Biomineral-Inspired Colloidal Liquid Crystals: From Assembly of Hybrids Comprising Inorganic Nanocrystals and Organic Polymer Components to Their Functionalization.

Bioinspired organic/inorganic synthetic composites have been studied as high-performance and functional materials. In nature, biominerals such as pearls, teeth, and bones are self-organized organic/inorganic composites. The inorganic components are composed of calcium carbonate (CaCO3) and hydroxyapatite (HAp), while the organic components consist of peptides and polysaccharides. These composites are used as structural materials in hard biological tissues. Biominerals do not show significantly higher performances than synthetic composites such as glass-fiber- or carbon-fiber-reinforced plastics. However, biominerals consist of environmentally friendly and biocompatible components that are prepared under mild conditions. Moreover, they form elaborate nanostructures and self-organized hierarchical structures. Much can be learned about material design from these biomineral-based hierarchical and nanostructured composites to assist in the preparation of functional materials.Inspired by these biological hard tissues, we developed nanostructured thin films and bulk hybrid crystals through the self-organization of organic polymers and inorganic crystals of CaCO3 or HAp. In biomineralization, the combination of insoluble components and soluble acidic macromolecules controls the crystallization process. We have shown that poly(acrylic acid) (PAA) or acidic peptides called polymer additives induce the formation of thin film crystals of CaCO3 or HAp by cooperation with insoluble organic templates such as chitin and synthetic polymers bearing the OH group. Moreover, we recently developed CaCO3- and HAp-based nanostructured particles with rod and disk shapes. These were obtained in aqueous media using a macromolecular acidic additive, PAA, without using insoluble polymer templates. At appropriate concentrations, the anisotropic particles self-assembled and formed colloidal liquid-crystalline (LC) phases.LC materials are generally composed of organic molecules. They show ordered and mobile states. The addition of stimuli-responsive properties to organic rod-like LC molecules led to the successful development of informational displays, which are now widely used. On the other hand, colloidal liquid crystals are colloidal self-assembled dispersions of anisotropic organic and inorganic nano- and micro-objects. For example, polysaccharide whiskers, clay nanosheets, gibbsite plate-shaped particles, and silica rod-shaped particles exhibit colloidal LC states.In this Account, we focused on the material design and hierarchical aspects of biomineral-based colloidal LC polymer/inorganic composites. We describe the design and preparation, nanostructures, and self-assembled behavior of these new bioinspired and biocompatible self-organized materials. The characterization results for these self-assembled nanostructured colloidal liquid crystals found using high-resolution transmission electron microscopy, small-angle X-ray scattering, and neutron scattering and rheological measurements are also reported. The functions of these biomineral-inspired liquid crystals are presented. Because these biomineral-based LC colloidal liquid crystals can be prepared under mild and aqueous conditions and they consist of environmentally friendly and biocompatible components, new functions are expected for these materials.

High Virus Removal by Self-Organized Nanostructured 2D Liquid-Crystalline Smectic Membranes for Water Treatment.

To obtain high quality of drinking water free from biocontaminants is especially important issue. A new strategy employing smectic liquid-crystalline ionic membranes exhibiting 2D structures of layered nanochannels for water treatment is proposed for efficient virus removal and sufficient water flux. The smectic A (SmA) liquid-crystalline membranes obtained by in situ polymerization of an ionic mesogenic monomer are examined for removal of three distinct viruses with small size: Qß bacteriophage, MS2 bacteriophage, and Aichi virus. The semi-bilayer structure of the SmA significantly obstructs the virus penetration with an average log reduction value of 7.3 log10 or the equivalent of reducing 18 million viruses down to 1. Furthermore, the layered nanochannels of the SmA liquid crystal allow efficient water permeation compared to other types of liquid-crystalline membrane consisting of nanopores.

Static structure and dynamical behavior of colloidal liquid crystals consisting of hydroxyapatite-based nanorod hybrids.

