Publications by authors named "Tingfei Xi"

56 Publications

Effect of extrusion process on the mechanical and in vitro degradation performance of a biomedical Mg-Zn-Y-Nd alloy.

Bioact Mater 2020 Jun 21;5(2):219-227. Epub 2020 Feb 21.

Shenzhen Institute, Peking University, Shenzhen, 518057, China.

A new type of biomedical Mg-Zn-Y-Nd alloy was developed and thermal extruded by different processes to investigate the effect of extrusion ratio and extrusion pass on its microstructure, mechanical property and degradation performance. The results show that the increase of extrusion ratio could promote the dynamic recrystallization (DRX) process and led to the coarsening of DRXed grains. While the increase of extrusion pass also contributes to the DRX process but refines the DRXed grains. The simultaneous increasing of extrusion ratio and extrusion pass refines the secondary phases obviously. The increase of extrusion ratio has reduced the tensile strength but improved the elongation of the alloy significantly. However, the increase of extrusion pass could enhance the tensile strength and elongation simultaneously, especially the strength. The degradation performance has been optimized effectively through increasing the extrusion ratio and extrusion pass.
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http://dx.doi.org/10.1016/j.bioactmat.2020.02.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7036737PMC
June 2020

A tannic acid-modified fluoride pre-treated Mg-Zn-Y-Nd alloy with antioxidant and platelet-repellent functionalities for vascular stent application.

J Mater Chem B 2019 12 1;7(46):7314-7325. Epub 2019 Nov 1.

Academy for Advanced Interdisciplinary Studies, Peking University, No. 5, Yiheyuan Road HaiDian District, Beijing 100871, China.

Vascular stent interventional therapy, as a regular and effective therapy, has been widely used to treat coronary artery diseases. However, adverse events occur frequently after stent intervention, especially restenosis and late stent thrombosis. The targeted implanting site will suffer from severe atherosclerosis, which is considered as a chronic inflammatory disease. Meanwhile, with the over-expanding use of endovascular mechanical intervention, vascular injury has become an increasingly common issue. Lesions and newly induced vascular injury result in inflammatory and oxidative stress; meanwhile, activated macrophages and granulocytes generate high levels of reactive oxygen species (ROS), contributing to endothelial dysfunction and neointima hyperplasia. Therefore, attenuating oxidative stress and reducing ROS generation in the inflammatory response represent reasonable strategies to inhibit intimal hyperplasia and restenosis. Herein, we have developed a multifunctional surface for the MgZnYNd alloy with tannic acid (TA) coating, and the pH dependence of the coating deposition is also demonstrated. The phenolic hydroxyl groups on the coatings endow the modified surface with excellent antioxidant functions. We found that the coating can be recycled, and the scavenging activity hardly weakened within five cycles. Also, the TA coating has a promising strong antioxidant activity as it shows a radical scavenging activity over 80% in long term. Moreover, the TA coating possesses platelet-repellent capability. No significant inflammatory response was observed for the TA modified sample in the rat subcutaneous implantation test. Combining these performances, we envision that the vascular stent modified with TA coating can have great potential in various applications by virtue of its simplicity and effectiveness.
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http://dx.doi.org/10.1039/c9tb01587fDOI Listing
December 2019

In Vitro and in Vivo Studies on Two-Step Alkali-Fluoride-Treated Mg-Zn-Y-Nd Alloy for Vascular Stent Application: Enhancement in Corrosion Resistance and Biocompatibility.

ACS Biomater Sci Eng 2019 Jul 20;5(7):3279-3292. Epub 2019 Jun 20.

Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China.

Bioabsorbable magnesium alloys are becoming prominent materials for cardiovascular stents, as their desirable mechanical properties and favorable biosafety. However, the rapid corrosion of magnesium alloys under physiological conditions hinders their wider application as medical implant materials. Fluoride chemical conversion treatment is an effective and simple technique to improve the corrosion resistance for magnesium alloys. Despite previous literature reporting on fluoride chemical conversion treatment with hydrofluoric acid (HF) in different conditions, some defects are still present on the surface of the coating. In this study, we report on a two-step alkali-fluoride treatment of magnesium alloy by effectively removing the second phase in the substrate surface and form a dense and flawless magnesium fluoride (MgF) coating to endow the magnesium alloy greater corrosion resistance. The results showed that the serious pitting corrosion caused by galvanic corrosion could be effectively prevented after removing of the second phase of the surface. In vivo tests in a rat subcutaneous implantation model showed that two-step alkali-fluoride-treated MgZnYNd alloy (MgZnYNd-A-F) uniformly corroded with a low corrosion rate. No subcutaneous gas cavities or significant inflammatory cell infiltration were observed for MgZnYNd-A-F in in vivo tests. The two-step alkali-fluoride treatment can significantly improve the corrosion resistance and biocompatibility of magnesium alloy, which has great potential in the application of vascular stents because of its simplicity and effectiveness.
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http://dx.doi.org/10.1021/acsbiomaterials.9b00140DOI Listing
July 2019

An electrospun fiber reinforced scaffold promotes total meniscus regeneration in rabbit meniscectomy model.

Acta Biomater 2018 06 11;73:127-140. Epub 2018 Apr 11.

Institute of Orthopedics, Beijing Key Lab of Regenerative Medicine in Orthopedics, Key Lab of Musculoskeletal Trauma & War Injuries in PLA, Chinese PLA General Hospital, Beijing 100853, China. Electronic address:

Low vascularization in meniscus limits its regeneration ability after injury, and tissue engineering is the most promising method to achieve meniscus regeneration. In this study, we fabricated a kind of composite scaffold by decellularized meniscus extracellular matrix/polycaprolactone (DMECM/PCL) electrospinning fibers and porous DMECM, in which DMECM/PCL fibers were used as reinforcing component. The tensile modulus of the composite scaffold in longitudinal and crosswise directions were 8.5 ± 1.9 and 2.3 ± 0.3 MPa, respectively. Besides that, the DMECM/PCL electrospinning fibers enhanced suture resistance of the composite scaffold more than 5 times than DMECM scaffold effectively. In vitro cytocompatibility showed that the porous structure provided by DMECM component facilitated meniscus cells' proliferation. DMECM was also the main component to regulate cell behaviors, which promoted meniscus cells expressing extracellular matrix related genes such as COL I, COL II, SOX9 and AGG. Rabbits with total meniscectomy were used as animal model to evaluated the composited scaffolds performance in vivo at 3 and 6 months. Results showed that rabbits with scaffold implanting could regenerate neo-menisci in both time points. The neo-menisci had similar histology structure and biochemical content with native menisci. Although neo-menisci had inferior tensile modulus than native ones, its modulus was improved with implanting time prolonging. MRI imaging showed the signal of neo-meniscus in the body is clear, and X-ray imaging of knee joints demonstrated the implantation of scaffolds could relief joint space narrowing. Moreover, rabbits with neo-menisci had better cartilage condition in femoral condyle and tibial plateau compared than meniscectomy group.

