New frontiers in bio-sustainable multifunctional materials: ceramic templated eumelanin-like nanostructures

Organo-inorganic hybrids hold great promise for the design of new multifunctional materials with a large spectrum of known and as yet unknown properties. The need to address bio-sustainability issues has raised huge interest toward biocompatible and bioinspired materials boosting the investigation and the engineering of biomedical devices based on natural products. Among those, eumelanins, ubiquitous biological pigments, as well as eumelanin-like compounds, hold huge potential in developing biologically active materials, thanks to their intrinsic biocompatibility, biodegradability and multiple biological functions, including photoprotection, photosensitization, free radicals scavenging, metal ion chelation, protein binding and even intrinsic antimicrobial behavior. Furthermore, due to their semiconductor behavior and electrical properties they hold great promise for next-generation photovoltaics and bioelectronics. Eumelanins are produced in-vivo by oxidative polymerization of phenolic or indolic compounds within melanosomes that template melanin formation. We recently proved that eumelanins biological functions can be markedly enhanced if their formation occurs in the presence of a nanostructured ceramic phase, acting as catalyst and structure directing agent in biopolymers building up, thus mimicking melanosomes functions according to a bioinspired approach [1-4]. In this way, TiO2 high photocatalytic activity was exploited to drive 5,6-dihydroxyindole-2-carboxylic acid (DHICA) polymerization to eumelanin, via complex mediated electron transfer (LMCTC) involving DHICA and Ti4+ ions, that enabled TiO2 photo-activation under visible light [1]. Obtained eumelanin-TiO2 hybrid nanostructures showed striking antimicrobial activity even higher than bare melanin under visible light and peculiar antimicrobial mechanism [2,3]. This synthesis strategy was successfully extended to the design of stable, bioactive and biocompatible melanin-silica hybrid nanoparticles with potent antioxidant \u2028and cytoprotective activity associated with a specific subcellular\u2028localization [4]. Both systems disclose the great potential of this approach, that can be extended to eumelanin like compound in agri-food wastes, ultimately leading to cutting-edge functional hybrid materials featuring relevant biological properties, such as antimicrobial activity, selective cell interaction and signaling, as well as ionic- and electronic-based charge transport

Dabigatran etexilate versus enoxaparin for prevention of venous thromboembolism after total hip replacement: a randomised, double-blind, non-inferiority trial

After hip replacement surgery, prophylaxis following discharge from hospital is recommended to reduce the risk of venous thromboembolism. Our aim was to assess the oral, direct thrombin inhibitor dabigatran etexilate for such prophylaxis. Methods In this double-blind study, we randomised 3494 patients undergoing total hip replacement to treatment for 28\u201335 days with dabigatran etexilate 220 mg (n=1157) or 150 mg (1174) once daily, starting with a half-dose 1\u20134 h after surgery, or subcutaneous enoxaparin 40 mg once daily (1162), starting the evening before surgery. The primary efficacy outcome was the composite of total venous thromboembolism (venographic or symptomatic) and death from all causes during treatment. On the basis of the absolute difference in rates of venous thromboembolism with enoxaparin versus placebo, the non-inferiority margin for the difference in rates of thromboembolism was defined as 7\ub77%. Efficacy analyses were done by modified intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00168818. Findings Median treatment duration was 33 days. 880 patients in the dabigatran etexilate 220 mg group, 874 in the dabigatran etexilate 150 mg group, and 897 in the enoxaparin group were available for the primary efficacy outcome analysis; the main reasons for exclusion in all three groups were the lack of adequate venographic data. The primary efficacy outcome occurred in 60 (6\ub77%) of 897 individuals in the enoxaparin group versus 53 (6\ub70%) of 880 patients in the dabigatran etexilate 220 mg group (absolute difference \u20130\ub77%, 95% CI \u20132\ub79 to 1\ub76%) and 75 (8\ub76%) of 874 people in the 150 mg group (1\ub79%, \u20130\ub76 to 4\ub74%). Both doses were thus non-inferior to enoxaparin. There was no significant difference in major bleeding rates with either dose of dabigatran etexilate compared with enoxaparin (p=0\ub744 for 220 mg, p=0\ub760 for 150 mg). The frequency of increases in liver enzyme concentrations and of acute coronary events during the study did not differ significantly between the groups