Publications by authors named "Yuqin Qiao"

52 Publications

A Novel Stimuli-Responsive Injectable Antibacterial Hydrogel to Achieve Synergetic Photothermal/Gene-Targeted Therapy towards Uveal Melanoma.

Adv Sci (Weinh) 2021 Jul 31:e2004721. Epub 2021 Jul 31.

Department of Ophthalmology, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, 200025, P. R. China.

Uveal melanoma (UM) is the most prevalent primary intraocular malignant tumor with a high lethal rate. Patients who undergo conventional enucleation treatments consistently suffer permanent blindness, facial defects, and mental disorders, therefore, novel therapeutic modalities are urgently required. Herein, an injectable and stimuli-responsive drug delivery antibacterial hydrogel ([email protected]@DC_AC50) is constructed via a facile grinding method that is inspired by the preparation process of traditional Chinese medicine. The incorporation of gold nanorods can enhance the mechanical strength of the hydrogel and realize photothermal therapy (PTT) and thermosensitive gel-sol transformation to release the gene-targeted drug DC_AC50 on demand in response to low-density near-infrared (NIR) light. The orthotopic model of UM is built successfully and indicates the excellent efficiency of [email protected]@DC_AC50 in killing tumors without damage to normal tissue because of its synergistic mild temperature PTT and gene-targeted therapy. Moreover, the eyeball infection model reveals the remarkable antibacterial properties of the hydrogel which can prevent endophthalmitis in the eyeball. There is negligible difference between the [email protected]@DC_AC50+NIR group and normal group. This NIR light-triggered gene-targeted therapy/PTT/antibacterial treatment pattern provides a promising strategy for building multifunctional therapeutic platform against intraocular tumors and exhibits great potential for the clinical treatment of UM.
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http://dx.doi.org/10.1002/advs.202004721DOI Listing
July 2021

Synergistic effects of immunoregulation and osteoinduction of ds-block elements on titanium surface.

Bioact Mater 2021 Jan 14;6(1):191-207. Epub 2020 Aug 14.

State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, 200050, China.

Ds-block elements have been gaining increasing attention in the field of biomaterials modification, owing to their excellent biological properties, such as antibiosis, osteogenesis, etc. However, their function mechanisms are not well understood and conflicting conclusions were drawn by previous studies on this issue, which are mainly resulted from the inconsistent experimental conditions. In this work, three most widely used ds-block elements, copper, zinc, and silver were introduced on titanium substrate by plasma immersion ion implantation method to investigate the rule of ds-block elements in the immune responses. Results showed that the implanted samples could decrease the inflammatory responses compared with Ti sample. The trend of anti-inflammatory effects of macrophages on samples was in correlation with cellular ROS levels, which was induced by the implanted biomaterials and positively correlated with the number of valence electrons of ds-block elements. The co-culture experiments of macrophages and bone marrow mesenchymal stem cells showed that these two kinds of cells could enhance the anti-inflammation and osteogenesis of samples by the paracrine manner of PGE2. In general, in their steady states on titanium substrate (Cu, Zn, Ag), the ds-block elements with more valence electrons exhibit better anti-inflammatory and osteogenic effects. Moreover, molecular biology experiments indicate that the PGE2-related signaling pathway may contribute to the desired immunoregulation and osteoinduction capability of ds-block elements. These findings suggest a correlation between the number of valence electrons of ds-block elements and the relevant biological responses, which provides new insight into the selection of implanted ions and surface design of biomaterials.
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http://dx.doi.org/10.1016/j.bioactmat.2020.08.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7452063PMC
January 2021

Enhanced physicochemical and biological properties of C/Cu dual ions implanted medical titanium.

Bioact Mater 2020 Jun 19;5(2):377-386. Epub 2020 Mar 19.

State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, 200050, China.

It is increasingly popular for titanium and its alloys to be utilized as the medical implants. However, their bio-inert nature and lack of antibacterial ability limit their applications. In this work, by utilizing plasma immersion ion implantation and deposition (PIII&D) technology, the titanium surface was modified by C/Cu co-implantation. The mechanical property, corrosion resistance, antibacterial ability and cytocompatibility of modified samples were studied. Results indicate that after C/Cu co-implantation, copper nanoparticles were observed on the surface of titanium, and titanium carbide existed on the near surface region of titanium. The modified surface displayed good mechanical property and corrosion resistance. The Cu/C galvanic corrosion existed on the titanium surface implanted by C/Cu dual ions, and release of copper ions can be effectively controlled by the galvanic corrosion effect. Moreover, improved antibacterial performance of titanium surface can be achieved without cytotoxicity.
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http://dx.doi.org/10.1016/j.bioactmat.2020.02.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7083793PMC
June 2020

Corrigendum to "Mn-containing titanium surface with favorable osteogenic and antimicrobial functions synthesized by PIII&D" [Colloids Surf. B: Biointerfaces 152 (2017) 376-384].