Statement Of Significance: We fabricated the meniscus scaffold by combining porous decellularized meniscus extracellular matrix (DMECM) and DMECM/PCL electrospinning fibers together, which used the porous structure of DMECM, and the good tensile property of electrospinning fibers. We believe single material cannot satisfy increasing needs of scaffold. Therefore, we combined not only materials but also fabrication methods together to develop scaffold to make good use of each part. DMECM in electrospinning fibers also made these two components possible to be integrated through crosslinking. Compared to existing meniscus scaffold, the composite scaffold had (1) soft structure and extrusion would not happen after implantation, (2) ability to be trimmed to suitable shape during surgery, and (3) good resistance to suture.
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http://dx.doi.org/10.1016/j.actbio.2018.04.012DOI Listing
June 2018

A silk-based coating containing GREDVY peptide and heparin on Mg-Zn-Y-Nd alloy: improved corrosion resistance, hemocompatibility and endothelialization.

J Mater Chem B 2018 Feb 26;6(6):966-978. Epub 2018 Jan 26.

Academy for Advanced Interdisciplinary Studies, Peking University, Yi He Yuan Road No. 5, HaiDian District, Beijing 100871, China.

Magnesium (Mg) alloys have been intensively investigated as potential absorbable coronary stent materials as their use avoids risks such as late inflammation and restenosis generated by permanent metallic implants. Besides that, clinical trials on coronary stents fabricated from Mg alloys have made great progress recently. However, the over-rapid corrosion rate, magnesium corrosion-induced thrombosis formation and delayed endothelium regeneration continue to be problematic for coronary artery stent therapy. In this study, silk fibroin blended with heparin and GREDVY (Gly-Arg-Glu-Asp-Val-Tyr) peptide was immobilized on a HF-pretreated MgZnYNd alloy surface via a polydopamine layer to improve its corrosion resistance, blood compatibility and endothelialization. Standard electrochemical measurements along with the long-term immersion results indicated that the functionalized MgZnYNd alloy had preferable anti-corrosion abilities compared with the bare MgZnYNd alloy. The modified surface exhibited outstanding hemocompatibility with reduced platelet adhesion, hemolysis rate and prolonged blood coagulation time. Human umbilical vein endothelial cell (HUVEC) and vascular smooth muscle cell (VSMC) co-culture results revealed more attached HUVECs on the functionalized samples than on the MgZnYNd alloy surfaces. The excellent corrosion retardation, hemocompatibility and re-endothelialization of the multi-functional coating indicate a promising method in the field of biodegradable magnesium-based implantable cardiovascular stents.
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http://dx.doi.org/10.1039/c7tb02784bDOI Listing
February 2018

A high-throughput study on endothelial cell adhesion and growth mediated by adsorbed serum protein signaling pathway PCR array.

Regen Biomater 2018 Feb 13;5(1):25-34. Epub 2017 Dec 13.

R&D Center of Lifetech Scientific (Shenzhen) Co., Ltd, Shenzhen 518057, P.R. China.

The purpose of this paper is to utilize the signaling pathway polymerase chain reaction (PCR) arrays to investigate the activation of two important biological signaling pathways in endothelial cell adhesion and growth mediated by adsorbed serum protein on the surface of bare and titanium nitride (TiN)-coated nickel titanium (NiTi) alloys. First, the endothelial cells were cultured on the bare and TiN-coated NiTi alloys and chitosan films as control for 4 h and 24 h, respectively. Then, the total RNA of the cells was collected and the PCR arrays were performed. After that, the differentially expressed genes in the transforming growth factor beta (TGF-β) signaling pathway and the regulation of actin cytoskeleton pathway were screened out; and the further bioinformatics analyses were performed. The results showed that both TGF-β signaling pathway and regulation of actin cytoskeleton pathway were activated in the cells after 4 h and 24 h culturing on the surface of bare and TiN-coated NiTi alloys compared to the chitosan group. The activated TGF-β signaling pathway promoted cell adhesion; the activated regulation of actin cytoskeleton pathway promoted cell adhesion, spreading, growth and motility. In addition, the activation of both pathways was much stronger in the cells cultured for 24 h versus 4 h, which indicated that cell adhesion and growth became more favorable with longer time on the surface of two NiTi alloy materials.
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http://dx.doi.org/10.1093/rb/rbx030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5798144PMC
February 2018

The application of electrospinning used in meniscus tissue engineering.

J Biomater Sci Polym Ed 2018 04 17;29(5):461-475. Epub 2018 Jan 17.

b Academy for Advanced Interdisciplinary Studies , Peking University , Beijing , People's Republic of China.

Meniscus is a fibrocartilaginous organ to redistribute stress and enhance the stability of knee joint. Meniscus injury is common and still a formidable challenge to orthopedic surgeons. Surgical techniques and allograft transplantation were primary approaches to meniscus repair, but with intrinsic limitations in clinical practice. Tissue engineering is the most promising method to repair meniscus at present. Electrospinning is a method to fabricate fibers in small scale. With different materials and parameters, electrospinning materials could have different mechanical properties, porosity, and orientation, which could mimic architectural features and mechanical properties of native meniscus. Therefore, electrospinning materials could be used in meniscus regeneration and curing. This review gave a brief introduction of meniscus structure, injury, treatment and the application of electrospinning fibers in meniscus tissue engineering and curing. Besides that, we summarized materials commonly used in electrospinning to fabricate meniscus scaffolds, and discussed the form of electrospinning fibers used such as scaffold, substitute and patch. Finally, the function of electrospinning fibers, for example, carrying drugs, providing mechanical properties were described. The potential applications of electrospinning fibers in meniscus therapy were proposed.
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http://dx.doi.org/10.1080/09205063.2018.1425180DOI Listing
April 2018

Arginine-leucine based poly (ester urea urethane) coating for Mg-Zn-Y-Nd alloy in cardiovascular stent applications.

Colloids Surf B Biointerfaces 2017 Nov 29;159:78-88. Epub 2017 Jul 29.

