Yan Liu

West China Hospital of Stomatology, Chengdu, Sichuan Sheng, China

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Publications (18)66.62 Total impact

  • Article: Inorganic-Organic Nanocomposite Assembly Using Collagen as Template and Sodium Tripolyphosphate as A Biomimetic Analog of Matrix Phosphoprotein.
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    ABSTRACT: Nanocomposites created with polycarboxylic acid alone as a stabilization agent for prenucleation clusters-derived amorphous calcium phosphate exhibit non-periodic apatite deposition. In the present study, we report the use of inorganic polyphosphate as a biomimetic analog of matrix phosphoprotein for directing polyacrylic acid-stabilized amorphous nanoprecursor phases to assemble into periodic apatite-collagen nanocomposites. The sorption and desorption characteristics of sodium tripolyphosphate to type I collagen was examined. Periodic nanocomposite assembly with collagen as a template was demonstrated with TEM and SEM using a Portland cement-based resin composite and a phosphate-containing simulated body fluid. Apatite was detected within the collagen at 24 hours and became more distinct at 48 hours, with prenucleation clusters attaching to the collagen fibril surface during the initial infiltration stage. Apatite-collagen nanocomposites at 72 hours were heavily mineralized with periodically-arranged intrafibrillar apatite platelets. Defect-containing nanocomposites caused by desorption of TPP from collagen fibrils were observed in regions lacking the inorganic phase.
    Crystal Growth & Design 08/2011; 11(8):3504-3511. · 4.72 Impact Factor
  • Article: Intrafibrillar collagen mineralization produced by biomimetic hierarchical nanoapatite assembly.
    Advanced Materials 02/2011; 23(8):975-80. · 13.88 Impact Factor
  • Article: The use of sodium trimetaphosphate as a biomimetic analog of matrix phosphoproteins for remineralization of artificial caries-like dentin.
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    ABSTRACT: This study examined the use of sodium trimetaphosphate (STMP) as a biomimetic analog of matrix phosphoproteins for remineralization of artificial carious-affected dentin. Artificial carious lesions with lesion depths of 300±30μm were created by pH-cycling. 2.5% hydrolyzed STMP was applied to the artificial carious lesions to phosphorylate the partially-demineralized collagen matrix. Half of the STMP-treated specimens were bonded with One-Step. The adhesive and non-adhesive infiltrated specimens were remineralized in a Portland cement-simulated body fluid system containing polyacrylic acid (PAA) to stabilize amorphous calcium phosphate as nanoprecursors. Micro-computed tomography (micro-CT) and transmission electron microscopy (TEM) were used to evaluate the results of remineralization after a 4-month period. In absence of PAA and STMP as biomimetic analogs (control groups), there was no remineralization irrespective of whether the lesions were infiltrated with adhesive. For the STMP-treated experimental groups immersed in PAA-containing simulated body fluid, specimens without adhesive infiltration were more heavily remineralized than those infiltrated with adhesive. Statistical analysis of the 4-month micro-CT data revealed significant differences in the lesion depth, relative mineral content along the lesion surface and changes in ΔZ between the non-adhesive and adhesive experimental groups (p<0.05 for all the three parameters). TEM examination indicated that collagen degradation occurred in both the non-adhesive and adhesive control and experimental groups after 4 months of remineralization. Biomimetic remineralization using STMP is a promising method to remineralize artificial carious lesions particularly in areas devoid of seed crystallites. Future studies should consider the incorporation of MMP-inhibitors within the partially-demineralized collagen matrix to prevent collagen degradation during remineralization.
    Dental materials: official publication of the Academy of Dental Materials 02/2011; 27(5):465-77. · 2.88 Impact Factor
  • Article: A chimeric peptide that binds to titanium and mediates MC3T3-E1 cell adhesion.
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    ABSTRACT: PURPOSE OF WORK: Our study provides a promising alternative of biomimetic coating which functionalizes the dental implant with adhesion peptides and may be useful for enhancing the bone remodeling around Ti implants. A chimeric peptide consisting of an Arg-Gly-Asp (RGD) sequence (mediating cell adhesion) and a RKLPDA (minTBP-1) sequence (specifically recognizing and binding to Ti substrate) was designed and synthesized. The chimeric peptide affinity to Ti disks, as well as its role in mediating MC3T3-E1 cell attachment and afterwards spreading on pre-coated Ti disks, was investigated. The chimeric peptide not only showed favorable affinity to Ti surfaces but also facilitated the adhesion of MC3T3-E1 cells.
