Qichao Ruan

Dipolar molecules as impellers achieving electric-field-stimulated release.

Here we report the design of a new external electric field-controlled release system using functional dipolar molecules as nanoimpellers. The dipolar molecule 4-(3-cyanophenyl)butylene, which can reorient in response to external electric fields with different frequencies because of its strong inherent dipole moment, was synthesized and grafted onto the inner surfaces of mesopores. Under an alternating electric field, the swinging flexible molecular chains consequently push guest molecules out of the pore voids. This innovative approach to controlled release may provide important application opportunities in tumor treatment with a number of advantages in terms of local release with targetability, external remote control, and the nonelectrochemical nature of the process.

Amelogenin and Enamel Biomimetics.

Mature tooth enamel is acellular and does not regenerate itself. Developing technologies that rebuild tooth enamel and preserve tooth structure is therefore of great interest. Considering the importance of amelogenin protein in dental enamel formation, its ability to control apatite mineralization in vitro, and its potential to be applied in fabrication of future bio-inspired dental material this review focuses on two major subjects: amelogenin and enamel biomimetics. We review the most recent findings on amelogenin secondary and tertiary structural properties with a focus on its interactions with different targets including other enamel proteins, apatite mineral, and phospholipids. Following a brief overview of enamel hierarchical structure and its mechanical properties we will present the state-of-the-art strategies in the biomimetic reconstruction of human enamel.

An amelogenin-chitosan matrix promotes assembly of an enamel-like layer with a dense interface.

Biomimetic reconstruction of tooth enamel is a significant topic of study in materials science and dentistry as a novel approach to the prevention, restoration, and treatment of defective enamel. We have developed a new amelogenin-containing chitosan hydrogel for enamel reconstruction that works through amelogenin supramolecular assembly, stabilizing Ca-P clusters and guiding their arrangement into linear chains. These amelogenin Ca-P composite chains further fuse with enamel crystals and eventually evolve into enamel-like co-aligned crystals, anchored to the natural enamel substrate through a cluster growth process. A dense interface between the newly grown layer and natural enamel was formed and the enamel-like layer improved the hardness and elastic modulus compared with etched enamel. We anticipate that this chitosan hydrogel will provide effective protection against secondary caries because of its pH-responsive and antimicrobial properties. Our studies introduce an amelogenin-containing chitosan hydrogel as a promising biomaterial for enamel repair and demonstrate the potential of applying protein-directed assembly to biomimetic reconstruction of complex biomaterials.

Ultrasonic-irradiation-assisted oriented assembly of ordered monetite nanosheets stacking.

Bioactive monetite (anhydrous calcium hydrogen phosphate, CaHPO(4)) with orderly layered structure assembled by nanosheets has been successfully synthesized by a sonochemical-assisted method in the presence of cetyltrimethylammonium bromide (CTAB). The thicknesses of the nanosheets are 100-200 nm, and the lateral sizes are about 2 microm. Because of the strong affinity with the phosphate ions as well as the (200) faces of the crystals, CTAB molecules can make the formation and stabilization of monetite nanosheets with (200) exposed face. Ultrasonic irradiation makes the transition from disordered state to oriented state before the oriented assembly of monetite nanosheets. The ultrasonic irradiation provides enough external work to make the assemble process possible in thermodynamics. The drastic flow stirred by the supersonic jet in the solution accomplishes the transition and successive oriented assembly of nanosheets in dynamics. This study would offer a simple method to design and synthesize oriented-assembled materials.

Investigation of layer-by-layer assembled heparin and chitosan multilayer films via electrochemical spectroscopy.

The layer-by-layer (LbL) assembly as a simple and effective method has been extensively used to prepare polyelectrolyte films but the buildup mechanism is expected to be further clarified. In this work, the structure and formation mechanism of LbL-assembled heparin/chitosan multilayer composite films were characterized by electrochemical system, scanning electron microscope and atom force microscope. The results revealed that the film grew linearly in the first 10 bilayers based on measured linear increase of film resistance with number of layers, while the film grew exponentially in the later 10 bilayers based on measured nonlinear increase of film resistance. The charge-transfer resistance increased in an oscillatory way or a linear way at different growing stages, which was discussed with their formation mechanism and the interfacial structure on electrode. A buildup mode of the LbL film was suggested based on the structural and electrochemical characters.

Development of Amelogenin-chitosan Hydrogel for In Vitro Enamel Regrowth with a Dense Interface

Biomimetic enamel reconstruction is a significant topic in material science and dentistry as a novel approach for the treatment of dental caries or erosion. Amelogenin has been proven to be a critical protein for controlling the organized growth of apatite crystals. In this paper, we present a detailed protocol for superficial enamel reconstruction by using a novel amelogenin-chitosan hydrogel. Compared to other conventional treatments, such as topical fluoride and mouthwash, this method not only has the potential to prevent the development of dental caries but also promotes significant and durable enamel restoration. The organized enamel-like microstructure regulated by amelogenin assemblies can significantly improve the mechanical properties of etched enamel, while the dense enamel-restoration interface formed by an in situ regrowth of apatite crystals can improve the effectiveness and durability of restorations. Furthermore, chitosan hydrogel is easy to use and can suppress bacterial infection, which is the major risk factor for the occurrence of dental caries. Therefore, this biocompatible and biodegradable amelogenin-chitosan hydrogel shows promise as a biomaterial for the prevention, restoration, and treatment of defective enamel.

