Bio-Inspired Homogeneous Conductive Hydrogel with Flexibility and Adhesiveness for Information Transmission and Sign Language Recognition.

The wearable electronic technique is increasingly becoming an effective approach to overcoming the communication obstacles between signers and non-signers. However, the efficacy of conducting hydrogels currently proposed as flexible sensor devices is hindered by their poor processability and matrix mismatch, which frequently results in adhesion failure at the combined interfaces and deterioration of mechanical and electrochemical performance. Herein, we propose a hydrogel composed of a rigid matrix in which the hydrophobic and aggregated polyaniline was homogeneously embedded, while quaternate-functionalized nucleobase moieties endowed the flexible network with adhesiveness. Accordingly, the resulting hydrogel with chitosan-graft-polyaniline (chi-g-PANI) copolymers exhibited a promising conductivity (4.8 S·m-1) because of the uniformly dispersed polyaniline components and a high strain strength (0.84 MPa) because of the chain entanglement of chitosan after soaking. In addition, the modified adenine molecules not only realized synchronization in improving the stretchability (up to 1303%) and exhibiting a skin-like elastic modulus (≈184 kPa), but also provided a durable interfacial contact with various materials. The hydrogel was further fabricated into a strain-monitoring sensor for information encryption and sign language transmission based on its sensing stability and strain sensitivity of up to 2.77. The developed wearable sign language interpreting system provides an innovative strategy to assist auditory or speech-impaired people in communicating with non-signers using visual-gestural patterns including body movements and facial expressions.

The Holothuria leucospilota genome elucidates sacrificial organ expulsion and bioadhesive trap enriched with amyloid-patterned proteins.

Some tropical sea cucumbers of the family Holothuriidae can efficiently repel or even fatally ensnare predators by sacrificially ejecting a bioadhesive matrix termed the Cuvierian organ (CO), so named by the French zoologist Georges Cuvier who first described it in 1831. Still, the precise mechanisms for how adhesiveness genetically arose in CO and how sea cucumbers perceive and transduce danger signals for CO expulsion during defense have remained unclear. Here, we report the first high-quality, chromosome-level genome assembly of Holothuria leucospilota, an ecologically significant sea cucumber with prototypical CO. The H. leucospilota genome reveals characteristic long-repeat signatures in CO-specific outer-layer proteins, analogous to fibrous proteins of disparate species origins, including spider spidroin and silkworm fibroin. Intriguingly, several CO-specific proteins occur with amyloid-like patterns featuring extensive intramolecular cross-ß structures readily stainable by amyloid indicator dyes. Distinct proteins within the CO connective tissue and outer surface cooperate to give the expelled matrix its apparent tenacity and adhesiveness, respectively. Genomic evidence offers further hints that H. leucospilota directly transduces predator-induced mechanical pressure onto the CO surface through mediation by transient receptor potential channels, which culminates in acetylcholine-triggered CO expulsion in part or in entirety. Evolutionarily, innovative events in two distinct regions of the H. leucospilota genome have apparently spurred CO's differentiation from the respiratory tree to a lethal defensive organ against predators.

Mucoadhesive buccal tablet of leuprolide and its fatty acid conjugate: Design, in vitro evaluation and formulation strategies.

This study aimed to design mucoadhesive buccal tablets of leuprolide (LEU) and to manufacture and evaluate the properties of buccal tablets containing LEU-oleic acid conjugate (LOC) and self-assembled LEU-oleic acid nanoparticles (LON), which were developed in a previous study. Hydroxypropyl methylcellulose (HPMC 4000) was used as the mucoadhesive polymer, and tablets were prepared by direct compression. The formulations were characterized by weight, content uniformity, thickness, hardness, swelling index, disintegration time, mucoadhesion time, and drug release. The chosen formulation maintained an adhesion time of up to 6.43 h and a disintegration time of 4.10 h. Drug stability in the mucoadhesive tablets was confirmed after 2 h of storage in human mimic saliva (Phosphate buffer solution pH 6.8). Furthermore, the designed LEU formulation and the LOC and LON developed in a previous study were prepared as buccal tablets and compared. In the dissolution and permeation studies, LON-loaded buccal tablets showed the highest permeation rate. This study suggests that mucoadhesive buccal tablets containing self-assembled LON may effectively increase the medication adherence for pediatric and geriatric patients by improving the bioavailability and permeation rate of LEU.

