Production of a novel poly(ɛ-caprolactone)-methylcellulose electrospun wound dressing by incorporating bioactive glass and Manuka honey.

Wound dressings produced by electrospinning exhibit a fibrous structure close to the one of the extracellular matrix of the skin. In this article, electrospinning was used to fabricate fiber mats based on the well-known biopolymers poly(ɛ-caprolactone) (PCL) and methylcellulose (MC) using benign solvents. The blend fiber mats were cross-linked using Manuka honey and additionally used as a biodegradable platform to deliver bioactive glass particles. It was hypothesized that a dual therapeutic effect can be achieved by combining Manuka honey and bioactive glass. Morphological and chemical examinations confirmed the successful production of submicrometric PCL-MC fiber mats containing Manuka honey and bioactive glass particles. The multifunctional fiber mats exhibited improved wettability and suitable mechanical properties (ultimate tensile strength of 3-5 MPa). By performing dissolution tests using simulated body fluid, the improved bioactivity of the fiber mats by the addition of bioactive glass was confirmed. Additionally, cell biology tests using human dermal fibroblasts and human keratinocytes-like HaCaT cells showed the potential of the fabricated composite fiber mats to be used as wound dressing, specially due to the ability to support wound closure influenced by the presence of bioactive glass. Moreover, based on the results of the antibacterial tests, it is apparent that an optimization of the electrospun fiber mats is required to develop suitable wound dressing for the treatment of infected wounds.

Manuka honey and bioactive glass impart methylcellulose foams with antibacterial effects for wound-healing applications.

Wound dressings able to deliver topically bioactive molecules represent a new generation of wound-regeneration therapies. In this article, foams based on methylcellulose cross-linked with Manuka honey were used as a platform to deliver borate bioactive glass particles doped additionally with copper. Borate bioactive glasses are of great interest in wound-healing applications due to a combination of favorable features, such as angiogenic and antibacterial properties. The multifunctional composite providing the dual effect of the bioactive glass and Manuka honey was produced by freeze-drying, and the resulting foams exhibit suitable morphology characterized by high porosity. Moreover, the performed tests showed improved wettability and mechanical performance with the addition of bioactive glass particles. Dissolution studies using simulated body fluid and cell biology tests using relevant skin cells further proved the excellent bioactivity and positive effects of the foams on cell proliferation and migration. Most interestingly, by the dual release of Manuka honey and ions from the copper-doped bioactive glass, an antibacterial effect against E. coli and S. aureus was achieved. Therefore, the multifunctional foams showed promising outcomes as potential wound dressings for the treatment of infected wounds.

Multifunctional zinc ion doped sol - gel derived mesoporous bioactive glass nanoparticles for biomedical applications.

Mesoporous bioactive glasses have been widely investigated for applications in bone tissue regeneration and, more recently, in soft tissue repair and wound healing. In this study we produced mesoporous bioactive glass nanoparticles (MBGNs) based on the SiO2-CaO system. With the intention of adding subsidiary biological function, MBGNs were doped with Zn2+ ions. Zn-MBGNs with 8 mol% ZnO content were synthesized via microemulsion assisted sol-gel method. The synthesized particles were homogeneous in shape and size. They exhibited spherical shape, good dispersity, and a size of 130 ±â€¯10 nm. The addition of zinc precursors did not affect the morphology of particles, while their specific surface area increased in comparison to MBGNs. The presence of Zn2+ ions inhibited the formation of hydroxycarbonate apatite (HCAp) on the particles after immersion in simulated body fluid (SBF). No formation of HCAp crystals on the surface of Zn-MBGNs could be observed after 14 days of immersion. Interestingly, powders containing relatively high amount of zinc released Zn2+ ions in low concentration (0.6-1.2 mg L-1) but in a sustained manner. This releasing feature enables Zn-MBGNs to avoid potentially toxic levels of Zn2+ ions, indeed Zn-MBGNs were seen to improve the differentiation of osteoblast-like cells (MG-63). Additionally, Zn-MBGNs showed higher ability to adsorb proteins in comparison to MBGNs, which could indicate a favourable later attachment of cells. Due to their advantageous morphological and physiochemical properties, Zn-MBGNs show great potential as bioactive fillers or drug delivery systems in a variety of applications including bone regeneration and wound healing.

