Customized Titanium Mesh for Repairing Cranial Defects: A Method With Comprehensive Evaluation.

Titanium cranioplasty is one of the well-established and widely used techniques for repairing cranial defects. In this paper, we present an improved way to design and create titanium meshes with more evaluation process. Computed tomography scan data of patients were used to create three-dimensional virtual models. Implants were designed with NX ImageWare 13.2 (Siemens PLM Software, Plano, TX). Final titanium meshes were assessed by Geomagic Studio 12 (Geomagic, Inc., Morrisville, NC) and NX ImageWare 13.2.Titanium meshes were designed and applied to cranioplasty surgery on 8 patients. Postoperative results were evaluated by computed tomography scanning and further analyzed with rainbow difference tomography. All patients were satisfied with the outcome. With this method, surgeons, engineers, and patients work together to evaluate and edit implant design. Our method provides better communication and comprehensive evaluation, which result in a satisfying outcome.

3D-printing of biomass furan-based polyesters with robust mechanical performance and shape memory property.

3D-printing provides a feasible technique for realizing new materials into structural and intelligent parts. In this work, biomass furan-based polyesters poly (ethylene furanoate) (PEF), poly (trimethylene furanoate) (PTF), and poly (butylene furanoate) (PBF) were successfully synthesized in a 5 L reactor through the melt polycondensation process and fabricated into 3D-printing feedstocks. It was demonstrated that the three furan-based polyesters were additively-manufactured into complicated structures. Besides, the mechanical and thermal properties of furan-based polyesters could be tailored by the chain length of diol monomer. The mechanical performance of 3D-printed PEF, PTF and PBF were characterized and compared with commercial filaments. The tensile strength of PEF and PTF could reach 74.6 and 63.8 MPa respectively, which exhibited superior tensile property to poly(ether-ether-ketone) (PEEK), polyamide (PA) and polylactic acid (PLA). Meanwhile, the compression results demonstrated that the PEF and PTF possessed comparable energy absorption capacity with PEEK and PLA respectively, which indicated excellent mechanical properties of furan-based polyesters. It was interesting to find that the 3D-printed structures including solid cube, bionic flower and lattice structures were employed to prove that the PTF possessed excellent shape memory properties. Therefore, the proposed biomass furan-based polymers would offer more freedom in the field of 3D-printing.

Characterization and cytocompatibility of hierarchical porous TiO2 coatings incorporated with calcium and strontium by one-step micro-arc oxidation.

Calcium (Ca) and strontium (Sr) are beneficial for bone reconstruction. This study incorporated Ca and Sr into the TiO2 coatings by one-step micro-arc oxidation (MAO) treatment with CaO and SrO added in tetraborate electrolytes. The structure, composition, hydrophilicity, ion release, and cytocompatibility of the coatings were studied. The coatings combine layered micron-scale pores in various sizes and nano-scaled pores, forming a hierarchical structure. This hierarchical structure is highly porous and super-hydrophilic. The coatings are composed of Ti, O, and B, as well as Ca or Sr. Ca and Sr mainly distribute in the outer layer of the coatings and exist in the forms of carbonates and oxides. The formation of the coatings was discussed. Ca and Sr incorporated into the coatings are readily released into aqueous solutions. The homogeneous surface structure of the coatings leads to an excellent and approximating performance in hydrophilicity, as well as the adhesion and spreading of the human bone marrow-derived mesenchymal stem cells (hBMSCs). The simultaneous incorporation of Ca and Sr incorporation exhibits superior facilitation in the proliferation of hBMSCs compared with single Ca or Sr incorporation. This study shows a promising method to incorporate bioactive elements into the MAO coatings on titanium surfaces.

Micro/nano-hierarchical structured TiO2 coating on titanium by micro-arc oxidation enhances osteoblast adhesion and differentiation.