Biominerals such as bones and teeth have elaborate nanostructures composed of aligned anisotropic hydroxyapatite (HAp) nanocrystals, which results in excellent mechanical properties. Construction of such ordered structures of HAp nanocrystals in synthetic materials is challenging. Recently, we reported that HAp-nanorod-based colloidal liquid crystals could be obtained. In the present study, the static structure and dynamics of liquid-crystalline (LC) colloidal dispersions of HAp nanorods are investigated by using small-angle X-ray scattering (SAXS) and X-ray photon correlation spectroscopy (XPCS). The SAXS results reveal that the interparticle distance decreases with increasing HAp concentration, φHAp, and the decrease of the interparticle distance for the short-axis direction is significantly smaller in the LC phase than the interparticle distance in the isotropic phase. In the dynamical studies of the LC phase using XPCS, we observe the diffusive motion of the HAp colloids, with the diffusion coefficient being dependent on the wave number. The diffusive motion slows down with increasing φHAp. We observe anisotropic dynamics after long-term storage (160 days after sealing), whereas only isotropic dynamics are observed in the initial XPCS measurements after short-term storage (14 days after sealing). Moreover, we have found that the dynamics slows down with increasing storage time.

Biomineralization-Inspired Preparation of Zinc Hydroxide Carbonate/Polymer Hybrids and Their Conversion into Zinc Oxide Thin-Film Photocatalysts.

The development of ZnO thin films has been achieved through the conversion of zinc hydroxide carbonate thin-film crystals. Crystallization of this compound is induced by a biomineralization-inspired method with polymer-stabilized amorphous precursors. The crystals grow radially on polymer matrices, leading to the formation of zinc hydroxide carbonate/polymer thin-film hybrids that fully cover the substrate. These hybrids are converted into ZnO and retain their thin-film morphologies. The resultant ZnO thin films exhibit a preferential crystallographic orientation that is attributed to the alignment of zinc hydroxide carbonate crystals before conversion. In addition, a photocatalytic function of the ZnO thin films has been demonstrated by analyzing the oxidation reaction of 2-propanol. The biomineralization-inspired approach reported herein is a promising way to develop ZnO materials with controlled morphologies and structures for photocatalytic applications.

Formation of Helically Structured Chitin/CaCO3 Hybrids through an Approach Inspired by the Biomineralization Processes of Crustacean Cuticles.

Chitin/CaCO3 hybrids with helical structures are formed through a biomineralization-inspired crystallization process under ambient conditions. Liquid-crystalline chitin whiskers are used as helically ordered templates. The liquid-crystalline structures are stabilized by acidic polymer networks which interact with the chitin templates. The crystallization of CaCO3 is conducted by soaking the templates in the colloidal suspension of amorphous CaCO3 (ACC) at room temperature. At the initial stage of crystallization, ACC particles are introduced inside the templates, and they crystallize to CaCO3 nanocrystals. The acidic polymer networks induce CaCO3 crystallization. The characterization of the resultant hybrids reveals that they possess helical order and homogeneous hybrid structures of chitin and CaCO3 , which resemble the structure and composition of the exoskeleton of crustaceans.

Covalent attachment of mechanoresponsive luminescent micelles to glasses and polymers in aqueous conditions.

Covalent attachment of mechanoresponsive luminescent organic or organometallic compounds to other materials is a promising approach to develop a wide variety of mechanoresponsive luminescent materials. Here, we report covalently linkable mechanoresponsive micelles that change their photoluminescence from yellow to green in response to mechanical stimulation under aqueous conditions. These micelles are composed of a dumbbell-shaped amphiphilic pyrene derivative having amine groups at the peripheral positions of its dendrons. Using a well-established cross-linker, the micelles were covalently linked via their peripheral amine groups to the surface of glass beads, polylactic acid (PLA) beads, and living cells under aqueous conditions. Vortexing of glass beads bearing the micelles in a glass vial filled with water caused a photoluminescence color change from yellow to green. PLA beads bearing the micelles showed no change in photoluminescence color under the same conditions. We ascribe this result to the lower density and stiffness of the PLA beads, because the color of the PLA beads changed on vortexing in the presence of bare glass beads. HeLa cells and HL-60 cells bearing the micelles showed no obvious photoluminescence color change under vortexing. The structure, photophysical properties, and mechanism of photoluminescence color change of the micellar assemblies were examined.

Aragonite nanorods in calcium carbonate/polymer hybrids formed through self-organization processes from amorphous calcium carbonate solution.