Matrix metalloproteinase-20 mediates dental enamel biomineralization by preventing protein occlusion inside apatite crystals

Reconstruction of enamel-like materials is a central topic of research in dentistry and material sciences. The importance of precise proteolytic mechanisms in amelogenesis to form a hard tissue with more than 95% mineral content has already been reported. A mutation in the Matrix Metalloproteinase-20 (MMP-20) gene results in hypomineralized enamel that is thin, disorganized and breaks from the underlying dentin. We hypothesized that the absence of MMP-20 during amelogenesis results in the occlusion of amelogenin in the enamel hydroxyapatite crystals. We used spectroscopy and electron microscopy techniques to qualitatively and quantitatively analyze occluded proteins within the isolated enamel crystals from MMP-20 null and Wild type (WT) mice. Our results showed that the isolated enamel crystals of MMP-20 null mice had more organic macromolecules occluded inside them than enamel crystals from the WT. The crystal lattice arrangements of MMP-20 null enamel crystals analyzed by High Resolution Transmission Electron Microscopy (HRTEM) were found to be significantly different from those of the WT. Raman studies indicated that the crystallinity of the MMP-20 null enamel crystals was lower than that of the WT. In conclusion, we present a novel functional mechanism of MMP-20, specifically prevention of unwanted organic material entrapped in the forming enamel crystals, which occurs as the result of precise amelogenin cleavage. MMP-20 action guides the growth morphology of the forming hydroxyapatite crystals and enhances their crystallinity. Elucidating such molecular mechanisms can be applied in the design of novel biomaterials for future clinical applications in dental restoration or repair.

Amelogenin–chitosan matrix for human enamel regrowth: effects of viscosity and supersaturation degree

Abstract We recently reported an amelogenin-chitosan (CS-AMEL) hydrogel as a promising biomimetic material for future in situ human enamel regrowth. To further optimize the necessary conditions for clinical applicability of CS-AMEL hydrogel, herein we studied the effects of viscosity and supersaturation degree on the size and orientation of synthetic crystals by means of scanning electron microscopy (SEM) and X-ray diffraction (XRD). Raising the hydrogel viscosity by increasing chitosan concentration from 1% to 2% (w/v) improved the orientation of the crystals, while a higher supersaturation (σ(HAp) >10.06, [Ca2+] >5 mM) resulted in the formation of random crystals with larger sizes and irregular structures. We conclude that optimal conditions to produce organized enamel-like crystals in a CS-AMEL hydrogel are: 2% (w/v) chitosan, 2.5 mM calcium, and 1.5 mM phosphate (degree of supersaturation = 8.23) and 200 µg/ml of amelogenin.

Assembly of Layered Monetite-Chitosan Nanocomposite and Its Transition to Organized Hydroxyapatite

Bioinspired synthesis of hierarchically structured calcium phosphate (CaP) material is a highly promising strategy for developing improved bone substitute materials. However, synthesis of CaP materials with outstanding mechanical properties still remains an ongoing challenge. Inspired by the formation of lamellar structure in nacre, we designed an organic matrix composed of chitosan and cis-butenediolic acid (maleic acid, MAc) that could assemble into a layered complex and further guide the mineralization of monetite crystals, resulting in the formation of organized and parallel arrays of monetite platelets with a brick-and-mortar structure. Using the layered monetite-chitosan composite as a precursor, we were able to synthesize hydroxyapatite (HAp) with multiscale hierarchically ordered structure via a topotactic phase transformation process. On the nanoscale, needlelike HAp crystallites assembled into organized bundles that aligned to form highly oriented plates on the microscale. On the large-scale level, these plates with different crystal orientations were stacked together to form a layered structure. The organized structures and composite feature yielded CaP materials with improved mechanical properties close to those of bone. Our study introduces a biomimetic approach that may be practical for the design of advanced, mechanically robust materials for biomedical applications.

POLYMORPH SELECTION OF CALCIUM CARBONATE BY THE MORPHOLOGY OF BIOMACROMOLECULES: FROM ARAGONITE, VATERITE TO CALCITE

The selective polymorph synthesis of aragonite, vaterite and calcite was done by changing the conformation of chitosan molecules. Aragonite crystals in hexagonal prism-like shape were obtained in chitosan precipitates, vaterite crystals in hexagonal symmetrical plate-like shape were prepared in chitosan gel, and calcite nanoparticles were obtained in chitosan sol. The phenomenon of polymorph selection of biominerals by the morphology of biomacromolecules indicates that the studies on the relation between biominerals and biomacromelecules have general interest not only in bionics, but also in biometrics and related fields.