    Biotechnology Letters 01/2011; 33(1):191-7. · 1.68 Impact Factor
  • Article: Immobilization of a phosphonated analog of matrix phosphoproteins within cross-linked collagen as a templating mechanism for biomimetic mineralization.
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    ABSTRACT: Immobilization of phosphoproteins on a collagen matrix is important for the induction of intrafibrillar apatite mineralization. Unlike phosphate esters, polyphosphonic acid has no reactive sites for covalent binding to collagen amine groups. Binding of poly(vinyl phosphonic acid) (PVPA), a biomimetic templating analog of matrix phosphoproteins, to collagen was found to be electrostatic in nature. Thus, an alternative retention mechanism was designed for immobilization of PVPA on collagen by cross-linking the latter with carbodiimide (EDC). This mechanism is based on the principle of size exclusion entrapment of PVPA molecules within the internal water compartments of collagen. By cross-linking collagen with EDC, a zero length cross-linking agent, the sieving property of collagen is increased, enabling the PVPA to be immobilized within the collagen. The absence of covalent cross-linking between PVPA and collagen was confirmed by Fourier transform infrared spectroscopy. Based on these results, a concentration range for immobilized PVPA to template intrafibrillar apatite deposition was established and validated using a single layer reconstituted type I collagen mineralization model. In the presence of a polyacrylic acid-containing mineralization medium optimal intrafibrillar mineralization of the EDC-cross-linked collagen was achieved using 500 and 1000 μg ml⁻¹ PVPA. The mineralized fibrils exhibited a hierarchical order of intrafibrillar mineral infiltration, as manifested by the appearance of electron-dense periodicity within unstained fibrils. Understanding the basic processes in intrafibrillar mineralization of reconstituted collagen creates opportunities for the design of tissue engineering materials for hard tissue repair and regeneration.
    Acta biomaterialia 01/2011; 7(1):268-77. · 3.98 Impact Factor
  • Article: Can Caries-Affected Dentin be Completely Remineralized by Guided Tissue Remineralization?
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    ABSTRACT: INTRODUCTION: To date, there is no evidence that conventional remineralization techniques using calcium and phosphate ion- containing media will completely remineralize carious lesions in regions where remnant apatite seed crystallites are absent. Conversely, guided tissue remineralization using biomimetic analogs of dentin matrix proteins is successful in remineralizing thin layers of completely demineralized dentin. THE HYPOTHESIS: Conventional remineralization strategy depends on epitaxial growth over existing apatite crystallites. If there are no or few crystallites, there will be no remineralization. Guided tissue remineralization uses biomimetic analogs of dentin matrix proteins to introduce sequestered amorphous calcium phosphate nanoprecursors into the internal water compartments of collagen fibrils. Attachment of templating analogs of matrix phosphoproteins to the collagen fibrils further guided the nucleation and growth of apatite crystallites within the fibril. Such a strategy is independent of apatite seed crystallites. Our hypothesis is that 250-300 microns thick artificial carious lesions can be completely remineralized in vitro by guide tissue remineralization but not by conventional remineralization techniques. EVALUATION OF THE HYPOTHESIS: Validation of the hypothesis will address the critical barrier to progress in remineralization of caries- affected dentin and shift existing paradigms by providing a novel method of remineralization based on a nanotechnology-based bottom-up approach. This will also generate important information to support the translation of the proof-of-concept biomimetic strategy into a clinically-relevant delivery system for remineralizing caries-affected dentin created by micro-organisms in the oral cavity.
    Dental hypotheses. 01/2011; 2(2):74-82.
  • Article: Differences between top-down and bottom-up approaches in mineralizing thick, partially demineralized collagen scaffolds.
