[Effects of biologics on psychological status and quality of life in patients with inflammatory bowel disease: a multicenter study].

Objective: To investigate the effects of biologics on psychological status and quality of life in patients with inflammatory bowel disease (IBD). Methods: A cross-sectional survey was conducted in 42 hospitals in 22 provinces (autonomous regions and municipalities directly under the central government) from September 2021 to May 2022. General clinical information and the use of biologics were obtained from adult patients diagnosed with IBD who voluntarily participated in the study. Psychological status was evaluated using the Generalized Anxiety Disorder (GAD-7), Patient Health Questionnaire-9 (PHQ-9), Pittsburgh Sleep Quality Index (PSQI), and Inflammatory Bowel Disease Questionnaire (IBDQ) assessment tools. Counts were analyzed via the Chi-square test, and datasets that were not normally distributed were analyzed via nonparametric tests. P<0.05 was considered statistically significant. Results: A total of 2 478 valid questionnaires were collected. The GAD-7 score of the biologics group was significantly lower than that of the non-use group [6 (2, 9) vs. 7 (3, 10), Z=-3.49, P<0.001]. IBDQ scores [183 (158, 204) vs. 178 (152, 198), Z=-4.11, P<0.001], intestinal symptom scores [61 (52, 67) vs. 58 (49, 65), Z=-5.41, P<0.001], systemic symptom scores [28 (24, 32) vs. 27 (23, 31), Z=-2.37, P=0.018], emotional ability scores [69 (58, 77) vs. 67 (56, 75), Z=-3.58, P<0.001] and social ability scores [26 (22, 29) vs. 25 (22, 29), Z=-2.52, P=0.012] in the biologics group were significantly higher than in the non-use group. GAD-7 scores [5 (2, 9) vs. 6 (3, 10), Z=-3.50, P<0.001] and PSQI scores [6 (4, 9) vs. 6 (4, 9), Z=-2.55, P=0.011] were significantly lower in the group using infliximab than in the group not using it. IBDQ scores were significantly higher in patients using vedolizumab than in those not using it [186 (159, 205) vs. 181 (155, 201), Z=-2.32, P=0.021] and were also significantly higher in the group treated with adalimumab than in the group not treated with adalimumab [187 (159, 209) vs. 181 (155, 201), Z=-2.16, P=0.030]. However, ustekinumab had no significant effect on any of the scores. Conclusion: The use of biologics is strongly associated with improvements in anxiety status and quality of life in IBD patients.

[In vivo study of liposome-modified polyetheretherketone implant on bacteriostasis and osseointegration].

OBJECTIVE: To develop dexamethasone plus minocycline-loaded liposomes (Dex/Mino liposomes) and apply them to improve bioinert polyetheretherketone (PEEK) surface, which could prevent post-operative bacterial contamination, enhance ossification for physiologic osseointegration, and finally reduce implant failure rates. METHODS: Dex/Mino liposomes were covalently grafted onto the PEEK surface using polydopamine (pDA) coating as a medium. Confocal laser scanning microscopy was used to confirm the binding of fluorescently labeled liposomes onto the PEEK substrate, and a microplate reader was used to semiquantitatively measure the average fluorescence intensity of fluorescently labeled liposome-decorated PEEK surfaces. Moreover, the mouse subcutaneous infection model and the beagle femur implantation model were respectively conducted to verify the bioactivity of Dex/Mino liposome-modified PEEK in vivo, by means of micro computed tomography (micro-CT) and hematoxylin and eosin (HE) staining analysis. RESULTS: The qualitative and quantitative results of fluorescently labeled liposomes showed that, the red fluorescence intensity of the PEEK-pDA-lipo group was stronger than that of the PEEK-NF-lipo group (P < 0.05); the liposomes were successfully and uniformly decorated on the PEEK surfaces due to the pDA coating. After mouse subcutaneous implantation of PEEKs for 24 hours, HE staining results showed that the number of inflammatory cells in the PEEK-Dex/Mino lipo group were lower than that in the inert PEEK group (P < 0.05), indicating a lower degree of infection in the test group. These results suggested that the Mino released from the liposome-functionalized surface provided an effective bacteriostasis in vivo. After beagle femoral implantation of PEEK for 8 weeks, micro-CT results showed that the PEEK-Dex/Mino lipo group newly formed more continuous bone when compared with the inert PEEK group; HE staining results showed that more new bones were formed in the PEEK-Dex/Mino lipo group than in the inert PEEK group, which were firmly bonded to the functionalized PEEK surface and extended along the PEEK interface. These results suggested that the Dex released from the liposome-functionalized surface induced effective bone regeneration in vivo. CONCLUSION: Dex/Mino liposome modification enhanced the bioactivity of inert PEEK, the functionalized PEEK with enhanced antibacterial and osseointegrative capacity has great potential as an orthopedic/dental implant material for clinical application.

