Multidrug resistant
(MDR) bacteria have emerged as a major clinical
challenge. The unavailability of effective antibiotics has necessitated
the use of emerging nanoparticles as alternatives. In this work, we
have developed carbohydrate-coated bimetallic nanoparticles (Au-AgNP,
30–40 nm diameter) that are nontoxic toward mammalian cells
yet highly effective against MDR strains as compared to their monometallic
counterparts (Ag-NP, Au-NP). The Au-AgNP is much more effective against
Gram-negative MDR Escherichia coli and Enterobacter
cloacae when compared to most of the potent antibiotics.
We demonstrate that in vivo, Au-AgNP is at least
11000 times more effective than Gentamicin in eliminating MDR Methicillin
Resistant Staphylococcus aureus (MRSA) infecting
mice skin wounds. Au-AgNP is able to heal and regenerate infected
wounds faster and in scar-free manner. In vivo results
show that this Au-AgNP is very effective antibacterial agent against
MDR strains and does not produce adverse toxicity. We conclude that
this bimetallic nanoparticle can be safe in complete skin regeneration
in bacteria infected wounds.
A major limitation in the bio-medical sector is the availability of materials suitable for bone tissue engineering using stem cells and methodology converting the stochastic biological events towards definitive as well as efficient bio-mineralization. We show that osteoblasts and Bone Marrow-derived Mesenchymal Stem Cell Pools (BM-MSCP) express TRPM8, a Ca2+-ion channel critical for bone-mineralization. TRPM8 inhibition triggers up-regulation of key osteogenesis factors; and increases mineralization by osteoblasts. We utilized CMT:HEMA, a carbohydrate polymer-based hydrogel that has nanofiber-like structure suitable for optimum delivery of TRPM8-specific activators or inhibitors. This hydrogel is ideal for proper adhesion, growth, and differentiation of osteoblast cell lines, primary osteoblasts, and BM-MSCP. CMT:HEMA coated with AMTB (TRPM8 inhibitor) induces differentiation of BM-MSCP into osteoblasts and subsequent mineralization in a dose-dependent manner. Prolonged and optimum inhibition of TRPM8 by AMTB released from the gels results in upregulation of osteogenic markers. We propose that AMTB-coated CMT:HEMA can be used as a tunable surface for bone tissue engineering. These findings may have broad implications in different bio-medical sectors.
Multifunctional branched/hyperbranched copolymers from poly(vinyl alcohol) (PVA) and citric acid (CA) are synthesized by varying the mole compositions of PVA and CA and are used as a prospective vehicle for encapsulation and release of bioactive molecules and as a potential scaffold for cell adhesion and growth. The branched architecture is established from spectroscopy and rheological measurements. All the copolymers have shown a lower hydrodynamic size and viscosity than the linear, high molecular weight PVA because of spherical and more compact architecture. Importantly, the size of the highly branched copolymer is found independent of pH which proved that the branch ends are capped with OH groups. Lower viscosity at equivalent solid content, biocompatibility, high antibacterial property, and presence of adequate macromolecular voids make the branched/hyperbranched copolymers a potential platform for encapsulation and release of gentamicin and other bioactive molecules. The macromolecular voids and chain end functionality also promote adhesion and growth of differentiated primary cells as well as undifferentiated stem cells implying that the copolyester can also be used as a potential 2D/3D scaffold for tissue engineering applications.
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