Bioclickable and mussel adhesive peptide mimics for engineering vascular stent surfaces.

Thrombogenic reaction, aggressive smooth muscle cell (SMC) proliferation, and sluggish endothelial cell (EC) migration onto bioinert metal vascular stents make poststenting reendothelialization a dilemma. Here, we report an easy to perform, biomimetic surface engineering strategy for multiple functionalization of metal vascular stents. We first design and graft a clickable mussel-inspired peptide onto the stent surface via mussel-inspired adhesion. Then, two vasoactive moieties [i.e., the nitric-oxide (NO)-generating organoselenium (SeCA) and the endothelial progenitor cell (EPC)-targeting peptide (TPS)] are clicked onto the grafted surfaces via bioorthogonal conjugation. We optimize the blood and vascular cell compatibilities of the grafted surfaces through changing the SeCA/TPS feeding ratios. At the optimal ratio of 2:2, the surface-engineered stents demonstrate superior inhibition of thrombosis and SMC migration and proliferation, promotion of EPC recruitment, adhesion, and proliferation, as well as prevention of in-stent restenosis (ISR). Overall, our biomimetic surface engineering strategy represents a promising solution to address clinical complications of cardiovascular stents and other blood-contacting metal materials.

Impact of Different Mixing Methods on the Performance of Suspension-Based Transdermal Delivery Systems.

Suspension-based matrix transdermal delivery systems (TDSs) are specialized systems that maintain a continuous driving force for drug delivery over prolonged wear. The pressure-sensitive adhesive (PSA) is the most critical constituent of such systems. Our study aimed to determine the effect of different mixing methods on the performance of silicone PSA-based suspension TDSs. Lidocaine suspension TDSs were prepared using conventional slow rotary mixing, high-speed homogenization, bead-mill homogenization, vortex shaking, and by an unguator. Resultant TDSs were tested for tack, shear, and peel properties and correlated to coat weight, content uniformity, microstructure, and in vitro permeation across dermatomed human skin. Every mixing method tested caused a significant reduction in peel. However, bead-mill homogenization resulted in significant loss of all adhesive properties tested, while unguator-mixed TDSs retained most properties. Good linear correlation (R2 = 1.000) between the shear properties of the TDSs with the average cumulative amount of lidocaine permeated after 24 h was observed, with no significant difference between percutaneous delivery from slow rotary-mixed systems (1334 ± 59.21 µg/cm2) and unguator-mixed systems (1147 ± 108.3 µg/cm2). However, significantly lower delivery from bead-mill homogenized systems (821.1 ± 28.00 µg/cm2) was noted. While many factors affect TDS performance, careful consideration must also be given to the processing parameters during development as they have been shown to affect the resultant system's therapeutic efficacy. Extensive mixing with bead-mill homogenization demonstrated crystallization of drug, loss in adhesive properties, coat weight, and film thickness, with reduced transdermal delivery of lidocaine from the prepared system.

Mussel-Inspired Alternating Copolymer as a High-Performance Adhesive Material Both at Dry and Under-Seawater Conditions.

Marine mussels have the ability to cling to various surfaces at wet or underwater conditions, which inspires the research of catechol-functionalized polymers (CFPs) to develop high-performance adhesive materials. However, these polymeric adhesives generally face the problems of complex synthetic route, and it is still high challenging to prepare CFPs with excellent adhesive performance both at dry and underwater conditions. Herein, a mussel-inspired alternating copolymer, poly(dopamine-alt-2,2-bis(4-glycidyloxyphenyl)propane) (P(DA-a-BGOP)), is synthesized in one step by using commercially available monomers through epoxy-amino click chemistry. The incorporation of polar groups and rigid bisphenol A structures into the polymer backbone enhances the cohesion energy of polymer matrix. The alternating polymer structure endows the polymers with high catechol content and controlled polymer sequence. As a result, P(DA-a-BGOP) exhibits a strong bonding strength as high as 16.39 ± 2.13 MPa on stainless steel substrates after a hot pressing procedure and displays a bonding strength of 1.05 ± 0.05 MPa on glass substrates at an under-seawater condition, which surpasses most commercial adhesives.