[Study on the expression of non-coding microRNA-376b-3p in serum exosomes of patients with malignant glioma and the mechanism of anti-angiogenesis].

Objective: To screen the different microRNAs in the serum exosomes of patients with malignant glioma, to explore the effect of non-coding microRNA-376b-3p (miR-376b-3p) on the proliferation, invasion and tumor vasculogenic mimicry of glioma cells, and to verify its targeting effect on HOXD10. Methods: HiSeq/MiSeq high-throughput sequencing was used to screen the different microRNA expression profiles, target genes and action pathways in the serum exosomes of patients with malignant glioma. Samples were used to evaluate the expression of candidate microRNAs in serum exosomes of high-grade gliomas. The effects of miR-376b-3p on the proliferation, invasion and angiogenesis of glioma cells were detected by MTT assay, Transwell migration assay and Matrigel vasculogenic mimicry assay. The mRNA and protein expression of HOXD10 were detected to evaluate the regulatory effect of miR-376b-3p on it. Results: There were 144 different expression microRNAs in the serum exosomes between malignant glioma and the normal control. Focal adhesion and tumor protein polysaccharides were involved in the regulation of glioma enriched by KEGG(Kyoto Encyclopedia of Genes and Genomes). MiR-376b-3p was down regulated in malignant glioma, and AUC of malignant glioma was 0.85 (P<0.01). MTT test showed that the proliferation ability of miR-376b-3p inhibitor group was higher than that of the control group, and that of miR-376b-3p mimic group was lower than that of the control group. Transwell migration test showed that the number of transmembrane cells in miR-376b-3p inhibitor group was higher than that in NC inhibitor group, and the number of transmembrane cells in miR-376b-3p mimic group was lower than that in NC mimic group. The number of tubes of vasculogenic mimicry in miR-376b-3p mimic group was lower than that in NC mimic group. MiR-376b-3p inhibitor decreased the expression level of HOXD10 mRNA and protein, and miR-376b-3p mimic increased the expression level of HOXD10 mRNA and protein. Conclusions: MiR-376b-3p is down-regulated in the serum exosomes of malignant glioma patients. The up-regulated miR-376b-3p can reduce the proliferation and invasion of glioma cells, inhibit the formation of vasculogenic mimicry, and increase the expression of HOXD10, which is expected to inhibit the formation of two forms of angiogenesis at the same time. MiR-376b-3p may be a new therapeutic target of anti-angiogenesis for malignant glioma.

Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients.

Preclinical mouse models suggest that the gut microbiome modulates tumor response to checkpoint blockade immunotherapy; however, this has not been well-characterized in human cancer patients. Here we examined the oral and gut microbiome of melanoma patients undergoing anti-programmed cell death 1 protein (PD-1) immunotherapy (n = 112). Significant differences were observed in the diversity and composition of the patient gut microbiome of responders versus nonresponders. Analysis of patient fecal microbiome samples (n = 43, 30 responders, 13 nonresponders) showed significantly higher alpha diversity (P < 0.01) and relative abundance of bacteria of the Ruminococcaceae family (P < 0.01) in responding patients. Metagenomic studies revealed functional differences in gut bacteria in responders, including enrichment of anabolic pathways. Immune profiling suggested enhanced systemic and antitumor immunity in responding patients with a favorable gut microbiome as well as in germ-free mice receiving fecal transplants from responding patients. Together, these data have important implications for the treatment of melanoma patients with immune checkpoint inhibitors.

[Clinical analysis of lateral supraorbital microsurgical approach for ruptured anterior circulation aneurysm].