Center for Biomedical Materials and Tissue Engineering, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China; Shenzhen Research Institute, Peking University, Shenzhen 518055, China. Electronic address:

Selected from the family of self-designed biodegradable amino acid-based poly (ester urea urethane) (AA-PEUU) pseudo-protein biomaterials, arginine-leucine based poly (ester urea urethane)s (Arg-Leu-PEUUs) were used as protective and bio-functional coatings for bio-absorbable magnesium alloy MgZnYNd in cardiovascular stent applications. Comparing with poly (glycolide-co-lactide) (PLGA) coating, the Arg-Leu-PEUU coating had stronger bonding strength with the substrate; in vitro electrochemical and long-term immersion results verified a significantly better corrosion resistance. Acute blood contact tests proved a better hemocompatibility of Arg-Leu-PEUU coating. The immunofluorescent staining and cell proliferation test indicated that Arg-Leu-PEUU coating had a far better cytocompatibility. The Arg-Leu-PEUU coating stimulated human umbilical vein endothelial cells (HUVEC) to release reasonably increased amount of nitric oxide (NO), suggesting its potential in retarding thrombosis and restenosis. The superior corrosion resistance and biocompatibility as well as the indigenous NO production bio-functionality of the Arg-Leu-PEUU copolymer family indicate their capability to offer a far better protection of the magnesium-based implantable cardiovascular stent and bring their application closer to clinical reality.
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http://dx.doi.org/10.1016/j.colsurfb.2017.07.031DOI Listing
November 2017

Fabrication and characterization of electrospun nanofibers composed of decellularized meniscus extracellular matrix and polycaprolactone for meniscus tissue engineering.

J Mater Chem B 2017 Mar 8;5(12):2273-2285. Epub 2017 Mar 8.

Center for Biomedical Material and Tissue Engineering, Academy for Advanced Interdisciplinary Studies, Peking University, Yi He Yuan Road No. 5, HaiDian District, Beijing 100871, China.

Many kinds of scaffolds have been produced in meniscus tissue engineering, but few have matched the mechanical properties of native meniscus, making it impossible for them to sustain large stress at initial implantation. In this study, we used a differential centrifugation method to obtain decellularized meniscus extracellular matrix (DMECM) and combined the DMECM with polycaprolactone (PCL) via electrospinning to fabricate random and aligned microfibers. The FTIR results and biochemical assays demonstrated the successful mixing of these two elements, and the addition of DMECM improved the hydrophilicity of the microfibers. The blending of DMECM also enhanced the tensile modulus of the microfibers, and aligned fibers had tensile moduli ranging from 132.27 to 331.40 MPa, which match that of human meniscus. In addition, we defined yield stress as the lose-efficacy point. The results showed that DMECM/PCL fibers had higher yield stresses than the pure PCL fibers, and the aligned fibers had higher yield stress values than the randomly oriented fibers. Nanoindentation results showed that adding DMECM had no significant impact on modulus and hardness with the exception of fibers containing 80% DMECM, which exhibited an obvious increase in modulus. In vitro assay demonstrated that the DMECM/PCL fibers had no hemolysis or cytotoxicity. Meniscus cells could attach and proliferate on the fibers, and the fiber orientation had a direct influence on cell arrangement. RT-PCR results showed that meniscus cells had higher gene expressions of aggrecan, collagen I, collagen II and Sox 9 when seeded on fibers with higher DMECM contents.
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http://dx.doi.org/10.1039/c6tb03299kDOI Listing
March 2017

A novel biodegradable and biologically functional arginine-based poly(ester urea urethane) coating for Mg-Zn-Y-Nd alloy: enhancement in corrosion resistance and biocompatibility.

J Mater Chem B 2017 Mar 15;5(9):1787-1802. Epub 2017 Feb 15.

Center for Biomedical Materials and Tissue Engineering, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China.

A novel family of biodegradable pseudo-protein biomaterials, arginine (Arg)-based poly(ester urea urethane) (Arg-PEUU), were synthesized and applied as a better protective and bio-functional coating for bio-absorbable magnesium alloy MgZnYNd as a stent model. The Arg-PEUU coatings were stronger than poly(glycolide-co-lactide) (PLGA) coating with 11.9-103.4% higher critical lateral force. Electrochemical tests and in vitro immersion results demonstrated that the Arg-PEUU-coated MgZnYNd alloys have a significantly better corrosion resistance. The Arg-PEUU coating also showed reduced platelet adhesion and hemolysis rate in acute blood contact testing. Immunofluorescent actin and vinculin stainings showed that the Arg-PEUU coating had a far better cell adhesion of human umbilical vein endothelial cells (HUVEC), and also showed no cytotoxicity toward both HUVEC and human aortic smooth muscle cells (HASMC). The Arg-PEUU coating stimulated HUVEC to release significantly higher amounts of nitric oxide (NO) than the controls, suggesting the Arg-PEUU coating has the ability to retard thrombus and restenosis. The superb corrosion retardation, hemocompatibility and cytocompatibility of the Arg-PEUU coating as well as its induced indigenous NO production biofunctionality indicate that the newly developed Arg-PEUU biodegradable copolymer family may have the potential to offer a far greater protection of magnesium-based implantable cardiovascular stents.
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http://dx.doi.org/10.1039/c6tb03147aDOI Listing
March 2017

Functionalized Polymeric Membrane with Enhanced Mechanical and Biological Properties to Control the Degradation of Magnesium Alloy.

Adv Healthc Mater 2017 Apr 14;6(8). Epub 2017 Feb 14.

Department of Orthopaedics and Traumatology, The University of Hong Kong, Pokfulam, Hong Kong, China.

To achieve enhanced biological response and controlled degradation of magnesium alloy, a modified biodegradable polymer coating called polycaprolactone (PCL) is fabricated by a thermal approach in which the heat treatment neither alters the chemical composition of the PCL membrane nor the rate of magnesium ion release, pH value, or weight loss, compared with the untreated sample. The changes in the crystallinity, hydrophilicity, and oxygen content of heat-treated PCL coating not only improve the mechanical adhesion strength between the coating and magnesium substrate but also enhance the biological properties. Moreover, the thermally modified sample can lead to higher spreading and elongation of osteoblasts, due to the enhanced hydrophilicity and CO to CO functional group ratio. In the analyses of microcomputed tomography from one to four weeks postoperation, the total volume of new bone formation on the heat-treated sample is 10%-35% and 70%-90% higher than that of the untreated and uncoated controls, respectively. Surprisingly, the indentation modulus of the newly formed bone adjacent to the heat-treated sample is ≈20% higher than that of both controls. These promising results reveal the clinical potential of the modified PCL coating on magnesium alloy in orthopedic applications.
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http://dx.doi.org/10.1002/adhm.201601269DOI Listing
April 2017

Comparison of glutaraldehyde and carbodiimides to crosslink tissue engineering scaffolds fabricated by decellularized porcine menisci.