What is the food like that people choke on? A study on food bolus physical properties under different in vitro oral capacities.

People with oral impairments, such as poor denture status, poor muscle strength, and poor salivary secretion, have more difficulties performing oral processes, which results in the risk of choking. In this study, we aimed to understand, in vitro, how different oral impairments can affect the oral processing of food reported as a choking hazard. Six foods that frequently cause choking were selected and studied, varying three in vitro factors at two levels-saliva incorporation amount, cutting activity, and compression action. The median particle size (a50) and the particle size heterogeneity (a75/25) of the food fragmentation, the hardness, and adhesiveness of the bolus formation, and the final cohesiveness of the bolus were studied. The results showed that all the parameters studied varied depending on the food product. High compression reduced a50 (except in mochi that increased) and a75/25 (except in eggs and fish) but increased bolus adhesion and particle aggregation (except for mochi). Regarding cutting activity, when performing a greater number of strokes, the particle size for sausage and egg, and the hardness of the bolus for mochi and sausage were lower. In contrast, for some food products, the bolus adhesiveness (bread) and particle aggregation (pineapple) were higher at a high number of strokes. The amount of saliva also played an important role in the creation of the bolus. When high amounts of saliva were added, the a50 values (mochi) and hardness (mochi, egg, and fish) decreased; and increased the adhesiveness (mochi) and particle aggregation (bread, pineapple, and sausage). When all oral factors are compromised (lack of muscle strength, denture status, and saliva secretion), some food products create a choking hazard as individuals cannot achieve the right particle size, bolus cohesiveness, and mechanical properties of the bolus to be safe to swallow, there is still a need to elaborate a guide, considering all the safety parameters.

Evaluation of shear bond strength and enamel remineralizing effect of experimental orthodontic composite containing nano-hydroxyapatite: An in vitro study.

OBJECTIVE: The purpose of this study was to prepare an orthodontic composite containing hydroxyapatite nanoparticles to prevent demineralization and create a suitable environment for mineral deposition around orthodontic brackets, and to investigate the mechanical and remineralizing properties of the experimental adhesive composite. METHODS: Experimental orthodontic composite were formulated using varying percentages of nano-hydroxyapatite particles. Assessments were based on four groups: a control group (3M™ Transbond™ XT) and experimental composites containing 2% (HA2), 5% (HA5) and 10% (HA10) hydroxyapatite. Vickers Microhardness test was performed to investigate the remineralizing effect in 3 stages: initial stage, after demineralization and after 4 weeks of exposure to artificial saliva. Scanning electron microscopy with energy dispersive X-ray spectroscopy analyser (SEM/EDAX) was used to evaluate hydroxyapatite precipitation and elemental composition of enamel surface. Shear Bond Strength tests were carried out using a universal testing machine and the debonding pattern was assessed using Adhesive Remnant Index (ARI). RESULTS: All groups showed clinically acceptable SBS values. The highest SBS was achieved in the HA2 group, followed by Transbond™ XT, HA5 and HA10. There was no significant difference in the ARI scores. In terms of microhardness properties, HA5 and HA10 demonstrated a significant increase after 4 weeks. The results of SEM analysis showed the precipitation of hydroxyapatite crystals and EDAX analysis indicated the increase of calcium and phosphate ion peaks compared to the demineralized sample. The data were analysed using one-way ANOVA and Tukey's Post-hoc test. CONCLUSIONS: Addition of hydroxyapatite nanoparticles to orthodontic composite can increase the mineral content and microhardness of the adjacent enamel. However, increasing the amount of nanoparticles reduces shear bond strength in a decreasing trend. The above-mentioned findings showed that incremental increase of nanoparticles of HA can be incorporated in composite to a certain extent and limitations are determined by mechanical properties (SBS) required for bracket bonding.