Objective: To explore the safety and efficiency of lateral supraorbital (LSO) approach for the ruptured anterior circulation aneurysm. Methods: The clinical data of 23 patients with grade Ⅰ-Ⅲ ruptured anterior circulation aneurysm via LSO at the Second Hospital of Shandong University from February 2016 to December 2016 were retrospectively analyzed. The clinical data included their clinical manifestations, radiological finding, microsurgical techniques and follow-up results. Results: All patients were diagnosed as anterior circulation aneurysm by preoperative CT angiography (CTA) or Digital Subtraction Angiography (DSA). They all accepted aneurysm clipping via LSO. The operations carried out smoothly, with no operation related complications. They were followed up for 2 to 12 months, and the Glasgow outcome scales (GOS) were 5 in 18 patients (78.3%), 4 in 2 patients (8.7%), 3 in 2 patients (8.7%), and 1 in 1 patient (4.3%). Conclusion: LSO could provide adequate exposure for the anterior circulation aneurysm, so the clipping could be carried out safely and effectively. LSO is a simple and minimally invasive surgical approach, and when it is used by the skilled master of pterion approach, its advantage could be fully played.

Evaluation of luteinizing hormone regulation of maturation and apoptosis, expression of LHR and FSHR in cumulus-oocyte complexes in Lanzhou fat-tailed sheep.

The present study aimed to assess LH effects on in vitro maturation (IVM) and apoptosis and also to explore the gene expressions of LHR and FSHR in cumulus-oocyte complexes (COCs) of the sheep. COCs were in vitro matured 24h in the IVM medium supplemented with varying concentrations of LH (0, 5, 10, 20 and 30 µg/mL). They were allocated into LH-1 (control group), LH-2, LH-3, LH-4 and LH-5 groups, respectively. FSH (10 IU/mL) addition was as a positive control (FSH group). COCs apoptosis was assessed by TUNEL. The qPCR and Western blotting were utilized to detect mRNA and protein expressions of FSHR and LHR, respectively. The results showed maturation rates of oocytes improved as LH concentration increased from 0 to 10 µg/mL (IU/mL), reaching a peak value of 44.3% in the LH-3 group. Maturation rate of LH-5 group was lower than that of LH-3 and FSH-treated groups. The lowest apoptosis rate was found in LH-3 group. The germinal vesicle break down (GVBD) rates of LH-2, LH-3 and LH-4 groups were also increased in comparison with that found in LH-1 group (control group). GVBD rate of LH-5 was lower than that in LH-3 group. The germinal vesicle (GV) rates in LH-3 and LH-4 groups were lower than those in LH-1 and LH-5 groups (p<0.05, or p<0.01). The lowest GV rate was found in LH-3 group. GV rates in LH-2, LH-4 and LH-5 groups were higher than that in FSH group (p<0.05). At hours 20, 22 and 24 after oocytes IVM, caspase-3 concentrations in four LH-treated groups were decreased in comparison with that in LH-1 group. At 24h, caspase-3 concentrations of LH-2 and LH-3 groups were lower than that in LH-1 group (p<0.05). Expression levels of FSHR and LHR mRNAs rose when LH concentrations in IVM medium increased. The greatest expressions of FSHR and LHR mRNAs were found in LH-5 and LH-3 groups (p<0.01) in comparison with those in the control group (LH-1). Meanwhile, FSHR mRNA expressions in LH-2, LH-3 and LH-4 groups were lower than that in FSH group (p<0.01 or p<0.05). Expression levels of FSHR proteins revealed no significant differences among all groups. Expression levels in LHR proteins were increased. LHR protein level in LH-2 group was higher than that in LH-1 group. In conclusion, LH treatment could promote the maturation rate and GVBD rate. LH reduced apoptosis rate, GV rate of sheep oocytes, and caspase-3 concentrations in IVM medium fluids and additionally enhanced expressions of FSHR and LHR mRNAs of sheep COCs.

Equine chorionic gonadotropin influence on sheep oocyte in vitro maturation, apoptosis, and follicle-stimulating hormone receptor and luteinizing hormone receptor expression.

