Mussel Glue Research Articles

Self-Cross-Linkable Chitosan-Alginate Complexes Inspired by Mussel Glue Chemistry.

In this study, mussel-inspired chemistry, based on catechol-amine reactions, was adopted to develop self-cross-linkable chitosan-alginate (Chi-Alg) complexes. To do so, the biopolymers were each substituted with ∼20% catechol groups (ChiC and AlgC), and then four complex combinations (Chi-Alg, ChiC-Alg, Chi-AlgC, ChiC-AlgC) were prepared at the surface and in bulk solution. Based on QCM-D and lap shear adhesion tests, the complex with catechol only on Chi (ChiC-Alg) did not show a significant variation from the control complex (Chi-Alg). Conversely, the complexes with catechol on alginate (Chi-AlgC and ChiC-AlgC) rendered a self-cross-linking property and enhanced cohesive properties.

In vivo Sealing of Fetoscopy-Induced Fetal Membrane Defects by Mussel Glue

Introduction: The benefits of fetal surgery are impaired by the high incidence of iatrogenic preterm prelabor rupture of the fetal membranes (iPPROM), for which chorioamniotic separation has been suggested as a potential initiator. Despite the urgent need to prevent iPPROM by sealing the fetoscopic puncture site after intervention, no approach has been clinically translated. Methods: A mussel-inspired biomimetic glue was tested in an ovine fetal membrane (FM) defect model. The gelation time of mussel glue (MG) was first optimized to make it technically compatible with fetal surgery. Then, the biomaterial was loaded in polytetrafluoroethylene-coated nitinol umbrella-shaped receptors and applied on ovine FM defects (N = 10) created with a 10 French trocar. Its sealing performance and tissue response were analyzed 10 days after implantation by amniotic fluid (AF) leakage and histological methods. Results: All ewes and fetuses recovered well after the surgery, and 100% ewe survival and 91% fetal survival were observed at explantation. All implants were tight at explantation, and no AF leakage was observed in any of them. Histological analysis revealed a mild tissue response to the implanted glue. Conclusion: MG showed promising properties for the sealing of FM defects and thereby the prevention of preterm birth. Studies to analyze the long-term tissue response to the sealant should be performed.

Promoting soluble expression of hybrid mussel foot proteins by SUMO-TrxA tags for production of mussel glue

Mussel foot proteins (Mfps) display application potential with strong adhesion, enabling mussels to adhere firmly to various surfaces. Mytilus galloprovincialis foot protein 3B (Mgfp-3B) exhibits this characteristic remarkably. However, it remains a challenge for further research due to the low soluble expression of heterologous production. In this study, a small ubiquitin-related modifier (SUMO) and thioredoxin A (TrxA), which catalyzed the proper folding of disulfide bridges, were selected to increase the soluble expression of mfps. An additional ribosome binding site was introduced between the molecular chaperones and Mgfp-3B (fp-3) to form a bicistronic translation-coupled expression vector for co-expression. The results revealed that the combination of SUMO-TrxA increased the soluble expression of fp-3 by 18.07 %. Furthermore, the SUMO-TrxA also boosted the soluble expression of hybrid mfps Mgfp-3B-Mfp-1 (fp-3-1) by 11.29 %, Mgfp-3B-Mgfp-3B (fp-3-3) by 19.91 %, and Mgfp-3B-Mgfp-5 (fp-3-5) by 14.03 %. Ultimately, by high cell density cultivation in a 5 L bioreactor, the yields of fp-3, fp-3-3, and fp-3-5 co-expressed with SUMO-TrxA reached 217.75 mg/L, 127.2 mg/L, and 97.28 mg/L, respectively. Consequently, soluble production of mfps holds great potential for the sustainable supply of protein adhesive materials.

Implementing Zn2+ ion and pH-value control into artificial mussel glue proteins by abstracting a His-rich domain from preCollagen.

