Mussel Adhesion Mechanism Research Articles

Improving the Biocompatibility of Polymeric Membrane Potentiometric Ion Sensors by Using a Mussel-Inspired Polydopamine Coating.

Polymeric membrane potentiometric ion sensors have been widely used in clinical diagnosis for the detection of electrolyte ions and account for billions of measurements every year throughout the world. However, in many cases of practical relevance, biofouling, which might lead to sensor failure, usually occurs due to the lack of biocompatibility of these sensors. Herein, we describe a simple and robust approach for improving the biocompatibility of the polymeric ion-selective membranes. A marine mussel-inspired polydopamine polymer is used as a hydrophilic coating on the surface of conventional potentiometric ion sensors. Such a coating can be easily formed by self-polymerization of dopamine and robustly deposited on the sensor surface mimicking the adhesion mechanism of mussels. The classical poly(vinyl chloride) membrane-based calcium ion-selective electrode (ISE) is chosen as a model. Compared to the unmodified Ca2+ ISE, the polydopamine modified electrode shows a significantly reduced blood platelet adsorption while retaining original potentiometric ion response properties, which clearly indicates a high antifouling capability induced by the hydrophilic polydopamine coating. We believe that the proposed approach can provide an appealing way to improve the biocompatibility in the development of polymeric membrane electrochemical and optical sensors.

Magnetic digital microfluidics on a bioinspired surface for point-of-care diagnostics of infectious disease.

Magnetic digital microfluidics uses magnetic force to manipulate droplets on a Teflon-coated substrate through the added magnetic particles. To achieve a wide range of droplet manipulation, hydrophilic patterns, known as surface energy traps, are introduced onto the Teflon-coated hydrophobic substrate. However, the Teflon-coated substrate is difficult to modify because it is nonwettable, and existing techniques for patterning surface energy traps have many limitations. Inspired by the mussel adhesion mechanism, we use polydopamine, a bioinspired substance that adheres strongly to almost any materials, to pattern surface energy traps on the Teflon-coated substrate with a great ease. We have optimized the polydopamine coating protocol and characterized the surface properties of the polydopamine surface energy traps. Droplet operations including particle extraction, liquid dispensing, liquid shaping, and cross-platform transfer have been demonstrated on the polydopamine surface energy trap-enabled magnetic digital microfluidic platform in both single-plate and two-plate configurations. Furthermore, the detection of hepatitis B surface antigen using ELISA has been demonstrated on the new magnetic dgitial microfluidic platform. This new bioinspired magnetic digital microfluidic platform is easy to fabricate and operate, showing a great potential for point-of-care applications.

Improving Hydrophilicity and Inducing Bone-Like Apatite Formation on PPBES by Polydopamine Coating for Biomedical Application.

Copoly(phthalazinone biphenyl ether sulfone) (PPBES) as a commercially available polyarylether is a promising orthopaedic implant material because its mechanical properties are similar to bone. However, the bioinert surface of polyarylether causes some clinical problems after implantation, which limits its application as an implant material. In this study, the surface of PPBES was modified by a biomineralization method of polydopamine-assisted hydroxyapatite formation (pHAF) to enhance its cytocompatibility. Polydopamine (PDA) coating, inspired by the adhesion mechanism of mussels, can readily endow PPBES with high hydrophilicity and the ability to integrate via the bone-like apatite coating. PPBES and PDA-coated PPBES were evaluated by scanning electronic microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and contact angle measurement. The water contact angles were reduced significantly after coating with PDA. PDA was successfully synthesized on PPBES and more PDA was obtained by increasing the temperature. Bone-like apatite on PPBES (apatite-coated PPBES) was confirmed by SEM and transmission electron microscopy (TEM). The cytotoxicity of pristine PPBES and apatite-coated PPBES were characterized by culturing of NIH-3T3 cells. Bone-like apatite synthesized by pHAF could further enhance cytocompatibility in vitro. This study provides a promising alternative for biofunctionalized PPBES with improved cytocompatibility for bone implant application.

