Deposition of Antioxidant and Cytocompatible Caffeic Acid-Based Thin Films onto Ti6Al4V Alloys through Hexamethylenediamine-Mediated Crosslinking.

A promising approach for advanced bone implants is the deposition on titanium surfaces of organic thin films with improved therapeutic performances. Herein, we reported the efficient dip-coating deposition of caffeic acid (CA)-based films on both polished and chemically pre-treated Ti6Al4V alloys by exploiting hexamethylenediamine (HMDA) crosslinking ability. The formation of benzacridine systems, resulting from the interaction of CA with the amino groups of HMDA, as reported in previous studies, was suggested by the yellow/green color of the coatings. The coated surfaces were characterized by means of the Folin-Ciocalteu method, fluorescence microscopy, water contact angle measurements, X-ray photoelectron spectroscopy (XPS), zeta-potential measurements, and Fourier transform infrared spectroscopy, confirming the presence of a uniform coating on the titanium surfaces. The optimal mechanical adhesion of the coating, especially on the chemically pre-treated substrate, was also demonstrated by the tape adhesion test. Interestingly, both films exhibited marked antioxidant properties (2,2-diphenyl-1-picrylhydrazyl and ferric reducing antioxidant power assays) that persisted over time and were not lost even after prolonged storage of the material. The feature of the coatings in terms of the exposed groups (XPS and zeta potential titration evidence) was apparently dependent on the surface pre-treatment of the titanium substrate. Cytocompatibility, scavenger antioxidant activity, and antibacterial properties of the developed coatings were evaluated. The most promising results were obtained in the case of the chemically pre-treated CA/HMDA-based coated surface that showed good cytocompatibility and high reactive oxygen species' scavenging ability, preventing their intracellular accumulation under pro-inflammatory conditions; moreover, an anti-fouling effect preventing the formation of 3D biofilm-like bacterial aggregates was observed by scanning electron microscopy. These results open new perspectives for the development of innovative titanium surfaces with thin coatings from naturally occurring phenols for bone contact implants.

Disentangling the Puzzling Regiochemistry of Thiol Addition to o-Quinones.

The addition of thiol compounds to o-quinones, as exemplified by the biologically relevant conjugation of cysteine to dopaquinone, displays an anomalous 1,6-type regiochemistry compared to the usual 1,4-nucleophilic addition, for example, by amines, which has so far eluded intensive investigations. By means of an integrated experimental and computational approach, herein, we provide evidence that the addition of glutathione, cysteine, or benzenethiol to 4-methyl-o-benzoquinone, modeling dopaquinone, proceeds by a free radical chain mechanism triggered by the addition of thiyl radicals to the o-quinone. In support of this conclusion, DFT calculations consistently predicted the correct regiochemistry only for the proposed thiyl radical-quinone addition pathway. These results would prompt a revision of the commonly accepted mechanisms for thiol-o-quinone conjugation and stimulate further work aimed at assessing the impact of the free radical processes in biologically relevant thiol-quinone interactions.

An Intensive Educational Intervention Significantly Improves the Adoption of Single Fractionation Radiotherapy in Uncomplicated Bone Metastases.

INTRODUCTION: An education strategy was employed in our department to increase the rate of patients with uncomplicated painful bone metastases undergoing single fractionation radiotherapy (SFRT). The purpose of this report is to analyze the results of this strategy over a 5 year period. MATERIALS AND METHODS: In January 2015, two meetings were organized in our department. In the first, data from an audit on the current SFRT rate were shown. In the second, evidence of SFRT efficacy in the relief of pain from uncomplicated bone metastases was presented. In addition, during the weekly discussion of clinical cases, the opportunity to use the SFRT was systematically recalled. Using our institutional database, all patients treated with radiotherapy for uncomplicated painful bone metastases in the period between 2014 (year considered as a reference) and 2019 were retrieved. Data regarding treatment date (year), radiotherapy fractionation, and tumor, patients, and radiation oncologists characteristics were collected. RESULTS: A total of 627 patients were included in the analysis. The rate of patients undergoing SFRT increased from 4.0% in 2014 to 63.5% in 2019 (p < 0.001). At multivariable analysis, the delivery of SFRT was significantly correlated with older patients age (>80 years), lung cancer as the primary tumor, treatment prescribed by a radiation oncologist dedicated to palliative treatments, and treatment date (2014 vs 2015-2019). CONCLUSIONS: This retrospective single-center analysis showed that a simple but intensive and prolonged departmental education strategy can increase the rate of patients treated with SFRT by nearly 16 times.

Structural Basis of Polydopamine Film Formation: Probing 5,6-Dihydroxyindole-Based Eumelanin Type Units and the Porphyrin Issue.

The role of 5,6-dihydroxyindole (DHI)-based oligomers, including porphyrin-like tetramers, in polydopamine (PDA) film formation was addressed by a comparative structural investigation against model polymers from DHI and its 2,7'-dimer. MALDI-MS data showed that (a) PDA is structurally different from DHI melanin and does not contain species compatible with DHI-based oligomers as primary building blocks; (b) PDA films and precipitate display a single main peak at m/ z 402 in common; (c) no species matching the range of m/ z values expected for cyclic porphyrin-type tetramers was detected in DHI melanin produced in the presence or in the absence of folic acid (FA) as templating agent, nor by oxidation of the 2,7'-dimer of DHI as putative precursor. 15N NMR resonances and Raman spectra predicted by extensive DFT calculations on porphyrin-type structures at various oxidation levels did not match spectral data for PDA or DHI melanin. Notably, unlike PDA, which gave structurally homogeneous films on quartz on atomic force microscopy (AFM) and micro-Raman spectroscopy, DHI melanin did not form any adhesive deposit after as long as 24 h. It is concluded that PDA film deposition involves structural components unrelated to DHI-based oligomers or porphyrin-type tetramers, which, on mechanism-based analysis, may arise by quinone-amine conjugation leading to polycyclic systems with extensive chain breakdown.