Publications by authors named "Liping Ouyang"

14 Publications

  • Page 1 of 1

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

Strontium ranelate incorporated 3D porous sulfonated PEEK simulating MC3T3-E1 cell differentiation.

Regen Biomater 2021 Feb 28;8(1):rbaa043. Epub 2020 Nov 28.

Department of Pharmacy, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China.

Polyetheretherketone (PEEK) has been used as an implant material because it has similar mechanical properties to natural bone. However, inferior osseointegration and bioinertness hamper the clinical application of PEEK. In this study, the surfaces of sulfonated three-dimensional (3D) PEEK porous structures were loaded with different concentrations of strontium ranelate, a compound commonly used in the treatment or prevention of osteoporosis by promoting bone formation and inhibiting bone resorption. Field-emission scanning electron microscopy was used to characterize the topography of the structures, elemental carbon, oxygen and strontium contents were measured by X-ray photoelectron spectroscopy, and surface zeta potentials and water-contact angle were also measured. The results indicated that strontium ranelate was successfully loaded onto the 3D porous structures. cellular results showed that strontium ranelate-treated sulfonated PEEK (SP-SR) strengthened the adhesion of MC3T3-E1 cells. The activity of alkaline phosphatase, collagen secretion and extracellular matrix mineralization deposition of MC3T3-E1 cells were also improved on the surface of SP-SR. These results indicate that SP-SR could serve a new implant candidate for surgical treatment.
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http://dx.doi.org/10.1093/rb/rbaa043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947580PMC
February 2021

Sodium butyrate-modified sulfonated polyetheretherketone modulates macrophage behavior and shows enhanced antibacterial and osteogenic functions during implant-associated infections.

J Mater Chem B 2019 09;7(36):5541-5553

Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.

Prevention of implant-associated infections and insufficient bone tissue integration is critical to exploit the immunomodulatory properties and antibacterial effects of implant materials, which have attracted considerable attention. Modulation of the functions of immune cells in different environments is crucial for managing infection and inferior bone integration via immunomodulation. In this work, sodium butyrate, a fermentation product of gut microbiota, was loaded onto 3D porous sulfonated polyetheretherketone (SP) to modulate the immune responses of cells in different environments. Evaluation of in vitro antibacterial effects showed that sodium butyrate-loaded SP exhibited superior antibacterial activity, especially in the samples containing high concentrations of sodium butyrate. Under bacterial stimulation, the phagocytic activity of macrophages increased with an increase in the sodium butyrate concentration via the production of reactive oxygen species (ROS), which favoured bactericidal activity in the implant-associated infection stage. For bacterial elimination, sodium butyrate-containing SP could polarize macrophages to the M2 phenotype and subsequently stimulate anti-inflammatory cytokine secretion, which is considered beneficial for bone regeneration in the tissue repair stage. In vitro osteogenesis was evaluated and the results demonstrated that treatment with sodium butyrate-containing SP increased the expression of osteogenic genes and proteins. An in vivo rat osteomyelitis model was used to evaluate the protective effect of the SP-loaded with sodium butyrate on bone destruction and osteolysis under infection conditions. To study osteogenesis in vivo, a rat femoral model without infection was used. The results indicated that the SP-B2 group exhibited superior anti-infection capacity and induced new bone formation around the implant in vivo. Treatment with sodium butyrate-containing porous SP modulated the macrophage response under different stimuli, thereby serving as a new approach for the design of smart implant materials with superior antibacterial and bone repair properties.
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http://dx.doi.org/10.1039/c9tb01298bDOI 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

Nano Textured PEEK Surface for Enhanced Osseointegration.

ACS Biomater Sci Eng 2019 Mar 12;5(3):1279-1289. Epub 2019 Feb 12.

