Oxygenated Hydrogel Promotes Re-Epithelialization and Reduces Inflammation in a Perturbed Wound Model in Rat.

Chronic wounds can take months or even years to heal and require proper medical intervention. Normal wound healing processes require adequate oxygen supply. Accordingly, destroyed or inefficient vasculature leads to insufficient delivery to peripheral tissues and impair healing. Oxygen is critical for vital processes such as proliferation, collagen synthesis and antibacterial defense. Hyperbaric oxygen therapy (HBOT) is commonly used to accelerate healing however, this can be costly and requires specialized training and equipment. Efforts have turned to the development of topical oxygen delivery systems. Oxysolutions has developed oxygenated gels (P407, P407/P188, nanocellulose based gel (NCG)) with high levels of dissolved oxygen. This study aims to evaluate the efficacy of these newly developed oxygenated products by assessing their impact on healing rates in a rat perturbed wound model. Here, P407/P188 oxygenated gels demonstrated greater re-epithelialization distances compared to its controls at Day 3. In addition, all oxygenated gels had a higher proportion of wounds with complete wound closure. All three oxygenated gels also minimized further escalation in inflammation from Day 3 to Day 10. This highlights the potential of this newly-developed oxygenated gels as an alternative to existing oxygen therapies.

Challenges faced in developing an ideal chronic wound model.

INTRODUCTION: Chronic wounds are a major drain on healthcare resources and can lead to substantial reductions in quality of life for those affected. Moreover, they often precede serious events such as limb amputations and premature death. In the long run, this burden is likely to escalate with an ageing population and lifestyle diseases such as obesity. Thus far, the identification of beneficial therapeutics against chronic wounds have been hindered by the lack of an ideal chronic wound animal model. Although animal models of delayed healing have been developed, none of these models fully recapitulate the complexity of the human chronic wound condition. Furthermore, most animals do not develop chronic wounds. Only the thoroughbred racehorse develops chronic ulcers. AREAS COVERED: In this review, the different characteristics of chronic wounds that highlight its complexity are described. In addition, currently available models reflecting different aspects of chronic wound pathology and their relevance to human chronic wounds are discussed. This article concludes by listing relevant features representative of an ideal chronic wound model. Additionally, alternative approaches for the development of chronic wound models are discussed. EXPERT OPINION: Delayed models of healing, including the streptozotocin diabetic model, skin flap model and magnet-induced IR models have emerged. While these models have been widely adopted for preclinical therapeutic testing, their relevance towards human chronic wounds remains debatable. In particular, current delayed healing models often fail to fully incorporate the key characteristics of chronic ulcers. Ultimately, more representative models are required to expedite the advancement of novel therapeutics to the clinic.

Changes in connexin 43 in inflammatory skin disorders: Eczema, psoriasis, and Steven-Johnson syndrome/toxic epidermal necrolysis.

BACKGROUND: Connexin 43 (Cx43) plays a central role in the inflammatory response and wound healing. Targeting Cx43 expression reduces inflammation in a variety of injuries. The expression pattern of Cx43 has not been described for many inflammatory skin diseases. OBJECTIVES: To describe the expression patterns of Cx43 in eczema, psoriasis, Steven-Johnson syndrome/toxic epidermal necrolysis. METHODS: Archival skin biopsies from patients with eczema, psoriasis, and Steven-Johnson syndrome/toxic epidermal necrosis were identified and examined, with sister sections stained for Cx43 and imaged by confocal microscopy. All samples were compared to age and site-matched normal skin controls. RESULTS: Epidermal Cx43 is reduced in acute eczema, absent in regions of spongiosis, and is highly elevated in subacute and chronic eczema. In plaque psoriasis, Cx43 is overexpressed in areas with psoriasiform hyperplasia with a fish-scale-like appearance but is lost in regions surrounding neutrophil microabscesses. Cx43 staining is strong in the neutrophils within these microabscesses. In SJS/TEN, Cx43 expression is elevated in areas bordering normal tissue but is rapidly lost in areas of keratinocyte necrosis. CONCLUSIONS: Dynamic changes in Cx43 levels are seen in inflammatory skin diseases and may represent future potential therapeutic targets.

A flexible multiplexed immunosensor for point-of-care in situ wound monitoring.

Chronic wounds arise from interruption of normal healing due to many potential pathophysiological factors. Monitoring these multivariate factors can provide personalized diagnostic information for wound management, but current sensing technologies use complex laboratory tests or track a limited number of wound parameters. We report a flexible biosensing platform for multiplexed profiling of the wound microenvironment, inflammation, and infection state at the point of care. This platform integrates a sensor array for measuring inflammatory mediators [tumor necrosis factor-α, interleukin-6 (IL-6), IL-8, and transforming growth factor-ß1], microbial burden (Staphylococcus aureus), and physicochemical parameters (temperature and pH) with a microfluidic wound exudate collector and flexible electronics for wireless, smartphone-based data readout. We demonstrate in situ multiplexed monitoring in a mouse wound model and also profile wound exudates from patients with venous leg ulcers. This technology may facilitate more timely and personalized wound management to improve chronic wound healing outcomes.

Secondary structure of cyclosporine in a spray-dried liquid crystal by FTIR.

The conformational state of cyclosporine in liquid crystalline spray-dried powders and the solution structure of cyclosporine, in a series of organic solvents where solvent dipole and hydrogen bonding ability varied, were determined. Fourier transformed infrared spectra (FTIR) were obtained on cyclosporine powders, and cyclosporine solutions in a series of organic solvents. Tetragonal crystalline cyclosporine revealed an intermolecular aggregate band at 1614 cm(-1), a beta-sheet band at 1627 cm(-1), a gamma-loop band at 1648 cm(-1), a gamma-turn band at 1658 cm(-1) (formed from a hydrogen bond between D-Ala(8)NH and MeLeu(6)Cdbond;O) and a Type II beta-turn band at 1673 cm(-1) (centered at the hydrogen bond betweenVal(5)NH to Abu(2)Cdbond;O). A similar conformation was observed in chloroform or octanol (apolar), where a second beta-sheet band emerged at 1638 cm(-1) and a turn structure associated with the beta-OH on MeBmt(1) appeared at 1685 cm(-1). However, the spray dried liquid crystal structure resembled the solution conformation in acetone or acetonitrile (hydrogen bond acceptor). The conformation in acetone suggested that the beta-sheet, gamma-loop, Type II beta-turn and MeBmt(1) turn remained intact. Interestingly, the spray-dried powder conformations did not resemble the solution structure of the solvent (ethanol) from which they had been obtained. The conformation in ethanol and methanol (hydrogen bond donor) showed only beta-sheet, gamma-turn, MeBmt(1) turn structure. Only a small population of molecules retained the Type II beta-turn. Finally, cyclosporine is essentially insoluble in water, so the water conformation has never been elucidated; however, a conformation resembling the active structure was obtained in a cosolvent solution containing both hydrogen bond donors and acceptors. This conformation is in good agreement with molecular modelling studies where cyclosporine is docked in the active site of cyclophilin. Spray-dried cyclosporine formed a liquid crystal that can be described as maintaining the Type II beta-turn, beta-sheet, and gamma-loop structures seen in crystalline material. However, the hydrogen bond between D-Ala(8)NH and MeLeu(6)Cdbond;O was disrupted.