A His-rich domain of preCollagen-D found in byssal threads is derivatized with Cys and Dopa flanks to allow for mussel-inspired polymerization. Artificial mussel glue proteins are accessed that combine cysteinyldopa for adhesion with sequences for pH or Zn2+ induced β-sheet formation. The artificial constructs show strong adsorption to Al2O3, the resulting coatings tolerate hypersaline conditions and cohesion is improved by activating the β-sheet formation, that enhances E-modulus up to 60%.

Chemical Reactivities of ortho-Quinones Produced in Living Organisms: Fate of Quinonoid Products Formed by Tyrosinase and Phenoloxidase Action on Phenols and Catechols.

Tyrosinase catalyzes the oxidation of phenols and catechols (o-diphenols) to o-quinones. The reactivities of o-quinones thus generated are responsible for oxidative browning of plant products, sclerotization of insect cuticle, defense reaction in arthropods, tunichrome biochemistry in tunicates, production of mussel glue, and most importantly melanin biosynthesis in all organisms. These reactions also form a set of major reactions that are of nonenzymatic origin in nature. In this review, we summarized the chemical fates of o-quinones. Many of the reactions of o-quinones proceed extremely fast with a half-life of less than a second. As a result, the corresponding quinone production can only be detected through rapid scanning spectrophotometry. Michael-1,6-addition with thiols, intramolecular cyclization reaction with side chain amino groups, and the redox regeneration to original catechol represent some of the fast reactions exhibited by o-quinones, while, nucleophilic addition of carboxyl group, alcoholic group, and water are mostly slow reactions. A variety of catecholamines also exhibit side chain desaturation through tautomeric quinone methide formation. Therefore, quinone methide tautomers also play a pivotal role in the fate of numerous o-quinones. Armed with such wide and dangerous reactivity, o-quinones are capable of modifying the structure of important cellular components especially proteins and DNA and causing severe cytotoxicity and carcinogenic effects. The reactivities of different o-quinones involved in these processes along with special emphasis on mechanism of melanogenesis are discussed.

Toward Artificial Mussel-Glue Proteins: Differentiating Sequence Modules for Adhesion and Switchable Cohesion.

Artificial mussel‐glue proteins with pH‐triggered cohesion control were synthesized by extending the tyrosinase activated polymerization of peptides to sequences with specific modules for cohesion control. The high propensity of these sequence sections to adopt β‐sheets is suppressed by switch defects. This allows enzymatic activation and polymerization to proceed undisturbed. The β‐sheet formation is regained after polymerization by changing the pH from 5.5 to 6.8, thereby triggering O→N acyl transfer rearrangements that activate the cohesion mechanism. The resulting artificial mussel glue proteins exhibit rapid adsorption on alumina surfaces. The coatings resist harsh hypersaline conditions, and reach remarkable adhesive energies of 2.64 mJ m−2 on silica at pH 6.8. In in situ switch experiments, the minor pH change increases the adhesive properties of a coating by 300 % and nanoindentation confirms the cohesion mechanism to improve bulk stiffness by around 200 %.

Toward Artificial Mussel‐Glue Proteins: Differentiating Sequence Modules for Adhesion and Switchable Cohesion

AbstractArtificial mussel‐glue proteins with pH‐triggered cohesion control were synthesized by extending the tyrosinase activated polymerization of peptides to sequences with specific modules for cohesion control. The high propensity of these sequence sections to adopt β‐sheets is suppressed by switch defects. This allows enzymatic activation and polymerization to proceed undisturbed. The β‐sheet formation is regained after polymerization by changing the pH from 5.5 to 6.8, thereby triggering O→N acyl transfer rearrangements that activate the cohesion mechanism. The resulting artificial mussel glue proteins exhibit rapid adsorption on alumina surfaces. The coatings resist harsh hypersaline conditions, and reach remarkable adhesive energies of 2.64 mJ m−2 on silica at pH 6.8. In in situ switch experiments, the minor pH change increases the adhesive properties of a coating by 300 % and nanoindentation confirms the cohesion mechanism to improve bulk stiffness by around 200 %.