Nanostructured inorganic/polymer hybrid thin films comprising aragonite nanorods derived from aqueous suspensions of amorphous calcium carbonate (ACC) are prepared. For the formation of calcium carbonate (CaCO3)/polymer hybrids, spincoated and annealed films of poly(vinyl alcohol) (PVA) that function as polymer matrices are soaked in aqueous colloidal solutions dispersing ACC stabilized by poly(acrylic acid) (PAA). In the initial stage, calcite thin films form on the surface. Subsequently, aragonite crystals start to form inside the PVA matrix that contains PVA crystallites which induce aragonite nucleation. Nanostructured hybrids composed of calcite thin films consisting of nanoparticles and assembled aragonite nanorods are formed in the matrices of PVA.

Stimuli-responsive photoluminescent liquid crystals.

We describe mechanochromic and thermochromic photoluminescent liquid crystals. In particular, mechanochromic photoluminescent liquid crystals found recently, which are new stimuli-responsive materials are reported. For example, photoluminescent liquid crystals having bulky dendritic moieties with long alkyl chains change their photoluminescent colors by mechanical stimuli associated with isothermal phase transitions. The photoluminescent properties of molecular assemblies depend on their assembled structures. Therefore, controlling the structures of molecular assemblies with external stimuli leads to the development of stimuli-responsive luminescent materials. Mechanochromic photoluminescent properties are also observed for a photoluminescent metallomesogen and a liquid-crystalline polymer. We also show thermochromic photoluminescent liquid crystals based on origo-(p-phenylenevinylene) and anthracene moieties and a thermochromic photoluminescent metallocomplex.

Analysis of carotid artery deformation in different head and neck positions for maxillofacial catheter navigation in advanced oral cancer treatment.

BACKGROUND: To improve the accuracy of catheter navigation, it is important to develop a method to predict shifts of carotid artery (CA) bifurcations caused by intraoperative deformation. An important factor affecting the accuracy of electromagnetic maxillofacial catheter navigation systems is CA deformations. We aimed to assess CA deformation in different head and neck positions. METHODS: Using two sets of computed tomography angiography (CTA) images of six patients, displacements of the skull (maxillofacial segments), C1-C4 cervical vertebrae, mandible (mandibular segment), and CA along with its branches were analyzed. Segmented rigid bones around CA were considered the main causes of CA deformation. After superimposition of maxillofacial segments, C1-C4 and mandible segments were superimposed separately for displacement measurements. Five bifurcation points (vA-vE) were assessed after extracting the CA centerline. A new standardized coordinate system, regardless of patient-specific scanning positions, was employed. It was created using the principal axes of inertia of the maxillofacial bone segments of patients. Position and orientation parameters were transferred to this coordinate system. CA deformation in different head and neck positions was assessed. RESULTS: Absolute shifts in the center of gravity in the bone models for different segments were C1, 1.02 ± 0.9; C2, 2.18 ± 1.81; C3, 4.25 ± 3.85; C4, 5.90 ± 5.14; and mandible, 1.75 ± 2.76 mm. Shifts of CA bifurcations were vA, 5.52 ± 4.12; vB, 4.02 ± 3.27; vC, 4.39 ± 2.42; vD, 4.48 ± 1.88; and vE, 2.47 ± 1.32. Displacements, position changes, and orientation changes of C1-C4 segments as well as the displacements of all CA bifurcation points were similar in individual patients. CONCLUSIONS: CA deformation was objectively proven as an important factor contributing to errors in maxillofacial navigation. Our study results suggest that small movements of the bones around CA can result in small CA deformations. Although patients' faces were not fixed properly during CT scanning, C1-C4 and vA-vE displacements were similar in individual patients. We proposed a novel method for accumulation of the displacement data, and this study indicated the importance of surrounding bone displacements in predicting CA bifurcation.

3D interconnected ionic nano-channels formed in polymer films: self-organization and polymerization of thermotropic bicontinuous cubic liquid crystals.