Development of Adhesive and Conductive Resilin-Based Hydrogels for Wearable Sensors.

Integrating multifunctionality such as stretchability, adhesiveness, and electroconductivity on a single protein hydrogel is highly desirable for various applications, and remains a challenge. Here we present the development of such multifunctional hydrogels based on resilin, a natural rubber-like material with remarkable extensibility and resilience. First, genetically engineered reslin-like proteins (RLPs) with varying molecular weight were biosynthesized to tune mechanical strength and stiffness of the cross-linked RLP hydrogels. Second, glycerol was incorporated into the hydrogels to endow adhesive properties. Next, a graphene-RLP conjugate was synthesized for cross-linking with the unmodified, pristine RLP to form an integrated network. The obtained hybrid hydrogel could be stretched to over four times of its original length, and self-adhered to diverse substrate surfaces due to its high adhesion strength of ∼24 kPa. Furthermore, the hybrid hydrogel showed high sensitivity, with a gauge factor of 3.4 at 200% strain, and was capable of real-time monitoring human activities such as finger bending, swallowing, and phonating. Due to these favorable attributes, the graphene/resilin hybrid hydrogel was a promising material for use in wearable sensors. In addition, the above material design and functionalization strategy may provide intriguing opportunities to generate innovative materials for broad applications.

Advances in Rosin-Based Chemicals: The Latest Recipes, Applications and Future Trends.

A comprehensive review of the publications about rosin-based chemicals has been compiled. Rosin, or colophony, is a natural, abundant, cheap and non-toxic raw material which can be easily modified to obtain numerous useful products, which makes it an excellent subject of innovative research, attracting growing interest in recent years. The last extensive review in this research area was published in 2008, so the current article contains the most promising, repeatable achievements in synthesis of rosin-derived chemicals, published in scientific literature from 2008 to 2018. The first part of the review includes low/medium molecule weight compounds: Especially intermediates, resins, monomers, curing agents, surfactants, medications and biocides. The second part is about macromolecules: mainly elastomers, polymers for biomedical applications, coatings, adhesives, surfactants, sorbents, organosilicons and polysaccharides. In conclusion, a critical evaluation of the publications in terms of data completeness has been carried out with an indication of the most promising directions of rosin-based chemicals development.

Synthesis and Characterization of Thiolated PVP-Iodine Complexes: Key to Highly Mucoadhesive Antimicrobial Gels.

The aim of this study was to synthesize iodine containing polymeric excipients for mucosal treatment of microbial infection exhibiting a prolonged mucosal residence time by forming an adhesive gel on the mucosal surface. In order to achieve this aim, 2-(2 acryloylamino-ethyldisulfanyl)-nicotinic acid (ACENA) was copolymerized with N-vinylpyrrolidone (NVP) to obtain thiolated polyvinylpyrrolidone (PVP) for complexation with iodine. The average molecular mass of different thiolated PVP variants was determined by size exclusion chromatography. The structure of thiolated PVP was confirmed by 1H NMR. Thiolated PVP variants were characterized for thiol content, cytotoxicity, iodine loading capacity, rheological behavior, and adhesion time on mucosa. The highest achieved degree of thiolation was 610 ± 43 µmol/g, and the maximum recorded iodine loading was 949 ± 31 µmol/g of polymer. Thiolated PVP variants (0.5% m/v) showed no toxicity after incubation on Caco-2 cells for the period of 3 and 24 h, respectively. Thiolated PVP and thiolated PVP-iodine complexes exhibited a 5.4- and 4.4-fold increased dynamic viscosity in porcine mucus in comparison to PVP and PVP-iodine complex, respectively. Compared to PVP and PVP-iodine complex thiol-functionalized PVP and PVP-iodine complexes demonstrated significantly prolonged attachment to mucosal surface over a period of 3 h. Thiol functionalized PVP proved to be a promising novel excipient for complexation with iodine and to exhibit strongly improved mucoadhesive properties.