Bioinspired Double‐Dynamic‐Bond Crosslinked Bioadhesive Enables Post‐Wound Closure Care

AbstractMost existing bioadhesives, even those showing superiority in wound closure effectiveness, do not assist in the post‐wound closure process. A bioinspired, in situ formed, double‐dynamic‐bond crosslinked hydrogel bioadhesive that is capable of efficiently closing open wounds and enabling post‐wound closure care is reported. Catechol‐modified ε‐poly‐l‐lysine and oxidized dextran are employed as natural polymer backbones and they are in situ crosslinked using Schiff's base dynamic bond and catecholFe coordinate dynamic bond through a process inspired by that used to cure marine mussel glue, forming a hydrogel bioadhesive. The unique double‐dynamic‐bond crosslinked structure endows the bioadhesive with higher mechanical and adhesive strength while retaining quick dissociation and good self‐healing capacities. Accordingly, the bioadhesive can exhibit multiple desirable functions, such as dissolution on demand, repeatable adhesiveness, adhesive and mechanical strength sufficient for wound closure, injectability, and good biocompatibility (DREAMING). After efficiently closing skin incisions, the bioadhesive can be facilely removed or repeatedly close the reopened wounds, thus enabling post‐wound closure care. On the basis of favorable functions in wound closure and the ability to enable post‐wound closure care, the bioadhesive demonstrates great potential in dealing with skin wounds.

Pro- and Anti-oxidant Properties of Redox-Active Catechol-Chitosan Films.

Catechols are abundant in nature and are believed to perform diverse biological functions that include photoprotection (e.g., melanins), molecular signaling (e.g., catecholamine neurotransmitters), and mechanical adhesion (e.g., mussel glue). Currently, the structure-property-function relationships for catechols remain poorly resolved, and this is especially true for redox-based properties (e.g., antioxidant, pro-oxidant, and radical scavenging activities). Importantly, there are few characterization methods available to probe the redox properties of materials. In this review, we focus on recent studies with redox-active catechol-chitosan films. First, we describe film fabrication methods to oxidatively-graft catechols to chitosan through chemical, enzymatic, or electrochemical methods. Second, we discuss a new experimental characterization method to probe the redox properties of catechol-functionalized materials. This mediated electrochemical probing (MEP) method probes the redox-activities of catechol-chitosan films by: (i) employing diffusible mediators to shuttle electrons between the electrode and grafted catechols; (ii) imposing tailored sequences of input voltages to “tune” redox probing; and (iii) analyzing the output current response characteristics to infer properties. Finally, we demonstrate that the redox properties of catechol-chitosan films enable them to perform antioxidant radical scavenging functions, as well as a pro-oxidant (reactive oxygen-generation) antimicrobial functions. In summary, our increasing knowledge of catechol-chitosan films is enabling us to better-understand the functions of catechols in biology as well as enhancing our capabilities to create advanced functional materials.

Mussel-inspired approach to cross-linked functional 3D nanofibrous aerogels for energy-efficient filtration of ultrafine airborne particles

Polymer aerogels fabricated using conventional methods typically have relatively narrow mono-modal pore size distribution (PSD), and relatively thick and tight pore walls. Herein, inspired by mussel glue, cross-linked three-dimensional (3D) polyacrylonitrile (PAN) nanofibrous aerogels (NFAs) with ultrahigh porosity, hierarchical porous structures, and good compression resistance are successfully fabricated via electrospinning, facile polydopamine (PDA) coating and crosslinking by ferric ions (Fe3+) followed by freeze-drying. Morphology characterization and compression tests show that both multiple hydrogen bonding facilitated by the PDA coating and Fe3+-PDA coordination bonding could effectively induce the formation of inter-fiber junctions, enhancing compression resistance of the 3D NFAs and leading to hierarchical porous structures with a very wide PSD. When a thin layer of the optimized 3D NFA with a large specific surface area (85.7 m2 g−1) is combined with a commercial air filter, the composite filter obtained exhibits high filtration efficiencies of 99.72% and 99.85% for airborne particles with sizes of <100 nm and <500 nm, respectively, at a low pressure drop of only 54.1 Pa. The results show that the cross-linked NFAs could act as a highly efficient air filter for ultrafine particles while not increasing the overall pressure-drop significantly, which are due to the good adhesive properties of PDA, electrostatic charge induced by Fe3+, and high porosity and hierarchical porous structures of the 3D NFAs.