Colloids Surf B Biointerfaces 2020 07 21;191:110970. Epub 2020 Mar 21.

State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, China. Electronic address:

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http://dx.doi.org/10.1016/j.colsurfb.2020.110970DOI Listing
July 2020

Dose-response relationships between copper and its biocompatibility/antibacterial activities.

J Trace Elem Med Biol 2019 Sep 19;55:127-135. Epub 2019 Jun 19.

State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, China; Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address:

Background: Copper has already been widely used in the modification of biomaterials because it possesses multifunctional biological effects like osteogenic, angiogenic and antibacterial activities. However, it is still not clear how different cell lines and bacteria will respond to different concentrations of Cu, which is very critical to the application of copper-doped implants.

Methods: This study aimed to explore the dose-response relationships of Cu and its biological effects in vitro. Rat bone marrow mesenchymal stem cell (rBMSCs), mouse osteoblastic cell line (MC3T3-E1), and human umbilical vein endothelial cells (HUVECs) were used to evaluate cellular behaviors. Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) were used to evaluate bacterial behaviors.

Results: Results showed that the HUVECs exhibited significantly higher tolerance to copper ions than MC3T3-E1 and rBMSCs. The IC values of copper for HUVECs, MC3T3-E1 and HUVECs were approximated to 327.9 μM, 134.6 μM, and 0.7 μM, respectively. Besides, the threshold concentration of copper for effective inhibition against bacteria growth is 37 μM. When the concentration exceeded the threshold value, antibacterial activity could increase dramatically.

Conclusions: These results altogether establish a technological foundation for the application of copper-doped biomaterials in bone growth and remodeling.
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http://dx.doi.org/10.1016/j.jtemb.2019.06.015DOI Listing
September 2019

Nanostructural Surfaces with Different Elastic Moduli Regulate the Immune Response by Stretching Macrophages.

Nano Lett 2019 06 22;19(6):3480-3489. Epub 2019 May 22.

State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics , Chinese Academy of Sciences , Shanghai 200050 , China.

A proper immune response is key for the successful implantation of biomaterials, and designing and fabricating biomaterials to regulate immune responses is the future trend. In this work, three different nanostructures were constructed on the surface of titanium using a hydrothermal method, and through a series of in vitro and in vivo experiments, we found that the aspect ratio of nanostructures can affect the elastic modulus of a material surface and further regulate immune cell behaviors. This work demonstrates that nanostructures with a higher aspect ratio can endow a material surface with a lower elastic modulus, which was confirmed by experiments and theoretical analyses. The deflection of nanostructures under the cell adsorption force is a substantial factor in stretching macrophages to enhance cell adhesion and spreading, further inducing macrophage polarization toward the M1 phenotype and leading to intense immune responses. In contrast, a nanostructure with a lower aspect ratio on a material surface leads to a higher surface elastic modulus, making deflection of the material difficult and creating a surface that is not conducive to macrophage adhesion and spreading, thus reducing the immune response. Moreover, molecular biology experiments indicated that regulation of the immune response by the elastic modulus is primarily related to the NF-κB signaling pathway. These findings suggest that the immune response can be regulated by constructing nanostructural surfaces with the proper elastic modulus through their influence on cell adhesion and spreading, which provides new insights into the surface design of biomaterials.
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http://dx.doi.org/10.1021/acs.nanolett.9b00237DOI Listing
June 2019

PEO/Mg-Zn-Al LDH Composite Coating on Mg Alloy as a Zn/Mg Ion-Release Platform with Multifunctions: Enhanced Corrosion Resistance, Osteogenic, and Antibacterial Activities.

ACS Biomater Sci Eng 2018 Dec 26;4(12):4112-4121. Epub 2018 Oct 26.

State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, China.

The design of advanced multifunctional Mg-based bone implants with enhanced corrosion resistance, antibacterial, and osteogenic activities should be brought to the forefront to fulfill the requirement of clinical medicine. In this work, a PEO/Mg-Zn-Al layered double hydroxide (LDH) composite coating on Mg alloy was developed via plasma electrolytic oxidation (PEO) and hydrothermal treatment. The porous structure formed during the PEO process was filled by Mg-Zn-Al LDH. The as-prepared coating exhibited better corrosion resistance than the PEO/Mg-Al LDH composite coating. In addition, the composite coating showed strong antimicrobial ability against Gram-positive , which was attributed to the release of Zn ions. When Zn content was controlled at 1.17 at% in the composite coating, rBMSCs showed long-term cytocompatibility and enhanced initial adhesion. Moreover, with the synergistic functions of Zn and Mg ions, cells on the composite coating showed a higher level of alkaline phosphatase activity and expression of osteopontin (OPN). With enhanced corrosion resistance, antibacterial, and osteogenic differentiation abilities, the PEO/Mg-Zn-Al LDH composite coating exhibits a promising application in bone-related implants.
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http://dx.doi.org/10.1021/acsbiomaterials.8b01184DOI Listing
December 2018

Effect of Local Alkaline Microenvironment on the Behaviors of Bacteria and Osteogenic Cells.