Thermotropic bicontinuous cubic (Cub(bi)) liquid-crystalline (LC) compounds based on a polymerizable ammonium moiety complexed with a lithium salt have been designed to obtain lithium ion-conductive all solid polymeric films having 3D interconnected ionic channels. The monomer shows a Cub(bi) phase from -5 to 19 °C on heating. The complexes retain the ability to form the Cub(bi) LC phase. They also form hexagonal columnar (Col(h)) LC phases at temperatures higher than those of the Cub(bi) phases. The complex of the monomer and LiBF(4) at the molar ratio of 4:1 exhibits the Cub(bi) and Col(h) phases between -6 to 19 °C and 19 to 56 °C, respectively, on heating. The Cub(bi) LC structure formed by the complex has been successfully preserved by in situ photopolymerization through UV irradiation in the presence of a photoinitiator. The resultant nanostructured film is optically transparent and free-standing. The X-ray analysis of the film confirms the preservation of the self-assembled nanostructure. The polymer film with the Cub(bi) LC nanostructure exhibits higher ionic conductivities than the polymer films obtained by photopolymerization of the complex in the Col(h) and isotropic phases. It is found that the 3D interconnected ionic channels derived from the Cub(bi) phase function as efficient ion-conductive pathways.

Methoxy-Functionalized Glycerol-Based Aliphatic Polycarbonate: Organocatalytic Synthesis, Blood Compatibility, and Hydrolytic Property.

Polymers that are biocompatible and degradable are desired for tissue engineering approaches in the treatment of vascular diseases, especially for those involving small-diameter blood vessels. Herein, we report the compatibility of a newly developed glycerol-based aliphatic polycarbonate possessing simple methoxy side groups, named poly(5-methoxy-1,3-dioxan-2-one) (PMDO), with blood cells and plasma proteins as well as its susceptibility to hydrolysis. As a consequence of the organocatalytic ring-opening polymerization (ROP) of a methoxy-functionalized cyclic carbonate derived from glycerol, PMDO with a sufficiently high molecular weight (Mn 14 kg/mol) and a narrow distribution (D̵M 1.12) was obtained for evaluation as a bulk biomaterial. This study demonstrates for the first time the organocatalytic ROP of a glycerol-based cyclic carbonate in a controlled manner. Compared with the clinically applied aliphatic polycarbonate poly(trimethylene carbonate) (PTMC), PMDO inhibits platelet adhesion by 33% and denaturation of fibrinogen by 23%. Although the wettability of PMDO based on water contact angle was almost comparable to those of PTMC and poly(ethylene terephthalate), the reason for the inhibited platelet adhesion and protein denaturation appeared to be related to the presence of specific hydrated water formed in the hydrated polymer. The improved hydration of PMDO also enhanced the susceptibility to hydrolysis, with PMDO demonstrating a slightly higher hydrolytic property than PTMC. This simple glycerol-based aliphatic polycarbonate has the following benefits: bio-based characteristics of glycerol and improved blood compatibility and hydrolytic biodegradability stemming from moderate hydration of the methoxy side groups.

Nanostructured liquid crystals combining ionic and electronic functions.

New molecular materials combining ionic and electronic functions have been prepared by using liquid crystals consisting of terthiophene-based mesogens and terminal imidazolium groups. These liquid crystals show thermotropic smectic A phases. Nanosegregation of the pi-conjugated mesogens and the ionic imidazolium moieties leads to the formation of layered liquid-crystalline (LC) structures consisting of 2D alternating pathways for electronic charges and ionic species. These nanostructured materials act as efficient electrochromic redox systems that exhibit coupled electrochemical reduction and oxidation in the ordered bulk states. For example, compound 1 having the terthienylphenylcyanoethylene mesogen and the imidazolium triflate moiety forms the smectic LC nanostructure. Distinct reversible electrochromic responses are observed for compound 1 without additional electrolyte solution on the application of double-potential steps between 0 and 2.5 V in the smectic A phase at 160 degrees C. In contrast, compound 2 having a tetrafluorophenylterthiophene moiety and compound 3 having a phenylterthiophene moiety exhibit irreversible cathodic reduction and reversible anodic oxidation in the smectic A phases. The use of poly(3,4-ethylenedioxythiophene)-poly(4-styrene sulfonate) (PEDOT-PSS) as an electron-accepting layer on the cathode leads to the distinct electrochromic responses for 2 and 3. These results show that new self-organized molecular redox systems can be built by nanosegregated pi-conjugated liquid crystals containing imidazolium moieties with and without electroactive thin layers on the electrodes.