Mater Sci Eng C Mater Biol Appl 2017 Feb 31;71:891-900. Epub 2016 Oct 31.

Beijing Key Lab of Regenerative Medicine in Orthopaedics, Institute of Orthopaedics, Chinese PLA General Hospital, Beijing 100853, China; Key Laboratory of Musculoskeletal Trauma & War Injuries, Institute of Orthopaedics, Chinese PLA General Hospital, Beijing 100853, China. Electronic address:

The objectives of this study were to fabricate porous scaffolds using decellularized meniscus, and to explore a preferable crosslinking condition to enhance mechanical properties of scaffolds. Moreover, the microstructure, porosity, biodegradation and cytotoxicity were also evaluated. EDAC or GTA in different concentration was used to crosslink scaffolds. FTIR demonstrated functional groups change in crosslinking process. SEM photography showed that crosslinked scaffolds had blurry edges, which resulted scaffolds crosslinked by 1.2mol/l EDAC had smaller porosity than other groups. The structure change enhanced antidegradation property. After immersing in enzyme solution for 96h, scaffolds crosslinked by GTA and EDAC could maintain their mass >70% and 80%. Most importantly, mechanical properties of crosslinked scaffolds were also improved. Uncrosslinked Scaffolds had only 0.49kPa in compression modulus and 12.81kPa in tensile modulus. The compression and tensile modulus of scaffolds crosslinked by 1.0% GTA were 1.42 and 567.44kPa respectively. The same value of scaffolds crosslinked by 1.2mol/l EDAC were 1.49 and 532.50kPa. Scaffolds crosslinked by 1.0% and 2.5% GTA were toxic to cells, while EDAC groups showed no cytotoxicity. Chondrocytes could proliferate and infiltrate within scaffolds after seeding. Overall, 1.2mol/l EDAC was a preferable crosslinking condition.
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http://dx.doi.org/10.1016/j.msec.2016.10.074DOI Listing
February 2017

[Preparation and Characterization of Chitosan-Poloxamer-based Antibacterial Hydrogel Containing Silver Nanoparticles].

Sheng Wu Yi Xue Gong Cheng Xue Za Zhi 2016 Dec;33(6):1124-32

In order to solve the problem of high cytotoxicity in vitro of nano-silver antibacterial gel,and the problem of large nano-silver particle size and size distribution,this study prepared nano-silver antibacterial gel with better biocompatibility and good antibacterial effect by using physical cross-linking method and using poloxamer as dispersant when prepared nano-silver.In this study,nano-silver was prepared by photo-initiator method and by adding poloxamer as a dispersant,and then UV-visible absorption spectrum test and scanning electron microscopy(SEM)test were carried out using prepared nano-silver mixture and particles after drying respectively.The gel was prepared through adjusting its pH value by using sodium bicarbonate,and then pH value test,SEM test for cross-section of gel,swelling ratio test,viscosity test,inhibition zone test and in vitro cytotoxicity test were carried out.The test results showed that the maximum absorption wavelength of prepared nano-silver,using poloxamer as dispersant and ultra-pure water as solvent,was 414 nm,and the average nano-silver size was about 60 nm.The prepared nano-silver using poloxamer as dispersant had smaller particle diameter and narrower particle size distribution than those using PVP as dispersant.Similarly,the prepared nano-silver using ultra-pure water as solvent also had smaller particle diameter and narrower particle size distribution than those using distilled water as solvent.The pH value of the prepared gel was between 5.8~6.1.The dried gel section had many holes.The water absorption of gel was fine and the viscosity of gel was fit to coat on the gauze.In addition,the prepared gel with nano-silver had greater ability to inhibit Escherichia coli and Staphyloccocus aureus at the concentrations of 24,18 and 12μg/mL.And the biocompatibility of the prepared gel with nano-silver was good when the concentration below 24μg/mL.Based on the above features,the nano-silver antibacterial gel could be used in the treatment of burn or other wounds.
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December 2016

Additively Manufactured Macroporous Titanium with Silver-Releasing Micro-/Nanoporous Surface for Multipurpose Infection Control and Bone Repair - A Proof of Concept.

ACS Appl Mater Interfaces 2016 Oct 12;8(42):28495-28510. Epub 2016 Oct 12.

Beijing AKEC Medical Company Ltd. , Beijing 102200, China.

Restoring large-scale bone defects, where osteogenesis is slow while infections lurk, with biomaterials represents a formidable challenge in orthopedic clinics. Here, we propose a scaffold-based multipurpose anti-infection and bone repairing strategy to meet such restorative needs. To do this, personalized multifunctional titanium meshes were produced through an advanced additive manufacturing process and dual "TiO-poly(dopamine)/Ag (nano)" post modifications, yielding macroporous constructs with micro-/nanoporous walls and nanosilver bullets immobilized/embedded therein. Ultrahigh loading capacity and durable release of Ag were accomplished. The scaffolds were active against planktonic/adherent bacteria (Gram-negative and positive) for up to 12 weeks. Additionally, they not only defended themselves from biofilm colonization but also helped destroy existing biofilms, especially in combination with antibiotics. Further, the osteoblasts/bacteria coculture study displayed that the engineered surfaces aided MG-63 cells to combat bacterial invasion. Meanwhile, the scaffolds elicited generally acceptable biocompatibility (cell adhesion, proliferation, and viability) and hastened osteoblast differentiation and maturation (alkaline phosphatase production, matrix secretion, and calcification), by synergy of micro-/nanoscale topological cues and bioactive catecholamine chemistry. Although done ex vivo, these studies reveal that our three-in-one strategy (infection prophylaxis, infection fighting, and bone repair) has great potential to simultaneously prevent/combat infections and bridge defected bone. This work provides new thoughts to the use of enabling technologies to design biomaterials that resolve unmet clinical needs.
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http://dx.doi.org/10.1021/acsami.6b10473DOI Listing
October 2016

Proteomic profile of mouse fibroblasts exposed to pure magnesium extract.

Mater Sci Eng C Mater Biol Appl 2016 Dec 1;69:522-31. Epub 2016 Jul 1.

College of Engineering, Peking University, Beijing 100871, China.