ACS Appl Mater Interfaces 2018 Dec 27;10(49):42018-42029. Epub 2018 Nov 27.

State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics , Chinese Academy of Sciences , Shanghai 200050 , China.

The interactions between material surfaces and bacteria/cells have been widely investigated, based on which biomaterials with antibacterial and osteogenic abilities can be designed to conquer implant failures. The pH of environments is known to affect bacterial growth and bone formation/resorption, and it is possible that the antibacterial and osteogenic abilities of biomaterials can be simultaneously improved by regulating their surface alkalinity. Herein, we fabricated many kinds of films with various alkalinity levels on titanium surface to explore the effect of local alkaline microenvironments around material surfaces on the behaviors of bacteria and osteogenic cells. Both Gram-positive and -negative bacteria were cultured on sample surfaces to investigate their antibacterial effects. Cell adhesion, proliferation, and alkaline phosphatase (ALP) activities were investigated by culturing both bone mesenchymal stem cells (MSCs) and osteoblast cells on sample surfaces. The results show that an appropriate local alkaline environment can effectively inhibit the growth of both Gram-positive and -negative bacteria through inactivating ATP synthesis and inducing oxidative stress. Meanwhile, it can promote the osteogenic differentiation of bone MSCs and enhance the proliferation and ALP activities of osteoblast cells. In conclusion, material surfaces endowed with appropriate alkalinity can possess antibacterial and osteogenic properties, which provide a novel strategy to design multifunctional biomaterials for bone generation.
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http://dx.doi.org/10.1021/acsami.8b15724DOI Listing
December 2018

Synergistic Effects of N/Cu Dual Ions Implantation on Stimulating Antibacterial Ability and Angiogenic Activity of Titanium.

ACS Biomater Sci Eng 2018 Sep 22;4(9):3185-3193. Epub 2018 Aug 22.

State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, China.

Titanium and its alloys have been commonly used as implant materials. However, the inherent bioinert nature hinders its good osseointegration which limits its permanent clinical applications. In this work, nitrogen (N) and copper (Cu) dual ions were implanted into titanium by plasma immersion ion implantation and deposition (PIII&D) technology. The corrosion resistance, mechanical property, antibacterial ability, and angiogenic activity of the modified titanium surfaces were investigated. Experimental results show that titanium nitride (TiN) film embedded with Cu nanoparticles (Cu NPs) forms on the surface of the N/Cu dual ions implanted titanium. The N/Cu dual ions implanted titanium exhibits excellent corrosion resistance and mechanical property. The galvanic corrosion of Cu/TiN can effectively control copper ion release to enhance the antibacterial and angiogenic performances of the Ti surface.
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http://dx.doi.org/10.1021/acsbiomaterials.8b00501DOI Listing
September 2018

Controllable and durable release of BMP-2-loaded 3D porous sulfonated polyetheretherketone (PEEK) for osteogenic activity enhancement.

Colloids Surf B Biointerfaces 2018 Nov 8;171:668-674. Epub 2018 Aug 8.

State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, 200050, China. Electronic address:

Polyetheretherketone (PEEK) is ideal for dental and orthopedic applications because its mechanical properties are similar to cortical bones. However, its inherent inert ability hinders its clinical applications. In this work, bone morphogenetic protein-2 (BMP-2) was immobilized onto the sulfonated PEEK (SPEEK) using lyophilization technology. The surface morphologies of the samples were analyzed by field-emission scanning electron microscopy (FE-SEM), and the chemical compositions were analyzed by energy-dispersive X-ray spectrometry (EDS). The release content of BMP-2 of the samples immersed in the PBS (pH = 7.4) was detected by a human BMP-2 ELISA kit. The results indicated that controllable and durable BMP-2 release was accomplished due to the three-dimensional (3D) network of sulfonated PEEK. The in vitro cellular experiments showed that the BMP-2-immobilized samples significantly enhanced the initial adhesion and spreading of rat bone mesenchymal stem cells (rBMSCs). Moreover, the collagen secretion, extracellular matrix mineralization and ALP activity were also improved. Thus, the BMP-2-immobilized samples greatly promoted the osteogenic differentiation of rBMSCs, which revealed that BMP-2 immobilization paves the way for the use of PEEK in clinical applications.
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http://dx.doi.org/10.1016/j.colsurfb.2018.08.012DOI Listing
November 2018

Layered double hydroxide/poly-dopamine composite coating with surface heparinization on Mg alloys: improved anticorrosion, endothelialization and hemocompatibility.