Bioengineered mussel glue incorporated with a cell recognition motif as an osteostimulating bone adhesive for titanium implants.

Successful titanium implantation strongly depends on early fixation through an osseointegration between the titanium fixture and adjacent bone tissue. From a clinical perspective, rapid recruitment of functional biomolecules from the blood and osteogenic cell binding is critical for osseointegration immediately after implant insertion. Thus, surface modifications aiming to improve the interactions between the blood and implant and to enhance the binding of osteogenic cells onto the implant surface can contribute to successful osseointegration. Mussel adhesive proteins (MAPs) derived from marine mussels have been considered as promising bioadhesives that have strong adhesion and coating abilities onto organic and inorganic surfaces, even in wet environments. Here, we investigated the in vitro and in vivo osteostimulating ability of the bioengineered mussel glue MAP-RGD, which is a recombinant MAP fused with an Arg-Gly-Asp (RGD) peptide, an effective cell recognition motif for activating intracellular signaling pathways, using a titanium mesh (Ti-mesh) as a model titanium implant. We found that the in vitro cell behaviors of pre-osteoblast cells, such as attachment, proliferation, spreading, and osteogenic differentiation, increased significantly on the MAP-RGD-coated Ti-mesh surface. In vitro blood responses including blood wetting, blood clotting, and platelet adhesion were also highly enhanced on the MAP-RGD-coated surface. Importantly, implantation of the MAP-RGD-coated Ti-mesh resulted in a remarkable acceleration of in vivo bone regeneration and maturation of a new bone in a rat calvarial defect. Consequently, the bioengineered mussel glue can be successfully utilized as an osteostimulating bone bioadhesive for titanium implant applications with further expansion to general bone tissue engineering.

Mussel mimetic tissue adhesive (mussel glue) for fetal membrane repair in vivo

Mussel mimetic tissue adhesive (mussel glue) for fetal membrane repair in vivo

Mussel mimetic tissue adhesive for fetal membrane repair: initial in vivo investigation in rabbits

ObjectiveIatrogenic preterm prelabour rupture of fetal membranes (iPPROM) remains the main complication after invasive interventions into the intrauterine cavity. The aim of this study was to evaluate the sealing capability and tissue interaction of mussel-mimetic tissue adhesive (mussel glue) in comparison to fibrin glue on punctured fetal membranes in vivo. Study designA mid-gestational rabbit model was used for testing the materials. The fetal sacs of pregnant rabbits at day 23 were randomly assigned into experimental groups: unoperated (negative control), unclosed puncture (positive control), commercially available fibrin glue (FG) with decellularized amnion scaffold (DAM), mussel glue (MG) with DAM, or mussel glue alone. Evaluation was done at term (30 days’ gestation) assessing fetal survival, fetal membrane integrity and histology of the membranes. ResultsFetal survival was not significantly lower in any of the treatment groups compared to the negative control. All plugging materials could be found at the end of the pregnancy and no adverse effects on the fetus or the pregnant does could be observed. Sac integrity was higher in all treatment groups compared to the positive control group but significant only in the FG+DAM group. Cellular infiltration could be seen in fibrin glue and DAM in contrast to mussel glue which was only tightly adhering to the surrounding tissue. These cells were mostly of mesenchymal phenotype staining positive for vimentin. CD68 positive macrophages were found clustered around all the plugging materials, but their numbers were only significantly increased for the mussel glue alone group compared to negative controls. ConclusionsMussel glues performance in sealing fetal membranes in the rabbit model was comparable to that of fibrin glue. Taking into account its other favorable properties, it is a noteworthy candidate for a clinically applicable fetal membrane sealant.