We assessed the effects of equine chorionic gonadotropin (eCG) on oocyte in vitro maturation (IVM), apoptosis, and follicle-stimulating hormone receptor (FSHR), luteinizing hormone receptor (LHR), and gonadotropin-releasing hormone receptor (GnRHR) expression and mRNA levels. Cumulus-oocyte complexes (COCs) were recovered from sheep ovaries and pooled in groups, before being cultured in IVM media containing varying eCG concentrations. Maturation and apoptosis rates were then calculated. Expression of FSHR, LHR, and GnRHR mRNA in oocytes was measured using quantitative reverse transcription polymerase chain reaction. Protein levels were ascertained by western blotting. Matured oocytes displayed and released an intact first polar body. Sheep oocyte maturation rates gradually increased as eCG concentration was raised from 0 to 20 µg/mL. Apoptosis rates of eCG-treated oocytes were lower than those of the control group, and were lowest using 20 µg/mL eCG. FSHR, LHR, and GnRHR mRNA expression increased (P < 0.01, P < 0.05, and P < 0.05, respectively, compared to 0 µg/mL eCG) with eCG concentration, being highest following exposure to 20 µg/mL. FSHR and GnRHR protein levels were significantly higher in oocytes administered 20 µg/mL eCG compared with those matured in the absence of eCG. eCG dose positively correlated with FSHR, LHR, and GnRHR mRNA and protein expression. In conclusion, eCG enhances maturation and decreases apoptosis of oocytes undergoing IVM, and heightens FSHR, LHR, and GnRHR expression. Such increased expression may facilitate oocyte IVM. These findings contribute to our understanding of the mechanisms of underlying hormonal control of sheep oocyte IVM, advancing ovine reproductive methods.

Splicing mutation of a gene within the Duchenne muscular dystrophy family.

The aim of this study was to identify the mutation site and phenotype of the Duchenne muscular dystrophy (DMD) gene in a DMD family. The DMD gene is by far the largest known gene in humans. Up to 34% of the point mutations reported to date affect splice sites of the DMD gene. However, no hotspot mutation has been reported. Capture sequencing of second-generation exons was used to investigate the DMD gene in a proband. Sanger sequencing was performed for mutation scanning in eight family members. Scale-invariant feature transform and PolyPhen were applied to predict the functional impact of protein mutations. A hemizygous splicing mutation IVS44ds +1G-A (c.6438 +1G>A) that induces abnormal splicing variants during late transcription and produces abnormal proteins was located in intron 44. Four missense mutations (p.Arg2937Gln, p.Asp882Gly, p.Lys2366Gln, and p.Arg1745His) that are known multiple-polymorphic sites were found in the coding region of the DMD gene. A heterozygous c.6438+1G>A mutation was detected on the X chromosome of the proband's mother and maternal grandmother.

Hes1 Increases the Invasion Ability of Colorectal Cancer Cells via the STAT3-MMP14 Pathway.

The Notch pathway contributes to self-renewal of tumor-initiating cell and inhibition of normal colonic epithelial cell differentiation. Deregulated expression of Notch1 and Jagged1 is observed in colorectal cancer. Hairy/enhancer of split (HES) family, the most characterized targets of Notch, involved in the development of many cancers. In this study, we explored the role of Hes1 in the tumorigenesis of colorectal cancer. Knocking down Hes1 induced CRC cell senescence and decreased the invasion ability, whereas over-expression of Hes1 increased STAT3 phosphorylation activity and up-regulated MMP14 protein level. We further explored the expression of Hes1 in human colorectal cancer and found high Hes1 mRNA expression is associated with poor prognosis in CRC patients. These findings suggest that Hes1 regulates the invasion ability through the STAT3-MMP14 pathway in CRC cells and high Hes1 expression is a predictor of poor prognosis of CRC.

AML1/ETO cooperates with HIF1α to promote leukemogenesis through DNMT3a transactivation.

The mechanisms by which AML1/ETO (A/E) fusion protein induces leukemogenesis in acute myeloid leukemia (AML) without mutagenic events remain elusive. Here we show that interactions between A/E and hypoxia-inducible factor 1α (HIF1α) are sufficient to prime leukemia cells for subsequent aggressive growth. In agreement with this, HIF1α is highly expressed in A/E-positive AML patients and strongly predicts inferior outcomes, regardless of gene mutations. Co-expression of A/E and HIF1α in leukemia cells causes a higher cell proliferation rate in vitro and more serious leukemic status in mice. Mechanistically, A/E and HIF1α form a positive regulatory circuit and cooperate to transactivate DNMT3a gene leading to DNA hypermethylation. Pharmacological or genetic interventions in the A/E-HIF1α loop results in DNA hypomethylation, a re-expression of hypermethylated tumor-suppressor p15(INK4b) and the blockage of leukemia growth. Thus high HIF1α expression serves as a reliable marker, which identifies patients with a poor prognosis in an otherwise prognostically favorable AML group and represents an innovative therapeutic target in high-risk A/E-driven leukemia.

