Made by cells for cells - extracellular vesicles as next-generation mainstream medicines.

Current medicine has only taken us so far in reducing disease and tissue damage. Extracellular vesicles (EVs), which are membranous nanostructures produced naturally by cells, have been hailed as a next-generation medicine. EVs deliver various biomolecules, including proteins, lipids and nucleic acids, which can influence the behaviour of specific target cells. Since EVs not only mirror composition of their parent cells but also modify the recipient cells, they can be used in three key areas of medicine: regenerative medicine, disease detection and drug delivery. In this Review, we discuss the transformational and translational progress witnessed in EV-based medicine to date, focusing on two key elements: the mechanisms by which EVs aid tissue repair (for example, skin and bone tissue regeneration) and the potential of EVs to detect diseases at an early stage with high sensitivity and specificity (for example, detection of glioblastoma). Furthermore, we describe the progress and results of clinical trials of EVs and demonstrate the benefits of EVs when compared with traditional medicine, including cell therapy in regenerative medicine and solid biopsy in disease detection. Finally, we present the challenges, opportunities and regulatory framework confronting the clinical application of EV-based products.

Interactions between bioactive components determine antioxidant, cytotoxic and nutrigenomic activity of cocoa powder extract.

Numerous studies have shown, rather disappointingly, that isolated bioactive phytochemicals are not as biologically effective as natural plant products. Such a discrepancy may be explained by the concept of food synergy, which was verified in this research for cocoa extract versus its major components with regard to cancer chemoprevention. The evaluation embraced the relationship between redox properties evaluated in cell-free systems with the aid of free radicals scavenging method and differential pulse voltammetry, and redox associated anticarcinogenic activities (cellular antioxidant activity, cytotoxicity, nutrigenomic activity) in human colon adenocarcinoma cell line exposed to either cocoa powder extract or artificial mixtures of cocoa bioactives at matching concentrations. In contrast to expectations, our results showed that the stepwise enrichment with antioxidants caused no gradual increase in the antioxidant activity of the model mixtures; also, these model mixtures did not reach the reducing potential of cocoa in the cell-free systems or cellular model employed. Further, the biological activities examined in colon adenocarcinoma cells did not alter in a stepwise manner that could reflect the gradual changes in composition of bioactive ingredients. In conclusion, the experiments presented here showed that the growing complexity of a mixture of phytochemicals seems to create a new redox bioactive substance rather than enrich the mixture with new activities, characteristic of the compound added. It follows that no simple, predictable relationship can be expected between the chemopreventive potential and the composition of real food items containing a complicated set of non-toxic redox active ingredients. Our observations suggest that the interactions between different bioactive compounds and food matrix components are cooperating factors determining the final bioactivity of foods.

Injectable hybrid delivery system composed of gellan gum, nanoparticles and gentamicin for the localized treatment of bone infections.

OBJECTIVES: Bone infections are treated with antibiotics administered intravenously, antibiotic-releasing bone cements or collagen sponges placed directly in the infected area. These approaches render limited effectiveness due to the lack of site specificity and invasiveness of implanting cements and sponges. To address these limitations, we developed a novel polysaccharide hydrogel-based injectable system that enables controlled delivery of gentamicin (GENT). Its advantages are minimal invasiveness, and localized and finely regulated release of the drug. METHODS: GENT was incorporated both directly within the gellan gum hydrogel and into poly(L-lactide-co-glycolide) nanoparticles embedded into the hydrogel. RESULTS: We confirmed the injectability of the system and measured extrusion force was 15.6 ± 1.0 N, which is suitable for injections. The system set properly after the injection as shown by rheological measurements. Desired burst release of the drug was observed within the first 12 h and the dose reached ~27% of total GENT. Subsequently, GENT was released gradually and sustainably: ~60% of initial dose within 90 days. In vitro studies confirmed antimicrobial activity of the system against Staphylococcus spp. and cytocompatibility with osteoblast-like cells. CONCLUSIONS: Developed injectable system enables minimally invasive, local and sustained delivery of the pharmaceutically relevant doses of GENT to combat bone infections.

Scalable surface area characterization by electrokinetic analysis of complex anion adsorption.

By means of the in situ electrokinetic assessment of aqueous particles in conjunction with the addition of anionic adsorbates, we develop and examine a new approach to the scalable characterization of the specific accessible surface area of particles in water. For alumina powders of differing morphology in mildly acidic aqueous suspensions, the effective surface charge was modified by carboxylate anion adsorption through the incremental addition of oxalic and citric acids. The observed zeta potential variation as a function of the proportional reagent additive was found to exhibit inverse hyperbolic sine-type behavior predicted to arise from monolayer adsorption following the Grahame-Langmuir model. Through parameter optimization by inverse problem solving, the zeta potential shift with relative adsorbate addition revealed a nearly linear correlation of a defined surface-area-dependent parameter with the conventionally measured surface area values of the powders, demonstrating that the proposed analytical framework is applicable for the in situ surface area characterization of aqueous particulate matter. The investigated methods have advantages over some conventional surface analysis techniques owing to their direct applicability in aqueous environments at ambient temperature and the ability to modify analysis scales by variation of the adsorption cross section.

Effect of surface treatment on the bioactivity of nickel-titanium.

In this paper, the bioactive properties of Ni-Ti alloy after different surface treatments were evaluated in different media (Hanks' balanced salt solution, Dulbecco's modified Eagle's medium and osteogenic). Evaluation was performed on the basis of X-ray photoelectron spectroscopy and atomic force microscopy studies after immersing samples for up to 24h in the relevant media. This allowed assessment of the kinetics of Ca(2+) and P(5+) precipitation and early interaction of the media with surfaces. In addition, the surface free energy was measured and the influence of heat treatment on phase transformation temperatures and rate of nickel and titanium ion release was investigated. The most favourable bioactive properties were observed for simply ground Ni-Ti samples when evaluated in HBSS, which showed similar properties to reference positive samples (BioactiveTi). On the other hand, samples heat-treated at 600 degrees C showed very low levels of precipitation of Ca and P. Most interestingly, evaluation in the media containing organic components (protein, vitamins, antibiotics and drugs) revealed that bioactivity for all the samples was at the same level (except for the reference negative) irrespective of the surface preparation method. It demonstrated that organic components interact with the surface rapidly, forming a thin protein layer, and this altered the surface properties of the samples, making them bioactive. No significant difference in kinetics of the Ca(2+) and P(5+) precipitation were observed. Nevertheless, further ion release and chemical composition evaluation revealed that alkali treatment and spark oxidation cannot be considered as a useful for biomedical application due to very high levels of Ni in the top layer (alkali-treated) and high rate of Ni release (spark-oxidized and alkali-treated).