Nano-structured and micro/nano-hierarchical structured TiO2 coatings were produced on polished titanium by the micro-arc oxidation (MAO) technique. This study was conducted to screen a suitable structured TiO2 coating for osteoblast adhesion and differentiation in dental implants. The formulation was characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD) and wettability testing. Adhesion, proliferation and osteogenic differentiation of MG63 cells were analysed by SEM, Cell Counting Kit-8 (CCK-8) and quantitative real-time PCR. The micro/nano-hierarchical structured TiO2 coating with both slots and pores showed the best morphology and wettability. XRD analysis revealed that rutile predominated along with a minor amount of anatase in both TiO2 coatings. Adhesion and extension of MG63 cells on the micro/nano-hierarchical structured TiO2 coating were the most favourable. MG63 cells showed higher growth rates on the micro/nano-hierarchical structured TiO2 coating at 1 and 3 days. Osteogenic-related gene expression was markedly increased in the micro/nano-hierarchical structured TiO2 coating group compared with the polished titanium group at 7, 14 and 21 days. These results revealed the micro/nano-hierarchical structured TiO2 coating as a promising surface modification and suitable biomaterial for use with dental implants.

Coumarinolignoids and lignanoids from the stems and leaves of Sapium discolor.

Two new coumarinolignoids, sapiumins D (1) and E (2), a new lignanoid, lariciresinol 9'-benzoate (3), together with six known coumarinolignoids (4-9) and eight known lignanoids (10-17), were isolated from the stems and leaves of Sapium discolor. The structures of the isolated compounds were elucidated by extensive spectroscopic methods, including NMR, MS, and single crystal X-ray diffraction experiments. Compounds 5, 10, 11, and 13 significantly inhibited nitric oxide production in lipopolysaccharide-induced BV-2 microglial cells, with IC50 values in the range of 2.13-11.37 µM.

[Progress in researches of biodegradable intravascular stents].

Biodegradable intravascular stents (BIS) become degraded after the short-term need for a stent and thus avoid the potential long-term complications of metal stents. In this paper, the research progress of BIS was reviewed; the materials, fabrication, design, experimental and clinical tests of biodegradable polymeric intravascular stents (BPIS) are introduced.

[Study of bioactive nano-multiplayer films on medical stainless steel fabrication and haemocompatibility].

To improve the biocompatibility of metallic implants, bioactive nano-multilayer films consisting of polyethylenimine (PEI) and hyaluronan (HA) were prepared on biomedical 316L stainless steel surface via electrostatic self-assembly. Small angle X-ray diffraction curve revealed that multilayer films arranged regularly layer-by-layer. Atomic force micrcscopy (AFM) was applied to determine the surface topograph and roughness. The results showed that the coated surface became smoother with the increase of number of layers. Platelet adhesion experiment indicated that the nano-multilayer films significantly reduced the platelet adhesion on the surfaces and exhibited obviously improved haemocompatibility.

[Preparation and in-vitro degradation of polylactide and poly(L-lactide-co-glycolide)].

In this paper, DL-lactide, L-lactide and glycolide were synthesized from DL-lactic acid, L-lactic acid and glycolic acid respectively. A set of homopolymerizations of lactide with stannous octoate as initiator and laurly alcohol as co-initiator was carried out; a series of copolymers of poly (L-lactide-co-glycolide) (PLGA) were prepared via ring-opening polymerization of DL-lactide or L-lactide and glycolide with stannous octoate in high vacuum. The structure and properties of homopolymers and copolymers were characterized by 1H-NMR spectroscopy, differential scanning calorimetry and gel permeation chromatography. The in vitro degradation behavior of polylactide (PLA) and PLGA films in Hank's solution was investigated. The hydrolytic degradation of the PLA and PLGA was monitored by measuring the changes of inherent viscosity and weight loss of the resulting samples. The degradation rate of PLGA could be adjusted by changing the composition of the copolymer and be enhanced with the glycolide content increasing. It is suggested that the PLGA copolymer is a potential material as drug elusion coating on coronary stents.

Formation and in vitro/in vivo performance of "cortex-like" micro/nano-structured TiO2 coatings on titanium by micro-arc oxidation.

