Biocompatibility of platinum-based bulk metallic glass in orthopedic applications.

Bulk metallic glasses (BMGs) are a class of amorphous metals that exhibit high strength, ductility paired with wear and corrosion resistance. These properties suggest that they could serve as an alternative to conventional metallic implants that suffer wear and failure. In the present study, we investigated Platinum (Pt)-BMG biocompatibility in bone applications. Specifically, we investigated osteoclast formation on flat and nanopatterned Pt57.5Cu14.7Ni5.3P22.5(atomic percent) as well as titanium (control). Specifically, receptor activator of NF-κB (RANK) ligand-induced murine bone marrow derived mononuclear cell fusion was measured on multiple nanopatterns and was found to be reduced on nanorods (80 and 200 nm in diameter) and was associated with reduced tartrate-resistant acid phosphatase (TRAP) and matrix metalloproteinase (MMP9) expression. Evaluation of mesenchymal stem cell (MSC) to osteoblast differentiation on nanopatterned Pt-BMG showed significant reduction in comparison to flat, suggesting that further exploration of nanopatterns is required to have simultaneous induction of osteoblasts and inhibition of osteoclasts.Invivo studies were also pursued to evaluate the biocompatibility of Pt-BMG in comparison to titanium. Rods of each material were implanted in the femurs of mice and evaluated by x-ray, mechanical testing, micro-computed tomography (micro-CT), and histological analysis. Overall, Pt-BMG showed similar biocompatibility with titanium suggesting that it has the potential to improve outcomes by further processing at the nanoscale.

An improved method for extraction of polar and charged metabolites from cyanobacteria.

A key requirement for 13C Metabolic flux analysis (13C-MFA), a widely used technique to estimate intracellular metabolic fluxes, is an efficient method for the extraction of intermediate metabolites for analysis via liquid chromatography mass spectrometry (LC/MS). The 13C isotopic labeling results in further distribution of an already sparse pool of intermediate metabolites into isotopologues, each appearing as a separate chromatographic feature. We examined some of the reported solvent systems for the extraction of polar intracellular metabolites from three strains of cyanobacteria of the genus Synechococcus, viz., Synechococcus sp. PCC 7002, Synechococcus elongatus PCC 7942, and a newly isolated Synechococcus elongatus PCC 11801 (manuscript under review). High resolution-LC/MS was used to assess the relative abundance of the extracted metabolites. The different solvent systems used for extraction led to statistically significant changes in the extraction efficiency for a large number of metabolites. While a few hundred m/z features or potential metabolites were detected with different solvent systems, the abundance of over a quarter of all metabolites varied significantly from one solvent system to another. Further, the extraction methods were evaluated for a targeted set of metabolites that are important in 13C-MFA studies of photosynthetic organisms. While for the strain PCC 7002, the reported method using methanol-chloroform-water system gave satisfactory results, a mild base in the form of NH4OH had to be used in place of water to achieve adequate levels of extraction for PCC 7942 and PCC 11801. While minor changes in extraction solvent resulted in dramatic changes in the extraction efficiency of a number of compounds, certain metabolites such as amino acids and organic acids were adequately extracted in all the solvent systems tested. Overall, we present a new improved method for extraction using a methanol-chloroform-NH4OH system. Our method improves the extraction of polar compounds such as sugar phosphates, bisphosphates, that are central to 13C-MFA studies.

Regulation of Mesenchymal Stem Cell Differentiation by Nanopatterning of Bulk Metallic Glass.

Mesenchymal stem cell (MSC) differentiation is regulated by surface modification including texturing, which is applied to materials to enhance tissue integration. Here, we used Pt57.5Cu14.7Ni5.3P22.5 bulk metallic glass (Pt-BMG) with nanopatterned surfaces achieved by thermoplastic forming to influence differentiation of human MSCs. Pt-BMGs are a unique class of amorphous metals with high strength, elasticity, corrosion resistance, and an unusual plastic-like processability. It was found that flat and nanopattened Pt-BMGs induced osteogenic and adipogenic differentiation, respectively. In addition, osteogenic differentiation on flat BMG exceeded that observed on medical grade titanium and was associated with increased formation of focal adhesions and YAP nuclear localization. In contrast, cells on nanopatterned BMGs exhibited rounded morphology, formed less focal adhesions and had mostly cytoplasmic YAP. These changes were preserved on nanopatterns made of nanorods with increased stiffness due to shorter aspect ratios, suggesting that MSC differentiation was primarily influenced by topography. These observations indicate that both elemental composition and nanotopography can modulate biochemical cues and influence MSCs. Moreover, the processability and highly tunable nature of Pt-BMGs enables the creation of a wide range of surface topographies that can be reproducibly and systematically studied, leading to the development of implants capable of engineering MSC functions.