Mussel-inspired nano-building block assemblies for mimicking extracellular matrix microenvironments with multiple functions

The assembly of nano-building blocks is an effective way to produce artificial extracellular matrix microenvironments with hierarchical micro/nano structures. However, it is hard to assemble different types of nano-building blocks, to form composite coatings with multiple functions, by traditional layer-by-layer (LbL) self-assembly methods. Inspired by the mussel adhesion mechanism, we developed polydopamine (PDA)-decorated bovine serum albumin microspheres (BSA-MS) and nano-hydroxyapatite (nano-HA), and assembled them to form bioactive coatings with micro/nano structures encapsulating bone morphogenetic protein-2 (BMP-2). First, PDA-decorated nano-HA (nano-pHA) was obtained by oxidative polymerization of dopamine on nano-HA. Second, BMP-2-encapsulated BSA microspheres were prepared through desolvation, and then were also decorated by PDA (pBSA-MS). Finally, the nano-pHA and pBSA-MS were assembled using the adhesive properties of PDA. Bone marrow stromal cell cultures and in vivo implantation, showed that the pHA/pBSA (BMP-2) coatings can promote cell adhesion, proliferation, and benefited for osteoinductivity. PDA decoration was also applied to assemble various functional nanoparticles, such as nano-HA, polystyrene, and Fe3O4 nanoparticles. In summary, this study provides a novel strategy for the assembly of biofunctional nano-building blocks, which surpasses traditional LbL self-assembly of polyelectrolytes, and can find broad applications in bioactive agents delivery or multi-functional coatings.

Mussel-Inspired Adhesive and Tough Hydrogel Based on Nanoclay Confined Dopamine Polymerization.

Adhesive hydrogels are attractive biomaterials for various applications, such as electronic skin, wound dressing, and wearable devices. However, fabricating a hydrogel with both adequate adhesiveness and excellent mechanical properties remains a challenge. Inspired by the adhesion mechanism of mussels, we used a two-step process to develop an adhesive and tough polydopamine-clay-polyacrylamide (PDA-clay-PAM) hydrogel. Dopamine was intercalated into clay nanosheets and limitedly oxidized between the layers, resulting in PDA-intercalated clay nanosheets containing free catechol groups. Acrylamide monomers were then added and in situ polymerized to form the hydrogel. Unlike previous single-use adhesive hydrogels, our hydrogel showed repeatable and durable adhesiveness. It adhered directly on human skin without causing an inflammatory response and was easily removed without causing damage. The adhesiveness of this hydrogel was attributed to the presence of enough free catechol groups in the hydrogel, which were created by controlling the oxidation process of the PDA in the confined nanolayers of clay. This mimicked the adhesion mechanism of the mussels, which maintain a high concentration of catechol groups in the confined nanospace of their byssal plaque. The hydrogel also displayed superior toughness, which resulted from nanoreinforcement by clay and PDA-induced cooperative interactions with the hydrogel networks. Moreover, the hydrogel favored cell attachment and proliferation, owning to the high cell affinity of PDA. Rat full-thickness skin defect experiments demonstrated that the hydrogel was an excellent dressing. This free-standing, adhesive, tough, and biocompatible hydrogel may be more convenient for surgical applications than adhesives that involve in situ gelation and extra agents.

Bioinspired Design of Polycaprolactone Composite Nanofibers as Artificial Bone Extracellular Matrix for Bone Regeneration Application.

The design and development of functional biomimetic systems for programmed stem cell response is a field of topical interest. To mimic bone extracellular matrix, we present an innovative strategy for constructing drug-loaded composite nanofibrous scaffolds in this study, which could integrate multiple cues from calcium phosphate mineral, bioactive molecule, and highly ordered fiber topography for the control of stem cell fate. Briefly, inspired by mussel adhesion mechanism, a polydopamine (pDA)-templated nanohydroxyapatite (tHA) was synthesized and then surface-functionalized with bone morphogenetic protein-7-derived peptides via catechol chemistry. Afterward, the resulting peptide-loaded tHA (tHA/pep) particles were blended with polycaprolactone (PCL) solution to fabricate electrospun hybrid nanofibers with random and aligned orientation. Our research demonstrated that the bioactivity of grafted peptides was retained in composite nanofibers. Compared to controls, PCL-tHA/pep composite nanofibers showed improved cytocompatibility. Moreover, the incorporated tHA/pep particles in nanofibers could further facilitate osteogenic differentiation potential of human mesenchymal stem cells (hMSCs). More importantly, the aligned PCL-tHA/pep composite nanofibers showed more osteogenic activity than did randomly oriented counterparts, even under nonosteoinductive conditions, indicating excellent performance of biomimetic design in cell fate decision. After in vivo implantation, the PCL-tHA/pep composite nanofibers with highly ordered structure could significantly promote the regeneration of lamellar-like bones in a rat calvarial critical-sized defect. Accordingly, the presented strategy in our work could be applied for a wide range of potential applications in not only bone regeneration application but also pharmaceutical science.

