High-throughput screening of multifunctional nanocoatings based on combinations of polyphenols and catecholamines.

Biomimetic surface coatings based on plant polyphenols and catecholamines have been used broadly in a variety of applications. However, the lack of a rational cost-effective platform for screening these coatings and their properties limits the true potential of these functional materials to be unleashed. Here, we investigated the oxidation behavior and coating formation ability of a library consisting of 45 phenolic compounds and catecholamines. UV-vis spectroscopy demonstrated significant acceleration of oxidation and polymerization under UV irradiation. We discovered that several binary mixtures resulted in non-additive behavior (synergistic or antagonistic effect) yielding much thicker or thinner coatings than individual compounds measured by ellipsometry. To investigate the properties of coatings derived from new combinations, we used a miniaturized high-throughput strategy to screen 2,532 spots coated with single, binary, and ternary combinations of coating precursors in one run. We evaluated the use of machine learning models to learn the relation between the chemical structure of the precursors and the thickness of the nanocoatings. Formation and stability of nanocoatings were investigated in a high-throughput manner via discontinuous dewetting. 30 stable combinations (hits) were used to tune the surface wettability and to form water droplet microarray and spot size gradients of water droplets on the coated surface. No toxicity was observed against eukaryotic HeLa cells and Pseudomonas aeruginosa (strain PA30) bacteria after 24 h incubation at 37 °C. The strategy introduced here for high-throughput screening of nanocoatings derived from combinations of coating precursors enables the discovery of new functional materials for various applications in science and technology in a cost-effective miniaturized manner.

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

OBJECTIVE: Iatrogenic 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 DESIGN: A 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. RESULTS: Fetal 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. CONCLUSIONS: Mussel 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 C(1)=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.

Mussel-Inspired Adhesives and Coatings.

Mussels attach to solid surfaces in the sea. Their adhesion must be rapid, strong, and tough, or else they will be dislodged and dashed to pieces by the next incoming wave. Given the dearth of synthetic adhesives for wet polar surfaces, much effort has been directed to characterizing and mimicking essential features of the adhesive chemistry practiced by mussels. Studies of these organisms have uncovered important adaptive strategies that help to circumvent the high dielectric and solvation properties of water that typically frustrate adhesion. In a chemical vein, the adhesive proteins of mussels are heavily decorated with Dopa, a catecholic functionality. Various synthetic polymers have been functionalized with catechols to provide diverse adhesive, sealant, coating, and anchoring properties, particularly for critical biomedical applications.

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

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Molecular resurfacing of cartilage with proteoglycan 4.

Early loss of proteoglycan 4 (PRG4), a lubricating glycoprotein implicated in boundary lubrication, from the cartilage surface has been associated with degeneration of cartilage and early onset of osteoarthritis. Viscosupplementation with hyaluronic acid and other macromolecules has been proposed as a treatment of osteoarthritis. However, the efficacy of viscosupplementation is variable and may be influenced by the short residence time of lubricant in the knee joint after injection. Recent studies have demonstrated the use of aldehyde (CHO) modified extracellular matrix proteins for targeted adherence to a biological tissue surface. It is hypothesized that CHO could be exploited to enhance the binding of lubricating proteoglycans to the surface of PRG4-depleted cartilage. The objective of this study was to determine the feasibility of molecular resurfacing of cartilage with CHO-modified PRG4. PRG4 was chemically functionalized with aldehyde (PRG4-CHO) and aldehyde plus Oregon Green (OG) fluorophore (PRG4-OG-CHO) to allow for differentiation of endogenous and exogenous PRG4. Cartilage disks depleted of native PRG4 were then treated with solutions of PRG4, PRG4-CHO, or PRG4-OG-CHO and then assayed for the presence of PRG4 by immunohistochemistry, ELISA, and fluorescence imaging. Repletion of cartilage surfaces was significantly enhanced with the inclusion of CHO compared with repletion with unmodified PRG4. These findings suggest a generalized approach which may be used for molecular resurfacing of tissue surfaces with PRG4 and other lubricating biomolecules, perhaps leading in the future to a convenient method for overcoming loss of lubrication during the early stages of osteoarthritis.

Mimicking mussel adhesion to improve interfacial properties in composites.

The macroscale properties of polymer-matrix composites depend immensely on the quality of the interaction between the reinforcement phase and the bulk polymer. This work presents a method to improve the interfacial adhesion between metal-oxides and a polymer matrix by performing surface-initiated polymerization (SIP) by way of a biomimetic initiator. The initiator was modeled after 3,4-dihydroxy-L-phenylalanine (dopa), an amino acid that is highly concentrated in mussel foot adhesive proteins. Mechanical pull out tests of NiTi and Ti-6Al-4V wires from poly (methyl methacrylate) (PMMA) were performed to directly test the interfacial adhesion. These tests demonstrated improvements in maximum interfacial shear stress of 116% for SIP-modified NiTi wires and 60% for SIP-modified Ti-6Al-4V wires over unmodified specimens. Polymer chain growth from the metal oxides was validated using x-ray photoemission spectroscopy (XPS), ellipsometry, scanning electron microscopy (SEM), and contact angle analysis.

