Surface hardening of Ti-Al-V superalloy spinal implant by using the boronization method.

BACKGROUND: We compared the raw Ti-Al-V super alloy transpedicular implant screws with boronized and surface-hardened transpedicular implant screws. OBJECTIVE: To improve patients' postoperative prognosis with the production of harder and less fragile screws. METHODS: Surface hardening was achieved by applying green-body encapsulation of the specimen with elemental boron paste which is sintered at elevated temperatures to ensure the boron-metal diffusion. Boron transported into the Ti-Al-V super alloy matrix gradually while suppressing aluminum and a homogeneously boronized surface with a thickness of ∼15 microns was obtained. The uniform external shell was enriched with TiB2, which is one of the hardest ceramics. The Ti-Al-V core material, where boron penetration diminishes, shows cohesive transition and ensures intact core-surface structure. RESULTS: Scanning electron microscope images confirmed a complete homogeneous, uniform and non-laminating surface formation. Energy-dispersive X-ray monitored the elemental structural mapping and proved the replacement of the aluminum sites on the surface with boron ending up the TiB2. The procedure was 8.6 fold improved the hardness and the mechanical resistance of the tools. CONCLUSIONS: Surface-hardened, boronized pedicular screws can positively affect the prognosis. In vivo studies are needed to prove the safety of use.

Assessment of Collagen in Translational Models of Lung Research.

The extracellular matrix (ECM) plays an important role in lung health and disease. Collagen is the main component of the lung ECM, widely used for the establishment of in vitro and organotypic models of lung disease, and as scaffold material of general interest for the field of lung bioengineering. Collagen also is the main readout for fibrotic lung disease, where collagen composition and molecular properties are drastically changed and ultimately result in dysfunctional "scarred" tissue. Because of the central role of collagen in lung disease, quantification, determination of molecular properties, and three-dimensional visualization of collagen is important for both development and characterization of translational models of lung research. In this chapter, we provide a comprehensive overview on the various methodologies currently available for quantification and characterization of collagen including their detection principles, advantages, and disadvantages.

Pioglitazone inhibits oxidative stress, MMP-mediated inflammation and vascular dysfunction in high glucose-induced human saphenous vein grafts.

AIMS: The aim of this study was to investigate the effects of pioglitazone on reactive oxygen species (ROS), expressions/activities of MMPs and TIMP-2, and VSMC proliferation and vascular reactivity in high glucose (HG)-induced human saphenous vein (HSV) grafts. METHODS: HSV grafts (n = 10) obtained from patients undergoing CABG were incubated with 30 mM glucose and/or 10 µM pioglitazone or 0.1 % DMSO for 24 h after endothelium removal. ROS levels were examined by chemiluminescence assay, MMP-2,-9,-14, TIMP-2, and α-SMA expression/activity was determined by gelatine zymography/immunohistochemistry. Vascular reactivity to potassium chloride, noradrenaline, serotonin, prostaglandin F2α and papaverine was assessed in HSVs. RESULTS: HG induced superoxide anion (SA) (123 %) and other ROS levels (159 %), up-regulated MMP-2 expression (180 %)/activity (79 %), MMP-14 expression (24 %) and MMP-9 activity while down-regulating TIMP-2 expression (27 %). HG elevated total MMP-2/TIMP-2 ratio (483 %) and MMP-14/TIMP-2 ratio (78 %). However, HG plus pioglitazone inhibited SA (30 %) and other ROS levels (29 %), down-regulated MMP-2 expression (76 %)/activity (83 %), MMP-14 expression (38 %) and MMP-9 activity, while reversing TIMP-2 expression (44 %). HG plus pioglitazone decreased total MMP-2/TIMP-2 ratio (91 %) and MMP-14/TIMP-2 ratio (59 %). HG impaired contractions to all agents but pioglitazone improved them. CONCLUSIONS: Pioglitazone may contribute to the prevention of restenosis and maintaining vascular function in HSV grafts of DM patients undergoing CABG.

Collagen Biosynthesis, Processing, and Maturation in Lung Ageing.

In addition to providing a macromolecular scaffold, the extracellular matrix (ECM) is a critical regulator of cell function by virtue of specific physical, biochemical, and mechanical properties. Collagen is the main ECM component and hence plays an essential role in the pathogenesis and progression of chronic lung disease. It is well-established that many chronic lung diseases, e.g., chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) primarily manifest in the elderly, suggesting increased susceptibility of the aged lung or accumulated alterations in lung structure over time that favour disease. Here, we review the main steps of collagen biosynthesis, processing, and turnover and summarise what is currently known about alterations upon lung ageing, including changes in collagen composition, modification, and crosslinking. Recent proteomic data on mouse lung ageing indicates that, while the ER-resident machinery of collagen biosynthesis, modification and triple helix formation appears largely unchanged, there are specific changes in levels of type IV and type VI as well as the two fibril-associated collagens with interrupted triple helices (FACIT), namely type XIV and type XVI collagens. In addition, levels of the extracellular collagen crosslinking enzyme lysyl oxidase are decreased, indicating less enzymatically mediated collagen crosslinking upon ageing. The latter contrasts with the ageing-associated increase in collagen crosslinking by advanced glycation endproducts (AGEs), a result of spontaneous reactions of protein amino groups with reactive carbonyls, e.g., from monosaccharides or reactive dicarbonyls like methylglyoxal. Given the slow turnover of extracellular collagen such modifications accumulate even more in ageing tissues. In summary, the collective evidence points mainly toward age-induced alterations in collagen composition and drastic changes in the molecular nature of collagen crosslinks. Future work addressing the consequences of these changes may provide important clues for prevention of lung disease and for lung bioengineering and ultimately pave the way to novel targeted approaches in lung regenerative medicine.

Low-dose doxycycline inhibits hydrogen peroxide-induced oxidative stress, MMP-2 up-regulation and contractile dysfunction in human saphenous vein grafts.

Background: Cardiopulmonary bypass (CPB) applied during coronary artery bypass grafting (CABG), promotes inflammation, generation of reactive oxygen species (ROS) and up-regulation of matrix metalloproteinases (MMPs). All these complications may lead to contractile dysfunction, restenosis and early graft failure, restricting long-term efficacy of bypass grafts. Low-dose doxycycline is a potent MMP inhibitor and ROS scavenger. In this study, we aimed to investigate the effects of doxycycline on ROS generation, MMP regulation and contractile dysfunction induced by H2O2 in human saphenous vein (HSV) grafts. Methods: HSV grafts (n=7) were divided into four groups after removing endothelial layer by mechanical scratching and incubated with 10 µM H2O2 and/or 10 µM doxycycline for 16 hrs. Untreated segments served as control. Concentration-response curves to noradrenaline (NA), potassium chloride (KCl), serotonin (5-HT) and papaverine were performed. Superoxide anion and other ROS levels were determined by using lucigenin- and luminol-enhanced chemiluminescence assays, respectively. Expression/activity of gelatinases (MMP-2/MMP-9) was examined by gelatin zymography. MMP-13 expression was evaluated by immunostaining/immunoscoring. Results: H2O2 incubation increased superoxide anion and other ROS levels. Doxycycline prevented these increments. H2O2 suppressed contractile responses to NA, KCl and 5-HT. Doxycycline ameliorated contractions to NA and KCl but not to 5-HT. H2O2 or doxycycline did not altered relaxation to papaverine. MMP-2 and MMP-13 expression increased with H2O2, but doxycycline inhibited MMP-2 up-regulation/activation. Conclusion: Low-dose doxycycline may have beneficial effects on increased oxidative stress, MMP up-regulation/activation and contractile dysfunction in HSV grafts.