Highly Adhesive and Stretchable Epidermal Electrode for Bimodal Recording Patch.

For numerous biological and human-machine applications, it is critical to have a stable electrophysiological interface to obtain reliable signals. To achieve this, epidermal electrodes should possess conductivity, stretchability, and adhesiveness. However, limited types of materials can simultaneously satisfy these requirements to provide satisfying recording performance. Here, we present a dry electromyography (EMG) electrode based on conductive polymers and tea polyphenol (CPT), which offers adhesiveness (0.51 N/cm), stretchability (157%), and low impedance (14 kΩ cm2 at 100 Hz). The adhesiveness of the electrode is attributed to the interaction between catechol groups and hydroxyls in the polymer blend. This adhesive electrode ensures stable EMG recording even in the presence of vibrations and provides signals with a high signal-to-noise ratio (>25 dB) for over 72 h. By integrating the CPT electrode with a liquid metal strain sensor, we have developed a bimodal rehabilitation monitoring patch (BRMP) for sports injuries. The patch utilizes Kinesio Tape as a substrate, which serves to accelerate rehabilitation. It also tackles the challenge of recording with knee braces by fitting snugly between the brace and the skin, due to its thin and stretchable design. CPT electrodes not only enable BRMP to assist clinicians in formulating effective rehabilitation plans and offer patients a more comfortable rehabilitation experience, but also hold promise for future applications in biological and human-machine interface domains.

Capillary adhesion of stick insects.

Scientific progress within the last few decades has revealed the functional morphology of an insect's sticky footpads-a compliant pad that secretes thin liquid films. However, the physico-chemical mechanisms underlying their adhesion remain elusive. Here, we explore these underlying mechanisms by simultaneously measuring adhesive force and contact geometry of the adhesive footpads of live, tethered Indian stick insects, Carausius morosus, spanning more than two orders of magnitude in body mass. We find that the adhesive force we measure is similar to the previous measurements that use a centrifuge. Our measurements afford us the opportunity to directly probe the adhesive stress in vivo and use existing theory on capillary adhesion to predict the surface tension of the secreted liquid and compare it to previous assumptions. From our predictions, we find that the surface tension required to generate the adhesive stresses we observed ranges between 0.68 and 12 mN m - 1 ${\rm m}^{-1}$ . The low surface tension of the liquid would enhance the wetting of the stick insect's footpads and promote their ability to conform to various substrates. Our insights may inform the biomimetic design of capillary-based, reversible adhesives and motivate future studies on the physico-chemical properties of the secreted liquid.

Highly Adaptive Kirigami-Metastructure Adhesive with Vertically Self-Aligning Octopus-like 3D Suction Cups for Efficient Wet Adhesion to Complexly Curved Surfaces.

An essential requirement for biomedical devices is the capability of conformal adaptability on diverse irregular 3D (three-dimensional) nonflat surfaces in the human body that may be covered with liquids such as mucus or sweat. However, the development of reversible adhesive interface materials for biodevices that function on complex biological surfaces is challenging due to the wet, slippery, smooth, and curved surface properties. Herein, we present an ultra-adaptive bioadhesive for irregular 3D oral cavities covered with saliva by integrating a kirigami-metastructure and vertically self-aligning suction cups. The flared suction cup, inspired by octopus tentacles, allows adhesion to moist surfaces. Additionally, the kirigami-based auxetic metastructure with a negative Poisson's ratio relieves the stress caused by tensile strain, thereby mitigating the stress caused by curved surfaces and enabling conformal contact with the surface. As a result, the adhesive strength of the proposed auxetic adhesive is twice that of adhesives with a flat backbone on highly curved porcine palates. For potential application, the proposed auxetic adhesive is mounted on a denture and performs successfully in human subject feasibility evaluations. An integrated design of these two structures may provide functionality and potential for biomedical applications.

An Overview on the Adhesion Mechanisms of Typical Aquatic Organisms and the Applications of Biomimetic Adhesives in Aquatic Environments.