Tunicate-Inspired Gallol Polymers for Underwater Adhesive: A Comparative Study of Catechol and Gallol.

Man-made glues often fail to stick in wet environments because of hydration-induced softening and dissolution. The wound healing process of a tunicate inspired the synthesis of gallol-functionalized copolymers as underwater adhesive. Copolymers bearing three types of phenolic groups, namely, phenol, catechol, and gallol, were synthesized via the methoxymethyl protection/deprotection route. Surprisingly, the newly synthesized copolymers bearing gallol groups exhibited stronger adhesive performances (typically 7× stronger in water) than the widely used catechol-functionalized copolymers under all tested conditions (in air, water, seawater, or phosphate-buffered saline solution). The higher binding strength was ascribed to the tridentate-related interfacial interaction and chemical cross-linking. Moreover, gallol-functionalized copolymers adhered to all tested surfaces including plastic, glass, metal, and biological material. In seawater, the performance of gallol-functionalized copolymer even exceeds the commercially available isocyanate-based glue. The insights from this study are expected to help in the design of biomimetic materials containing gallol groups that may be utilized as potential bioadhesives and for other applications. The results from such a kind of comparable study among phenol, catechol, and gallol suggests that tridentate structure should be better than bidentate structure for bonding to the surface.

Comparative studies of adhesion peptides based on l- or d-amino acids.

Detailed studies comparing solid-supported l- or d-amino acid adhesion peptides based on the sequence KLHRIRA were performed. Stability towards proteases and levels of cellular adhesion to the otherwise inert surface of PEGA resin were compared by using fluorescently labelled peptides. A clear difference in the peptide stability towards cleavage by subtilisin, trypsin, or papain was observed. However, all of the on-bead peptides provided an optimal surface for cell adhesion and proliferation. In long-term experiments, these properties were still found to be similar on the resins modified either with l- or with d-amino acids and unaffected by the nature of their fluorescence labelling at either terminus. These results support that the more accessible l-amino acids can be utilized for cell adhesion experiments and confirm the nonspecific interaction mechanism of cell binding to these peptides on the bead surface. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.

Synthesis of grafted bromoisobutyryl esterified starch using electron transfer atom transfer radical polymerization method with high-performance adhesion and film properties.

Nowadays, few investigations on the process parameters of grafted starch synthesized using electron transfer atom transfer radical polymerization (ARGET ATRP) and its applications in warp sizing and paper-making are presented. Therefore, this study aimed to survey the appropriate process parameters of bromoisobutyryl esterified starch-g-poly(acrylic acid) (BBES-g-PAA) synthesized by the ARGET ATRP, and also aimed to provide a new biobased BBES-g-PAA adhesive. The appropriate synthesis process parameters were 1.2, 0.32, and 0.6 in the molar ratios of vitamin C, CuBr2, and pentamethyldivinyltriamine to BBES, respectively, at 40 °C for 5 h. The BBES-g-PAA samples with a grafting ratio range of 4.63-14.14 % exhibited bonding forces of 57.8-64.6 N to wool fibers [55.5 N (BBES) and 53.8 N (ATS)], and their films showed breaking elongations of 3.29-3.80 % [2.74 % (BBES) and 2.49 % (ATS)] and tensile strengths of 29.1-25.4 MPa [30.4 MPa (BBES) and 34.7 MPa (ATS)]. Compared with BBES, significantly increased bonding forces and film elongations, and decreased film strengths for the BBES-g-PAA samples with grafting ratios ≥10.54 % were displayed (p < 0.05). The time (100-42 s) taken for the BBES-g-PAA films was significantly shorter than that of ATS (246 s) and BBES (196 s) films (p < 0.05), corresponding to better desizability.

Synthesis of novel bioadhesive hydrogels via facile Thiol-Ene click chemistry for wound healing applications.