A novel "cortex-like" micro/nano dual-scale structured TiO2 coating was prepared on a titanium surface by micro-arc oxidation (MAO) with tetraborate electrolytes. This structure, which combines microslots with nanopores, exhibits super hydrophilicity. This coating modified the surface structure, chemistry, and hydrophilicity in a one-step treatment. Evolution of the coating together with its surface and structure properties was studied. We propose a forming mechanism of the dual-scale structure in which the oxides formed during the MAO discharge dissolve in the tetraborate electrolytes, leaving little or no deposition outside the discharge channels. We performed in vitro tests using human bone marrow-derived mesenchymal stem cells (hBMSCs) that compared this coating with a "volcano-like" MAO coating and a commercial sandblasted, large-grit and acid-etched (SLA) coating. The adhesion, morphology, proliferation, and differentiation of hBMSCs, together with the matrix mineralization, were investigated. Results suggest that the "cortex-like" structure significantly promotes the adhesion, spreading, and differentiation of cells and increases the matrix mineralization. In vivo tests with mongrel dogs showed an excellent osseointegration of the "cortex-like" coating. The combination of the dual-scale structure and the hydrophilicity of the "cortex-like" TiO2 coating synergistically resulted in an outstanding cytocompatibility and osseointegration, which may facilitate a higher level of implant success.

Degradation of porous poly(D,L-lactic-co-glycolic acid) films based on water diffusion.

Poly(D,L-lactic-co-glycolic acid) has been extensively used as a controlled release carrier for drug delivery due to its good biocompatibility, biodegradability, and mechanical strength. Effects of dense and porous film's degradation behavior have been systematically investigated up to 17 weeks in Hank's Simulated Body Fluid at 37 degrees C. The degradation of the films was studied by measuring changes in weight, molecular weight and its distribution, morphology, composition etc.. A special thing was that the differences in water diffusion in dense and porous structure films caused the different degradation behavior. According to the characteristic changes of various properties of films, the degradation process is suggested to be roughly divided into four stages, tentatively named as water absorption stage, dramatic loss of molecular weight or micro-pores formed stage, loss of weight or enlarged-pores formed stage, pores diminished or pores collapse stage.

Delivery and release of nitinol stent in carotid artery and their interactions: a finite element analysis.

Carotid angioplasty and stenting (CAS) has emerged as an effective alternative to carotid endarterectomy, and nitinol stents are commonly used in CAS. To evaluate biomechanical properties of nitinol carotid stents and their interactions with carotid arteries, a finite element method (FEM) model was built which is composed of a stenotic carotid tissue, a segmented-design nitinol stent and a sheath. Two different stents were considered to show the influence of stent design on the stent-vessel interactions. Results show that the superelastic stents were delivered into the stenotic vessel lumen through the sheath and self-expanded in the internal and common carotid artery. The stent with shorter struts may have better clinical results and the different stent designs can cause different carotid vessel geometry changes. This FEM can provide a convenient way to test and improve biomechanical properties of existing carotid stents and give clues for new nitinol carotid stent designs.

[Pharmacodynamics of China-made rapamycin-polylactide-co-glycolide peripheral arterial eluting stent membrane: in vitro experiment].

OBJECTIVE: To evaluate the property and drug releasing pattern of the China-made rapamycin-polylactide-co-glycolide (PLGA) peripheral arterial eluting stent membrane. METHODS: Rapamycin was put into PLGA so as to made rapamycin-PLGA complex. Twelve nickel-titanium self-expanding stents were dipped into the complex to make drug-eluting stents. Somatotype microscope was used to observe the macro-form of the surface of the eluting membrane, and atom force microscope was used to analyzing the three-dimensional appearance and surface roughness of the membrane. The stents were put into fluid with platelets to observe the form of platelets blood compatibility by scanning electron microscopy. The extra degradation of the coating layer, by putting the stents into a simulation system of internal environment. High efficacy liquid chromatography was used to study the pharmacokinetics of the stents. Standard curve and stimulative curve, and drug release curve of multiple stents were drawn and analyzed. RESULTS: The membranes of all 12 stents had smooth surfaces and regular thickness and no membrane falling-off was observed. The platelets on the surfaces of the stents were inactivated and the number of the platelets adhering to the surfaces of the stents were reduced obviously in comparison with the blank control. PLGA degraded by 20% within 2 weeks and then the degradation speed accelerated until complete degradation occurred within 6 weeks, and the drug releasing lasted more than 50 days. The percentage of accumulative drug release was 11.02% in 24 hours, 41.23% in 9 days, and 79.44% in 30 days. CONCLUSION: Smooth and even, and capable of controlling the drug release, rapamycin-PLGA peripheral arterial eluting stent membrane coating has the potential clinical value in preventing in-stent stenosis.