Induction of mRNA expression of osteogenesis-related genes by guaiacol in human dental pulp cells.

To investigate the stimulating effect of endodontic medications on the mRNA expression of some osteogenesis-related genes associated with reparative dentinogenesis and hard-tissue formation, human dental pulp cells (D824 cells) were treated with calcium hydroxide (Ca (OH)(2)), formocresol, or guaiacol. The effect on growth was determined by growth curves of D824 cells treated for 1-3 days with 0.03-0.3 mM Ca (OH)(2), 0.0007%-0.0014% formocresol, or 0.24-2.43 mM guaiacol. The mitotic activity of individual cells and the mRNA expression of the osteogenesis-related genes for alkaline phosphatase (ALP), type I collagen (COL-1), and bone sialoprotein (BSP) in the cells treated for 24 h with the same concentrations of the medications as described above were determined by colony-forming efficiency and by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis, respectively. Cellular growth and mitotic activity were scarcely affected by Ca (OH)(2), but were significantly reduced by formocresol or guaiacol. The mRNA expression of the osteogenesis-related genes was little affected by Ca (OH)(2) or formocresol, but was significantly enhanced by guaiacol. The results indicate that guaiacol may stimulate the mRNA expression of genes associated with reparative dentinogenesis and hard-tissue formation in human dental pulp cells, suggesting that the novel property of guaiacol provides new insights into the utilization of guaiacol in endodontic therapy.

Liquid-Crystalline Hydroxyapatite/Polymer Nanorod Hybrids: Potential Bioplatform for Photodynamic Therapy and Cellular Scaffolds.

Recently, we found that self-organization of hydroxyapatite (HAp) with poly(acrylic acid) (PAA) leads to the formation of liquid-crystalline (LC) nanorod hybrids that form aligned films and show stimuli-responsive properties. Here, we demonstrate that these biocompatible HAp/PAA hybrid nanorods represent a platform technology as drug nanocarriers for photodynamic cancer therapy and as bioscaffolds for the control of cellular alignment and growth. To use hybrid nanorods as a drug nanocarrier, we introduced methylene blue (MB), a typical photosensitizer for photodynamic therapy, into the PAA nanolayer covering the surface of the HAp nanocrystals through electrostatic interactions. The stable MB-loaded HAp/PAA hybrid nanorods efficiently produced singlet oxygen from MB upon light irradiation and showed remarkable photodynamic therapeutic effects in cancer cells. Moreover, taking advantage of the mechanically responsive LC alignment properties of the HAp/PAA hybrid nanorods, macroscopically oriented bioscaffolds were prepared through a spin-coating process. The cells cultured on the oriented scaffolds showed cellular alignment and elongation along the oriented direction of the hybrid nanorods. The HAp/PAA hybrid nanorods demonstrate potential in drug delivery and tissue engineering. These unique LC HAp/PAA hybrid nanorods have significant potential as a platform for the development of various types of biomaterial.

Highly Efficient Virus Rejection with Self-Organized Membranes Based on a Crosslinked Bicontinuous Cubic Liquid Crystal.

To remove viruses from water, the use of self-assembling liquid crystals is presented as a novel method for the synthesis of membranes with a regular pore size (below 1 nm) and controlled pore structures. Nanostructured bicontinuous cubic liquid-crystalline (LC) thin films are photopolymerized onto a polysulfone support layer. It is found that these membranes reject the virus, Qß bacteriophage (≈20 nm diameter) by >99.9999%. Prepressurization of the membrane appears to enhance their virus rejection properties. This is the first example of nanostructured LC membranes that are used for virus rejection, for which they show great potential.

Treatment of Miller Class III recessions with enamel matrix derivative (Emdogain) in combination with subepithelial connective tissue grafting.

