Antimicrobial Nitric Oxide-Releasing Electrospun Dressings for Wound Healing Applications.

Nonhealing and chronic wounds represent a major problem for the quality of life of patients and have cost implications for healthcare systems. The pathophysiological mechanisms that prevent wound healing are usually multifactorial and relate to patient overall health and nutrition, vascularity of the wound bed, and coexisting infection/colonization. Bacterial infections are one of the predominant issues that can stall a wound, causing it to become chronic.

Antimicrobial Nitric Oxide Releasing Contact Lens Gels for the Treatment of Microbial Keratitis.

Microbial keratitis is a serious sight threatening infection affecting approximately two million individuals worldwide annually. While antibiotic eye drops remain the gold standard treatment for these infections, the significant problems associated with eye drop drug delivery and the alarming rise in antimicrobial resistance has meant that there is an urgent need to develop alternative treatments. In this work, a nitric oxide releasing contact lens gel displaying broad spectrum antimicrobial activity against two of the most common causative pathogens of microbial keratitis is described.

Artificial cell membrane binding thrombin constructs drive in situ fibrin hydrogel formation.

Cell membrane re-engineering is emerging as a powerful tool for the development of next generation cell therapies, as it allows the user to augment therapeutic cells to provide additional functionalities, such as homing, adhesion or hypoxia resistance. To date, however, there are few examples where the plasma membrane is re-engineered to display active enzymes that promote extracellular matrix protein assembly. Here, we report on a self-contained matrix-forming system where the membrane of human mesenchymal stem cells is modified to display a novel thrombin construct, giving rise to spontaneous fibrin hydrogel nucleation and growth at near human plasma concentrations of fibrinogen.

Functionalized Triblock Copolymer Vectors for the Treatment of Acute Lymphoblastic Leukemia.

The chemotherapeutic Parthenolide is an exciting new candidate for the treatment of acute lymphoblastic leukemia, but like many other small-molecule drugs, it has low aqueous solubility. As a consequence, Parthenolide can only be administered clinically in the presence of harmful cosolvents. Accordingly, we describe the synthesis, characterization, and testing of a range of biocompatible triblock copolymer micelles as particle-based delivery vectors for the hydrophobic drug Parthenolide.

Enhanced non-vitreous cryopreservation of immortalized and primary cells by ice-growth inhibiting polymers.

Cell cryopreservation is an essential tool in modern biotechnology and medicine. The ability to freeze, store and distribute materials underpins basic cell biology and enables storage of donor cells needed for transplantation and regenerative medicine. However, many cell types do not survive freezing and the current state-of-the-art involves the addition of significant amounts of organic solvents as cryoprotectants, which themselves can be cytotoxic, or simply interfere with assays.

Glycerol-Free Cryopreservation of Red Blood Cells Enabled by Ice-Recrystallization-Inhibiting Polymers.

Cryopreservation is fundamental in prolonging the viabilities of cells and tissues of clinical and biotechnological relevance ex vivo. Furthermore, there is an increasing need to address storage at more easily accessible temperatures in the developing world because of limited resources. Here, the cryopreservation of erythrocytes (red blood cells) with storage at -20 °C using hydroxyethyl starch (HES) and the ice recrystallization inhibitor poly(vinyl alcohol) (PVA), which is a biomimetic of naturally occurring antifreeze (glyco)proteins (AF(G)Ps), is described.

Using molecular rotors to probe gelation.

A series of fluorescent probes, including a number of molecular rotors, have been used to follow the self-assembly of dipeptide-based low molecular weight gelators. We show that these probes can be used to gain an insight into the assembly process. Thioflavin T, a commonly used stain for β-sheets, appears to act as a molecular rotor in these gelling systems, with the fluorescence data closely matching that of other rotors.

Synthesis and characterisation of glucose-functional glycopolymers and gold nanoparticles: study of their potential interactions with ovine red blood cells.

Carbohydrate-protein interactions can assist with the targeting of polymer- and nano-delivery systems. However, some potential protein targets are not specific to a single cell type, resulting in reductions in their efficacy due to undesirable non-specific cellular interactions. The glucose transporter 1 (GLUT-1) is expressed to different extents on most cells in the vasculature, including human red blood cells and on cancerous tissue.

Synthetic polymers enable non-vitreous cellular cryopreservation by reducing ice crystal growth during thawing.

The cryopreservation of cells, tissue and organs is fundamental to modern biotechnology, transplantation medicine and chemical biology. The current state-of-the-art method of cryopreservation is the addition of large amounts of organic solvents such as glycerol or dimethyl sulfoxide, to promote vitrification and prevent ice formation. Here we employ a synthetic, biomimetic, polymer, which is capable of slowing the growth of ice crystals in a manner similar to antifreeze (glyco)proteins to enhance the cryopreservation of sheep and human red blood cells.

Uptake of poly(2-hydroxypropylmethacrylamide)-coated gold nanoparticles in microvascular endothelial cells and transport across the blood-brain barrier.

The facile and modular functionalization of gold nanoparticles makes them versatile tools in nanomedicine, for instance, photothermal therapy, contrast agents or as model nanoparticles to probe drug-delivery mechanisms. Since endothelial cells from various locations in the body exhibit unique phenotypes we quantitatively examined the amount of different sized poly(2-hydroxypropylmethacrylamide)-coated gold nanoparticles internalized into primary human dermal endothelial cells or human brain endothelial cells (hCMEC/D3) by inductively coupled plasma atomic emission spectroscopy (ICP-AES) and visualized the nanoparticles using light and electron microscopy. Poly(2-hydroxypropylmethacrylamide)-coated gold nanoparticles exhibited high uptake into brain endothelial cells and were used to examine transport mechanisms across the blood-brain barrier using a well-established in vitro model of the blood-brain barrier.

Ice recrystallisation inhibition by polyols: comparison of molecular and macromolecular inhibitors and role of hydrophobic units.

The ability of polyols to act as ice recrystallisation inhibitors (IRI), inspired by antifreeze (glyco)proteins are studied. Poly(vinyl alcohol), PVA, a known IRI active polymer was compared to a panel of mono and polysaccharides, with the aim of elucidating why some polyols are active and others show no activity. When corrected for total hydroxyl concentration all the carbohydrate-based polyols displayed near identical activity with no significant influence of molecular weight.

Exploiting thermoresponsive polymers to modulate lipophilicity: interactions with model membranes.

Upon heating above their lower critical solution temperature (LCST) poly[oligo(ethyleneglycol)methacrylate]s (POEGMA) were shown to undergo a shift in their partition coefficient triggering aqueous to organic phase transfer, which indicated their potential to partition into cell membranes upon application of an external stimulus. Fluorescence-based assays indicated that the LCST transition did not induce lysis of model phospholipid vesicles but did promote fusion, as confirmed by dynamic light scattering. Membrane perturbation assays and linear dichroism spectroscopy investigations suggest that POEGMAs above their transition temperatures can interact with, or insert into, membranes.