Biomater Sci 2018 Jun;6(7):1846-1858

Department of Cardiac Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China.

Magnesium (Mg) and its alloys are promising cardiovascular stent materials due to their favourable physical properties and complete degradation in vivo. However, rapid degradation and poor cytocompatibility hinder their clinical applications. To enhance the corrosion resistance and endothelialization of the AZ31 alloy, a layered double hydroxide (LDH)/poly-dopamine (PDA) composite coating (LDH/PDA) was successfully fabricated. Polarization curves and the electrochemical impedance spectroscopy Nyquist spectrum test proved that the corrosion resistance of the LDH/PDA sample was significantly improved in vitro. The LDH/PDA sample greatly improved the adherence process and the proliferation rate of human umbilical vein endothelial cells (HUVECs). After culturing for 10 days, the number of living HUVECs on the LDH/PDA sample was comparable to that on the Ti sample whereas the cells barely survived on the AZ31 or LDH coating. Furthermore, heparin was immobilized on LDH/PDA via a covalent bond (LDH/PDA/HEP). The corrosion resistance and long-term proliferation of HUVECs after the introduction of heparin were mildly decreased compared with the L/P sample, but were still greatly improved compared with AZ31, the LDH coating and the PDA coating. Furthermore, the LDH/PDA/HEP sample greatly improved the HUVEC migration rate compared with the LDH/PDA sample, and inhibited platelet adhesion which was intense on the LDH/PDA sample. Both LDH/PDA and LDH/PDA/HEP samples had a low hemolysis rate (2.52% and 0.65%, respectively) in vitro and eliminated the adverse biocompatible effects of the direct PDA coating on the AZ31 substrate in vivo. Our results suggest that the LDH/PDA composite coating with further heparinization is a promising method to modify the surface of Mg alloys by significantly improving corrosion resistance, endothelialization and hemocompatibility.
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http://dx.doi.org/10.1039/c8bm00298cDOI Listing
June 2018

NIR-Triggered Crystal Phase Transformation of NiTi-Layered Double Hydroxides Films for Localized Chemothermal Tumor Therapy.

Adv Sci (Weinh) 2018 Apr 7;5(4):1700782. Epub 2018 Feb 7.

State Key Laboratory of High Performance Ceramics and Superfine Microstructure Shanghai Institute of Ceramics Chinese Academy of Sciences Shanghai 200050 China.

Construction of localized drug-eluting systems with synergistic chemothermal tumor-killing abilities is promising for biomedical implants directly contacting with tumor tissues. In this study, an intelligent and biocompatible drug-loading platform, based on a gold nanorods-modified butyrate-inserted NiTi-layered double hydroxides film ([email protected]/B), is prepared on the surface of nitinol alloy. The prepared films function as drug-loading "sponges," which pump butyrate out under near-infrared (NIR) irradiation and resorb drugs in water when the NIR laser is shut off. The stimuli-responsive release of butyrate is verified to be related with the NIR-triggered crystal phase transformation of [email protected]/B. In vitro and in vivo studies reveal that the prepared films possess excellent biosafety and high efficiency in synergistic thermochemo tumor therapy, showing a promising application in the construction of localized stimuli-responsive drug-delivery systems.
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http://dx.doi.org/10.1002/advs.201700782DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5908485PMC
April 2018

Graphene oxide as a dual Zn/Mg ion carrier and release platform: enhanced osteogenic activity and antibacterial properties.

J Mater Chem B 2018 Apr 21;6(13):2004-2012. Epub 2018 Mar 21.

State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, China.

Implant failure of titanium and its alloys still occurs due to insufficient osseointegration and implant associated infections. Therefore, titanium implants with enhanced osseointegration and antibacterial activities are desirable. To achieve this goal, graphene oxide (GO) as a dual zinc/magnesium (Zn/Mg) ion carrier and release platform was constructed on the titanium surface by cathode electrophoresis deposition. Rat bone mesenchymal stem cells were used to investigate the osteogenic activity. Gram-negative E. coli was utilized to assess the antibacterial activities. Results show that GO co-doped with Mg and Zn ions with a sustained and slow release exhibited the best osteogenic activity among all the samples by stimulating the expressions of osteogenesis related genes containing alkaline phosphatase (ALP), type I collagen (Col-I), osteocalcin (OCN), and osteopontin (OPN), and by promoting the alkaline phosphatase activity and extracellular matrix mineralization. The existence of GO endowed titanium with superior antibacterial activities against Gram-negative E. coli. Due to the synergistic effects of GO, Mg and Zn ions, a titanium surface with enhanced osseointegration and antibacterial activities was achieved.
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http://dx.doi.org/10.1039/c8tb00162fDOI Listing
April 2018

Smart release of doxorubicin loaded on polyetheretherketone (PEEK) surface with 3D porous structure.