Water molecules pose a significant obstacle to conventional adhesive materials. Nevertheless, some marine organisms can secrete bioadhesives with remarkable adhesion properties. For instance, mussels resist sea waves using byssal threads, sandcastle worms secrete sandcastle glue to construct shelters, and barnacles adhere to various surfaces using their barnacle cement. This work initially elucidates the process of underwater adhesion and the microstructure of bioadhesives in these three exemplary marine organisms. The formation of bioadhesive microstructures is intimately related to the aquatic environment. Subsequently, the adhesion mechanisms employed by mussel byssal threads, sandcastle glue, and barnacle cement are demonstrated at the molecular level. The comprehension of adhesion mechanisms has promoted various biomimetic adhesive systems: DOPA-based biomimetic adhesives inspired by the chemical composition of mussel byssal proteins; polyelectrolyte hydrogels enlightened by sandcastle glue and phase transitions; and novel biomimetic adhesives derived from the multiple interactions and nanofiber-like structures within barnacle cement. Underwater biomimetic adhesion continues to encounter multifaceted challenges despite notable advancements. Hence, this work examines the current challenges confronting underwater biomimetic adhesion in the last part, which provides novel perspectives and directions for future research.

Structure, mechanical and adhesive properties of the cellulosic mucilage in Ocimum basilicum seeds.

Plant seeds and fruits, like those of Ocimum basilicum, develop a mucilaginous envelope rich in pectins and cellulosic fibers upon hydration. This envelope promotes adhesion for attachment to soils and other substrates for dispersal and protection of the seed for a safe germination. Initially at hydration, the mucilage envelope demonstrates low adhesion and friction, but shows increasing adhesive and frictional properties during dehydration. However, the mechanisms underlying the cellulose fiber arrangement and the mechanical properties, especially the elasticity modulus of the mucilage envelope at different hydration conditions are not fully known. In this study, which is based on scanning electron microscopy (SEM), confocal laser scanning microscopy (CLSM) and light microscopy, the structure of the seed coat and arrangement of the cellulose fibers of basil seeds were characterized. Moreover, we performed pull-off force measurements to estimate adhesive properties and JKR-tests to estimate E-modulus of the mucilage at different hydration levels. Microscopy results demonstrate that cellulose fibers are split at their free ends into smaller fibrils, which might enhance the adhesive properties of the mucilage. Adhesive forces in contact increased during dehydration and reached maximum of 33 mN shortly before complete dehydration. The E-modulus of the mucilage changed from 1.4 KPa in water to up to 2.1 MPa in the mucilage at the maximum of its adhesion performance. Obtained results showed hydrogel-like mechanical properties during dehydration and cellulose fiber structures similar to the nanofibrous systems in other organisms with strong adhesive properties. STATEMENT OF SIGNIFICANCE: This paper reveals the hierarchical cellulose fiber structure in Ocimum basilicum's mucilaginous seed coat, suggesting increased fiber splitting towards the end, potentially enhancing adhesion contact areas. Mechanical tests explore elasticity modulus and adhesion force during various hydration stages, crucial as these properties evolve with mucilage desiccation. A rare focus on mucilaginous seed coat mechanical properties, particularly cellulose-reinforced fibers, provides insight into the hydrogel-like mucilage of plant seeds. Adhesion forces peak just before complete desiccation and then decline rapidly. As mucilage water content decreases, the E-modulus rises, displaying hydrogel-like properties during early dehydration stages with higher water content. This study might bring the focus to plant seeds as inspiration for biodegradable glues and applications for hydrogel research.

Nanostructured ZnO thin film to enhance gutta-percha's adhesion to endodontic sealers.

BACKGROUND: Gutta-percha (GP) combined with an endodontic sealer is still the core material most widely used for tridimensional obturation. The sealer acts as a bonding agent between the GP and the root dentinal walls. However, one of the main drawbacks of GP core material is the lack of adhesiveness to the sealer. ZnO thin films have many remarkable features due to their considerable bond strength, good optical quality, and excellent piezoelectric, antibacterial, and antifungal properties, offering many potential applications in various fields. This study aimed to explore the influence of GP surface's functionalization with a nanostructured ZnO thin film on its adhesiveness to endodontic sealers. METHODS: Conventional GP samples were divided randomly into three groups: (a) Untreated GP (control); (b) GP treated with argon plasma (PT); (c) Functionalized GP (PT followed by ZnO thin film deposition). GP's surface functionalization encompassed a multi-step process. First, a low-pressure argon PT was applied to modify the GP surface, followed by a ZnO thin film deposition via magnetron sputtering. The surface morphology was assessed using SEM and water contact angle analysis. Further comprehensive testing included tensile bond strength assessment evaluating Endoresin and AH Plus Bioceramic sealers' adhesion to GP. ANOVA procedures were used for data statistical analysis. RESULTS: The ZnO thin film reproduced the underlying surface topography produced by PT. ZnO thin film deposition decreased the water contact angle compared to the control (p < 0.001). Endoresin showed a statistically higher mean bond strength value than AH Plus Bioceramic (p < 0.001). There was a statistically significant difference between the control and the ZnO-functionalized GP (p = 0.006), with the latter presenting the highest mean bond strength value. CONCLUSIONS: The deposition of a nanostructured ZnO thin film on GP surface induced a shift towards hydrophilicity and an increased GP's adhesion to Endoresin and AH Bioceramic sealers.