X-ray visible and doxorubicin-loaded beads based on inherently radiopaque poly(lactic acid)-polyurethane for chemoembolization therapy.

The aim of current study was to develop drug-loaded polymeric beads with intrinsic X-ray visibility as embolic agents, targeting for noninvasive intraoperative location and postoperative examination during chemoembolization therapy. To endow polymer with inherent radiopacity, 4,4'-isopropylidinedi-(2,6-diiodophenol) (IBPA) was firstly synthesized and employed as a contrast agent, and then a set of radiopaque iodinated poly(lactic acid)-polyurethanes (I-PLAUs) via chain extender method were synthesized and characterized. These I-PLAU copolymers possessed sufficient radiopacity, in vitro non-cytotoxicity with human adipose-derived stem cells, and in vivo biocompatibility and degradability in rabbit model via intramuscular implantation. Doxorubicin (DOX), as a chemotherapeutic agent, was further incorporated into I-PLAU beads via a double emulsification (W/O/W) method. For drug release, two ratios of DOX-loaded I-PLAU beads exhibited calibrated size (200-550µm), porous internal structure, good X-ray visibility, evenly drug loading as well as tunable drug release. A preliminary test on in vitro tumor cell toxicity demonstrated that the DOX-loaded I-PLAU beads performed efficient anti-tumor effect. This study highlights novel X-ray visible drug-loaded I-PLAU beads used as promising embolic agents for non-invasive in situ X-ray tracking and efficient chemotherapy, which could bring opportunities to the next generation of multifunctional embolic agents.

Effect of copper addition on mechanical properties, corrosion resistance and antibacterial property of 316L stainless steel.

The effects of addition of different Cu content (0, 2.5 and 3.5wt%) on mechanical properties, corrosion resistance and antibacterial performance of 316L austenitic stainless steel (SS) after solution and aging treatment were investigated by mechanical test, transmission electron microscope (TEM), X-ray diffraction (XRD), electrochemical corrosion, X-ray photoelectron spectroscopy (XPS) and antibacterial test. The results showed that the Cu addition and heat treatment had no obvious influence on the microstructure with complete austenite features. The yield strength (YS) after solution treatment was almost similar, whereas the aging treatment obviously increased the YS due to formation of tiny Cu-rich precipitates. The pitting and protective potential of the solution treated Cu-bearing 316L SS in 0.9wt% NaCl solution increased with increasing Cu content, while gradually declined after aging, owing to the high density Cu-rich precipitation. The antibacterial test proved that higher Cu content and aging were two compulsory processes to exert good antibacterial performance. The XPS results further indicated that aging enhanced the Cu enrichment in passive film, which could effectively stimulate the Cu ions release from the surface of passive film.

Early osseointegration of implants with cortex-like TiO2 coatings formed by micro-arc oxidation: A histomorphometric study in rabbits.

In our previous studies, a novel cortex-like TiO2 coating was prepared on Ti surface through micro-arc oxidation (MAO) by using sodium tetraborate as electrolyte, and the effects of the coating on cell attachment were testified. This study aimed to investigate the effects of this cortex-like MAO coating on osseointegration. A sand-blasting and acid-etching (SLA) coating that has been widely used in clinical practice served as control. Topographical and chemical characterizations were conducted by scanning electron microscopy, energy dispersive X-ray spectrometer, X-ray diffraction, contact angle meter, and step profiler. Results showed that the cortex-like coating had microslots and nanopores and it was superhydrophilic, whereas the SLA surface was hydrophobic. The roughness of MAO was similar to that of SLA. The MAO and SLA implants were implanted into the femoral condyles of New Zealand rabbits to evaluate their in-vivo performance through micro-CT, histological analysis, and fluorescent labeling at the bone-implant interface four weeks after surgery. The micro-CT showed that the bone volume ratio and mean trabecular thickness were similar between MAO and SLA groups four weeks after implantation. Histological analysis and fluorescent labeling showed no significant differences in the bone-implant contact between the MAO and SLA surfaces. It was suggested that with micro/nanostructure and superhydrophilicity, the cortex-like MAO coating causes excellent osseointegration, holding a promise of an application to implant modification.