A comparative study of the hypolipidaemic effects of a new polysaccharide, mannan Candida albicans serotype A, and atorvastatin in mice with poloxamer 407-induced hyperlipidaemia.

OBJECTIVES: We evaluated the hypolipidaemic effect of mannan Candida albicans serotype A, relative to atorvastatin, in a mouse model of hyperlipidaemia. METHODS: Mannan serotype A was investigated in vitro and in vivo to determine its effects on macrophage proliferation, nitric oxide (NO) production by cultured macrophages, serum and liver lipids, changes in liver morphology and serum chitotriosidase activity and its expression in the liver. KEY FINDINGS: Mannan serotype A stimulates the macrophage proliferation and NO production in murine peritoneal macrophages in vitro. The activity of serum chitotriosidase (an enzyme released from the activated macrophages) was found to be significantly increased in P-407-induced hyperlipidaemic mice pretreated with low-dose mannan compared with mice administered P-407 only. Mannan treatment in mice was shown to significantly increase the chitotriosidase expression in the liver of both non-hyperlipidaemic and P-407-induced hyperlipidaemic mice. Lastly, mice pretreated with mannan before the induction of hyperlipidaemia with P-407 showed a significant reduction in the serum concentration of atherogenic LDL cholesterol, total cholesterol, triglycerides and liver triglycerides. CONCLUSIONS: It is suggested that mannan serotype A, like ß-glucan, may represent another hypolipidaemic agent, which could potentially be used as an adjunctive therapy with conventional antihyperlipidaemic drugs (statins and fibrates) in humans.

Preparation and characterization of cationic and amphoteric mannans from Candida albicans.

Cationic and amphoteric mannans from Candida albicans were prepared by chemical modification with (3-chloro-2-hydroxypropyl)trimethylammonium chloride (CHPTAC) and sodium chloroacetate under aqueous alkaline conditions. The optimal reaction conditions for mannan cationization were found to be 6h, 60°C, and NaOH/CHPTAC ratio of 1.0. Adjusting the molar ratio of cationization agent to anhydromannose unit, cationic and amphoteric mannans with degree of substitution ranging from 0.07 to 0.57 were obtained. Their structure was confirmed by elemental analysis as well as FTIR and NMR spectroscopies. Moderate decrease of molecular weight of both cationic and amphoteric mannans was recorded by size exclusion chromatography. With increasing level of modification, reduction of the antibody-binding capacity was observed by enzyme-linked immunosorbent assay.

Vaccination with mannan protects mice against systemic aspergillosis.

Invasive aspergillosis is a major cause of mortality in immunocompromised patients and therapeutic options are often limited, thus a vaccine would be desirable. We presently studied acid-stable cell-wall mannan (α-1, 6-linked backbone highly branched with α-1, 2; α-1, 3; and ß-1, 2-linked manno-oligomers) derived from C. albicans, with or without conjugation to bovine serum albumin (BSA), as a vaccine against systemic aspergillosis. Mice were vaccinated subcutaneously with mannan or mannan-BSA conjugate weekly 3 times, ending 2 weeks prior to infection with A. fumigatus conidia. Results showed that the protection induced by mannan is dose-dependent; 12 mg unconjugated mannan alone or > 0.3 mg mannan-BSA consistently enhanced survival (P < 0.05). Fungal burdens in brains and kidneys were reduced after > 0.3 mg of mannan-BSA (all P < 0.05). Mannan-induced protection was improved about 40-fold by conjugation of BSA to mannan. Mannan-BSA (500 kDa) was more protective than 40 kDa mannan-BSA. Mannan is a candidate for a cross-protective conjugate fungal vaccine.

B cells - ontogenesis and immune memory development.

Functional diversity in the distinct developmental stages as well as anti-pathogen effectiveness and memory functionality make B cells unique and attractive object of physiology studies of the immune system. B cells are produced throughout the life of an organism, originate from the hematopoietic stem cells before birth and continue to differentiate to terminal stages. Over the past decade, there has been considerable progress in the research of all B cell intermediates and developmental processes. In this review, we will try to bring brief and comprehensive description of the current understanding of this fascinating topic.