Characterization of Prototype Gummy Formulations Provides Insight into Setting Quality Standards.

Gummy formulations are considered suitable alternatives to traditional oral dosage forms like tablets and capsules due to their merits that include chewability, softness/flexibility, improved drug release, administration without water, appealing organoleptic properties, better patient compliance, easy preparation and usefulness for persons of different ages (e.g. children). Though there is increasing interest in gummy formulations containing drugs, measurable parameters, and specification limits for evaluating their quality are scarce. Quality check forms an essential part of the pharmaceutical development process because drug products must be distributed as consistently stable, safe, and therapeutically effective entities. Consequently, some quality parameters that could contribute to the overall performance of typical gummy formulations were investigated employing six brands of non-medicinal gummies as specimens. Accordingly, key physicochemical and micromechanical characteristics namely adhesiveness (0.009 - 0.028 mJ), adhesive force (0.009 - 0.055 N), chewiness (2.780 - 6.753 N), cohesiveness (0.910 - 0.990), hardness (2.984 - 7.453 N), springiness (0.960 - 1.000), and resilience (0.388 - 0.572), matrix firmness - compression load (2.653 - 6.753 N) and work done (3.288 - 6.829 mJ), rupture (5.315 - 29.016 N), moisture content (< 5%), weight uniformity (< 2.5 g; < 7.5% deviation), and intraoral dissolution pH (≥ 3.5 ≤ 6.8) were quantified to identify measures that may potentially function as specification limits and serve as prospective reference points for evaluating the quality of gummy formulations. Findings from this work contribute to ongoing efforts to standardize the quality control strategies for gummy formulations, particularly those intended for oral drug delivery.

A review of bioinspired dry adhesives: from achieving strong adhesion to realizing switchable adhesion.

In the early twenty-first century, extensive research has been conducted on geckos' ability to climb vertical walls with the advancement of microscopy technology. Unprecedented studies and developments have focused on the adhesion mechanism, structural design, preparation methods, and applications of bioinspired dry adhesives. Notably, strong adhesion that adheres to both the principles of contact splitting and stress uniform distribution has been discovered and proposed. The increasing popularity of flexible electronic skins, soft crawling robots, and smart assembly systems has made switchable adhesion properties essential for smart adhesives. These adhesives are designed to be programmable and switchable in response to external stimuli such as magnetic fields, thermal changes, electrical signals, light exposure as well as mechanical processes. This paper provides a comprehensive review of the development history of bioinspired dry adhesives from achieving strong adhesion to realizing switchable adhesion.

Association of mucoadhesive polymeric matrices and liposomes for local delivery of miconazole: A new approach for the treatment of oral candidiasis.

Since the local treatment of oral candidiasis usually requires long-term administration of the antifungal drug, an ideal dosage form should be able to maintain the drug release over an extended period, assuring an adequate concentration at the infection site. In this context, we have considered the possibility of a buccal delivery of miconazole nitrate (MN) by mucoadhesive polymeric matrices. The loading of the antifungal drug in a hydrophilic matrix was made possible by taking advantage of the amphiphilic nature of liposomes (LP). The MN-loaded LP were prepared by a thin film evaporation method followed by extrusion, while solid matrices were obtained by freeze-drying a suspension of the LP in a polymeric solution based on chitosan (CH), sodium hyaluronate (HYA), or hydroxypropyl methylcellulose (HPMC). MN-loaded LP measured 284.7 ± 20.1 nm with homogeneous size distribution, adequate drug encapsulation efficiency (86.0 ± 3.3 %) and positive zeta potential (+47.4 ± 3.3). CH and HYA-based formulations almost completely inhibited C. albicans growth after 24 h, even if the HYA-based one released a higher amount of the drug. The CH-based matrix also provided the best mucoadhesive capacity and therefore represents the most promising candidate for the local treatment of oral candidiasis.