Development of outstanding, cost-effective and elastic hydrogels as bioadhesive using Thiol-Ene click chemistry was verified. The visible light photocrosslinkable hydrogels composed of methacrylated chitosan/2,2'-(Ethylenedioxy) diethanethiol formed in presence of eosin-Y photoinitiator. Such hydrogels hold great promise for wound healing applications due to their tunable properties. Main components of hydrogels were extensively characterized using spectroscopic techniques for chemical analysis, thermal analysis, and topologic nanostructure. Various optimization conditions for best gelation time were investigated. Mechanical properties of tensile strength and elongation at break (%) were verified for best wound healing applications. Optimum hydrogel was subjected to for cytotoxicity and microbial suppression evaluation and in-vivo wound healing test for efficient wound healing evaluations. Our results demonstrate the potential use of injectable hydrogels as valuable bioadhesives in bioengineering and biomedical applications, particularly in wound closure and patches.

Formulation of emulsion adhesives with removal properties by using alkali soluble resins.

This study was aimed at developing environmental friendly adhesion materials using alkali soluble resins (ASRs). Water-borne emulsion pressure-sensitive adhesives show good compatibility with different polymer emulsions, high solid contents, and good working property, thereby allowing adjustment of the extensive viscosity. On the other hand, it is not easily recyclable and its adhesion and water-resistance properties are not optimal. Herein, ASR was used as the polymeric surfactant. ASR presents good emulsion stabilization, high molecular weight, and solubility in alkali solutions. ASR contains both hydrophobic and hydrophilic groups, thereby reducing the surface tension of the aqueous phase stabilizing monomer droplet or polymer particles. Additionally, it can form aggregates as a result of inter- and intramolecular hydrophobic interactions. The large number of carboxyl groups of this resin stabilizes polymer particles by an electrostatic effect. The recycling and adhesion properties of this resin were assessed by using UTM, a weight method. Further properties of the resin were determined by DSC, GPC, and ETC.

Waterborne polyacrylic/PEDOT nanocomposites for conductive transparent adhesives.

A new nanocomposite for conductive transparent adhesives (CTAs) was synthesized by emulsion polymerization of acrylate monomers dispersed with poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS). Polymer particles of waterborne CTAs were uniform, and the average size of the particles was 330 nm. The conductive transparent adhesive nanocomposites (CTANs) were casted onto various substrates including slide glass, indium tin oxide (ITO) glass, and PET film. Upon thermal processing at 80 degrees C, highly transparent adhesive films were obtained with surface uniformity. The stress of the CTANs was affected by the contents of PEDOT:PSS, and a 7.5 wt% CTAN film had the highest maximum stress of 0.33 MPa. Importantly, polyacrylic nanoparticles were well dispersed with conductive filler PEDOT:PSS in water because of their high dispersity in water. Therefore, the polyacrylic/PEDOT nanocomposite had a low percolation threshold of approximately 8% due to the enhanced connection between conductive channels. The CTANs with an optimum content (10 wt%) of PEDOT:PSS had high electromagnetic interference shielding effectiveness (36 dB) and transparency (75%) for application to electronics including displays and solar cells.

Surface Force Measurements of Mussel-Inspired Pressure-Sensitive Adhesives.

Translating fundamental studies of marine mussel adhesion into practical mussel-inspired wet adhesives remains an important technological challenge. To adhere, mussels secrete adhesive proteins rich in the catecholic amino acid 3,4-dihydroxyphenylalanine (Dopa) and positively charged lysine. Consequently, numerous synthetic adhesives incorporating catecholic and cationic functionalities have been designed. However, despite widespread research, uncertainties remain about the optimal design of synthetic mussel-inspired adhesives. Here, we present a study of the adhesion of mussel-inspired pressure-sensitive adhesives. We explore the effects of catechol content, molecular architecture, and solvent quality on pressure-sensitive adhesive (PSA) adhesion and cohesion measured in a surface forces apparatus. Our findings demonstrate that the influence of catechol content depends on the choice of solvent and that adhesive performance is dictated by film composition rather than molecular architecture. Our results also highlight the importance of electrostatic and hydrophobic interactions for adhesion and cohesion in aqueous environments. Together, our findings contribute to an improved understanding of the interplay between materials chemistry, environmental conditions, and adhesive performance to facilitate the design of bioinspired wet adhesives.

Nanocomposite adhesive hydrogels: from design to application.