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    ABSTRACT: Biominerals exhibit complex hierarchical structures derived from bottom-up self-assembly mechanisms. Type I collagen serves as the building block for mineralized tissues such as bone and dentin. In the present study, 250-300 μm thick, partially demineralized collagen scaffolds exhibiting a gradient of demineralization from the base to surface were mineralized using a classical top-down approach and a non-classical bottom-up approach. The top-down approach involved epitaxial growth over seed crystallites. The bottom-up approach utilized biomimetic analogs of matrix proteins to stabilize amorphous calcium phosphate nanoprecursors and template apatite nucleation and growth within the collagen matrix. Micro-computed tomography and transmission electron microscopy were employed to examine mineral uptake and apatite arrangement within the mineralized collagen matrix. The top-down approach could mineralize only the base of the partially demineralized scaffold, where remnant seed crystallites were abundant. Minimal mineralization was observed along the surface of the scaffold; extrafibrillar mineralization was predominantly observed. Conversely, the entire partially demineralized scaffold, including apatite-depleted collagen fibrils, was mineralized by the bottom-up approach, with evidence of both intrafibrillar and extrafibrillar mineralization. Understanding the different mechanisms involved in these two mineralization approaches is pivotal in adopting the optimum strategy for fabricating novel nanostructured materials in bioengineering research.
    Acta biomaterialia 11/2010; 7(4):1742-51. · 3.98 Impact Factor
  • Article: A chemical phosphorylation-inspired design for Type I collagen biomimetic remineralization.
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    ABSTRACT: Type I collagen alone cannot initiate tissue mineralization. Sodium trimetaphosphate (STMP) is frequently employed as a chemical phosphorylating reagent in the food industry. This study examined the feasibility of using STMP as a functional analog of matrix phosphoproteins for biomimetic remineralization of resin-bonded dentin. Equilibrium adsorption and desorption studies of STMP were performed using demineralized dentin powder (DDP). Interaction between STMP and DDP was examined using Fourier transform-infrared spectroscopy. Based on those results, a bio-inspired mineralization scheme was developed for chemical phosphorylation of acid-etched dentin with STMP, followed by infiltration of the STMP-treated collagen matrix with two etch-and-rinse adhesives. Resin-dentin interfaces were remineralized in a Portland cement-simulated body fluid system, with or without the use of polyacrylic acid (PAA) as a dual biomimetic analog. Remineralized resin-dentin interfaces were examined unstained using transmission electron microscopy. Analysis of saturation binding curves revealed the presence of irreversible phosphate group binding sites on the surface of the DDP. FT-IR provided additional evidence of chemical interaction between STMP and DDP, with increased in the peak intensities of the PO and P-O-C stretching modes. Those peaks returned to their original intensities after alkaline phosphatase treatment. Evidence of intrafibrillar apatite formation could be seen in incompletely resin-infiltrated, STMP-phosphorylated collagen matrices only when PAA was present in the SBF. These results reinforce the importance of PAA for sequestration of amorphous calcium phosphate nanoprecursors in the biomimetic remineralization scheme. They also highlight the role of STMP as a templating analog of dentin matrix phosphoproteins for inducing intrafibrillar remineralization of apatite nanocrystals within the collagen matrix of incompletely resin-infiltrated dentin.
    Dental materials: official publication of the Academy of Dental Materials 11/2010; 26(11):1077-89. · 2.88 Impact Factor
  • Article: Hierarchical and non-hierarchical mineralisation of collagen.
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    ABSTRACT: Biomineralisation of collagen involves functional motifs incorporated in extracellular matrix protein molecules to accomplish the objectives of stabilising amorphous calcium phosphate into nanoprecursors and directing the nucleation and growth of apatite within collagen fibrils. Here we report the use of small inorganic polyphosphate molecules to template hierarchical intrafibrillar apatite assembly in reconstituted collagen in the presence of polyacrylic acid to sequester calcium and phosphate into transient amorphous nanophases. The use of polyphosphate without a sequestration analogue resulted only in randomly-oriented extrafibrillar precipitations along the fibrillar surface. Conversely, the use of polyacrylic acid without a templating analogue resulted only in non-hierarchical intrafibrillar mineralisation with continuous apatite strands instead of discrete crystallites. The ability of using simple non-protein molecules to recapitulate different levels of structural hierarchy in mineralised collagen signifies the ultimate simplicity in Nature's biomineralisation design principles and challenges the need for using more complex recombinant matrix proteins in bioengineering applications.
