme polymer patch provides a new option to promote periodontitis treatment.

A Laparoscopically Compatible Rapid-Adhesion Bioadhesive for Asymmetric Adhesion, Non-Pressing Hemostasis, and Seamless Seal.

Bioadhesive hydrogels offer unprecedented opportunities in hemostatic agents and tissue sealing; however, the application of existing bioadhesive hydrogels through narrow spaces to achieve strong adhesion in fluid-rich physiological environments is challenged either by undesired indiscriminate adhesion or weak wet tissue adhesion. Here, a laparoscopically compatible asymmetric adhesive hydrogel (aAH) composed of sprayable adhesive hydrogel powders and injectable anti-adhesive glue is proposed for hemostasis and to seal the bloody tissues in a non-pressing way, allowing for preventing postoperative adhesion. The powders can seed on the irregular bloody wound to rapidly absorb interfacial fluid, crosslink, and form an adhesive hydrogel to hemostatic seal (blood clotting time and tissue sealing in 10 s, ≈200mm Hg of burst pressure in sealed porcine tissues). The aAH can be simply formed by crosslinking the upper powder with injectable glue to prevent postoperative adhesion (adhesive strength as low as 1kPa). The aAH outperforms commercial hemostatic agents and sealants in the sealing of bleeding organs in live rats, demonstrating superior anti-adhesive efficiency. Further, the hemostatic seamless sealing by aAH succeeds in shortening the time of warm ischemia, decreasing the blood loss, and reducing the possibility of rebleeding in the porcine laparoscopic partial nephrectomy model.

Biomimetic biphasic microsphere preparation based on the thermodynamic incompatibility of glycosaminoglycan with gelatin methacrylate for hair regeneration

Hair follicle (HF) tissue engineering is promising for hair loss treatment especially for androgenetic alopecia. Physiologically, the initiation of HF morphogenesis relies on the interactions between hair germ mesenchymal and epithelial layers. To simulate this intricate process, in this study, a co-flowing microfluidic-assisted technology was developed to produce dual aqueous microdroplets capturing growth factors and double-layer cells for subsequent use in hair regeneration. Microspheres, called G/HAD, were generated using glycosaminoglycan-based photo-crosslinkable biological macromolecule (HAD) shells and gelatin methacrylate (GelMA) cores to enclose mesenchymal cells (MSCs) and mouse epidermal cells (EPCs). The findings indicated that the glycosaminoglycan-based HAD shells display thermodynamic incompatibility with GelMA cores, resulting in the aqueous phase separation of G/HAD cell spheres. These G/HAD microspheres exhibited favorable characteristics, including sustained growth factor release and wet adhesion properties. After transplantation into the dorsal skin of BALB/c nude mice, G/HAD cell microspheres efficiently induced the regeneration of HFs. This approach enables the mass production of approximately 250 dual-layer microspheres per minute. Thus, this dual-layer microsphere fabrication method holds great potential in improving current hair regeneration techniques and can also be combined with other tissue engineering techniques for various regenerative purposes.

Facile Bond Exchanging Strategy for Engineering Wet Adhesion and Antioxidant/Antibacterial Thin Layer over a Dynamic Hydrogel via the Carbon Dots Derived from Tannic Acid/ε-Polylysine.

Adhesive hydrogels, playing an essential role in stretchable electronics, soft robotics, tissue engineering, and so forth, upon functioning often need to adhere to various substrates in wet conditions and simultaneously exhibit antibacterial/antioxidant properties while possessing the intrinsic stretchability and elasticity of the hydrogel network intact. Therefore, simple approaches to conveniently access adhesive hydrogels with multifunctional surfaces are being pursued. Herein, a facile strategy has been proposed to construct multifunctional adhesive hydrogels via surface engineering of a multifunctional carbon dot (CD)-decorated polymeric thin layer by dynamic bond exchange. By this strategy, a double cross-linked network hydrogel of polyacrylamide (PAM) and oxidized dextran (ODA) was engineered with a unique dense layer over the Schiff base hydrogel matrix by aqueous solution immersion of PA-120, versatile CDs derived from tannic acid (TA) and ε-polylysine (PL). Without any additional agents, the PA-120 CDs with residual polyphenolic/catechol and amine moieties were incorporated into the surface structure of the hydrogel network by the combined action of the Schiff base and hydrogen bonds to form a dense surface layer that can exhibit high wet adhesive performance via the amine-polyphenol/catechol pair. The armor-like dense architecture also endowed hydrogels with considerably enhanced tensile/compression properties and excellent antioxidant/antibacterial abilities. Besides, the single-sided modified Janus hydrogel and completely surface-modified hydrogel can be flexibly developed through this approach. This strategy will provide new insights into the preparation and application of surface-modified hydrogels featuring multiple functions and tunable interfacial properties.

Robust and Wet Adhesive Self-Gelling Powders for Rapid Hemostasis and Efficient Wound Healing.