Eggshell membrane-incorporated cell friendly tough hydrogels with ultra-adhesive property.

Adhesive and tough hydrogels have received increased attention for their potential biomedical applications. However, traditional hydrogels have limited utility in tissue engineering because they tend to exhibit low biocompatibility, low adhesiveness, and poor mechanical properties. Herein, the use of the eggshell membrane (ESM) for developing tough, cell-friendly, and ultra-adhesive hydrogels is described. The ESM enhances the performance of the hydrogel network in three ways. First, its covalent cross-linking with the polyacrylamide and alginate chains strengthens the hydrogel network. Second, it provides functional groups, such as amine and carboxyl moieties, which are well known for enhancing the surface adhesion of biomaterials, thereby increasing the adhesiveness of the hydrogel. Third, it is a bioactive agent and improves cell adhesion and proliferation on the constructed scaffold. In conclusion, this study proposes the unique design of ESM-incorporated hydrogels with high toughness, cell-friendly, and ultra-adhesive properties for various biomedical engineering applications.

Transfer of the zp3a gene results in changes in egg adhesiveness and buoyancy in transgenic zebrafish.

Reproductive strategies and spawning habits play key roles in the evolution of endemic East Asian cyprinids. However, the molecular mechanisms underlying the regulation of spawning habits are not well understood. We recently identified zona pellucida (Zp) as the top differentially expressed protein between East Asian cyprinids that produce adhesive and semi-buoyant eggs, suggesting that Zp protein may play important roles in the regulation of egg type. In this work, we generated transgenic zebrafish in which oocyte-specific expression of zp genes from rare minnow ( Gobiocypris rarus), an East Asian cyprinid laying adhesive eggs, was driven by a zebrafish zp3.2 gene promoter. We found that the transgenic eggs obtained partial adhesiveness and exhibited alteration in hydration and buoyancy. Abnormal metabolism of vitellogenin (VTG) may contribute to enhanced hydration and/or buoyancy. Our work shows that expression of the exogenous zp3a gene from an adhesive-egg producing fish is sufficient to induce changes in both egg adhesiveness and buoyancy in zebrafish, emphasizing the important role of zp genes in the regulation of spawning habits. Our results thus provide new insights into how endemic East Asian cyprinids may have adapted to the Yangtze river-lake system via changes in spawning habits.

Influence of surface free energy of the substrate and flooded water on the attachment performance of stick insects (Phasmatodea) with different adhesive surface microstructures.

Stick and leaf insects (Phasmatodea) are exclusively herbivores. As they settle in a broad range of habitats, they need to attach to and walk on a wide variety of plant substrates, which can vary in their surface free energy (SFE). The adhesive microstructures (AMs) on the euplantulae of phasmids are assumed to be adapted to such substrate properties. Moreover, the natural substrates can often be covered with water as a result of high relative humidity or rain. Although considerable experimental research has been carried out on different aspects of stick insect attachment, the adaptations to cope with the influence of flooded water on attachment performance remain unclear. To elucidate the role of AMs in this context, we here measured attachment forces in three species of stick insects with different AMs. The results show that attachment forces of the three species studied were influenced by the SFE and the presence of water: they all showed higher pull-off (vertical) and traction (horizontal) forces on dry surfaces, compared with when the surfaces were covered with a water film. However, the extent to which the surface properties influenced attachment differed depending on the species and its AMs. All three species showed approximately the same attachment performance on dry surfaces with different surface free energy but maintained attachment underwater to different extents.

Dual-crosslinked bioadhesive hydrogel as NIR/pH stimulus-responsiveness platform for effectively accelerating wound healing.