Colloids Surf B Biointerfaces 2018 Mar 26;163:175-183. Epub 2017 Dec 26.

State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, PR China. Electronic address:

It is important to fabricate an implant possessing environment sensitive drug delivery. In this work, the construction of 3D porous structure on polyetheretherketone (PEEK) surface and pH sensitive polymer, chitosan, was introduced. The smart release of doxorubicin can be realized on the 3D porous surface of PEEK loading chitosan. We give a feasible explanation for the effect of chitosan on smart drug release according to Henderson-Hasselbalch equation. Furthermore, the intracellular drug content of the cell cultured on the samples with highest chitosan is significantly higher at pH 4.0, whereas lower at pH 7.4 than other samples. The smart release of doxorubicin via modification with chitosan onto 3D porous PEEK surface paves the way for the application of PEEK in drug loading platform for recovering bone defect caused by malignant bone tumor.
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http://dx.doi.org/10.1016/j.colsurfb.2017.12.045DOI Listing
March 2018

Si-doped porous TiO coatings enhanced in vitro angiogenic behavior of human umbilical vein endothelial cells.

Colloids Surf B Biointerfaces 2017 Nov 7;159:493-500. Epub 2017 Aug 7.

State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, PR China. Electronic address:

Recent evidence demonstrates that vessel involvement is crucial in various bone remodeling situations, indicating that blood vessel formation within or surrounding the implant is essential for establishment of rigid implant fixation. In this work, the ability of the silicon-doped porous TiO coatings fabricated via plasma electrolyte oxidation method (PEO) to enhance the angiogenic potential of human umbilical vein endothelial cells (HUVECs) were investigated. The cellular responses of HUVECs on the silicon-doped porous TiO coatings were studied through cell proliferation, vascular endothelial growth factor (VEGF) secretion, and angiogenic-associated gene (VEGF, HIF-1α and HGF) expression analysis. The results show that small amount of silicon significantly enhanced angiogenic activity of HUVECs, while larger amount of silicon appears excessive. Hence, the silicon-doped TiO coating offers a potential solution to improve bone vascularization to achieve efficient osseointegration and restoration of function after implantation.
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http://dx.doi.org/10.1016/j.colsurfb.2017.08.010DOI Listing
November 2017

Sealing the Pores of PEO Coating with Mg-Al Layered Double Hydroxide: Enhanced Corrosion Resistance, Cytocompatibility and Drug Delivery Ability.

Sci Rep 2017 08 15;7(1):8167. Epub 2017 Aug 15.

State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, 200050, China.

In recent years, magnesium (Mg) alloys show a promising application in clinic as degradable biomaterials. Nevertheless, the poor corrosion resistance of Mg alloys is the main obstacle to their clinical application. Here we successfully seal the pores of plasma electrolytic oxidation (PEO) coating on AZ31 with Mg-Al layered double hydroxide (LDH) via hydrothermal treatment. PEO/LDH composite coating possess a two layer structure, an inner layer made up of PEO coating (~5 μm) and an outer layer of Mg-Al LDH (~2 μm). Electrochemical and hydrogen evolution tests suggest preferable corrosion resistance of the PEO/LDH coating. Cytotoxicity, cell adhesion, live/dead staining and proliferation data of rat bone marrow stem cells (rBMSCs) demonstrate that PEO/LDH coating remarkably enhance the cytocompatibility of the substrate, indicating a potential application in orthopedic surgeries. In addition, hemolysis rate (HR) test shows that the HR value of PEO/LDH coating is 1.10 ± 0.47%, fulfilling the request of clinical application. More importantly, the structure of Mg-Al LDH on the top of PEO coating shows excellent drug delivery ability.
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http://dx.doi.org/10.1038/s41598-017-08238-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5557750PMC
August 2017

Layer-Number Dependent Antibacterial and Osteogenic Behaviors of Graphene Oxide Electrophoretic Deposited on Titanium.

ACS Appl Mater Interfaces 2017 Apr 31;9(14):12253-12263. Epub 2017 Mar 31.

State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences , Shanghai 200050, China.