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

Polyetheretherketone (PEEK) is widely used in orthopedic and dental applications because of its similar mechanical properties to those of natural bones. However, the inferior osseointegration and bioinertness hamper the clinic application. The surface texture of biomaterials plays an essential role in controlling cell differentiation through affecting the cell-generated physical forces, thus improving the osseointegration of the substrate. In this work, argon PIII and subsequently hydrogen peroxide treatment are applied to construct the nanostructure on the PEEK surface. The in vitro results show that the cell adhesion, collagen secretion, and extracellular matrix (ECM) deposition can be enhanced on both nanostructured surfaces. The in vivo tests exhibit that the surface fabricated by physical-chemical treatment is more favorable for fibrous tissue filtration inhibition and osseointegration than that fabricated by argon PIII only. This work provides a candidate approach for improving the osseointegration ability of PEEK implant by constructing the nanostructure on its surface, which paves the way of applying PEEK in orthopedic and dental applications.
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http://dx.doi.org/10.1021/acsbiomaterials.8b01425DOI Listing
March 2019

Pravastatin regulates host foreign-body reaction to polyetheretherketone implants via miR-29ab1-mediated SLIT3 upregulation.

Biomaterials 2019 05 1;203:12-22. Epub 2019 Mar 1.

Department of Pharmacy, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China. Electronic address:

Host rejection to biomaterials can induce uncontrolled foreign-body reactions (FBR), resulting in a dense fibrous encapsulation that blocks mass transport and/or communication between the host and the implant. Adequate angiogenesis between the body and the implant has been implicated as a key regulator for overcoming FBR. Thus, approaches for stimulating neovascularization and/or suppressing FBR are under investigation. In this study, pravastatin (Pra) was loaded onto a 3D network surface of sulfonated polyetheretherketone (SP) to achieve superior local drug effects. The SP loaded with Pra (SP-Pra) promoted angiogenesis and mitigated FBR via miR-29 dependent SLIT3 upregulation in wild-type (WT) mice. miR-29a and miR-29b1 were significantly downregulated in the SP-Pra capsule compared to levels in the SP capsule, while SLIT3 and neovascularization were substantially upregulated in WT mice. However, the above effects presented in the WT mice were not detected in miR-29ab1 knockout mice which was generated by the CRISPR/Cas9 approach. Overall, the results suggest that miR-29 plays a critical role in reducing FBR to these implants by targeting SLIT3. Suppression of FBR by SP-Pra implants offers the potential to improve the performance of current medical devices.
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http://dx.doi.org/10.1016/j.biomaterials.2019.02.027DOI Listing
May 2019

Multifunctional sulfonated polyetheretherketone coating with beta-defensin-14 for yielding durable and broad-spectrum antibacterial activity and osseointegration.

Acta Biomater 2019 03 11;86:323-337. Epub 2019 Jan 11.

Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China. Electronic address:

To address periprosthetic joint infection (PJI), a formidable complication after joint arthroplasty, an implant with excellent osseointegration and effective antibacterial activity has being extensively pursued and developed. In this work, the mouse beta-defensin-14 (MBD-14) was immobilized on the polyetheretherketone (PEEK) surface with three-dimensional (3D) porous structure to improve its antibacterial activity and osseointegration. An in vitro antibacterial evaluation showed that the porous PEEK loaded with MBD-14 wages a durable and effective fight against both Staphylococcus aureus (gram-positive) and Pseudomonas aeruginosa (gram-negative). In addition to the superior antibacterial activity, we found that the enhanced proliferation and osteogenic differentiation of bone mesenchymal stem cells were verified through various in vitro analyses. To evaluate the in vivo bactericidal effect and osseointegration of the samples, the rat femoral models with infection and non-infection were established. The enhanced osseointegration of the MBD-14-loaded samples was found in both two in vivo models. And no bacteria survived on the surfaces of samples with a relatively high MBD-14 concentration. Above results indicate that the 3D porous PEEK coating loaded with MBD-14 simultaneously yields excellent osseointegration while exerting durable and broad-spectrum antibacterial activity. And it paves the way for PEEK to be applied clinically to address PJI. STATEMENT OF SIGNIFICANCE: (1). By using the physio-chemical technique including sulfonation and lyophilization etc., a three-dimensional porous network is developed on polyetheretherketone (PEEK) surface, in which mouse beta-defensin-14 (MBD-14, a broad-spectrum antimicrobial peptide) is then loaded. It endows PEEK with antibacterial activity and osseointegration. (2). Two in vivo animal models with infection and non-infection are used to prove the new bone formation around the samples. (3). Supplementary material also proves that MBD-14 promotes the osteogenic differentiation of BMSCs. However, its potential mechanism needs to be further studied in future. (4). The modified PEEK, including excellent osseointegration and a durable and broad-spectrum antibacterial activity, could be applied clinically to address PJI which is a hot potato for surgeons and patients undergoing total joint arthroplasty.
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http://dx.doi.org/10.1016/j.actbio.2019.01.016DOI Listing
March 2019