This report examines the clinical parameters and radiographic characteristics of two patients with Class III gingival recession who were treated with combined connective tissue grafting and root coverage with enamel matrix derivative. Both patients presented with multiple Class III recessions in the mandibular central incisors. Root coverage was achieved by connective tissue grafting in conjunction with the application of enamel matrix derivative. Soft tissue coverage of the root surfaces was achieved clinically, and radiographs showed improvement in the interproximal vertical bone defects.

Endoscopic transantral orbital floor repair with antral bone grafts.

OBJECTIVE: To evaluate the endoscopic transantral insertion of antral bone grafts into the orbit for repair of orbital floor defects. DESIGN: A retrospective analysis with a mean follow-up of 5.3 months. PATIENTS: Eleven patients who underwent surgical repair of orbital floor fractures. SETTING: Municipal hospital. MAIN OUTCOME MEASURES: Preoperative and postoperative Hess screen tests and the presence of diplopia, enophthalmos, donor site complications, cosmetic deformity, infection, and graft extrusion. RESULTS: Subjectively, 3 patients with diplopia had complete resolution of their symptoms after surgery, and 8 patients had improvement of their symptoms. Objectively, 11 patients had significant improvement in the postoperative Hess area ratio compared with the preoperative Hess area ratio. In 1 patient with a floor defect measuring 2.5 cm, enophthalmos existed after surgery, but reoperation was not performed in this case because diplopia was improved. There were no donor site complications, cosmetic deformity, infection, or graft extrusion. CONCLUSIONS: The endoscopic transantral insertion of antral bone grafts through the floor defect into the orbit is an effective technique that prevents injury to the lower eyelid, carries minimal donor site morbidity, and provides an optimal support function for the globe. It merits consideration in cases of orbital defects less than 2 cm in diameter.

Marked improvement of thrombocytopenia in a murine model of idiopathic thrombocytopenic purpura by pegylated recombinant human megakaryocyte growth and development factor.

OBJECTIVE: We examined the stimulatory effect of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) on platelet production in male (NZW x BXSB) F(l) (W/B F(1)) mice, a murine model of idiopathic thrombocytopenic purpura. MATERIALS AND METHODS: A cohort of 19- to 25-week-old, severely thrombocytopenic male W/B F(1) mice were given PEG-rHuMGDF at different dosing schedules. Before and at various times after therapy, platelet counts, reticulated platelets, platelet lifespan, and levels of platelet-associated immunoglobulin G were measured. Analysis of megakaryocytic cells was performed. RESULTS: Treatment of male W/B F(1) mice with PEG-rHuMGDF (30 microg/kg/day) three times per week for several weeks resulted in sustained thrombocytosis, accompanied by increased megakaryocytopoiesis in both the bone marrow and spleen. The degree of the platelet response to PEG-rHuMGDF varied between individual mice, likely reflecting the heterogeneity of the disease. Production of new platelets in response to PEG-rHuMGDF was manifested by an increase in reticulated platelets. Levels of platelet-associated immunoglobulin G decreased inversely during periods of thrombocytosis. PEG-rHuMGDF therapy also improved thrombocytopenia in male W/B F(1) mice refractory to splenectomy. Platelet lifespan was not affected by PEG-rHuMGDF. Male W/B F(1) mice treated with pegylated murine MGDF, a homologue of PEG-rHuMGDF, had persistent thrombocytosis for at least 7 months, suggesting that antiplatelet antibody production was not enhanced. CONCLUSIONS: PEG-rHuMGDF therapy potently stimulated platelet production, effectively ameliorating thrombocytopenia in a murine model of idiopathic thrombocytopenic purpura.

Liquid-Crystalline Biomacromolecular Templates for the Formation of Oriented Thin-Film Hybrids Composed of Ordered Chitin and Alkaline-Earth Carbonate.

Macroscopically ordered inorganic thin films have been formed on unidirectionally oriented, liquid-crystalline chitin matrices. In the presence of poly(acrylic acid) (PAA), unidirectionally oriented chitin films act as templates for the formation of oriented thin-film crystals of alkaline-earth carbonates such as SrCO3 and BaCO3. The morphology and orientation of crystals are dependent on the metal ion concentration. For SrCO3 crystallization, unidirectional thin films and hexagonal-shaped thin films have been deposited from 200 and 25 mm concentration strontium solutions, respectively.