Graphene oxide has attracted widespread attention in the biomedical fields due to its excellent biocompatibility. Herein we investigated the layer-number dependent antibacterial and osteogenic behaviors of graphene oxide in biointerfaces. Graphene oxide with different layer numbers was deposited on the titanium surfaces by cathodal electrophoretic deposition with varied deposition voltages. The initial cell adhesion and spreading, cell proliferation, and osteogenic differentiation were observed from all the samples using rat bone mesenchymal stem cells. Both Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus were used to investigate the antibacterial effect of the modified titanium surfaces. Cocultures of human gingival fibroblasts (HGF) cells with Escherichia coli and Staphylococcus aureus were conducted to simulate the conditions of the clinical practice. The results show that the titanium surfaces with graphene oxide exhibited excellent antibacterial and osteogenic effects. Increasing the layer-number of graphene oxide resulted in the augment of reactive oxygen species levels and the wrinkling, which led to the antibacterial and osteogenic effects, respectively. Compared to pure titanium surface in the cells-bacteria coculture process, the modified titanium surfaces with graphene oxide exhibited higher surface coverage percentage of cells.
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http://dx.doi.org/10.1021/acsami.7b00314DOI Listing
April 2017

Mn-containing titanium surface with favorable osteogenic and antimicrobial functions synthesized by PIII&D.

Colloids Surf B Biointerfaces 2017 Apr 26;152:376-384. Epub 2017 Jan 26.

State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, China. Electronic address:

Reasonable incorporation of manganese into titanium is believed to be able to enhance the osteogenic and antibacterial activities of orthopedic implants. However, it is still a challenge to compromise Mn-induced cytotoxicity and better develop its biocompatibility and antimicrobial ability. To pinpoint this issue, a stable Mn ion release platform was created on Ti using plasma immersion ion implantation and deposition (PIII&D) technique. Compared with as-etched titanium, as a result, promoted antibacterial abilities against gram-negative bacteria species and enhanced osteogenic-related gene expressions on rBMMSC were observed on Mn-containing sample. Meanwhile, the Mn-containing samples showed no obvious cytotoxicity. Our results here provide insight to be better understanding the relationships between additives-induced biological performance and the dose, state, and stability of the doped element.
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http://dx.doi.org/10.1016/j.colsurfb.2017.01.047DOI Listing
April 2017

Dual ions implantation of zirconium and nitrogen into magnesium alloys for enhanced corrosion resistance, antimicrobial activity and biocompatibility.

Colloids Surf B Biointerfaces 2016 Dec 31;148:200-210. Epub 2016 Aug 31.

State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, China. Electronic address:

Biodegradable magnesium-based alloys have shown great potential for medical applications due to their superior biological performances and mechanical properties. However, on one hand, some side effects including inferior biocompatibility, a local high-alkaline environment and gas cavities caused by a rapid corrosion rate, hinder their clinical application. On the other hand, it is also necessary to endow Mg alloys with antibacterial properties, which are crucial for clinic orthopedic applications. In this study, Zr and N ions are simultaneously implanted into AZ91 Mg alloys by plasma immersion ion implantation (PIII). A modified layer with a thickness of approximately 80nm is formed on the surface of AZ91 Mg alloys, and the hydrophobicity and roughness of these AZ91 Mg alloys obviously increase after Zr and N implantation. The in vitro evaluations including corrosion resistance tests, antimicrobial tests and cytocompatibility and alkaline phosphatase (ALP) activity tests, revealed that the dual ions implantation of Zr and N not only enhanced the corrosion resistance of the AZ91 Mg alloy but also provided better antimicrobial properties in vitro. Furthermore, the formation of biocompatible metal nitrides and metal oxides layer in the near surface of the Zr-N-implanted AZ91 Mg alloy provided a favorable implantation surface for cell adhesion and growth, which in return further promoted the bone formation in vivo. These promising results suggest that the Zr-N-implanted AZ91 Mg alloy shows potential for future application in the orthopedic field.
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http://dx.doi.org/10.1016/j.colsurfb.2016.08.056DOI Listing
December 2016

Poly(styrenesulfonate)-Modified Ni-Ti Layered Double Hydroxide Film: A Smart Drug-Eluting Platform.

ACS Appl Mater Interfaces 2016 Sep 12;8(37):24491-501. Epub 2016 Sep 12.

State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences , Shanghai 200050, China.

Drug-eluting stents (DESs) are widely used in the palliative treatment of many kinds of cancers. However, the covered polymers used in DESs are usually associated with stent migration and acute cholecystitis. Therefore, developing noncovered drug-loading layers on metal stents is of great importance. In this work, Ni-Ti layered double hydroxide (Ni-Ti LDH) films were prepared on the surface of nitinol via hydrothermal treatment, and the LDH films were further modified by poly(styrenesulfonate) (PSS). The anticancer drug doxorubicin could be effectively loaded onto the modified films, and drug release could be smartly controlled by the pH. Besides, the drug absorption amounts of cancer cells cultured on the films could be effectively improved. These results indicate that the PSS-modified LDH film may become a promising drug-loading platform that can be used in the design of DESs.
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http://dx.doi.org/10.1021/acsami.6b09697DOI Listing
September 2016

Tantalum implanted entangled porous titanium promotes surface osseointegration and bone ingrowth.