Intestinal detoxification time of hand-foot-and-mouth disease in children with EV71 infection and the related factors.

BACKGROUND: Hand-foot-and-mouth disease (HFMD) is a common pediatric infectious disease caused by a variety of intestinal viruses. Enterovirus 71 (EV71) is the primary pathogen that might cause severe symptoms and even death in children with HFMD. This study aimed to investigate the intestinal detoxification time of HFMD children with EV71 infection and its related factors. METHODS: Sixty-five HFMD children with EV71 infection were followed up. Their stool samples were collected once every 4 to 7 days. Viral nucleic acids were detected by fluorescent polymerase chain reaction until the results became negative. The positive rates of viral nucleic acids were analyzed by the Kaplan-Meier method. The Log-rank test and Cox-Mantel test were used to analyze factors affecting the HFMD children with EV71 infection. RESULTS: On the 2nd, 4th, 6th and 10th week, the positive rates of viral nucleic acids in stool samples of the 65 children were 94.6%, 48.1%, 17.2% and 0, respectively. Univariate analysis showed that the intestinal detoxification time of the children were related to gender, pre-admission disease course, severity of disease, and use of steroids or gamma globulin (P<0.05). Multivariate analysis showed that the severity of disease was an independent factor affecting the intestinal detoxification time (P<0.05), with a relative risk of 2.418. CONCLUSIONS: The longest intestinal detoxification time of HFMD children with EV71 infection was 10 weeks. The severity of disease was an important factor affecting the intestinal detoxification time of HFMD children with EV71 infection. Severe HFMD children with EV71 infection had a longer intestinal detoxification time.

Biodegradable radiopaque iodinated poly(ester urethane)s containing poly(ε-caprolactone) blocks: synthesis, characterization, and biocompatibility.

Biodegradable radiopaque iodinated poly(ester-urethane) (I-PU), consisting of poly(ε-caprolactone) (PCL) diol and iodinated bisphenol A (IBPA), has been successfully synthesized via a coupling reaction of PCL-diisocyanate and IBPA with varying compositions. The IBPA with four iodine atoms per molecule was applied as a chain extender to endow the I-PUs with intrinsic X-ray visibility. The chemical structure and molecular weights of I-PUs were characterized by Fourier transform infrared spectroscopy (FT-IR), proton-nuclear magnetic resonance, and gel permeation chromatography (GPC). The effects of IBPA on the physical properties of I-PUs were systematically studied by means of differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and wide-angle X-ray diffraction (WAXD). The DSC results showed that the crystallization of PCL segments in I-PUs was restrained with increasing amount of IBPA, which was also confirmed by WAXD. In the X-radiography analysis, all the synthesized I-PUs exhibited high radiopacity compared with an aluminum wedge of equivalent thickness. Enzymatic degradation tests showed that the incorporation of IBPA prolonged the degradation of I-PUs and distinct mass loss and degradation happened in the third month. Basic cytocompatibility conducted using rat adipose-derived cells proved that all the I-PUs and their biodegradation products were nontoxic. The radiopaque I-PUs is expected to possess a significant advantage over the traditional polymer counterparts in some related biomedical fields.

Functional study of dextran-graft-poly((2-dimethyl amino)ethyl methacrylate) gene delivery vector for tumor therapy.

The obstacle of gene therapy is the shortage of efficient delivery system. The development of the gene delivery system with high transfection efficiency and low toxicity appears to be crucial. Recently, we reported that the dextran-graft-poly((2-dimethyl amino)ethyl methacrylate) (DPD) can be potentially used as efficient gene vector. Herein, DPD was systematically studied for its potential in tumor gene therapy. DPD was synthesized and characterized by agarose gel electrophoresis, particle size and zeta potential. The particle size and zeta potential of the DPD/enhanced green fluorescent protein (pEGFP-C1) plasmid complexes at various N/P ratios were 130-150 nm and about 40 mV, respectively. The results showed that DPD exhibit a higher transfection effect compared with Lipofectamine 2K (Lipo 2K), a commercialized vector. The possibility of DPD in gene therapy was evaluated using p53, a gene that has been wildly applied in the research of cancer gene therapy. DPD/pEGFP-C1-p53 complex was found to be able to inhibit tumor cell proliferation through cell cycle arrest and apoptosis. Moreover, the tumor growth was found to be restrained when DPD/pEGFP-C1-p53 complex was used in a xenograft MCF7 tumor model in vivo. These observations indicated that DPD/pEGFP-C1-p53 complex may be considered to be an efficient delivery system for tumor gene therapy.