With the rapid development of hydrogels, hydrogel adhesion has attracted increasing attention in the last decade, but strong adhesion remains a challenge due to the large amount of water in hydrogels. The factors that affect hydrogel adhesion mainly include chemistries of bonds, topologies of connection, and mechanisms of energy dissipation. Strategies such as surface modification, surface initiation, bulk modification, bridging polymers, topological adhesion, and the use of nanocomposites have been developed to achieve strong hydrogel adhesion. In nanocomposite hydrogels, nanoparticles interlink with polymer chains to form strong bonds, which lower adhesion energy and offer energy dissipation, thus enhancing the adhesion. This review emphatically outlines nanocomposite adhesive hydrogels from design to application and provides useful understanding for the design and further development of nanocomposite adhesive hydrogels.

An in situ catechol functionalized ε-polylysine/polyacrylamide hydrogel formed by hydrogen bonding recombination with high mechanical property for hemostasis.

In situ hydrogel has attracted widely attention in hemostasis due to its ability to match irregular defects, but its application is limited by insufficient mechanical strength and long gelation time. Although some specifical in situ chemically cross-linked hydrogels could be fast formed and exhibit high mechanical strength, they unable to absorb blood. Hence their applications were further limited in emergency hemostasis usage. In this study, a robust hydrogel formed by hydration of powders was developed using multiple hydrogen bonds crosslinking. Here, catechol groups modified ε-polylysine (PL-CAT) and polyacrylamide (PAAM) were used to construct the PL-CAT/PAAM hydrogel. This hydrogel could be formed within 7 s to adhere and seal bleeding sites. The catechol groups endowed the hydrogel outstanding adhesive strength, which was 3.5 times of fibrin glue. Besides, the mechanical performance of in-situ PL-CAT/PAAM hydrogel was explored and the results showed that the hydrogel exhibited high compressive strength (0.47 MPa at 85% strain). Most importantly, the blood loss of wound treated with PL-CAT/PAAM hydrogel powders was 1/7 of untreated group, indicating the hydrogel's excellent hemostatic effect. And the cytotoxicity studies indicated that the PL-CAT/PAAM hydrogel had low toxicity. To summarize, this hydrogel could be a potential hemostatic material in emergency situations.

Enhanced skin adhesive property of α-cyclodextrin/nonanyl group-modified poly(vinyl alcohol) inclusion complex film.

For skin contact medical devices, realizing a strong contact with skin is essential to precisely detect human biological information and enable human-machine interaction. In this study, we aimed to fabricate and characterize an inclusion complex film (ICF) for skin adhesion using α-cyclodextrin (α-CD) and nonanyl group-modified PVA (C9-PVA) under wet conditions. Based on the water insolubility of C9-PVA and the inclusion ability of α-CD for alkyl groups, α-CD/C9-PVA ICF was prepared. Among the prepared ICFs, α-CD/2.5C9-PVA (w/w = 0.5) ICF showed the highest bonding strength and T-peeling strength to porcine skin. Furthermore, α-CD/2.5C9-PVA (w/w = 0.5) ICF had better water vapor transmission rate than that of commercial tapes. In addition, the ion permeability test revealed that α-CD/2.5C9-PVA (w/w = 0.5) ICF exhibited excellent Na and Cl ion permeability. These results demonstrated that the multi-functional α-CD/2.5C9-PVA (w/w = 0.5) ICF can be a promising adhesive for skin contact medical devices.

Stretchable and Bioadhesive Gelatin Methacryloyl-Based Hydrogels Enabled by in Situ Dopamine Polymerization.