Sci Rep 2016 05 17;6:26248. Epub 2016 May 17.

State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, China.

Porous Ti is considered to be an ideal graft material in orthopaedic and dental surgeries due to its similar spatial structures and mechanical properties to cancellous bone. In this work, to overcome the bioinertia of Ti, Ta-implanted entangled porous titanium (EPT) was constructed by plasma immersion ion implantation &deposition (PIII&D) method. Ca-implanted and unimplanted EPTs were investigated as control groups. Although no difference was found in surface topography and mechanical performances, both Ca- and Ta-implanted groups had better effects in promoting MG-63 cell viability, proliferation, differentiation, and mineralization than those of unimplanted group. The expression of osteogenic-related markers examined by qRT-PCR and western blotting was upregulated in Ca- and Ta-implanted groups. Moreover, Ta-implanted EPT group could reach a higher level of these effects than that of Ca-implanted group. Enhanced osseointegration of both Ca- and Ta-implanted EPT implants was demonstrated through in vivo experiments, including micro-CT evaluation, push-out test, sequential fluorescent labeling and histological observation. However, the Ta-implanted group possessed more stable and continuous osteogenic activity. Our results suggest that Ta-implanted EPT can be developed as one of the highly efficient graft material for bone reconstruction situations.
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http://dx.doi.org/10.1038/srep26248DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4869100PMC
May 2016

Antibacterial activity, osteogenic and angiogenic behaviors of copper-bearing titanium synthesized by PIII&D.

J Mater Chem B 2016 Feb 25;4(7):1296-1309. Epub 2016 Jan 25.

State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, China.

Cu-bearing biomaterials have drawn considerable interest in hard tissue replacement. However, a better compromise between the biocompatibility and cytotoxicity of incorporated copper is still required. In this work, two types of Cu-bearing surfaces were obtained on Ti by altering the processing parameters during PIII&D. One with a certain amount of copper in metallic form on the Ti surface shows enhanced antibacterial ability, osteogenic and angiogenic capabilities, whereas unfavorable biocompatibility is observed from the other Ti surface in the presence of Cu-bearing nanoparticles. Disparate biological differences between two types of Cu-bearing Ti surfaces synthesized by the same single technique provides insights for better understanding of the underlying mechanism between the positive and negative bioeffects of Cu-bearing biomaterials.
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http://dx.doi.org/10.1039/c5tb02300aDOI Listing
February 2016

A strontium-incorporated nanoporous titanium implant surface for rapid osseointegration.

Nanoscale 2016 Mar;8(9):5291-301

Department of Prosthodontics, Oral Bioengineering and Regenerative Medicine Lab, Ninth People's Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, 639 Zhizaoju Road, Shanghai 200011, China.

Rapid osseointegration of dental implants will shorten the period of treatment and enhance the comfort of patients. Due to the vital role of angiogenesis played during bone development and regeneration, it might be feasible to promote rapid osseointegration by modifying the implant surface to gain a combined angiogenesis/osteogenesis inducing capacity. In this study, a novel coating (MAO-Sr) with strontium-incorporated nanoporous structures on titanium implants was generated via a new micro-arc oxidation, in an attempt to induce angiogenesis and osteogenesis to enhance rapid osseointegration. In vitro, the nanoporous structure significantly enhanced the initial adhesion of canine BMSCs. More importantly, sustained release of strontium ions also displayed a stronger effect on the BMSCs in facilitating their osteogenic differentiation and promoting the angiogenic growth factor secretion to recruit endothelial cells and promote blood vessel formation. Advanced mechanism analyses indicated that MAPK/Erk and PI3K/Akt signaling pathways were involved in these effects of the MAO-Sr coating. Finally, in the canine dental implantation study, the MAO-Sr coating induced faster bone formation within the initial six weeks and the osseointegration effect was comparable to that of the commercially available ITI implants. These results suggest that the MAO-Sr coating has the potential for future use in dental implants.
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http://dx.doi.org/10.1039/c5nr08580bDOI Listing
March 2016

Enhanced Osseointegration of Hierarchical Micro/Nanotopographic Titanium Fabricated by Microarc Oxidation and Electrochemical Treatment.

ACS Appl Mater Interfaces 2016 Feb 3;8(6):3840-52. Epub 2016 Feb 3.

Department of Prosthodontics, Oral Bioengineering, and Regenerative Medicine Lab, Ninth People's Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine , 639 Zhizaoju Road, Shanghai 200011, China.