[Observation on virus shedding periods of enterovirus-71 and coxsackievirus A 16 monitored by nucleic acids determination in stool samples of children with hand, foot and mouth disease].

OBJECTIVE: To observe the duration of enterovirus-71 (EV71) and coxsackievirus A 16 (CoxA16) viral shedding in stool samples of children with hand, foot and mouth disease (HFMD) infected with EV71 and CoxA16 and to explore the relationship between the duration of intestinal virus shedding and the severity of illness of children with HFMD. METHOD: Totally 113 laboratory-confirmed cases of children with HFMD infected with EV71 and CoxA16 were followed up. The stool samples were collected with the interval of 4 to7 days and the viral nucleic acids were detected by fluorescent PCR until the stool viral nucleic acids of infected children turned to be negative. The cases in EV71 group were further divided into "ordinary EV71 group" and "severe EV71 group" according to the severity of the illness. The positive rates of viral nucleic acid and the differences of distribution among different groups were analyzed by Kaplan-Meier survival analysis during the follow-up period. RESULT: The 113 cases of infected children were grouped as follows: 65 cases of EV71 positive children, 44 cases of CoxA16 positive children, 4 cases of EV71/CoxA16 mixed infection. The median duration of the stool viral nucleic acids turning to negative was 26 (18.25-32.50) days in EV71 group and 27 (14.50-33.75) days in CoxA16 group (Z = 1.51, P > 0.05). At 1, 4, 6 and 10 weeks, the positive rates of stool viral nucleic acid of children with HFMD in EV71 group were 100%, 48.1%, 17.2% and 0 respectively. At 1, 4 and 6 weeks, the positive rates of stool viral nucleic acid of children with HFMD in CoxA16 group were 95.5%, 53.8% and 0 respectively (χ(2) = 0.18, P > 0.05). At 1, 4 and 6 weeks, the positive rates of stool viral nucleic acid of children with HFMD in ordinary EV71 group were 100%, 23.5% and 0 respectively, while at 1, 4, 6 and 10 weeks, the positive rates of stool viral nucleic acid of children with HFMD in severe EV71 group were 100%, 62.4%, 26.0% and 0 respectively (χ(2) = 5.689, P < 0.05). CONCLUSION: The duration of enterovirus shedding in stool samples of children with HFMD lasted for a long period. The maximum duration of EV71 and CoxA16 in stool of children with HFMD was 10 weeks and 6 weeks, respectively. The duration of intestinal virus shedding of children with HFMD infected with EV71 was related with the severity of the illness.

[Preliminary development of photoelastic resin occlusal film].

PURPOSE: To develop an occlusal film that can be intuitively and easily used clinically to observe the stress distribution of occlusion, based on the photoelastic resin material properties. METHODS: Using self-made silicone rubber vaginal mold, the epoxy resin occlusal films were poured into 2 different thickness and 4 different plasticizer ratio. The hardness and bitability were evaluated in 10 cases of natural dentition and 5 cases of complete denture dentition, while the bite blot was recorded using light bomb instrument at the same time. The data was analyzed and compared with T-Scan system. RESULTS: 2-50 occlusal film presented not only a right bite comfort, but also a clear response to occlusion blotting, which showed a comparable manifestation with T-Scan system. CONCLUSIONS: Compared with traditional inspection methods, occlusal photoelastic film can provide more intuitive occlusal stress distribution and benefit the diagnosis and efficacy evaluation of bite-related diseases. Supported by Research Fund of Science and Technology Commission of Shanghai Municipality (Grant No.08DZ2271100) and Shanghai Leading Academic Discipline Project (Grant No.T0202).