Healing traumatic wounds is arduous, leaving miscellaneous demands for ideal wound dressings, such as rapid hemostasis, superior wet tissue adhesion, strong mechanical properties, and excellent antibacterial activity. Herein, we report a self-gelling, wet adhesive, stretchable (polyethylenimine/poly(dimethylammonium chloride)/(poly(acrylic acid)/poly(sodium styrenesulfonate)/alkylated chitosan)) ((PEI/PDDA)/(PAA/PSS)/ACS) powder as a new option. The self-gel utilizes noncovalent interactions among in situ formed PDDA/PSS nanoparticles and PEI/PAA polymetric matrices to earn sensational mechanical properties and tensile strength while incorporating ACS to obtain fast hemostasis and therapeutic capacities. The powder can form a hydrogel patch in situ within 3 s upon liquid absorption, capable of resisting pressure higher than twice the blood pressure. Deposition of the self-gelling powders on various wounds, such as rat liver and femoral artery wounds, can stop bleeding in 10 s and lessen the amount of bleeding 6-fold plus in corresponding models. Furthermore, the self-gelling powders can significantly advance the chronic wound healing process by displaying a high wound healing rate and a low inflammatory response and promoting the formation of new blood vessels and tissue regeneration. The satisfactory mechanical properties, strong wet adhesion, sufficient antibacterial properties, ease of usage, adaptability to complex wounds, rapid hemostasis, and superior therapeutic capacities of (PEI/PDDA)/(PAA/PSS)/ACS self-gelling powders render them as a profound wound dressing biomaterial.

One-Step Synthesis of Hydrogel Adhesive with Acid-Responsive Tannin Release for Diabetic Oral Mucosa Defects Healing.

The complex preparation, weak wet tissue adhesion, and limited biological activity of traditional oral wound dressings usually impede their efficient treatment and healing for diabetic oral mucosal defects. To overcome these problems, a novel hydrogel adhesive (named CFT hydrogel) is rapidly constructed using a one-step method based on dual-dynamic covalent cross-linking. Compared with the commercial oral patches, the CFT hydrogel shows superior in vivo (rat tongue) wet tissue adhesion performance. Additionally, the CFT hydrogel exhibits unique acid-responsive properties, thereby facilitating the release of bioactive molecule tannic acid in the acidic diabetic wound microenvironment. And a series of in vitro experiments substantiate the favorable biocompatibility and bioactivity properties (including antibacterial, antioxidative, anti-inflammatory, and angiogenetic effects) exhibited by CFT hydrogel. Moreover, in vivo experiments conducted on a diabetic rat model with oral mucosal defects demonstrate that the CFT hydrogel exhibits significant efficacy in protecting against mucosal wounds, alleviating inflammatory reactions, thereby facilitating the wound-healing process. Taken together, this study provides a promising and comprehensive therapeutic option with great potential for the clinical management of oral mucosa defects in diabetic patients.

Nature-Inspired Wet Drug Delivery Platforms.

Nature has created various organisms with unique chemical components and multi-scale structures (e.g., foot proteins, toe pads, suckers, setose gill lamellae) to achieve wet adhesion functions to adapt to their complex living environments. These organisms can provide inspirations for designing wet adhesives with mediated drug release behaviors in target locations of biological surfaces. They exhibit conformal and enhanced wet adhesion, addressing the bottleneck of weaker tissue interface adhesion in the presence of body fluids. Herein, it is focused on the research progress of different wet adhesion and bioinspired fabrications, including adhesive protein-based adhesion and inspired adhesives (e.g., mussel adhesion); capillarity and Stefan adhesion and inspired adhesive surfaces (e.g., tree frog adhesion); suction-based adhesion and inspired suckers (e.g., octopus' adhesion); interlocking and friction-based adhesion and potential inspirations (e.g., mayfly larva and teleost adhesion). Other secreted protein-induced wet adhesion is also reviewed and various suckers for other organisms and their inspirations. Notably, one representative application scenario of these bioinspired wet adhesives is highlighted, where they function as efficient drug delivery platforms on target tissues and/or organs with requirements of both controllable wet adhesion and optimized drug release. Finally, the challenges of these bioinspired wet drug delivery platforms in the future is presented.

Bioinspired Microstructured Janus Bioadhesive for the Prevention of Abdominal and Intrauterine Adhesions

AbstractAbdominal and intrauterine adhesions are common postoperative problems that can cause serious complications. Current adhesives are usually double sided and suffer from poor wet adhesion, nondegradability, and monofunctionality, which limits their application in preventing postoperative adhesions. Herein, a bioinspired microstructured Janus bioadhesive, named OD/GM@PG, with a wet adhesive inner layer and an antiadhesive outer layer is prepared by combining electrostatic spun and adhesive materials. By using both capillary suction and a catechol‐based strategy, the wet adhesive strength and interfacial toughness of the Janus bioadhesive reach 98 kPa and 325 J m−2, respectively, which are much higher than those of commercial fibrin glues and cyanoacrylate glues. The electrostatic spun outer layer acts as a physical barrier with antiadhesive and friction‐reducing effects. Additionally, the Janus bioadhesive demonstrates biodegradable, hemostatic, antioxidative, anti‐inflammatory, and prohealing properties. In vivo results show that the asymmetric adhesion effect of the Janus bioadhesive effectively preventing postoperative abdominal and intrauterine adhesions. Notably, tandem mass tags‐labeled quantitative proteomics analysis demonstrate that the expression of inflammatory response‐associated proteins (S100A8, S100A9) is associated with adhesion; the Janus bioadhesive significantly downregulates this expression. Therefore, the OD/GM@PG Janus bioadhesive is a promising candidate for preventing postoperative adhesions.