Rapid osseointegration is recognized as a critical factor in determining the success rate of orthopedic and dental implants. Microarc oxidation (MAO) fabricated titanium oxide coatings with a porous topography have been proven to be a potent approach to enhance osteogenic capacity. Now we report two kinds of new hierarchical coatings with similar micromorphologies but different nanotopographies (i.e., MAO and MAO-AK coatings), and both coatings significantly promote cell attachment and osteogenic differentiation through mediating the integrin β1 signaling pathway. In this study, titanium with a unique hierarchical micro/nanomorphology surface was fabricated by a novel duplex coating process, that is, the first a titanium oxide layer was coated by MAO, and then the coating was electrochemically reduced in alkaline solution (MAO-AK). A series of in vitro stem cell differentiation and in vivo osseointegration experiments were carried out to evaluate the osteogenic capacity of the resulting coatings. In vitro, the initial adhesion of the canine bone marrow stem cells (BMSCs) seeded on the MAO and MAO-AK coatings was significantly enhanced, and cell proliferation was promoted. In addition, the expression levels of osteogenesis-related genes, osteorix, alkaline phosphates (ALP), osteopontin, and osteocalcin, in the canine BMSCs, were all up-regulated after incubation on these coatings, especially on the MAO-AK coating. Also, the in vitro ALP activity and mineralization capacity of canine BMSC cultured on the MAO-AK group was better than that on the MAO group. Furthermore, 6 weeks after insertion of the titanium implants into canine femurs, both the bone formation speed and the bone-implant contact ratio of the MAO-AK group were significantly higher than those of the MAO group. All these results suggest that this duplex coating process is promising for engineering titanium surfaces to promote osseointegration for dental and orthopedic applications.
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http://dx.doi.org/10.1021/acsami.5b10633DOI Listing
February 2016

Influence of sulfur content on bone formation and antibacterial ability of sulfonated PEEK.

Biomaterials 2016 Mar 6;83:115-26. Epub 2016 Jan 6.

State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, 200050, China. Electronic address:

Polyetheretherketone (PEEK) is desirable in orthopedic and dental applications because its mechanical properties are similar to those of natural bones but the bioinertness and inferior osteoconduction of PEEK have hampered many clinical applications. In this work, PEEK is sulfonated by concentrated sulfuric acid to fabricate a three-dimensional (3D) network. A hydrothermal treatment is subsequently conducted to remove the residues and the temperature is adjusted to obtain different sulfur concentrations. In vitro cell proliferation and real-time PCR analyses disclose enhanced proliferation and osteogenic differentiation of rat bone mesenchymal stem cells (rBMSCs) on the samples with small sulfur concentrations. The in vitro antibacterial evaluation reveals that all the sulfonated samples possess excellent resistance against Staphylococcus aureus and Escherichia coli. The in vivo rat femur implantation model is adopted and X-ray, micro-CT, and histological analyses indicate that not only the premeditated injected bacteria cells are sterilized, but also new bone forms around the samples with small sulfur concentrations. The in vitro and in vivo results reveal that the samples subjected to the hydrothermal treatment to remove excess sulfur have better osseointegration and antibacterial ability and PEEK modified by sulfonation and hydrothermal treatment is promising in orthopedic and dental applications.
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http://dx.doi.org/10.1016/j.biomaterials.2016.01.017DOI Listing
March 2016

Zn/Ag micro-galvanic couples formed on titanium and osseointegration effects in the presence of S. aureus.

Biomaterials 2015 Oct 23;65:22-31. Epub 2015 Jun 23.

Department of Physics and Materials Science, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong, China.

Titanium implants possessing simultaneous osseointegration and antibacterial ability are desirable. In this work, three types of Zn/Ag micro-galvanic couples are fabricated on titanium by plasma immersion ion implantation to investigate the osseointegration and antibacterial effects as well as the involved mechanisms. The in vitro findings disclose enhanced proliferation, osteogenic differentiation, and gene expressions of the rat bone mesenchymal stem cells (rBMSCs), as well as good antibacterial ability on all three micro-galvanic couples. Excellent antimicrobial ability is also observed in vivo and the micro-CT and histological results reveal notable osseointegration in vivo despite the presence of bacteria. The Zn/Ag micro-galvanic couple formed on Zn/Ag dual-ion co-implanted titanium shows the best osseointegration as well as good antibacterial properties in vivo obtained from a rabbit tibia model. The difference among the three Zn/Ag micro-galvanic couples can be ascribed to the contact between the Ag NPs and Zn film, which affects the corrosion process. Our results indicate that the biological behavior can be controlled by the corrosion process of the Zn/Ag micro-galvanic couples.
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http://dx.doi.org/10.1016/j.biomaterials.2015.06.040DOI Listing
October 2015
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