Magnesium and its alloys gain wide attention as degradable biomaterials. In order to reveal the molecular mechanism of the influence of biodegradable magnesium on cells, proteomics analysis was performed in this work. After mouse fibroblasts (L929) were cultured with or without Mg degradation products (Mg-extract) for 8, 24, and 48h, changes in protein expression profiles were obtained using isobaric tags for relative and absolute quantitation (iTRAQ) coupled two dimensional liquid chromatography-tandem mass spectrometry (2D LC MS/MS). A total of 867 proteins were identified (relying on at least two peptides). Compared to the control group, 205, 282, and 217 regulated proteins were identified at 8, 24, and 48h, respectively. 65 common proteins were up or down- regulated within all the three time points, which were involved in various physiological and metabolic activities. Consistent with viability, proliferation, and cell cycle analysis, stimulated energy metabolism as well as protein synthesis pathways were discussed, indicating a possible effect of Mg-extract on L929 proliferation. Furthermore, endocytosis and focal adhesion processes were also discussed. This proteomics study uncovers early cellular mechanisms triggered by Mg degradation products and highlights the cytocompatibility of biodegradable metallic materials for biomedical applications such as stents or orthopaedic implants.
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http://dx.doi.org/10.1016/j.msec.2016.06.100DOI Listing
December 2016

How Microelectrode Array-Based Chick Forebrain Neuron Biosensors Respond to Glutamate NMDA Receptor Antagonist AP5 and GABA Receptor Antagonist Musimol.

Sens Biosensing Res 2016 Sep;10:9-14

We have established a long-term, stable primary chick forebrain neuron (FBN) culture on a microelectrode array platform as a biosensor system for neurotoxicant screening and for neuroelectrophysiological studies for multiple purposes. This paper reports some of our results, which characterize the biosensor pharmacologically. Dose-response experiments were conducted using NMDA receptor antagonist AP5 and GABA receptor agonist musimol (MUS). The chick FBN biosensor (C-FBN-biosensor) responds to the two agents in a pattern similar to that of rodent counterparts; the estimated ECs (the effective concentration that causes 50% inhibition of the maximal effect) are 2.3 μM and 0.25 μM, respectively. Intercultural and intracultural reproducibility and long-term reusability of the C-FBN-biosensor are addressed and discussed. A phenomenon of sensitization of the biosensor that accompanies intracultural reproducibility in paired dose-response experiments for the same agent (AP5 or MUS) is reported. The potential application of the C-FBN-biosensor as an alternative to rodent biosensors in shared sensing domains (NMDA receptor and GABA receptor) is suggested.
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http://dx.doi.org/10.1016/j.sbsr.2016.06.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4991211PMC
September 2016

Enhanced in Vitro and in Vivo Performance of Mg-Zn-Y-Nd Alloy Achieved with APTES Pretreatment for Drug-Eluting Vascular Stent Application.

ACS Appl Mater Interfaces 2016 Jul 5;8(28):17842-58. Epub 2016 Jul 5.

School of Materials Science and Engineering, Zhengzhou University , Zhengzhou 450002, China.

Bioabsorbable magnesium alloys are becoming prominent as temporary functional implants, as they avoid the risks generated by permanent metallic implants such as persistent inflammation and late restenosis. Nevertheless, the overfast corrosion of Mg alloys under physiological conditions hinders their wider application as medical implant materials. Here we investigate a simple one-step process to introduce a cross-linked 3-amino-propyltrimethoxysilane (APTES) silane physical barrier layer on the surface of Mg-Zn-Y-Nd alloys prior to electrostatic spraying with rapamycin-eluting poly(lactic-co-glycolic acid) (PLGA) layer. Surface microstructure was characterized by scanning electron microscope and Fourier transform infrared spectroscopy. Nanoscratch test verified the superior adhesion strength of PLGA coating in the group pretreated with APTES. Electrochemical tests combined with long-term immersion results suggested that the preferable in vitro anticorrosion behavior could be achieved by dense APTES barrier. Cell morphology and proliferation data demonstrated that APTES pretreated group resulted in remarkably preferable compatibility for both human umbilical vein endothelial cells and vascular smooth muscle cells. On the basis of excellent in vitro mechenical property, the animal study on the APTES pretreated Mg-Zn-Y-Nd stent implanted into porcine coronary arteries confirmed benign tissue compatibility as well as re-endothelialization without thrombogenesis or in-stent restenosis at six-month followup.
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http://dx.doi.org/10.1021/acsami.6b05038DOI Listing
July 2016

From Solution to Biointerface: Graphene Self-Assemblies of Varying Lateral Sizes and Surface Properties for Biofilm Control and Osteodifferentiation.

ACS Appl Mater Interfaces 2016 Jul 28;8(27):17151-65. Epub 2016 Jun 28.

Center for Biomedical Materials and Tissue Engineering, Academy for Advanced Interdisciplinary Studies, ‡Department of Advanced Materials and Nanotechnology, College of Engineering, and §Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Peking University , Beijing 100871, China.

Bringing multifunctional graphene out of solution through facile self-assembly to form 2D surface nanostructures, with control over the lateral size and surface properties, would be an intriguing accomplishment, especially in biomedical fields where biointerfaces with functional diversity are in high demand. Guided by this goal, in this work, we built such graphene-based self-assemblies on orthopedic titanium, attempting to selectively regulate bacterial activities and osteoblastic functions, which are both crucial in bone regeneration. Briefly, large-area graphene oxide (GO) sheets and functionalized reduced GO (rGO) micro-/nanosheets were self-assembled spontaneously and controllably onto solid Ti, through an evaporation-assisted electrostatic assembly process and a mussel-inspired one-pot assembly process, respectively. The resultant layers were characterized in terms of topological structure, chemical composition, hydrophilicity, and protein adsorption properties. The antibacterial efficacies of the assemblies were examined by challenging them with pathogenic Staphylococcus aureus (S. aureus) bacteria that produce biofilms, whereby around 50% antiadhesion effects and considerable antibiofilm activities were observed for both layer types but through dissimilar modes of action. Their cytocompatibility and osteogenic potential were also investigated. Interfaced with MC3T3-E1 cells, the functionalized rGO sheets evoked better cell adhesion and growth than GO sheets, whereas the latter elicited higher osteodifferentiation activity throughout a 28-day in vitro culture. In this work, we showed that it is technically possible to construct graphene interface layers of varying lateral dimensions and surface properties and confirmed the concept of using the obtained assemblies to address the two major challenges facing orthopedic clinics. In addition, we determined fundamental implications for understanding the surface-biology relationship of graphene biomaterials, in efforts to better design and more safely use them for future biomedicine.
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http://dx.doi.org/10.1021/acsami.6b05198DOI Listing
July 2016

Microelectrode Array-evaluation of Neurotoxic Effects of Magnesium as an Implantable Biomaterial.