    Biomaterials 10/2010; 32(5):1291-300. · 7.40 Impact Factor
  • Article: Biomimetic analogs for collagen biomineralization.
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    ABSTRACT: Inability of chemical phosphorylation of sodium trimetaphosphate to induce intrafibrillar mineralization of type I collagen may be due to the failure to incorporate a biomimetic analog to stabilize amorphous calcium phosphates (ACP) as nanoprecursors. This study investigated adsorption/desorption characteristics of hydrolyzed and pH-adjusted sodium trimetaphosphate (HPA-Na(3)P(3)O(9)) to collagen. Based on those results, a 5-minute treatment time with 2.8 wt% HPA-Na(3)P(3)O(9) was used in a single-layer reconstituted collagen model to confirm that both the ACP-stabilization analog and matrix phosphoprotein analog must be present for intrafibrillar mineralization. The results of that model were further validated by complete remineralization of phosphoric-acid-etched dentin treated with the matrix phosphoprotein analog and lined with a remineralizing lining composite, and with the ACP-stabilization analog supplied in simulated body fluid. An understanding of the basic processes involved in intrafibrillar mineralization of reconstituted collagen fibrils facilitates the design of novel tissue engineering materials for hard tissue repair and regeneration.
    Journal of dental research 10/2010; 90(1):82-7. · 3.46 Impact Factor
  • Article: Mineralisation of reconstituted collagen using polyvinylphosphonic acid/polyacrylic acid templating matrix protein analogues in the presence of calcium, phosphate and hydroxyl ions.
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    ABSTRACT: The complex morphologies of mineralised collagen fibrils are regulated through interactions between the collagen matrix and non-collagenous extracellular proteins. In the present study, polyvinylphosphonic acid, a biomimetic analogue of matrix phosphoproteins, was synthesised and confirmed with FTIR and NMR. Biomimetic mineralisation of reconstituted collagen fibrils devoid of natural non-collagenous proteins was demonstrated with TEM using a Portland cement-containing resin composite and a phosphate-containing fluid in the presence of polyacrylic acid as sequestration, and polyvinylphosphonic acid as templating matrix protein analogues. In the presence of these dual biomimetic analogues in the mineralisation medium, intrafibrillar and extrafibrillar mineralisation via bottom-up nanoparticle assembly based on the non-classical crystallisation pathway could be identified. Conversely, only large mineral spheres with no preferred association with collagen fibrils were observed in the absence of biomimetic analogues in the medium. Mineral phases were evident within the collagen fibrils as early as 4 h after the initially-formed amorphous calcium phosphate nanoprecursors were transformed into apatite nanocrystals. Selected area electron diffraction patterns of highly mineralised collagen fibrils were nearly identical to those of natural bone, with apatite crystallites preferentially aligned along the collagen fibril axes.
    Biomaterials 09/2010; 31(25):6618-27. · 7.40 Impact Factor
  • Article: Functional biomimetic analogs help remineralize apatite-depleted demineralized resin-infiltrated dentin via a bottom-up approach.
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    ABSTRACT: Natural biominerals are formed through metastable amorphous precursor phases via a bottom-up, nanoparticle-mediated mineralization mechanism. Using an acid-etched human dentin model to create a layer of completely demineralized collagen matrix, a bio-inspired mineralization scheme has been developed based on the use of dual biomimetic analogs. These analogs help to sequester fluidic amorphous calcium phosphate nanoprecursors and function as templates for guiding homogeneous apatite nucleation within the collagen fibrils. By adopting this scheme for remineralizing adhesive resin-bonded, completely demineralized dentin, we have been able to redeposit intrafibrillar and extrafibrillar apatites in completely demineralized collagen matrices that are imperfectly infiltrated by resins. This study utilizes a spectrum of completely and partially demineralized dentin collagen matrices to further validate the necessity for using a biomimetic analog-containing medium for remineralizing resin-infiltrated partially demineralized collagen matrices in which remnant seed crystallites are present. In control specimens in which biomimetic analogs are absent from the remineralization medium, remineralization could only be seen in partially demineralized collagen matrices, probably by epitaxial growth via a top-down crystallization approach. Conversely, in the presence of biomimetic analogs in the remineralization medium, intrafibrillar remineralization of completely demineralized collagen matrices via a bottom-up crystallization mechanism can additionally be identified. The latter is characterized by the transition of intrafibrillar minerals from an inchoate state of continuously braided microfibrillar electron-dense amorphous strands to discrete nanocrystals, and ultimately into larger crystalline platelets within the collagen fibrils. Biomimetic remineralization via dual biomimetic analogs has the potential to be translated into a functional delivery system for salvaging failing resin-dentin bonds.