Adhesive hydrogels have emerged as promising candidates to solve life-threatening infectious skin injuries. However, the inadequate mechanical characteristics and biological adherence limit the traditional wound dressing unable to adapt to high-frequency movement and real-time monitoring of wound healing, calling for the development of bioadhesive materials guided wound healing. In this work, a multifunctional bioadhesive hydrogel with double colorimetric-integrated of polyethylene glycol (PVA)-dextran (Dex)-borax-bromothymol blue (BTB)-fluorescein thiocyanate (FITC) and functionalization by tungsten disulfide-catechol nanozyme (CL/WS2) was created. Hydrogel is a perfect biological adhesive, which can achieve repeatable and strong tissue adhesion strength (8.3 ± 0.6 kPa), which is 1.66 times that of commercial dressings. Based on the strong biological adhesion of the hydrogel, a sensor is integrated into the hydrogel to collect visual image of bacterial infection from a smartphone and transform it into an on-site pH signal for remote evaluation of the wound's dynamic status in real time. Ultimately, the adhesiveness hydrogel has high worth in managing the burden related to wound healing and paving the way for intelligent wound management in the future.

Bond strength of bulk fill composite to teeth prepared with Er: YAG laser

Aim: The present in vitro study aimed to evaluate the bond strength of a bulk fill composite on dentin surfaces prepared with the Er: YAG laser. Methods: Twenty-four permanent third molars were selected and divided into 2 groups: CP - Conventional preparation with high-speed handpiece (control) and LA (laser) - Preparation with Er: YAG laser. The occlusal surface was removed to expose coronal dentin, which was subsequently prepared with a high-speed handpiece or Er: YAG laser (350mJ, 4Hz, 1.5 ml/min water flow). Both groups were restored with Filtek One Bulk Fill (3M ESPE) composite resin. After 24 hours, the samples were evaluated for microtensile bond strength (µTBS), fracture pattern, and scanning electron microscopy (SEM). Results: The data obtained in the µTBS test were submitted to t-test (α=0.05). The results showed no difference in µTBS when the different types of cavity preparation were compared (ρ=0.091). Fracture patterns revealed the prevalence of cohesive fracture in composite resin in CP (83.3%) and adhesive fracture in LA (92.1%). In the SEM analysis, the LA group demonstrated the presence of gaps between the composite resin and the irradiated dentin surface. The hybrid layer exhibited more regularity with the presence of longer and uniform resin tags in the CP group. Conclusion: The type of cavity preparation did not influence the values of bulk fill composite resin µTBS to dentin. Fracture patterns and scanning electron microscopy analyses suggested less interference at the adhesive interface in preparations performed using CP

Effect of heat-moisture treatment (HMT) on thermal stability of starch gel and the surface adhesiveness of vermicelli.

The molecular structure has an important influence on the surface adhesion of starch gel. In the present study, the surface adhesiveness of vermicelli after cooking was reduced by heat-moisture treatment (HMT), and the mechanism underlying the increased thermal stability was explored by measuring the changes in short-range order, crystallinity, the thickness of the crystalline layer, and the length of the double helix in the dry starch gel. The surface adhesiveness decreased by 72.12 % when the moisture content was 26 %. HMT increased the crystallinity, and the thickness of the crystalline layer of the starch gel increased from 14.61 nm to 14.83-17.30 nm at 20-26 % moisture content. The molecular rearrangement and destruction of unstable short double helixes increased the proportion of long double helixes, resulting in an increased crystallinity and layer thickness.

Biodegradable epoxy thermosetting system with high adhesiveness based on glycidate-acid anhydride curing.

Biodegradable epoxy thermosets were developed by curing through copolymerization of a diglycidate monomer, a bifunctional epoxide bearing ester linkages, with cyclic acid anhydrides as a biosafe thermosetting system. The cured products of the glycidate exhibit high adhesiveness, identical to analogous cured products of conventional glycidyl ethers. Even an inert cycloolefin polymer and polyimide can be adhered. The cured products of the glycidate can be hydrolytically and biologically degraded. The biodegradation of the glycidate thermoset in compost completely proceeded within 2 weeks.

Design as strategy for evaluation of the mechanical properties of binary mixtures composed of poly(methyl vinyl ether-alt-maleic anhydride) and Pluronic F127 for biomedical applications.