LPS receptor subunits have antagonistic roles in epithelial apoptosis and colonic carcinogenesis.

Colorectal carcinoma (CRC) is characterized by unlimited proliferation and suppression of apoptosis, selective advantages for tumor survival, and chemoresistance. Lipopolysaccharide (LPS) signaling is involved in both epithelial homeostasis and tumorigenesis, but the relative roles had by LPS receptor subunits CD14 and Toll-like receptor 4 (TLR4) are poorly understood. Our study showed that normal human colonocytes were CD14(+)TLR4(-), whereas cancerous tissues were CD14(+)TLR4(+), by immunofluorescent staining. Using a chemical-induced CRC model, increased epithelial apoptosis and decreased tumor multiplicity and sizes were observed in TLR4-mutant mice compared with wild-type (WT) mice with CD14(+)TLR4(+) colonocytes. WT mice intracolonically administered a TLR4 antagonist displayed tumor reduction associated with enhanced apoptosis in cancerous tissues. Mucosa-associated LPS content was elevated in response to CRC induction. Epithelial apoptosis induced by LPS hypersensitivity in TLR4-mutant mice was prevented by intracolonic administration of neutralizing anti-CD14. Moreover, LPS-induced apoptosis was observed in primary colonic organoid cultures derived from TLR4 mutant but not WT murine crypts. Gene silencing of TLR4 increased cell apoptosis in WT organoids, whereas knockdown of CD14 ablated cell death in TLR4-mutant organoids. In vitro studies showed that LPS challenge caused apoptosis in Caco-2 cells (CD14(+)TLR4(-)) in a CD14-, phosphatidylcholine-specific phospholipase C-, sphingomyelinase-, and protein kinase C-ζ-dependent manner. Conversely, expression of functional but not mutant TLR4 (Asp299Gly, Thr399Ile, and Pro714His) rescued cells from LPS/CD14-induced apoptosis. In summary, CD14-mediated lipid signaling induced epithelial apoptosis, whereas TLR4 antagonistically promoted cell survival and cancer development. Our findings indicate that dysfunction in the CD14/TLR4 antagonism may contribute to normal epithelial transition to carcinogenesis, and provide novel strategies for intervention against colorectal cancer.

Cell response of nanographene platelets to human osteoblast-like MG63 cells.

The biologic/cytotoxic effects of dispersed nanographene platelets (NGPs) on human osteosarcoma cells (MG63 cell line) were first studied by examining cell viability, cycle, apoptosis, change in morphology, lactate dehydrogenase (LDH) release, alkaline phosphatase (ALP) activity, and inflammation. The results shown that the cell cytotoxicity of the dispersed NGPs exhibited dose-dependent characters, which had no obvious cytotoxic effects to MG63 cells at the concentration less than 10 µg mL(-1), whereas could postpone cell cycle, promote cell apoptosis, damage cell microstructure, induce serious tumor necrosis factor-α expression and greatly reduce ALP activity of MG63 cells at higher concentration of NGPs (>10 µg mL(-1)). Besides, NGPs had little influence on the LDH leakage. The cytotoxic mechanism of NGPs to MG63 cells was speculated to be intracellular activity with no physical damage of plasma membrane.

Surface characteristics and electrochemical corrosion behavior of NiTi alloy coated with IrO2.

The aim of this work is to investigate the surface characteristics and corrosion behavior of NiTi (50.6 at.% Ni) shape memory alloy coated by a ceramic-like and highly biocompatible material, iridium oxide (IrO2). IrO2 coatings were prepared by thermal decomposition of H2IrCl6 · 6H2O precursor solution at the temperature of 300 °C, 400 °C and 500 °C, respectively. The surface morphology and microstructure of the coatings were investigated by scanning electron microscope (SEM) and glancing angle X-ray diffraction (GAXRD). X-ray photoelectron spectroscopy (XPS) was employed to determine the surface elemental composition. Corrosion resistance property of the coated samples was studied in a simulated body fluid at 37±1 °C by electrochemical method. It was found that the morphology and microstructure of the coatings were closely related to the oxidizing temperatures. A relatively smooth, intact and amorphous coating was obtained when the H2IrCl6·6H2O precursor solution (0.03 mol/L) was thermally decomposed at 300 °C for 0.5 h. Compared with the bare NiTi alloy, IrO2 coated samples exhibited better corrosion resistance behavior to some extent.