Enzymatically cross-linked hydrogels and their adhesive strength to biosurfaces.

OBJECTIVES: To design an in-situ gelling hydrogel capable of solidifying rapidly under physiologic conditions into a hydrogel capable of adhering tissue surfaces together. DESIGN: Multifunctional polymers containing covalently bound peptide substrates of transglutaminase were designed. EXPERIMENTAL VARIABLE: Enzyme cross-linked hydrogels were compared with commercial fibrin tissue adhesive. OUTCOME MEASURE: The shear strength between tissue surfaces or type 1 collagen membranes bonded with hydrogel was measured. RESULTS: The shear adhesive strength of transglutaminase cross-linked hydrogels was found to be equal to or better than fibrin sealant for tissue and collagen surfaces, respectively. CONCLUSION: Transglutaminase cross-linked hydrogels are injectable, in-situ formed, biodegradable, and expected to be useful in a variety of applications including sustained drug delivery, medical and dental adhesives, tissue repair and engineering as polymeric scaffolds, and gene therapy.

Triggered release of calcium from lipid vesicles: a bioinspired strategy for rapid gelation of polysaccharide and protein hydrogels.

The bioinspired strategy of triggered release of Ca2+ from liposomal compartments was used to induce rapid gelation of polysaccharide and protein-based hydrogels. Thermally triggerable liposomes were designed by entrapping CaCl2 within liposomes constructed of 90% dipalmitoylphosphatidylcholine and 10% dimyristoylphosphatidylcholine. These liposomes released greater than 90% of entrapped Ca2+ when heated to 37 degrees C. A precursor fluid containing liposomes suspended in aqueous sodium alginate remained fluid for several days at room temperature but gelled rapidly when heated to 37 degrees C, as a result of Ca2+ release and formation of crosslinked Ca-alginate. Alternatively, thermally triggered Ca2+ release from liposomes was used to activate enzyme-catalyzed crosslinking of proteins to form hydrogels. A mixture of Ca-loaded liposomes, fibrinogen, and a Ca2+-dependent transglutaminase enzyme (either human recombinant FXIII or guinea pig liver transglutaminase) remained fluid indefinitely when stored at room temperature, but gelled rapidly when heated to 37 degrees C. SDS-PAGE of the reaction mixture revealed that gelation was due to enzymatic crosslinking of the alpha and gamma chains of fibrinogen, and oscillating rheometry revealed gel formation within 10 min of heating to 37 degrees C. This new approach may be useful for developing rapidly gelling injectable biomaterials that can be stored at room temperature and injected in a minimally invasive manner into a body tissue or cavity, upon which rapid solidification would occur. This versatile bioinspired strategy could be utilized for the delivery of biomaterials for tissue repair and reconstruction, and local site-directed drug delivery.

New acrylic resin composite with improved thermal diffusivity.

STATEMENT OF PROBLEM: Studies have shown that physical characteristics of denture base materials may affect patient acceptance of denture prostheses by altering sensory experience of food during mastication. Thermal diffusivity is one material property that has been cited as being important in determining gustatory response, with denture base acrylic resins having low thermal diffusivity compared with denture base metal alloys. PURPOSE: This study prepared and characterized experimental acrylic resin composite material with increased thermal diffusivity. MATERIAL AND METHODS: Sapphire (Al2O3) whiskers were added to conventional denture base acrylic resin during processing to achieve loadings of 9.35% and 15% by volume. Cylindrical test specimens containing an embedded thermocouple were used to determine thermal diffusivity over a physiologic temperature range (0 degree to 70 degrees C). RESULTS: Thermal diffusivities of the sapphire containing composites were found to be significantly higher than the unmodified acrylic resin. Thermal diffusivity was found to increase in proportion to the volume percentage of sapphire filler, which suggested that the high aspect ratio ceramic particles formed a pathway for heat conduction through the insulating polymer matrix. CONCLUSION: The thermal diffusivity of denture base acrylic resin was increased by the addition of thermally conducting sapphire whiskers.

Stress enhancement and fatigue susceptibility of porous coated Ti-6Al-4V implants: an elastic analysis.

An elastic stress analysis of porous-coated implant surfaces was performed using the finite element method. Three-hundred-microns-diameter metal beads sinter bonded onto an implant surface were modeled with sinter neck radii of 5, 10, 20, and 50 microns. Smooth-surface, single-bead, single-layer, and double-layer systems were analyzed. The finite element models were loaded to simulate bone-bead contact forces and lateral hip implant tensile forces. Results showed that, for a single bead sinter-bonded onto an implant surface, concentration of stress occurs either at the base of the sinter neck or within the neck itself, depending on the type of load applied. Under lateral hip implant tensile loads, a maximum stress concentration factor of 1.97 was obtained for a single bead sinter-bonded onto a implant surface. Addition of a single layer of beads onto the implant surface resulted in a significant increase in stress at the most proximal and distal ends of the porous layer, with a maximum stress concentration factor of 4.3. Addition of a second layer of beads did not significantly increase the magnitude of the stress concentration occurring at the ends of the porous layer. The results of this study provide stress concentration factors for porous coatings with sinter necks of known dimensions under loading conditions similar to those present along the lateral surface of a hip prosthesis.