Picosecond laser-induced hybrid groove structures on Ti-6Al-4V bio-alloy to accelerate osseointegration.

Regulating cell growth, extracellular matrix deposition and mineralization of artificial implants are some important parameters that decide the longevity of implants in the body. Picosecond laser-induced hybrid groove structures have been shown to improve these properties of the Ti-6Al-4V bio-alloy. Two hybrid structures containing groove patterns with periodic and non-periodic substructures therein were generated on Ti-6Al-4V by varying the extent of laser pulse overlapping on sample surface. Laser-induced alteration in surface topography, chemical composition and wettability of Ti-6Al-4V resulted in 3-fold increase in the rate of hydroxyapatite growth, 2.5-fold increment in protein adsorption and 2-fold enhancement in cell adhesion in comparison to pristine sample. While the periodic substructure was found to guide cell growth, the nonperiodic sub structure offered homogenous growth leading to higher overall cell density on the substrate surface.

Influence of molecular interactions on structure, controlled release and cytotoxicity of curcumin encapsulated chitosan - Silica nanostructured microspheres.

Curcumin possesses numerous medicinal benefits including anti-cancer and anti-viral properties. However, its wide scale use as a drug is often hindered owing to the dearth of suitable drug-delivery systems which can solubilise it for long-term sustained-release and safeguard its beneficial properties. In this work, a fast, one-step method, employing evaporation induced assembly of colloids, has been employed for the synthesis of curcumin encapsulated organic-inorganic hybrid micron-sized spheres. Detailed physical properties of the microspheres, with scaffolds of silica nanoparticles (∼8.5 nm) cross linked by chitosan, are studied to trace the underlying mechanism of structural assembly in such systems, by tuning the polymer matrix with solubilizing agents, DMSO and Tween 20. A systematic modification in the hydrogen bonding network, conformations and interactions between macromolecules is revealed upon tuning the organic matrix. This in turn is found to control the assembly vis-à-vis the granular morphology, drug entrapment and packing fraction of nanoparticles in the microspheres, which have direct influence on the biological properties. Consequently, the microspheres are found to follow a first order drug release kinetics with a tunable rate constant which follows the ordering of packing fraction of silica nanoparticles in the micro-granules. A sustained curcumin release for a period extending up to 24 h has been achieved. Further studies using human lung and cervical cancer cell lines assert good anti-cancer properties of these nanostructured microspheres in cancer cells, while showing no toxicity towards normal cells. Thus, such hybrid organic-inorganic formulations achieved using multi-component colloidal assembly approach, with enhanced stability against degradation, are promising candidates for future clinical applications of water-insoluble drugs.

Spatio-temporal changes in glutathione and thioredoxin redox couples during ionizing radiation-induced oxidative stress regulate tumor radio-resistance.

Ionizing radiation (IR)-induced oxidative stress in tumor cells is effectively managed by constitutive and inducible antioxidant defense systems. This study was initiated to understand the relative contribution of different redox regulatory systems in determining the tumor radio-resistance. In this study, human T-cell lymphoma (Jurkat) cells were exposed to IR (4 Gy) and monitored for the spatio-temporal changes in cellular redox regulatory parameters. We monitored the changes in the levels of reactive oxygen species (ROS) (total, mitochondrial, primary, and secondary), thiols (total, surface, and intracellular), GSH/GSSG ratio, antioxidant enzyme activity viz. thioredoxin (Trx), Trx reductase (TrxR), glutathione peroxidase, and glutathione reductase with respect to time. We have also measured protein glutathionylation. We observed that tumor cells mount a biphasic response after IR exposure which can be divided into early (0-6 h) and late (16-48 h) responses in terms of changes in cellular redox parameters. During early response, constitutively active GSH and Trx systems respond to restore cellular redox balance to pre-exposure levels and help in activation of redox-sensitive transcription factor Nrf-2. During late response, increase in the levels of antioxidants GSH and Trx rescue cells against IR-mediated damage. We observed that disruption of either glutathione or thioredoxin metabolism led to partial impairment of ability of cells to survive against IR-induced damage. But simultaneous disruption of both the pathways significantly increased radio sensitivity of Jurkat cells. This highlighted the importance of these two antioxidant pathways in regulating redox homeostasis under conditions of IR-induced oxidative stress.