In vitro and in vivo studies on nanocrystalline Ti fabricated by equal channel angular pressing with microcrystalline CP Ti as control.

Bulk nanocrystalline Ti bars (Grade 4, Φ4 × 3000 mm(3)) were massively fabricated by equal channel angular pressing (ECAP) via follow-up conform scheme with the microcrystalline CP Ti as raw material. Homogeneous nanostructured crystals with the average grain size of 250 nm were identified for the ECAPed Ti, with extremely high tensile/fatigue strength (around 1240/620 MPa) and adorable elongation (more than 5%). Pronounced formation of bonelike apatite for the nanocrystalline Ti group after 14 days static immersion in simulated body fluids (SBF) reveals the prospective in vitro bioactive capability of fast calcification, whereas an estimated 17% increment in protein adsorption represents good bioaffinity of nanocrystalline Ti. The documentation onto the whole life circle of osteoblast cell lines (MG63) revealed the strong interactions and superior cellular functionalization when they are co-incubated with bulk nanocrystalline Ti sample. Moreover, thread-structured specimens were designed and implanted into the tibia of Beagles dogs till 12 weeks to study the in vivo responses between bone and metallic implant made of bulk nanocrystalline Ti, with the microcrystalline Ti as control. For the implanted nanostructured Ti group, neoformed bone around the implants underwent the whole-stage transformation proceeding from originally osteons or immature woven bone to mature lamellar bone (skeletonic trabecular), even with the remodeling being finished till 12 weeks. The phenomenal osseointegration of direct implant-bone contact can be revealed from the group of the ECAPed Ti without fibrous tissue encapsulation in the gap between the implant and autogenous bone.

Comparative study on corrosion resistance and in vitro biocompatibility of bulk nanocrystalline and microcrystalline biomedical 304 stainless steel.

OBJECTIVES: SUS 304 stainless steels have been widely used in orthodontics and implants such as archwires, brackets, and screws. The purpose of present study was to investigate the biocompatibility of both the commercial microcrystalline biomedical 304 stainless steel (microcrystalline 304ss) and novel-fabricated nanocrystalline 304 stainless steel (nanocrystalline 304ss). METHODS: Bulk nanocrystalline 304ss sheets had been successfully prepared by microcrystalline 304ss plates using severe rolling technique. The electrochemical corrosion and ion release behavior immersion in artificial saliva were measured to evaluate the property of biocorrosion in oral environment. The cell lines of murine and human cell lines from oral and endothelial environment were co-cultured with extracts to evaluate the cytotoxicity and provide referential evidence in vivo. RESULTS: The polarization resistance trials indicated that nanocrystalline 304ss is more corrosion resistant than the microcrystalline 304ss in oral-like environment with higher corrosion potential, and the amount of toxic ions released into solution after immersion is lower than that of the microcrystalline 304ss and the daily dietary intake level. The cytotoxicity results also elucidated that nanocrystalline 304ss is biologically compatible in vitro, even better than that of microcrystalline 304ss. SIGNIFICANCE: Based on the much higher mechanical and physical performances, nanocrystalline 304ss with enhanced biocorrosion property, well-behaved in vitro cytocompatibility can be a promising alternative in orthodontics and fixation fields in oral cavity.

In vitro and in vivo evaluation of SLA titanium surfaces with further alkali or hydrogen peroxide and heat treatment.

The present study aimed to evaluate the bioactivity of titanium surfaces sandblasted with large-grit corundum and acid etched (SLA) plus further alkali or hydrogen peroxide and heat treatment for dental implant application. Pure titanium disks were mechanically polished as control surface (Ti-control) and then sandblasted with large-grit corundum and acid etched (SLA). Further chemical modifications were conducted using alkali and heat treatment (ASLA) and hydrogen peroxide and heat treatment (HSLA) alternatively. The surface properties were characterized by scanning electron microscopy (SEM), x-ray photoelectron spectroscopy (XPS), and contact angle and roughness measurements. Further evaluation of surface bioactivity was conducted by MC3T3-E1 cell attachment, proliferation, morphology, alkaline phosphatase (ALP) activity and calcium deposition on the sample surfaces. After insertion in the beagle's mandibula for a specific period, cylindrical implant samples underwent micro-CT examination and then histological examination. It was found that ASLA and HSLA surfaces significantly increased the surface wettability and MC3T3-E1 cell attachment percentage, ALP activity and the quality of calcium deposition in comparison with simple SLA and Ti-control surfaces. Animal studies showed good osseointegration of ASLA and HSLA surfaces with host bone. In conclusion, ASLA and HSLA surfaces enhanced the bioactivity of the traditional SLA surface by integrating the advantages of surface topography, composition and wettability.