Hydrogel patches with high toughness, stretchability, and adhesive properties are critical to healthcare applications including wound dressings and wearable devices. Gelatin methacryloyl (GelMA) provides a highly biocompatible and accessible hydrogel platform. However, low tissue adhesion and poor mechanical properties of cross-linked GelMA patches (i.e., brittleness and low stretchability) have been major obstacles to their application for sealing and repair of wounds. Here, we show that adding dopamine (DA) moieties in larger quantities than those of conjugated counterparts to the GelMA prepolymer solution followed by alkaline DA oxidation could result in robust mechanical and adhesive properties in GelMA-based hydrogels. In this way, cross-linked patches with ∼140% stretchability and ∼19 000 J/m3 toughness, which correspond to ∼5.7 and ∼3.3× improvement, respectively, compared to that of GelMA controls, were obtained. The DA oxidization in the prepolymer solution was found to play an important role in activating adhesive properties of cross-linked GelMA patches (∼4.0 and ∼6.9× increase in adhesion force under tensile and shear modes, respectively) due to the presence of reactive oxidized quinone species. We further conducted a parametric study on the factors such as UV light parameters, the photoinitiator type (i.e., lithium phenyl-2,4,6-trimethylbenzoylphosphinate, LAP, versus 2-hydroxy-4'-(2-hydroxyethoxy)-2-methylpropiophenone, Irgacure 2959), and alkaline DA oxidation to tune the cross-linking density and thereby hydrogel compliance for better adhesive properties. The superior adhesion performance of the resulting hydrogel along with in vitro cytocompatibility demonstrated its potential for use in skin-attachable substrates.

Mussel-Inspired Bisphosphonated Injectable Nanocomposite Hydrogels with Adhesive, Self-Healing, and Osteogenic Properties for Bone Regeneration.

Injectable hydrogels have received much attention because of the advantages of simulation of the natural extracellular matrix, microinvasive implantation, and filling and repairing of complex shape defects. Yet, for bone repair, the current injectable hydrogels have shown significant limitations such as the lack of tissue adhesion, deficiency of self-healing ability, and absence of osteogenic activity. Herein, a strategy to construct mussel-inspired bisphosphonated injectable nanocomposite hydrogels with adhesive, self-healing, and osteogenic properties is developed. The nano-hydroxyapatite/poly(l-glutamic acid)-dextran (nHA/PLGA-Dex) dually cross-linked (DC) injectable hydrogels are fabricated via Schiff base cross-linking and noncovalent nHA-BP chelation. The chelation between bisphosphonate ligands (alendronate sodium, BP) and nHA favors the uniform dispersion of the latter. Moreover, multiple adhesion ligands based on catechol motifs, BP, and aldehyde groups endow the hydrogels with good tissue adhesion. The hydrogels possess excellent biocompatibility and the introduction of BP and nHA both can effectively promote viability, proliferation, migration, and osteogenesis differentiation of MC3T3-E1 cells. The incorporation of BP groups and HA nanoparticles could also facilitate the angiogenic property of endothelial cells. The nHA/PLGA-Dex DC hydrogels exhibited considerable biocompatibility despite the presence of a certain degree of inflammatory response in the early stage. The successful healing of a rat cranial defect further proves the bone regeneration ability of nHA/PLGA-Dex DC injectable hydrogels. The developed tissue adhesive osteogenic injectable nHA/PLGA-Dex hydrogels show significant potential for bone regeneration application.

Ultrafast in-situ forming halloysite nanotube-doped chitosan/oxidized dextran hydrogels for hemostasis and wound repair.

A series of halloysite nanotube (HNT)-doped chitosan (CS)/oxidized dextran (ODEX) adhesive hydrogels were developed through a Schiff base reaction. The resultant CS/ODEX/HNT hydrogels could not only form in situ on wounds within only 1 s when injected, but could also adapt to wounds of different shapes and depths after injection. We established four rat and rabbit hemorrhage models and demonstrated that the hydrogels are better than the clinically used gelatin sponge for reducing hemostatic time and blood loss, particularly in arterial and deep noncompressible bleeding wounds. Moreover, the natural antibacterial features of CS and ODEX provided the hydrogels with strong bacteria-killing effects. Consequently, they significantly promoted methicillin-resistant Staphylococcus aureus -infected-wound repair compared to commercial gelatin sponge and silver-alginate antibacterial wound dressing. Hence, our multifunctional hydrogels with facile preparation process and utilization procedure could potentially be used as first-aid biomaterials for rapid hemostasis and infected-wound repair in emergency injury events.