The synergism between thermoresponsive and bioadhesive polymers can lead to the optimization of materials with enhanced mechanical and bioadhesive properties. Quality by Design can assure the understanding and control of formulation variables. In this approach, Design of Experiment has been widely utilized as an important strategy. Poly(methyl vinyl ether-alt-maleic anhydride) (PVMMA) is a bioadhesive polymer and Pluronic F127 (PF127) shows thermoresponsiveness. The association of these two polymers has been poorly investigated. The aim of this work was to study the mechanical, bioadhesive and rheological properties of polymer mixtures composed of PVMMA and PF127, in order to select the best conditions and formulations for biomedical applications. Textural properties (hardness, compressibility, adhesiveness, cohesiveness and elasticity), softness index, bioadhesion and rheological characteristics (flow and viscoelasticity) showed that 17.5-20% (w/w) PF127-polymer mixtures displayed improved values of the parameters. However, the rheological interaction parameter showed low synergism, due to the polymers' characteristics and system organization. The formulations displayed gelation temperatures suitable for administration, with improved bioadhesive properties mainly at 34 °C and suggests the formulations can be used for biomedical applications. DoE constituted an important tool to investigate these systems showing the main effects that significantly influence the binary mixtures.

Injectable Dopamine-Polysaccharide In Situ Composite Hydrogels with Enhanced Adhesiveness.

Polysaccharide bio-adhesives used for non-invasive repair often show weak mechanical strength and tissue adhesion, even when covalently modified with dopamine (DA) from mussel proteins and its derivatives. Low cohesion of the polysaccharide adhesives and easy oxidation of DA may result in the low adhesion properties of the polysaccharide-DA adhesives. In this work, we aimed to prepare a series of injectable hydrogel adhesives to improve their cohesion and adhesion by in situ mixing DA with the polysaccharide without covalent modification. The injectable and rapid curing adhesives were prepared by mixing oxidized dextran (ODE) and chitosan (CS) through a Schiff base reaction in the presence (or absence) of DA. The gelation time of the adhesive was customized to be less than 20 s by controlling the amount of ODE, regardless of the amount of DA. Multi-cross-linked (MC) hydrogels were further prepared by adding cross-linking agents such as sodium periodate (NaIO4) and ferric trichloride (FeCl3), and their sol-gel transitions were easily adjusted by changing the amounts of the cross-linking agents. The MC-FeCl3 hydrogel adhesive displayed good tissue adhesion with a lap shear adhesion strength of 345 kPa, which was 43 times that of fibrin glue. Results from Raman spectra, texture profile analyses, and atomic force microscopy images confirmed the enhanced adhesion induced by a higher cohesion of MC-FeCl3, owing to the coordination of Fe3+ and DA and non-covalent and covalent bonds of DA. Moreover, the adhesives showed good biodegradability and biocompatibility. These results demonstrate that the injectable and sticky hydrogels with good adhesion are promising materials for tissue repair.

Development and Evaluation of Combined Effect Buccal Films for Treatment of Oral Candidiasis.

Buccal film formulations, including antifungal nystatin, anti-inflammatory agent hydrocortisone acetate, and local anesthetic lidocaine hydrochloride for pain relief, were developed. Bioadhesive films were fabricated with hydrophilic polymers, hydroxyethyl cellulose (HEC), and xanthan gum (XG) and dried in the incubator. Textural, swelling, and bioadhesive properties, physicochemical and in vitro release characteristics, and antifungal activities of bioadhesive films were evaluated.Bioadhesive films significantly extended nystatin release by prolonging retention time of the target area formulation while rapidly releasing hydrocortisone acetate and lidocaine HCl, reducing drug administration. The polymer type affected bioadhesion strength and erosion ratio, and XG formulations had more polymer suitability. Consequently, XT-O2 formulation that was prepared with xanthan gum and tween 80, was best for its highest antifungal film activity (20.00 ± 0.07 mm), released nystatin (44.296% ± 1.695), and lowest erosion matrix (36.719% ± 0.249). The selected formulation can be used for compatibility, stability and in vivo studies targeted oral candidiasis infections.