Enhancing mucoadhesion: Exploring rheological parameters and texture profile in starch solutions, with emphasis on micro-nanofiber influence.

This comprehensive analysis explores the rheological parameters and texture profile analysis (TPA) to effect starch solutions for mucoadhesion and assess the impact of micro-nanofibers (MNFs) on these parameters. The surface chemistry of all six samples was examined through the Fourier transform infrared (FTIR) technique. The spectrum of FTIR was recorded in the range of 500-4000 cm-1. The viscosity of different pHs (2-11) and temperatures (20-70 °C) of verious starches, potato, corn, and rice, decreased with the increasing of shear rate, exhibiting shear thinning behavior, which conformed to pseudoplastic fluid.The combination of chitosan and collagen MNFs significantly changed rheological properties, and the sample with the addtion of 1500 µL CC-MNF exhibited a greater viscosity of 59.8 mPa·s at a shear rate of 1.49 s-1. Potato starch emerged as a strong candidate for mucoadhesion due to its low hardness (4.62 ± 0.31 N), high adhesion (0.0322 ± 0.0053 mJ), cohesiveness (0.37 ± 0.03 Ratio), low chewiness (0.66 ± 0.12 mJ), and gumminess (1.69 ± 0.23 N). The inclusion of MNFs, especially collagen/chitosan MNFs showed the potential to further enhance adhesion.

Application of supercritical carbon dioxide to enhance the aroma of whole sorghum flour for use in 3D printing of sorghum cookies.

Sorghum is a promising ingredient for new food products due to its high fiber content, slow digestibility, drought resistance, and gluten-free nature. One of the main challenges in sorghum-based products is the unpleasant aroma compounds found in grain sorghum. Therefore, in this study, sorghum flour was treated via supercritical carbon dioxide (SC-CO2) to remove undesired aroma compounds. The resulting SC-CO2-treated flours were used to generate dough for 3D food printing. At the optimized conditions, sorghum cookies were 3D-printed using 60 % water and a nozzle diameter of 1.5 mm. All dough samples produced with untreated and SC-CO2-treated sorghum flours exhibited shear-thinning behavior. Changing the treatment pressure (8-15 MPa) or temperature (40-60 °C) did not significantly affect the viscosity of the dough samples. Moreover, the sorghum cookie doughs had higher G' and G″ values after the SC-CO2 treatments (G' > G″). Doughs generated from flours treated at 15 MPa - 40 °C and 8 MPa - 60 °C showed lower adhesiveness compared to the ones produced from untreated flour, whereas 15 MPa - 60 °C treatment did not affect the adhesiveness. After baking, the 3D-printed cookies from SC-CO2-treated flour exhibited significantly lower redness (a*), but the hardness of the cookies was not affected by SC-CO2 treatment. Overall, the SC-CO2 treatment of sorghum flour did not negatively affect the quality parameters of the 3D-printed cookies while enhancing the aroma of the flour.

Adhesion-Lubrication Paradox of Articular Cartilage.

The friction of solids is primarily understood through the adhesive interactions between the surfaces. As a result, slick materials tend to be nonstick (e.g., Teflon), and sticky materials tend to produce high friction (e.g., tires and tape). Paradoxically, cartilage, the slippery bearing material of human joints, is also among the stickiest of known materials. This study aims to elucidate this apparent paradox. Cartilage is a biphasic material, and the most cited explanation is that both friction and adhesion increase as load transfers from the pressurized interstitial fluid to the solid matrix over time. In other words, cartilage is slippery and sticky under different times and conditions. This study challenges this explanation, demonstrating the strong adhesion of cartilage under high and low interstitial hydration conditions. Additionally, we find that cartilage clings to itself (a porous material) and Teflon (a nonstick material), as well as other surfaces. We conclude that the unusually strong interfacial tension produced by cartilage reflects suction (like a clingfish) rather than adhesion (like a gecko). This finding is surprising given its unusually large roughness, which typically allows for easy interfacial flow and defeats suction. The results provide compelling evidence that cartilage, like a clingfish, conforms to opposing surfaces and effectively seals submerged contacts. Further, we argue that interfacial sealing is itself a critical function, enabling cartilage to retain hydration, load support, and lubrication across long periods of inactivity.