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

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

Enhanced Bioactivity and Bacteriostasis of Surface Fluorinated Polyetheretherketone.

ACS Appl Mater Interfaces 2017 May 11;9(20):16824-16833. Epub 2017 May 11.

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

Although polyetheretherketone (PEEK) has been considered as a potential orthopedic and dental application material due to its similar elastic modulus as bones, inferior osseointegration and bacteriostasis of PEEK hampers its clinical application. In this work, fluorinated PEEK was constructed via plasma immersion ion implantation (PIII) followed by hydrofluoric acid treatment to ameliorate the osseointegration and antibacterial properties of PEEK. The surface microstructure, composition, and hydrophilicity of all samples were investigated. Rat bone mesenchymal stem cells (rBMSCs) were cultured on their surfaces to estimate bioactivity. The fluorinated PEEK can enhance the cell adhesion, cell spreading, proliferation, and alkaline phosphatase (ALP) activity compared to pristine PEEK. Furthermore, the fluorinated PEEK surface exhibits good bacteriostatic effect against Porphyromonas gingivalis, which is one of the major periodontal pathogens. In summary, we provide an effective route to introduce fluorine and the results reveal that the fluorinated PEEK can enhance the osseointegration and bacteriostasis, which provides a potential candidate for dental implants.
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http://dx.doi.org/10.1021/acsami.7b02521DOI Listing
May 2017

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

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

Passive immunotherapy for influenza A H5N1 virus infection with equine hyperimmune globulin F(ab')2 in mice.

Respir Res 2006 Mar 23;7:43. Epub 2006 Mar 23.

Sun Yat-sen University, Guangzhou 510080, China.

Background: Avian influenza virus H5N1 has demonstrated considerable pandemic potential. Currently, no effective vaccines for H5N1 infection are available, so passive immunotherapy may be an alternative strategy. To investigate the possible therapeutic effect of antibody against highly pathogenic H5N1 virus on a mammal host, we prepared specific equine anti-H5N1 IgGs from horses vaccinated with inactivated H5N1 virus, and then obtained the F(ab')2 fragments by pepsin digestion of IgGs.

Methods: The horses were vaccinated with inactivated H5N1 vaccine to prepare anti-H5N1 IgGs. The F(ab')2 fragments were purified from anti-H5N1 hyperimmune sera by a protocol for 'enhanced pepsin digestion'. The protective effect of the F(ab')2 fragments against H5N1 virus infection was determined in cultured MDCK cells by cytopathic effect (CPE) assay and in a BALB/c mouse model by survival rate assay.

Results: By the protocol for 'enhanced pepsin digestion', total 16 g F(ab')2 fragments were finally obtained from one liter equine antisera with the purity of over 90%. The H5N1-specific F(ab')2 fragments had a HI titer of 1:1024, and the neutralization titre of F(ab')2 reached 1: 2048. The in vivo assay showed that 100 microg of the F(ab')2 fragments could protect BALB/c mice infected with a lethal dose of influenza H5N1 virus.

Conclusion: The availability of highly purified H5N1-specific F(ab')2 fragments may be promising for treatment of influenza H5N1 infection. Our work has provided experimental support for the application of the therapeutic equine immunoglobulin in future large primate or human trials.
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http://dx.doi.org/10.1186/1465-9921-7-43DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1459145PMC
March 2006
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