    Acta biomaterialia 07/2010; 6(7):2740-50. · 3.98 Impact Factor
  • Article: Peptide aptamers against titanium-based implants identified through phage display.
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    ABSTRACT: Commercially pure titanium (cp-Ti) is widely used in the field of long-term clinical oral implantology owing to its ability to allow close bone-implant apposition. The optimization of its function based on artificial proteins has become a key issue in the development of improved cp-Ti implants. Here, we set out to identify peptide aptamers with preferential adsorption towards titanium-based implants through the phage display methodology. Fifteen sequences were selected in the third round of biopanning. One sequence, ATWVSPY (named TBP1), had a 40% repetition rate and exhibited the strongest binding affinity to cp-Ti disks. Ten sequences were selected in the fourth round, among which the repetition rate is 80% for TBP1 and 20% for TBP2 (GVGLPHT). The peptide aptamers against cp-Ti disks can provide an alternative method of functional coating for biomaterial surfaces.
    Journal of Materials Science Materials in Medicine 04/2010; 21(4):1103-7. · 2.32 Impact Factor
  • Article: Biomimetic remineralization as a progressive dehydration mechanism of collagen matrices--implications in the aging of resin-dentin bonds.
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    ABSTRACT: Biomineralization is a dehydration process in which water from the intrafibrillar compartments of collagen fibrils are progressively replaced by apatites. As water is an important element that induces a lack of durability of resin-dentin bonds, this study has examined the use of a biomimetic remineralization strategy as a progressive dehydration mechanism to preserve joint integrity and maintain adhesive strength after ageing. Human dentin surfaces were bonded with dentin adhesives, restored with resin composites and sectioned into sticks containing the adhesive joint. Experimental specimens were aged in a biomimetic analog-containing remineralizing medium and control specimens in simulated body fluid for up to 12 months. Specimens retrieved after the designated periods were examined by transmission electron microscopy for the presence of water-rich regions using a silver tracer and for collagen degradation within the adhesive joints. Tensile testing was performed to determine the potential loss of bond integrity after ageing. Control specimens exhibited severe collagen degradation within the adhesive joint after ageing. Remineralized specimens exhibited progressive dehydration, as manifested by silver tracer reduction and partial remineralization of water-filled microchannels within the adhesive joint, as well as intrafibrillar remineralization of collagen fibrils that were demineralized initially as part of the bonding procedure. Biomimetic remineralization as a progressive dehydration mechanism of water-rich, resin-sparse collagen matrices enables these adhesive joints to resist degradation over a 12-month ageing period, as verified by the conservation of their tensile bond strength. The ability of the proof of concept biomimetic remineralization strategy to prevent bond degradation warrants further development of clinically relevant delivery systems.
    Acta biomaterialia 03/2010; 6(9):3729-39. · 3.98 Impact Factor
  • Article: Slanted orientations of dentine tubules on remineralized dentine surfaces.
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    ABSTRACT: Dentine carious lesions can be remineralized under optimal conditions, while the surface characteristics of the caries-attacked area may play an important role in the remineralization process. To understand such a surface mechanism, we examined the microstructures of the remineralized area pretreated with different methods. It was found that dentinal tubules on the remineralized surface orientated differently from intrinsic dentine tubules, with the specific alignment angle determined by different surface treatments. Various surface treatments included in this study were 37% phosphoric acid treatment (the etched group), 37% phosphoric acid etching followed by the application of 10% sodium hypochlorite treatment (the deproteinized group), and untreatment (the control group). These findings are helpful for understanding the non-restorative repair of dentine lesions and the remineralization process of the caries-affected dentin surface.