A mussel inspired polyvinyl alcohol/collagen/tannic acid bioadhesive for wet adhesion and hemostasis

Bioadhesives are useful in surgery for hemostasis, tissue sealing and wound healing. However, most bioadhesives have limitations such as weak adhesion in wet conditions, insufficient sealing and poor clotting performance. Inspired by the adhesion mechanism of marine mussels, a novel bioadhesive (PCT) was developed by simply combining polyvinyl alcohol (PVA), collagen (COL) and tannic acid (TA) together. The results showed that the adhesion, sealing and blood coagulation properties boosted with the increase of tannic acid content in PCT. The wet shear adhesion strength of PCT-5 (the weight ratio of PVA:COL:TA=1:1:5) was 60.8 ± 0.6 kPa, the burst pressure was 213.7 ± 0.7 mmHg, and the blood clotting index was 39.3% ± 0.6%, respectively. In rat heart hemostasis tests, PCT-5 stopped bleeding in 23.7 ± 3.2 s and reduced bleeding loss to 83.0 ± 19.1 mg, which outperformed the benchmarks of commercial gauze (53.3 ± 8.7 s and 483.0 ± 15.0 mg) and 3 M adhesive (Type No.1469SB, 35.3 ± 5.0 s and 264.0 ± 14.2 mg). The as-prepared bioadhesive could provide significant benefits for tissue sealing and hemorrhage control along its low cost and facile preparation process.

Hemostatic Tranexamic Acid-Induced Fast Gelation and Mechanical Reinforcement of Polydimethylacrylamide/Carboxymethyl Chitosan Hydrogel for Hemostasis and Wound Healing.

The combinational properties with excellent mechanical properties, adhesive performance, hemostatic ability, antibacterial action, and wound healing efficacy are highly desirable for injectable hydrogels' practical applications in hemorrhage control and wound closure, but designing one single hydrogel system integrating with such properties is still difficult. Herein, a simplified yet straightforward strategy is proposed to prepare an injectable and robust poly(N,N-dimethylacrylamide) (PDMAA)/carboxymethyl chitosan (CMCS) hydrogel induced by tranexamic acid (TXA). TXA not only promotes the rapid generation of free radicals but also introduces multiple hydrogen bonds into the hydrogel network. Moreover, as a common clinical hemostatic drug, TXA itself has excellent hemostatic effects. In addition, CMCS imparts sterilization and hemostasis effects to the hydrogel, thereby promoting wound healing. Besides, the amino and carboxyl groups on TXA molecules and the hydroxyl, amino, and carboxyl groups on CMCS molecules can form multiple hydrogen bonds with wet biological tissues, leading to good wet tissue adhesion of the hydrogel. As a result, the hydrogel with excellent mechanical properties (up to 1.83 MPa at 90% compression strain), adhesion performance (up to 18.7 kPa adhesion strength to porcine skin tissue), biocompatibility, hemostatic ability, antibacterial activity, and wound healing properties can be fabricated within several minutes. These combinational advantages enable the hydrogel to efficiently stop hemorrhage (blood loss amount: 110 mg; hemostasis time: 25 s) and promote the wound healing process (wound closure rate at 2 weeks: 83%), which can be verified using rat models of liver bleeding and infected full thickness skin defect. Overall, this facile strategy to design a hydrogel incorporating such unique advantages will greatly advance the hydrogel's clinical application in rapid hemostasis and wound healing.

Artificial Octopus-Limb-Like Adhesive Patches for Cupping-Driven Transdermal Delivery with Nanoscale Control of Stratum Corneum.

Drug delivery through complex skin is currently being studied using various innovative structural and material strategies due to the low delivery efficiency of the multilayered stratum corneum as a barrier function. Existing microneedle-based or electrical stimulation methods have made considerable advances, but they still have technical limitations to reduce skin discomfort and increase user convenience. This work introduces the design, operation mechanism, and performance of noninvasive transdermal patch with dual-layered suction chamber cluster (d-SCC) mimicking octopus-limb capable of wet adhesion with enhanced adhesion hysteresis and physical stimulation. The d-SCC facilitates cupping-driven drug delivery through the skin with only finger pressure. Our device enables nanoscale deformation control of stratum corneum of the engaged skin, allowing for efficient transport of diverse drugs through the stratum corneum without causing skin discomfort. Compared without the cupping effect of d-SCC, applying negative pressure to the porcine, human cadaver, and artificial skin for 30 min significantly improved the penetration depth of liquid-formulated subnanoscale medicines up to 44, 56, and 139%. After removing the cups, an additional acceleration in delivery to the skin was observed. The feasibility of d-SCC was demonstrated in an atopic dermatitis-induced model with thickened stratum corneum, contributing to the normalization of immune response.