J Mater Sci Technol 2016 Jan 20;32(1):89-96. Epub 2015 Aug 20.

Department of Bioengineering, Clemson University, Clemson, SC 29634, USA.

Magnesium (Mg)-based biomaterials have shown great potential in clinical applications. However, the cytotoxic effects of excessive Mg and the corrosion products from Mg-based biomaterials, particularly their effects on neurons, have been little studied. Although viability tests are most commonly used, a functional evaluation is critically needed. Here, both methyl thiazolyl tetrazolium (MTT) and lactate dehydrogenase (LDH) assays were used to test the effect of Mg and Mg-extract solution on neuronal viability. Microelectrode arrays (MEAs), which provide long-term, real-time recording of extracellular electrophysiological signals of in vitro neuronal networks, were used to test for toxic effects. The minimum effective concentrations (EC) of Mg from the MTT and LDH assays were 3 mmol/L and 100 mmol/L, respectively, while the EC obtained from the MEA assay was 0.1 mmol/L. MEA data revealed significant loss of neuronal network activity when the culture was exposed to 25% Mg-extract solution, a concentration that did not affect neuronal viability. For evaluating the biocompatibility of Mg-based biomaterials with neurons, MEA electrophysiological testing is a more precise method than basic cell-viability testing.
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http://dx.doi.org/10.1016/j.jmst.2015.08.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4840281PMC
January 2016

Inhibitor encapsulated, self-healable and cytocompatible chitosan multilayer coating on biodegradable Mg alloy: a pH-responsive design.

J Mater Chem B 2016 Apr 23;4(14):2498-2511. Epub 2016 Mar 23.

Center for Biomedical Materials and Tissue Engineering, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China.

The design of functional biomaterials that respond intelligently to external stimuli has become a rapidly growing area with widespread interest. This work contributes to the development of a feedback-active anticorrosion system with intriguing self-healing ability to protect magnesium (Mg) from biocorrosion. The system was constituted by an inner micro/nano-porous, ceramic-like pre-coating developed readily from the substrate, and an outermost inhibitor (nanosized cerium (Ce) oxides) containing chitosan (CS) multilayers. Here, the pre-coating acted as both an "anchoring" and a "barrier" layer to acquire structural integrity and improved impedance, respectively. Green CS served as cargo for Ce to be entrapped, harnessing Ce-NH complexation chemistry. The coating barrier properties were evaluated by electrochemical impedance spectroscopy. The active corrosion inhibition was assessed by immersion degradation tests with respect to Mg release, pH alteration, crack development, and scanning Kelvin potential. To our delight, the coatings effectively protected the substrate from biocorrosion in vitro compared with bare alloys. Putatively, the pH-triggered formation of Ce oxide precipitation, along with the pH-buffering activity and movable swelling capacity of CS macromolecules, should have contributed to restraining the anodic activity and healing the cracks/defects dynamically. Furthermore, the coated substrate had the biocompatibility to elicit better attachment and growth of osteoblasts.
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http://dx.doi.org/10.1039/c6tb00117cDOI Listing
April 2016

Bioinspired anchoring AgNPs onto micro-nanoporous TiO2 orthopedic coatings: Trap-killing of bacteria, surface-regulated osteoblast functions and host responses.

Biomaterials 2016 Jan 23;75:203-222. Epub 2015 Oct 23.

Department of Orthopedics, Peking University Third Hospital, Beijing 100191, China.

The therapeutic applications of silver nanoparticles (AgNPs) against biomedical device-associated infections (BAI), by local delivery, are encountered with risks of detachment, instability and nanotoxicity in physiological milieus. To firmly anchor AgNPs onto modified biomaterial surfaces through tight physicochemical interactions would potentially relieve these concerns. Herein, we present a strategy for hierarchical TiO2/Ag coating, in an attempt to endow medical titanium (Ti) with anticorrosion and antibacterial properties whilst maintaining normal biological functions. In brief, by harnessing the adhesion and reactivity of bioinspired polydopamine, silver nanoparticles were easily immobilized onto peripheral surface and incorporated into interior cavity of a micro/nanoporous TiO2 ceramic coating in situ grown from template Ti. The resulting coating protected the substrate well from corrosion and gave a sustained release of Ag(+) up to 28 d. An interesting germicidal effect, termed "trap-killing", was observed against Staphylococcus aureus strain. The multiple osteoblast responses, i.e. adherence, spreading, proliferation, and differentiation, were retained normal or promoted, via a putative surface-initiated self-regulation mechanism. After subcutaneous implantation for a month, the coated specimens elicited minimal, comparable inflammatory responses relative to the control. Moreover, this simple and safe functionalization strategy manifested a good degree of flexibility towards three-dimensional sophisticated objects. Expectedly, it can become a prospective bench to bedside solution to current challenges facing orthopedics.
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http://dx.doi.org/10.1016/j.biomaterials.2015.10.035DOI Listing
January 2016

6-Month Follow-Up of a Novel Biodegradable Drug-Eluting Stent Composed of Poly-L-Lactic Acid and Amorphous Calcium Phosphate Nanoparticles in Porcine Coronary Artery.

J Biomed Nanotechnol 2015 Oct;11(10):1819-25

Rationale: We reported previously, in porcine coronary arteries, that the novel biodegradable PowerStent Absorb paclitaxel-eluting stent had improved and sustained structural strength and functional performance at one month post-implantation.

Objective: To report the stent performance at 6-month follow-up.

Methods And Results: Six PowerStent Absorb and six TAXUS stents were randomly implanted in the left anterior descending and right coronary arteries of six Tibet miniature pigs. Quantitative coronary angiography (QCA) and intravascular ultrasound (IVUS) images were obtained at the time of implantation (T0) and at 6 months (T6). Two animals were sacrificed at T6 for histopathological evaluation. At T6, QCA showed that the mean luminal vascular diameter (mLD) between the PowerStent and the TAXUS stents were similar (2.36 ± 0.38 vs. 2.61 ± 0.31, respectively). Based on the IVUS analysis, the mLD and the mean lumen cross-sectional area (mCSA) in the PowerStent-treated arteries were similar between T0 and T6 (mLD: 2.74 ± 0.13 vs. 2.70 ± 0.20 and mCSA: 6.81 ± 0.62 mm2 vs. 6.68 ± 0.94 mm2). Histopathology showed that the PowerStent stents were well apposed to the vessel wall with no recoil, strut fracture and thrombus formation. The stents were fully covered with a layer of endothelial cells.