    Journal of Materials Science Materials in Medicine 02/2010; 21(5):1473-8. · 2.32 Impact Factor
  • Article: GEPIs-HA hybrid: a novel biomaterial for tooth repair.
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    ABSTRACT: Dental caries are slowly progressive and infectious disease, which result in localized dissolution and destruction of the calcified tissues. In routine clinical treatments, microleakage following with secondary caries usually occurs due to the discrepancy in physico-chemical property between filled materials and tooth. Ideal filling materials for tooth defect should be similar to the structure and chemical composition of natural tooth. Recently, molecular biomimetics developed a novel nanotechnology through biology, which fabricate materials based on molecular recognition between genetically engineered peptides for inorganics (GEPIs) and inorganic crystal. Since GEPIs can be used in the assembly of functional nanostructures, we hypothesis that an analogue of dental hard tissue, hybrid of GEPIs and HA crystal, might be engineered using the recognition properties between GEPIs and HA crystal.
    Medical Hypotheses 10/2008; 71(4):591-3. · 1.39 Impact Factor
  • Article: The effect of premixed schedule on the crystal formation of calcium phosphate cement-chitosan composite with added tetracycline.
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    ABSTRACT: In this study, calcium phosphate cements (CPC) were prepared by mixing cement powders of tetracalcium phosphate (TTCP) with a cement liquid of phosphate acid saline solution. Tetracycline (TTC)-CPC, chitosan-CPC and chitosan-TTC-CPC were investigated with different premixed schedule. It was demonstrate that both TTC and chitosan worked on the phase transition and crystal characteristics. TTCP mixed with phosphate acid saline solution had similar features of Fourier transform-infrared spectrometry (FT-IR) no matter it was mixed with chitosan or TTC or both. TTC premixed with cement liquid or powder had significant different features of FT-IR and 876 cm(-1) seemed to be a special peak for TTC when TTC was premixed with cement liquid. This was also supported by XRD analysis, which showed that TTC premixed with cement liquid improved phase transition of TTCP to OCP. Chitosan, as organic additive, regulates the regular crystal formation and inhibits the phase transition of TTCP to OCP, except when it is mingled with cement liquid premixed with TTC in field scanning electron microscope. It was concluded that the premixed schedule influences the crystal formation and phase transition, which may be associated with its biocompatibility and bioactivities in vivo.
    Journal of Huazhong University of Science and Technology 09/2008; 28(4):483-6. · 0.38 Impact Factor
  • Article: [Effect of premix schedule on crystal formation of compound calcium phosphate cements].
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    ABSTRACT: To investigate the effect of premix schedule on crystal formation of self-hardening calcium phosphate cements (CPC). CPC were prepared by mixing cement powders of tetracalcium phosphate(TTCP) with a cement liquid of phosphate acid saline solution. TTC-CPC, chitosan-CPC and chitosan-TTC-CPC were investigated with different premix schedules. The crystal formation was investigated by X-ray diffraction(XRD) and field scanning electron microscope(FSEM). TTC and chitosan both affected the phase transition and crystal character in CPC. Chitosan, as organic additive, regulated the regular crystal formation and inhibited the phase transition of TTCP into OCP. The premix schedule affects the crystal formation and phase transition, which may affect its biocompatibility and bioactivities in vivo.
    Shanghai kou qiang yi xue = Shanghai journal of stomatology 05/2008; 17(2):187-90.

Institutions

  • 2011
    • West China Hospital of Stomatology
      Chengdu, Sichuan Sheng, China
  • 2010–2011
    • Sun Yat-Sen University
      • Department of Conservative Dentistry & Endodontics
      Guangzhou, Guangdong Sheng, China
    • Tongji Hospital
      Wuhan, Hubei, China
    • Kyung Hee University
      • Department of Dentistry
      Seoul, Seoul, South Korea
    • Kyungpook National University
      • Department of Conservative Dentistry
      Sangju, North Gyeongsang, South Korea