Morphogen Electrochemically Triggered Self-Construction of Polymeric Films Based on Mussel-Inspired Chemistry.

Inspired by the strong chemical adhesion mechanism of mussels, we designed a catechol-based electrochemically triggered self-assembly of films based on ethylene glycol molecules bearing catechol groups on both sides and denoted as bis-catechol molecules. These molecules play the role of morphogens and, in contrast to previously investigated systems, they are also one of the constituents, after reaction, of the film. Unable to interact together, commercially available poly(allylamine hydrochloride) (PAH) chains and bis-catechol molecules are mixed in an aqueous solution and brought in contact with an electrode. By application of defined potential cycles, bis-catechol molecules undergo oxidation leading to molecules bearing "reactive" quinone groups which diffuse toward the solution. In this active state, the quinones react with amino groups of PAH through Michael addition and Schiff's base condensation reaction. The application of cyclic voltammetry (CV) between 0 and 500 mV (vs Ag/AgCl, scan rate of 50 mV/s) of a PAH/bis-catechol solution results in a fast self-construction of a film that reaches a thickness of 40 nm after 60 min. The films present a spiky structure which is attributed to the use of bis-functionalized molecules as one component of the films. XPS measurements show the presence of both PAH and bis-catechol cross-linked together in a covalent way. We show that the amine/catechol ratio is an important parameter which governs the film buildup. For a given amine/catechol ratio, it does exist an optimum CV scan rate leading to a maximum of the film thickness as a function of the scan rate.

Silver Core‐Shell Nanoclusters Exhibiting Strong Growth Inhibition of Plant‐Pathogenic Fungi

We introduced a novel method to prepare silver core‐shell nanoclusters (NCs) in which 3,4‐dihydroxyphenyl acetic‐conjugated oligochitosan (DHPAC) reduced silver salt and subsequently protected the produced nanosilver via mussel adhesion mechanism. Results indicated that the degree of conjugation was 14 dihydroxyphenyl acetamide moieties over 100 glucosamine units of oligochitosan. We used chitosan‐catechol derivative to prepare the well‐defined silver core‐shell NCs and applied UV‐visible spectroscopy, transmission electron microscopy (TEM), and X‐ray diffraction (XRD) techniques to characterize the NCs. The core‐shell NCs exhibited strong growth inhibition of plant‐pathogenic fungi such as Phytophthora capsici, Phytophthora nicotianae, and Phytophthora colocasiae. These positive results may offer great potential to produce silver core‐DHPAC shell NCs for several biomedical applications.

A fundamental understanding of catechol and water adsorption on a hydrophilic silica surface: exploring the underwater adhesion mechanism of mussels on an atomic scale.

Mussels have a remarkable ability to bond to solid surfaces under water. From a microscopic perspective, the first step of this process is the adsorption of dopa molecules to the solid surface. In fact, it is the catechol part of the dopa molecule that is interacting with the surface. These molecules are able to make reversible bonds to a wide range of materials, even underwater. Previous experimental and theoretical efforts have produced only a limited understanding of the mechanism and quantitative details of the competitive adsorption of catechol and water on hydrophilic silica surfaces. In this work, we uncover the nature of this competitive absorption by atomic scale modeling of water and catechol adsorbed at the geminal (001) silica surface using density functional theory calculations. We find that catechol molecules displace preadsorbed water molecules and bond directly on the silica surface. Using molecular dynamics simulations, we observe this process in detail. We also calculate the interaction force as a function of distance, and observe a maximum of 0.5 nN of attraction. The catechol has a binding energy of 23 kcal/mol onto the silica surface with adsorbed water molecules.