Conclusions: At six-month post-implantation, the PowerStent Absorb stents maintained their structural strength and functional performance. The development of restenosis was controlled, no stent thrombosis was observed and the stents were fully re-endothelialized. These results suggest the PowerStent Absorb stent is safe and effective for up to 6 months when implanted in porcine coronary arteries.
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http://dx.doi.org/10.1166/jbn.2015.2102DOI Listing
October 2015

Recommendation for modifying current cytotoxicity testing standards for biodegradable magnesium-based materials.

Acta Biomater 2015 Jul 15;21:237-49. Epub 2015 Apr 15.

Musculoskeletal Research Laboratory, Department of Orthopaedics & Traumatology, The Chinese University of Hong Kong, Hong Kong Special Administrative Region; Center for Translational Medicine Research and Development, Institute of Biomedical and Health Engineering, Chinese Academy of Sciences, Shenzhen 518055, China; Guangdong Innovation Team for Biodegradable Magnesium and Medical Implants, Dongguan E-ande Co. Ltd, Dongguan, China. Electronic address:

As one of the most promising medical metal implants, magnesium (Mg) or its alloys have shown significant advantages over other candidates attributed to not only their excellent biodegradability and suitable mechanical properties but also their osteopromotive effects for bone applications. Prior to approval mandated by the governmental regulatory body, the access to the medical market for Mg-based implants requires a series of testing for assurance of their safety and efficacy via preclinical evaluations and clinical tests including phase 1 and 2 evaluations, and phase 3 of multi-center randomized double blind and placebo-controlled clinical trials. However, as the most widely used protocols for biosafety evaluation of medical devices, current ISO 10993 standards should be carefully reevaluated when directly applying them to predict potential health risks of degradable Mg based biomaterials via cytotoxicity tests due to the huge gap between in vitro and in vivo conditions. Therefore, instead of a direct adoption, modification of current ISO standards for in vitro cytotoxicity test is desirable and justified. The differences in sensitivities of cells to in vitro and in vivo Mg ions and the capability of in vivo circulation system to dilute local degradation products were fully considered to propose modification of current ISO standards. This paper recommended a minimal 6 times to a maximal 10 times dilution of extracts for in vitro cytotoxicity test specified in ISO 10993 part 5 for pure Mg developed as potential orthopedic implants based on literature review and our specifically designed in vitro and in vivo tests presented in the study. Our work may contribute to the progress of biodegradable metals involved translational work.
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http://dx.doi.org/10.1016/j.actbio.2015.04.011DOI Listing
July 2015

Establishment of a Long-Term Chick Forebrain Neuronal Culture on a Microelectrode Array Platform.

RSC Adv 2015 Jan 18;5(69):56244-56254. Epub 2015 Jun 18.

Department of Bioengineering, Clemson University, 201-5 Rhodes Research Hall, Clemson, SC 29634, USA.

The biosensor system formed by culturing primary animal neurons on a microelectrode array (MEA) platform is drawing an increasing research interest for its power as a rapid, sensitive, functional neurotoxicity assessment, as well as for many other electrophysiological related research purposes. In this paper, we established a long-term chick forebrain neuron culture (C-FBN-C) on MEAs with a more than 5 month long lifespan and up to 5 month long stability in morphology and physiological function; characterized the C-FBN-C morphologically, functionally, and developmentally; partially compared its functional features with rodent counterpart; and discussed its pros and cons as a novel biosensor system in comparison to rodent counterpart and human induced pluripotent stem cells (hiPSCs). Our results show that C-FBN-C on MEA platform 1) can be used as a biosensor of its own type in a wide spectrum of basic biomedical research; 2) is of value in comparative physiology in cross-species studies; and 3) may have potential to be used as an alternative, cost-effective approach to rodent counterpart within shared common functional domains (such as specific types of ligand-gated ion channel receptors and subtypes expressed in the cortical tissues of both species) in large-scale environmental neurotoxicant screening that would otherwise require millions of animals.
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http://dx.doi.org/10.1039/C5RA09663DDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4792308PMC
January 2015

Hemolysis and cytotoxicity mechanisms of biodegradable magnesium and its alloys.

Mater Sci Eng C Mater Biol Appl 2015 Jan 19;46:202-6. Epub 2014 Aug 19.

Center for Biomedical Materials and Tissue Engineering, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China; Department of Materials Science and Engineering, State Key Laboratory for Turbulence and Complex System, College of Engineering, Peking University, Beijing 100871, China; Shenzhen Key Laboratory of Human Tissue Regeneration and Repair, Shenzhen Institute, Peking University, Shenzhen 518057, China.

Good hemocompatibility and cell compatibility are essential requirements for coronary stents, especially for biodegradable magnesium alloy stents, which could change the in situ environment after implanted. In this work, the effects of magnesium ion concentration and pH value on the hemolysis and cytotoxicity have been evaluated. Solution with different Mg(2+) concentration gradients and pH values of normal saline and cell culture media DMEM adjusted by MgCl2 and NaOH respectively were tested for the hemolysis and cell viability. Results show that even when the concentration of Mg(2+) reaches 1000 μg/mL, it has little destructive effect on erythrocyte, and the high pH value over 11 caused by the degradation is the real reason for the high hemolysis ratio. Low concentrations of Mg(2+) (<100 μg/mL) cause no cytotoxicity to L929 cells, of which the cell viability is above 80%, while high concentrations of Mg(2+) (>300 μg/mL) could induce obvious death of the L929 cells. The pH of the extract plays a synergetic effect on cytotoxicity, due to the buffer action of the cell culture medium. To validate this conclusion, commercial pure Mg using normal saline and PBS as extract was tested with the measurement of pH and Mg(2+) concentration. Pure Mg leads to a higher hemolysis ratio in normal saline (47.76%) than in buffered solution (4.38%) with different pH values and low concentration of Mg(2+). The Mg extract culture media caused no cytotoxicity, with pH=8.44 and 47.80 μg/mL Mg(2+). It is suggested that buffered solution and dynamic condition should be adopted in the hemolysis evaluation.
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http://dx.doi.org/10.1016/j.msec.2014.08.038DOI Listing
January 2015

Prolonging life in chick forebrain-neuron culture and acquiring spontaneous spiking activity on a microelectrode array.

Biotechnol Lett 2015 Mar 25;37(3):499-509. Epub 2014 Oct 25.