Balanced Coexistence of Reversible and Irreversible Covalent Bonds in a Conductive Triple Polymeric Network Enables Stretchable Hydrogels with High Toughness and Adhesiveness.

The application of soft hydrogels to stretchable devices has attracted increasing attention in deformable bioelectronics owing to their unique characteristic, "modulus matching between materials and organs". Despite considerable progress, their low toughness, low conductivity, and absence of tissue adhesiveness remain substantial challenges associated with unstable skin-interfacing, where body movements undesirably disturb electrical signal acquisitions. Herein, we report a material design of a highly tough strain-dissipative and skin-adhesive conducting hydrogel fabricated through a facile one-step sol-gel transition and its application to an interactive human-machine interface. The hydrogel comprises a triple polymeric network where irreversible amide linkage of polyacrylamide with alginate and dynamic covalent bonds entailing conjugated polymer chains of poly(3,4-ethylenedioxythiophene)-co-(3-thienylboronic acid) are simultaneously capable of high stretchability (1300% strain), efficient strain dissipation (36,209 J/m2), low electrical resistance (590 Ω), and even robust skin adhesiveness (35.0 ± 5.6 kPa). Based on such decent characteristics, the hydrogel was utilized as a multifunctional layer for successfully performing either electrophysiological cardiac/muscular on-skin sensors or an interactive stretchable human-machine interface.

Buccal films: A review of therapeutic opportunities, formulations & relevant evaluation approaches.

The potential of the mucoadhesive film technology is hard to ignore, owing to perceived superior patient acceptability versus buccal tablets, and significant therapeutic opportunities compared to conventional oral drug delivery systems, especially for those who suffer from dysphagia. In spite of this, current translation from published literature into the commercial marketplace is virtually non-existent, with no authorised mucoadhesive buccal films available in the UK and very few available in the USA. This review seeks to provide an overview of the mucoadhesive buccal film technology and identify key areas upon which to focus scientific efforts to facilitate the wider adoption of this patient-centric dosage form. Several indications and opportunities for development were identified, while discussing the patient-related factors influencing the use of these dosage forms. In addition, an overview of the technologies behind the manufacturing of these films was provided, highlighting manufacturing methods like solvent casting, hot melt extrusion, inkjet printing and three-dimensional printing. Over thirty mucoadhesive polymers were identified as being used in film formulations, with details surrounding their mucoadhesive capabilities as well as their inclusion alongside other key formulation constituents provided. Lastly, the importance of physiologically relevant in vitro evaluation methodologies was emphasised, which seek to improve in vivo correlations, potentially leading to better translation of mucoadhesive buccal films from the literature into the commercial marketplac.

Matrix Adhesiveness Regulates Myofibroblast Differentiation from Vocal Fold Fibroblasts in a Bio-orthogonally Cross-linked Hydrogel.

Repeated mechanical and chemical insults cause an irreversible alteration of extracellular matrix (ECM) composition and properties, giving rise to vocal fold scarring that is refractory to treatment. Although it is well known that fibroblast activation to myofibroblast is the key to the development of the pathology, the lack of a physiologically relevant in vitro model of vocal folds impedes mechanistic investigations on how ECM cues promote myofibroblast differentiation. Herein, we describe a bio-orthogonally cross-linked hydrogel platform that recapitulates the alteration of matrix adhesiveness due to enhanced fibronectin deposition when vocal fold wound healing is initiated. The synthetic ECM (sECM) was established via the cycloaddition reaction of tetrazine (Tz) with slow (norbornene, Nb)- and fast (trans-cyclooctene, TCO)-reacting dienophiles. The relatively slow Tz-Nb ligation allowed the establishment of the covalent hydrogel network for 3D cell encapsulation, while the rapid and efficient Tz-TCO reaction enabled precise conjugation of the cell-adhesive RGDSP peptide in the hydrogel network. To mimic the dynamic changes of ECM composition during wound healing, RGDSP was conjugated to cell-laden hydrogel constructs via a diffusion-controlled bioorthognal ligation method 3 days post encapsulation. At a low RGDSP concentration (0.2 mM), fibroblasts residing in the hydrogel remained quiescent when maintained in transforming growth factor beta 1 (TGF-ß1)-conditioned media. However, at a high concentration (2 mM), RGDSP potentiated TGF-ß1-induced myofibroblast differentiation, as evidenced by the formation of an actin cytoskeleton network, including F-actin and alpha-smooth muscle actin. The RGDSP-driven fibroblast activation to myofibroblast was accompanied with an increase in the expression of wound healing-related genes, the secretion of profibrotic cytokines, and matrix contraction required for tissue remodeling. This work represents the first step toward the establishment of a 3D hydrogel-based cellular model for studying myofibroblast differentiation in a defined niche associated with vocal fold scarring.