Mussel-mimetic tissue adhesive for fetal membrane repair: An ex vivo evaluation

Iatrogenic preterm prelabor rupture of membranes (iPPROM) remains the main complication after invasive interventions into the intrauterine cavity. Here, the proteolytic stability of mussel-mimetic tissue adhesive (mussel glue) and its sealing behavior on punctured fetal membranes are evaluated. The proteolytic degradation of mussel glue and fibrin glue were compared in vitro. Critical pressures of punctured and sealed fetal membranes were determined under close to physiological conditions using a custom-made inflation device. An inverse finite element procedure was applied to estimate mechanical parameters of mussel glue. Mussel glue was insensitive whereas fibrin glue was sensitive towards proteolytic degradation. Mussel glue sealed 3.7mm fetal membrane defect up to 60mbar (45mmHg) when applied under wet conditions, whereas fibrin glue needed dry membrane surfaces for reliable sealing. The mussel glue can be represented by a neo-Hookean material model with elastic coefficient C1=9.63kPa. Ex-vivo-tested mussel glue sealed fetal membranes and resisted pressures achieved during uterine contractions. Together with good stability in proteolytic environments, this makes mussel glue a promising sealing material for future applications.

Review: Biomimicry – Innovation Inspired by Nature

Necessity may be invention’s mom, but the producers of Biomimicry argue that “nature” is, in fact, a much better “mother.” The film warns students of the ways our vaunted technologies may be damaging our planet, and encourages them to look natureward when designing new problem-solving technologies. This unconventional film can both inspire and initiate discussion in its intended audience of grades 7–12. Based on the book by Janine Benyus, the two-part DVD introduces various novel technologies, the scientist(s) behind them, and their inspirations in nature. Examples of the technologies include synthetic compounds that mimic the process of photosynthesis in order to harvest energy, environmentally friendly rugs with patterns inspired by nature, adhesives that incorporate the compounds found in mussel glue, and even microprocessors made more effective by mimicking the abalone.The kiln of evolution has forged the internal processes of Earth’s organisms for millions of years. For this reason Wes Jackson of the Land Institute, Devens Just and the Moores at Arizona State University, among the other scientists featured, are encouraging students to seek solutions to our problems by imitating nature rather than merely consuming nature’s limited resources.One caveat: The film does not appear to have been made for youthful audiences in its pacing and music. The dialogue is stagey, the soundtrack old fashioned. But these minor flaws are trumped by the science, which is complex, top notch, relevant, and well explained. It doesn’t require further flash and panache to be absorbing. For the teacher choosing to share clips that enrich lessons on Biotechnology, chemistry, or natural resources, the film is very effective; it is also appropriate for older audiences.

Bioinspired Underwater Bonding and Debonding on Demand

Mussel glue: Bioinspired underwater chemical bonding with the possibility of phototriggered debonding is reported. A four-arm star-poly(ethyleneglycol) end-functionalized by nitrodopamine was synthesized. The nitrodopamine offered the reactivity of catechol and the chemistry of the photocleavable o-nitrophenyl ethyl group (see picture).

Ex vivo fetal membrane repair using the mussel-mimetic sealant

Ziel: Preterm prelabour rupture of the fetal membranes (PPROM) is an unsolved complication in pregnancy which limits the developing field of fetal surgery. The aim was to evaluate ex vivo sealing properties of a new mussel-mimetic tissue adhesive (mussel glue, MG) using punctured synthetic membranes.

Mussel‐mimetic tissue adhesive for fetal membrane repair: a standardized ex vivo evaluation using elastomeric membranes

Iatrogenic preterm premature rupture of membranes (iPPROM), the main complication of invasive interventions in the prenatal period, seriously limits the benefit of diagnostic or surgical prenatal procedures. This study aimed to evaluate preventive plugging of punctured fetal membranes in an ex vivo situation using a new mussel-mimetic tissue adhesive (mussel glue) to inhibit leakage. A novel biomechanical test device that tests the closure of injured membranes under near-physiological conditions was used. Mussel glue, a poly(ethylene glycol)-based hydrogel, was used to seal membrane defects of up to 3 mm in mechanically well-defined elastomeric membranes with three different degrees of stiffness. Elastomeric test membranes were successfully employed for testing mussel glue under well-defined conditions. Mussel glue plugs were distended by up to 94%, which translated to an improved sealing efficiency on elastomeric membranes with high stiffness. For the stiffest membrane tested, a critical burst pressure of 48 mbar (36 mmHg) was accomplished in this ex vivo setting. Mussel glue appears to efficiently seal membrane defects under well-standardized ex vivo conditions. As repaired membranes resist pressures measured in amniotic cavities, mussel glue might represent a novel sealing method for iatrogenic membrane defects.