Department of Bioengineering, Clemson University, 201-5 Rhodes Research Hall, Clemson, SC, 29634, USA.

Various types of animal neurons were cultured on a microelectrode array (MEA) platform to form biosensors to detect potential environmental neurotoxins. For a large-scale screening tool, rodent MEA-based cortical-neuron biosensors would be very costly but chick forebrain neurons (FBNs) are abundant, cost-effective, and easy to dissect. However, chick FBNs have a lifespan of ~14 days in vitro and their spontaneous spike activity (SSA) has been difficult to develop and detect. We used a high-density neuron-glia co-culture on an MEA to prolong chick FBN lifetime to 3 months with lifetime-long SSA. A remarkable embryonic age-dependency in the culture's morphology, lifespan, and most features of SSA signal was discovered. Our results show the feasibility of developing a chick FBN-MEA biosensor and also establish a new electrophysiological platform for functional study of an in vitro neuronal network.
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http://dx.doi.org/10.1007/s10529-014-1704-1DOI Listing
March 2015

Single-neuron axonal pathfinding under geometric guidance: low-dose-methylmercury developmental neurotoxicity test.

Lab Chip 2014 Sep 21;14(18):3564-71. Epub 2014 Jul 21.

Center for Biomedical Materials and Tissue Engineering, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China.

Because the nervous system is most vulnerable to toxicants during development, there is a crucial need for a highly sensitive developmental-neurotoxicity-test model to detect potential toxicants at low doses. We developed a lab-on-chip wherein single-neuron axonal pathfinding under geometric guidance was created using soft lithography and laser cell-micropatterning techniques. After coating the surface with L1, an axon-specific member of the Ig family of cell adhesion molecules (CAMs), and optimizing microunit geometric parameters, we introduced low-dose methylmercury, a well-known, environmentally significant neurotoxicant, in the shared medium. Its developmental neurotoxicity was evaluated using a novel axonal pathfinding assay including axonal turning and branching rates at turning points in this model. Compared to the conventional neurite-outgrowth assay, this model's detection threshold for low-dose methylmercury was 10-fold more sensitive at comparable exposure durations. These preliminary results support study of developmental effects of known and potential neurotoxicants on axon pathfinding. This novel assay model would be useful to study neuronal disease mechanisms at the single-cell level. To our knowledge, the potential of methylmercury chloride to cause acute in vitro developmental neurotoxicity (DNT) at such a low dosage has not been reported. This is the first DNT test model with high reproducibility to use single-neuron axonal pathfinding under precise geometric guidance.
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http://dx.doi.org/10.1039/c4lc00723aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4148692PMC
September 2014

[PROGRESS IN BIOLOGICAL TISSUE ENGINEERING SCAFFOLD MATERIALS].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2014 Jun;28(6):784-8

Objective: To analyze the progress in biological tissue engineering scaffold materials and the clinical application, as well as product development status.

Methods: Based on extensive investigation in the status of research and application of biological tissue engineering scaffold materials, a comprehensive analysis was made. Meanwhile, a detailed analysis of research and product development was presented.

Results: Considerable progress has been achieved in research, products transformation, clinical application, and supervision of biological scaffold for tissue engineering. New directions, new technology, and new products are constantly emerging. With the continuous progress of science and technology and continuous improvement of life sciences theory, the new direction and new focus still need to be continuously adjusted in order to meet the clinical needs.

Conclusion: From the aspect of industrial transformation feasibility, acellular scaffolds and extracellular matrix are the most promising new growth of both research and product development in this field.
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June 2014

The molecular mechanism for effects of TiN coating on NiTi alloy on endothelial cell function.

Biomaterials 2014 Aug 10;35(24):6195-205. Epub 2014 May 10.

R&D Center of Lifetech Scientific (Shenzhen) Co., Ltd, Shenzhen 518057, PR China.

The aim of this study is to systematically investigate the molecular mechanism of different effects of nickel titanium (NiTi) alloy surface and titanium nitride (TiN) coating on endothelial cell function. Release of nickel (Ni) ion from bare and TiN-coated NiTi alloys and proliferation of endothelial cells on the two materials were evaluated, and then influence of the two materials on cellular protein expression profiles was investigated by proteomic technology. Subsequently, proteomic data were analyzed with bioinformatics analyses and further validated using a series of biological experiments. Results showed that although the two materials did not affect cell proliferation, the Ni ions released from bare NiTi alloy generated inhibition on pathways associated with actin cytoskeleton, focal adhesion, energy metabolism, inflammation, and amino acid metabolism. In comparison, TiN coating not only effectively prevented release of Ni ions from NiTi alloy, but also promoted actin cytoskeleton and focal adhesion formation, increased energy metabolism, enhanced regulation of inflammation, and promoted amino acid metabolism. Furthermore, the two processes, "the initial mediation of adsorbed serum protein layer to endothelial cell adhesion and growth on the two materials" from our previous study, and "the following action of the two materials on cellular protein expression profile", were linked up and comprehensively analyzed. It was found that in stage of cell adhesion (within 4 h), release of Ni ions from bare NiTi alloy was very low, and the activation of adsorbed proteins to cell adhesion and growth related biological pathways (such as regulation of actin cytoskeleton, and focal adhesion pathways) was almost as same as TiN-coated NiTi alloy. This indicated that the released Ni ions did not affect the mediation of adsorbed proteins to endothelial cell adhesion. However, in stage of cell growth and proliferation, the release of Ni ions from bare NiTi alloy increased with time and reached a higher level, which inhibited endothelial cell function at molecular level, whereas TiN coating improved endothelial cell function.
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http://dx.doi.org/10.1016/j.biomaterials.2014.04.069DOI Listing
August 2014

[Progress of alginate-based biomedical materials].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2013 Aug;27(8):1015-20

Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100871, P R China.

Objective: To review the current situation of alginate-based biomedical materials, especially focus on the clinical strategies and research progress in the clinical applications and point out several key issues that should be concerned about.

Methods: Based on extensive investigation of domestic and foreign alginate-based biomedical materials research and related patent, literature, and medicine producted, the paper presented the comprehensive analysis of its research and development, application status, and then put forward several new research directions which should be focused on.

Results: Alginate-based biomedical materials have been widely used in clinical field with a number of patients, but mainly in the fields of wound dressings and dental impression. Heart failure treatment, embolization, tissue engineering, and stem cells culture are expected to become new directions of research and products development.

Conclusion: Development of alginate-based new products has good clinical feasibility and necessity, but a lot of applied basic researches should be carried out in the further investigations.
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August 2013