Gentamicin and bone morphogenic protein-2 (BMP-2)-delivering heparinized-titanium implant with enhanced antibacterial activity and osteointegration

Insufficient bonding of implants to bone tissues and bacterial infections lead to the failure of titanium (Ti)-based orthopedic and dental implants. The aim of this study is to develop novel Ti implants that enhance osteoblast functions, while simultaneously decreasing bacterial infections. First, the surface of pristine Ti was functionalized with heparin-dopamine by mimicking a mussel adhesion mechanism. Gentamicin sulfate (GS) and/or bone morphogenic protein-2 (BMP-2) was then sequentially immobilized to the heparinized-Ti (Hep-Ti) surface. The compositions of pristine Ti and Hep-Ti with or without gentamicin and/or BMP-2 were characterized by X-ray photoelectron spectroscopy (XPS) and the growth of Staphylococcus aureus on the substrates was assayed. Osteoblast functions of all Ti substrates were investigated by cell proliferation assays, alkaline phosphatase (ALP) activity, and calcium deposition. The results showed that the growth of bacteria on GS/Hep-Ti and GS/BMP-2/Hep-Ti was significantly lower compared to that on the pristine Ti and BMP-2/Hep-Ti. In addition, BMP-2/Hep-Ti and GS/BMP-2/Hep-Ti significantly enhanced ALP activity and calcium mineral deposition of osteoblast cells. Taken together, GS/BMP-2/Hep-Ti could achieve the dual functions of excellent antibacterial activity and osteoblast function promotion. Therefore, dual drug (antibiotics and osteoinductive protein)-eluting Ti substrates such as GS/BMP-2/Hep-Ti are a promising material for the enhanced osteointegration and implant longevity in orthopedics and dentistry.

Mussel‐Inspired Polydopamine Coating as a Universal Route to Hydroxyapatite Crystallization

AbstractBone tissue is a complex biocomposite material with a variety of organic (e.g., proteins, cells) and inorganic (e.g., hydroxyapatite crystals) components hierarchically organized with nano/microscale precision. Based on the understanding of such hierarchical organization of bone tissue and its unique mechanical properties, efforts are being made to mimic these organic–inorganic hybrid biocomposites. A key factor for the successful designing of complex, hybrid biomaterials is the facilitation and control of adhesion at the interfaces, as many current synthetic biomaterials are inert, lacking interfacial bioactivity. In this regard, researchers have focused on controlling the interface by surface modifications, but the development of a simple, unified way to biofunctionalize diverse organic and inorganic materials remains a critical challenge. Here, a universal biomineralization route, called polydopamine‐assisted hydroxyapatite formation (pHAF), that can be applied to virtually any type and morphology of scaffold materials is demonstrated. Inspired by the adhesion mechanism of mussels, the pHAF method can readily integrate hydroxyapatites on ceramics, noble metals, semiconductors, and synthetic polymers, irrespective of their size and morphology (e.g., porosity and shape). Surface‐anchored catecholamine moieties in polydopamine enriches the interface with calcium ions, facilitating the formation of hydroxyapatite crystals that are aligned to thec‐axes, parallel to the polydopamine layer as observed in natural hydroxyapatites in mineralized tissues. This universal surface biomineralization can be an innovative foundation for future tissue engineering.

General functionalization route for cell adhesion on non-wetting surfaces

We present a versatile route for promoting cell adhesion and viability on various non-wetting surfaces, inspired by mussel adhesion mechanism. The oxidative polymerization of dopamine, a small designer molecule of the DOPA-K motif found in mussels, results in the formation of a poly(dopamine) ad-layer on any material surface. We found that the poly(dopamine) coating can promote cell adhesion on any type of material surfaces including the well-known anti-adhesive substrate, poly(tetrafluoroethylene). According to our results, mammalian cells well adhered and underwent general cell adhesion processes (i.e., attachment to substrate, spreading, and cytoskeleton development) on poly(dopamine)-modified surfaces, while they barely adhered and spread on unmodified non-wetting surfaces. The mussel-inspired surface functionalization strategy is extremely useful because it does not require the time-consuming synthesis of complex linkers and the process is solvent-free and non-toxic. Therefore, it can be a powerful route for converting a variety of bioinert substrates into bioactive ones.