Moxifloxacin-loaded nanoparticles of thiolated xyloglucan for ocular drug delivery: Permeation, mucoadhesion and pharmacokinetic evaluation.

The current study goal was to improve mucoadhesive potential and ocular pharmacokinetics of nanoparticles of thiolated xyloglucan (TXGN) containing moxifloxacin (MXF). Thiolation of xyloglucan (XGN) was achieved with esterification with 3-mercaptopropionic acid. TXGN was characterized by NMR and FTIR analysis. The nanoparticles of TXGN were prepared using ionic-gelation method and evaluate the antibacterial properties. TXGN and nanoparticles were determined to possess 0.06 and 0.08 mmol of thiol groups/mg of polymer by Ellman's method. The ex-vivo bioadhesion time of TXGN and nanoparticles was higher than XGN in a comparative assessment of their mucoadhesive properties. The creation of a disulfide link between mucus and TXGN is responsible for the enhanced mucoadhesive properties of TXGN (1-fold) and nanoparticles (2-fold) over XGN. Improved MXF penetration in nanoparticulate formulation (80 %) based on TXGN was demonstrated in an ex-vivo permeation research utilizing rabbit cornea. Dissolution study showed 95 % release of MXF from nanoparticles. SEM images of nanoparticles showed spherical shape and cell viability assay showed nontoxic behavior when tested on RPE cell line. Antibacterial analysis revealed a zone of inhibition of 31.5 ± 0.5 mm for MXF, while NXM3 exhibited an expanded zone of 35.5 ± 0.4 mm (p < 0.001). In conclusion, thiolation of XGN improves its bioadhesion, permeation, ocular-retention and pharmacokinetics of MXF.

Tunable and fast-cured hyaluronic acid hydrogel inspired on catechol architecture for enhanced adhesion property.

Hyaluronic acid-based hydrogels have been broadly used in medical applications due to their remarkable properties such as biocompatibility, biodegradability, super hydroscopicity, non-immunogenic effect, etc. However, the inherent weak and hydrophilic polysaccharide structure of pure hyaluronic acid (HA) hydrogels has limited their potential use in muco-adhesiveness, wound dressing, and 3D printing. In this research, we developed in-situ forming of catechol-modified HA hydrogels with improved mechanical properties involving blue-light curing crosslinking reaction. The effect of catechol structure on the physicochemical properties of HA hydrogels was evaluated by varying the content (0-40 %). The as-synthesized hydrogel demonstrated rapid prototyping, excellent wetting adhesiveness, and good biocompatibility. Furthermore, an optimized hydrogel precursor solution was used as a blue light-cured bio-ink with high efficiency and good precision and successfully prototyped a microstructure that mimicked the human hepatic lobule by using DLP 3D printing method. This catechol-modified HA hydrogel with tunable physicochemical and rapid prototyping properties has excellent potential in biomedical engineering.

Janus Membrane-Based Wearable pH Sensor with Sweat Absorption, Gas Permeability, and Self-Adhesiveness.

Wearable biomedical sensors have enabled noninvasive and continuous physiological monitoring for daily health management and early detection of chronic diseases. Among biomedical sensors, wearable pH sensors attracted significant interest, as pH influences most biological reactions. However, conformable pH sensors that have sweat absorption ability, are self-adhesive to the skin, and are gas permeable remain largely unexplored. In this study, we present a pioneering approach to this problem by developing a Janus membrane-based pH sensor with self-adhesiveness on the skin. The sensor is composed of a hydrophobic polyurethane-polydimethylsiloxane porous hundreds nanometer-thick substrate and a hydrophilic poly(vinyl alcohol)-poly(acrylic acid) porous nanofiber layer. This Janus membrane exhibits a thickness of around 10 µm, providing a conformable adhesion to the skin. The simultaneous realization of solution absorption, gas permeability, and self-adhesiveness makes it suitable for long-term continuous monitoring without compromising the comfort of the wearer. The pH sensor was tested successfully for continuous monitoring for 7.5 h, demonstrating its potential for stable analysis of skin health conditions. The Janus membrane-based pH sensor holds significant promise for comprehensive skin health monitoring and wearable biomedical applications.