Biomechanics of byssal threads outside the Mytilidae: Atrina rigida and Ctenoides mitis

The byssus is the set of proteinaceous threads widely used by bivalves to attach themselves to the substrate. Previous researchers have focused on a single byssate family, the Mytilidae. However, the properties of byssal threads from species outside this family are of interest - first, because evolutionary patterns are only detectable if species from a range of taxa are examined, and second, because recent biomimetic research efforts would benefit from a wider range of ;mussel glue' exemplars. In the present study, we measured the mechanical properties of the byssal threads of two species outside the Mytilidae, the pen shell Atrina rigida Lightfoot and the flame ;scallop' Ctenoides mitis Lamarck. The mechanical properties of their byssal threads were significantly different from those of mytilids. For instance, the byssal threads of both species were significantly weaker than mytilid threads. Atrina rigida threads were significantly less extensible than mytilid threads, while C. mitis threads exhibited the highest extensibility ever recorded for the distal region of byssal threads. However, there were also interesting similarities in material properties across taxonomic groups. For instance, the threads of A. rigida and Modiolus modiolus Linnaeus both exhibited a prominent double-yield behavior, high stiffness combined with low extensibility, and similar correlations between stiffness and other thread properties. These similarities suggest that the thread properties of some semi-infaunal species may have evolved convergently. Further research on these patterns, along with biochemical analysis of threads which exhibit unusual properties like double-yield behavior, promises to contribute to both evolutionary biology and materials engineering.

Structure and Bonding of the Multifunctional Amino Acid l-DOPA on Au(110)

In investigations of the proteins which are responsible for the surface adhesion of the blue mussel Mytilus edulis, an unusually frequent appearance of the otherwise rare amino acid 3-(3,4-dihydroxyphenyl)-L-alanine (L-DOPA) has been observed. This amino acid is thought to play a major role in the mechanism of mussel adhesion. Here we report a detailed structural and spectroscopic investigation of the interface between L-DOPA and a single-crystalline Au(110) model surface, with the aim of understanding fundamentals about the surface bonding of this amino acid and its role in mussel adhesion. Molecular layers are deposited by organic molecular beam deposition (OMBD) in an ultrahigh-vacuum environment. The following experimental techniques have been applied: ex situ Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), low-energy electron diffraction (LEED), high-resolution electron energy loss spectroscopy (HREELS), and scanning tunneling microscopy (STM). Vibrational spectra of isolated L-DOPA molecules and the zwitterionic bulk have been calculated using density functional theory (DFT). The predicted modes are assigned to observed spectra, allowing conclusions regarding the molecule-substrate and molecule-molecule interactions at the L-DOPA/Au(110) interface. We find that zwitterionic L-DOPA forms a monochiral, one-domain commensurate monolayer on Au(110), with the catechol rings on top of [110] gold rows, oriented parallel to the surface. The (2 x 1)-Au(110) surface reconstruction is not lifted. The carboxylate group is found in a bidentate or bridging configuration, the amino group is tilted out of the surface plane, and the hydroxyl groups do not dehydrogenate on Au(110). Similar to the case for the bulk, molecules form dimers on Au(110). However, the number of hydrogen bridge bonds between L-DOPA molecules is reduced as compared to the bulk. Thicker layers which are deposited onto the commensurate interface do not order in the bulk structure. In conclusion, our study shows that the aromatic ring system of L-DOPA functions as a surface anchor. Since it is also known that the hydroxyl groups support cross-link reactions between L-DOPA residues in the mussel glue protein, we can conclude that the catechol ring supports surface adhesion of mussel proteins via two independent functions.