In vitro study on Zr-based bulk metallic glasses as potential biomaterials.

With pure Ti and pure Zr as controls, the corrosion resistance, ion release behavior, and in vitro biocompatibility of Be-containing Zr41Ti14Cu12Ni10Be23 bulk metallic glass (BMG) (LM1), Zr44Ti11Cu10Ni10Be25 BMG (LM1b), and Be-free Zr57Nb5Cu15.4Ni12.6Al10 BMG (LM106) were investigated in terms of electrochemical measurements in simulated body fluid (SBF) with pH value 7.4 and artificial saliva (AS) with pH value 6.3, and 3-[4,4-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay using L929 and NIH3T3 cells, aiming to assess the feasibility of Zr-based BMGs as potential biomaterial. It was found that LM1b showed superior corrosion resistance to LM106 and LM1 in both SBF and AS, and comparable with pure Ti and pure Zr. After 7200 s immersion, a two-layer structure oxide film was formed on LM1, LM1b, and pure Zr surfaces, while one-layer structure oxide film was formed on LM106 and pure Ti surfaces. The pitting corrosion potentials of LM1b were much higher than that of LM1, LM106, and pure Zr, resulting in very few ions releasing into the electrolytes. No Be ion could be detected but a little amount of Cu ion was detected for LM106, LM1, and LM1b after immersion in Dulbecco's modified Eagle's medium for 72 h at 37 °C. The indirect cytotoxicity results show that LM106, LM1, and LM1b extracts had no cytotoxicity to L929 and NIH3T3 cells. The direct cytotoxicity results show that cells could adhere well on the Zr-based BMG surface as in pure Ti and Zr. Lower cell proliferation rate of LM106 and LM1 is observed when compared with LM1b, which was found to be caused by Cu ion releasing rather than by Be ion.

In vitro corrosion, cytotoxicity and hemocompatibility of bulk nanocrystalline pure iron.

Bulk nanocrystalline pure iron rods were fabricated by the equal channel angular pressure (ECAP) technique up to eight passes. The microstructure and grain size distribution, natural immersion and electrochemical corrosion in simulated body fluid, cellular responses and hemocompatibility were investigated in this study. The results indicate that nanocrystalline pure iron after severe plastic deformation (SPD) would sustain durable span duration and exhibit much stronger corrosion resistance than that of the microcrystalline pure iron. The interaction of different cell lines reveals that the nanocrystalline pure iron stimulates better proliferation of fibroblast cells and preferable promotion of endothelialization, while inhibits effectively the viability of vascular smooth muscle cells (VSMCs). The burst of red cells and adhesion of the platelets were also substantially suppressed on contact with the nanocrystalline pure iron in blood circulation. A clear size-dependent behavior from the grain nature deduced by the gradual refinement microstructures was given and well-behaved in vitro biocompatibility of nanocrystalline pure iron was concluded.

Corrosion fatigue behaviors of two biomedical Mg alloys - AZ91D and WE43 - In simulated body fluid.

Magnesium alloys have been recently developed as biodegradable implant materials, yet there has been no study concerning their corrosion fatigue properties under cyclic loading. In this study the die-cast AZ91D (A for aluminum 9%, Z for zinc 1% and D for a fourth phase) and extruded WE43 (W for yttrium 4%, E for rare earth mischmetal 3%) alloys were chosen to evaluate their fatigue and corrosion fatigue behaviors in simulated body fluid (SBF). The die-cast AZ91D alloy indicated a fatigue limit of 50MPa at 107 cycles in air compared to 20MPa at 106 cycles tested in SBF at 37°C. A fatigue limit of 110MPa at 107 cycles in air was observed for extruded WE43 alloy compared to 40MPa at 107 cycles tested in SBF at 37°C. The fatigue cracks initiated from the micropores when tested in air and from corrosion pits when tested in SBF, respectively. The overload zone of the extruded WE43 alloy exhibited a ductile fracture mode with deep dimples, in comparison to a brittle fracture mode for the die-cast AZ91D. The corrosion rate of the two experimental alloys increased under cyclic loading compared to that in the static immersion test.