Development and in vitro/in vivo evaluation of famotidine hydrochloride bioadhesive sustained release suspension.

To develop a new kind of famotidine-resin microcapsule for gastric adhesion sustained release by screening out suitable excipients and designing reasonable prescriptions to improve patient drug activities to achieve the expected therapeutic effect. The famotidine drug resin was prepared using the water bath method with carbomer 934 used as coating material. Microcapsules were prepared using the emulsified solvent coating method and appropriate excipients were used to prepare famotidine sustained release suspension. Pharmacokinetics of the developed microcapsules were studied in the gastrointestinal tract of rats. The self-made sustained-release suspension of famotidine hydrochloride effectively reduced the blood concentration and prolonged the action time. The relative bioavailability of the self-made suspension of the famotidine hydrochloride to the commercially available famotidine hydrochloride was 146.44%, with an average retention time of about 5h longer, which indicated that the new suspension had acceptable adhesion properties. The findings showed that the newly developed famotidine-resin microcapsule increased the bioavailability of the drug with a significant sustained-release property.

Innovative Fusion of Probiotics and Mouth Fresheners: Investigating Unaltered Growth, Microscopic Analysis, and Mucoadhesive Strength.

Since ancient times, mouth fresheners in many different forms have been used throughout the world. Traditional knowledge describes the health benefits of mouth fresheners, and contemporary science is now investigating their benefits. Claims have been made that mouth fresheners not only improve digestion but also promote oral health. Similar, but in a more profound sense, probiotics offer astounding advantages in treating many disorders. In certain cases, probiotics also offer prophylactic effects. Numerous benefits for dental health are being studied for B. coagulans (MB-BCM9) and B. subtilis (MB-BSM12). In this current study, a probiotic and a mouth freshener were combined to ameliorate the impacts of both. The oral residence of probiotics was enhanced by employing mucoadhesive polymers. Numerous compositions were developed and evaluated for the unaltered growth of probiotics, along with other evaluations like microscopy, in vitro mucoadhesive strength, and stability studies. Xanthan gum and hydroxypropyl methylcellulose were used in the development of mucoadhesive probiotic powder by employing the lyophilization technique. More than five hours of residence time were observed in the in vitro study with goat oral mucosa. The enumeration study validated the label claims of MB-BCM9 and MB-BSM12. It also concluded that none of the components of the formulation had a detrimental effect on probiotics. In essence, the present work discloses the novel and stable formulation of a probiotic-based mouth freshener.

Development of a hydroxypropyl methyl cellulose/polyacrylic acid interpolymer complex formulated buccal mucosa adhesive film to facilitate the delivery of insulin for diabetes treatment.

Buccal mucosa administration is a promising method for insulin (INS) delivery with good compliance. However, buccal mucosa delivery systems still face challenges of long-term mucosal adhesion, sustained drug release, and mucosal drug penetration. To address these issues, a double-layer film consisting of a hydroxypropyl methylcellulose/polyacrylic acid interpolymer complex (IPC)-formulated mucoadhesive layer and an ethylcellulose (EC)-formulated waterproof backing layer (IPC/EC film) was designed. Protamine (PTM) and INS were co-loaded in the mucoadhesive layer of the IPC/EC film (PTM-INS-IPC/EC film). In ex vivo studies with porcine buccal mucosa, this film exhibited robust adhesion, with an adhesion force of 120.2 ±â€¯20.3 N/m2 and an adhesion duration of 491 ±â€¯45 min. PTM has been shown to facilitate INS mucosal transfer. Pharmacokinetic studies indicated that the PTM-INS-IPC/EC film significantly improved the absorption of INS, exhibiting a 1.45 and 2.24-fold increase in the area under the concentration-time curve (AUC0-∞) compared to the INS-IPC/EC film and free INS, respectively. Moreover, the PTM-INS-IPC/EC film effectively stabilized the blood glucose levels of type 1 diabetes mellitus (T1DM) rats with post oral glucose administration, maintaining lower glucose levels for approximately 8 h. Hence, the PTM-INS-IPC/EC film provides a promising noninvasive INS delivery system for diabetes treatment.