How Does Gecko Keratin Stick to Hydrophilic and Hydrophobic Surfaces in the Presence and Absence of Water? An Atomistic Molecular Dynamics Investigation.

We developed a united-atom model of gecko keratin to investigate the influence of electrostatic and van der Waals contributions to gecko adhesion in scenarios representing gecko's natural habitats. The keratin model assumes that only intrinsically disordered regions directly contact the surface. Contact angles of two generic substrate surfaces that we created match those previously used in AFM experiments on gecko adhesion. Force probe molecular dynamics simulations pulling the keratin from the surface show that the pull-off force increases with increased water content and is inversely related to the water contact angle of the surface. This matches experimental trends. We investigated the number and charge density of keratin and water at the surface, confirming a water-mediating effect and are able to show that keratin folds polar groups to the hydrophilic surface. We decomposed energetic contributions during pull-off, and our computational model shows that in contrast to popular hypotheses, long-range electrostatic interactions determine much of the pull-off process. The contribution of electrostatics to adhesion may be in the order of the van der Waals contributions.

3D printed bilayer mucoadhesive buccal film of estradiol: Impact of design on film properties, release kinetics and predicted in vivo performance.

Despite being an effective therapy for menopausal symptoms, the use of oral estrogen is associated with low bioavailability and serious adverse effects of venous thromboembolism. Individualized therapy has been recommended to maximize benefits and curb the adverse effects, but much has not been done in developing formulations that offer flexibility to personalize therapy. In the present study, we employed an innovative 3D printing technology to design and develop bi-layered estradiol film with different infill patterns with an aim of improving bioavailability and facilitating personalized treatment. Hydroxypropyl cellulose (HPC-H) based formulation exhibited suitable rheological properties and was used as a feedstock to fabricate estradiol films with different infill patterns namely honeycomb, rectangular and plain. The back layer was prepared from a hydroxyethyl cellulose-based formulation. The resulting films were subsequently characterized in terms of their physicochemical, mechanical, environmental impact, and release characteristics among others. Films with a plain infill pattern exhibited significantly higher % elongation break and tensile strength. The in vitro drug release study revealed the fastest drug release profile for rectangular infill (96 % within 4 h) and the slowest drug release was observed for the plain infill pattern (∼35 % within 4 h), highlighting the effect of the infill pattern on release kinetics. Films with honeycomb infill patterns were selected for further characterization based on mechanical and in vitro release properties. No interaction between components of the formulation was observed and the absence of crystallinity in the final product was confirmed by Differential Scanning Calorimetry (DSC) and X-Ray Powder Diffraction analyses (XRD). The force of adhesiveness for the film was 0.13 ± 0.03 N. The predicted AUC 0-4 h, Cmax, and Tmax were 144.85 ng·h/mL, 65.97 ng/mL, and 0.83 h for a film (honeycomb infill pattern) loaded with 1 mg of estradiol. The printing process of films with honeycomb and rectangular infill patterns was evaluated as "green" using the index of Greenness Assessment of Printed Pharmaceuticals (iGAPP) tool. Our finding demonstrates the development of bi-layered estradiol film using Pressure assisted microsyringe (PAM) 3D printing and the influence of infill patterns on release kinetics and mechanical properties. The fabricated film not only facilitates the move towards personalized medicine but could also improve the bioavailability of the drugs by bypassing the hepatic first-pass metabolism and decreasing wash-out by the saliva.