Deciphering protein-mediated underwater adhesion in an invasive biofouling ascidian: Discovery, validation, and functional mechanism of an interfacial protein.

Discovering macromolecules and understanding the associated mechanisms involved in underwater adhesion are essential for both studying the fundamental ecology of benthos in aquatic ecosystems and developing biomimetic adhesive materials in industries. Here, we employed quantitative proteomics to assess protein expression variations during the development of the distinct adhesive structure - stolon in the model fouling ascidian, Ciona robusta. We found 16 adhesive protein candidates with increased expression in the stolon, with ascidian adhesive protein 1 (AAP1) being particularly rich in adhesion-related signal peptides, amino acids, and functional domains. Western blot and immunolocalization analyses confirmed the prominent AAP1 signals in the mantle, tunic, stolon, and adhesive footprints, indicating the interfacial role of this protein. Surface coating and atomic force microscopy experiments verified AAP1's adhesion to diverse materials, likely through the specific electrostatic and hydrophobic amino acid interactions with various substrates. In addition, molecular docking calculations indicated the AAP1's potential for cross-linking via hydrogen bonds and salt bridges among Von Willebrand factor type A domains, enhancing its adhesion capability. Altogether, the newly discovered interfacial protein responsible for permanent underwater adhesion, along with the elucidated adhesion mechanisms, are expected to contribute to the development of biomimetic adhesive materials and anti-fouling strategies. STATEMENT OF SIGNIFICANCE: Discovering macromolecules and studying their associated mechanisms involved in underwater adhesion are essential for understanding the fundamental ecology of benthos in aquatic ecosystems and developing innovative bionic adhesive materials in various industries. Using multidisciplinary analytical methods, we identified an interfacial protein - Ascidian Adhesive Protein 1 (AAP1) from the model marine fouling ascidian, Ciona robusta. The interfacial functions of AAP1 are achieved by electrostatic and hydrophobic interactions, and the Von Willebrand factor type A domain-based cross-linking likely enhances AAP1's interfacial adhesion. The identification and validation of the interfacial functions of AAP1, combined with the elucidation of adhesion mechanisms, present a promising target for the development of biomimetic adhesive materials and the formulation of effective anti-fouling strategies.

Mucoadhesive polymers: Design of S-protected thiolated cyclodextrin-based hydrogels.

AIM: This study aims to design chemically crosslinked thiolated cyclodextrin-based hydrogels and to evaluate their mucoadhesive properties via mucosal residence time studies on porcine small intestinal mucosa and on porcine buccal mucosa. METHODS: Free thiol groups of heptakis(6-deoxy-6-thio)-ß-cyclodextrin (ß-CD-SH) were S-protected with 2-mercaptoethanesulfonic acid (MESNA) followed by crosslinking with citric acid. Cytotoxicity was assessed by hemolysis as well as resazurin assay. Hydrogels were characterized by their rheological and mucoadhesive properties. Ritonavir was employed as model drug for in vitro release studies from these hydrogels. RESULTS: The structure of S-protected ß-CD-SH was confirmed by IR and 1H NMR spectroscopy. Degree of thiolation was 390 ± 7 µmol/g. Hydrogels based on native ß-CD showed hemolysis of 12.5 ± 2.5 % and 13.6 ± 2.7 % within 1 and 3 h, whereas hemolysis of just 3.5 ± 2.8 % and 3.9 ± 3.0 % was observed for the S-protected thiolated CD hydrogels, respectively. Both native and S-protected thiolated hydrogels showed minor cytotoxicity on Caco-2 cells. Rheological investigations of S-protected thiolated ß-CD-based hydrogel (16.2 % m/v) showed an up to 13-fold increase in viscosity in contrast to the corresponding native ß-CD-based hydrogel. Mucosal residence time studies showed that thiolated ß-CD-based hydrogel is removed to a 16.6- and 2.4-fold lower extent from porcine small intestinal mucosa and porcine buccal mucosa in comparision to the native ß-CD-based hydrogel, respectively. Furthermore, a sustained release of ritonavir from S-protected thiolated ß-CD-based hydrogels was observed. CONCLUSION: Because of their comparatively high mucoadhesive and release-controlling properties, S-protected thiolated ß-CD-based hydrogels might be promising systems for mucosal drug delivery.