<p>  </p> <p>Infections of dermal wounds is a growing burden for the healthcare industry, with a 2017 market exceeding $17.5 USD. As the number of patients with severe infections continues to increase year after year, there is an alarming downward trend in efficacy for traditional antibiotic treatments. In large part, this is due to the increasing development of antibiotic resistance within common bacteria strains. As microbes evolve to protect themselves from previously effective drugs, there is a growing need for new antimicrobial therapies. While alternatives exist in the market, they are largely impaired by non-selective toxicity which can cause further damage to the cells in the wound bed, as is the case with silver and other strong antiseptics, or the need for high energy, specialized equipment, as with cold atmospheric surface treatments. Gaseous ozone is a promising alternative therapy for treating these wound infections. Because ozone is a strong natural oxidant, it exhibits significant antimicrobial properties, and has also been shown to help stimulate natural wound healing in many cases. Herein is presented the design of a portable system for the topical delivery of gaseous ozone as an antimicrobial treatment for infected dermal wounds. This includes the design and characterization of the portable system and a custom ozone application dressing, the characterization of the safety and efficacy of the system using <em>in vitro</em> and <em>in vivo</em> models, and a disposable system for wound infection monitoring. The system utilizes a portable corona discharge generator to produce gaseous ozone from the ambient environment. The ozone gas is delivered through a dressing engineered to have a hydrophobic interface at the wound bed and disperse the ozone gas across the patch surface for more uniform application. The antimicrobial strength and biocompatibility of the system was optimized at varying ozone output levels. Additionally, an adjunct therapy of topical antibiotics was shown to significantly increase the strength of the treatment without leading to greater cytotoxicity. This synergistic effect between ozone and antibiotics was shown to circumvent natural bacterial resistances to antibiotics, which will have a major impact on the wound care industry. This adjunct treatment was then validated on a porcine animal model for safety and pilot results for efficacy testing. Finally, the pH sensor which can be incorporated with use of the ozone therapy enables objective monitoring of wound condition and is able to signal when appropriate infection therapy should begin. As it stands, this portable ozone wound treatment system shows great promise as an alternative therapy to improve the quality of live for millions of patients.</p>

Introduktion: Olika typer av sår skapar stort lidande för den drabbade och Negative Pressure Wound Therapy (NPWT) är en behandlingsmetod som utvecklats för att effektivisera sårläkningsprocessen. Livskvaliteten och hälsan påverkas av såret och dess utveckling, vilket gör omvårdnaden vid sårbehandling grundläggande för patientens välmående. Syfte: Syftet var att belysa hur Negative Pressure Wound Therapy påverkar patientens livskvalitet och hälsa. Metod: Polit och Beck (2012) niostegsmodell användes för litteraturstudien. Artikelsökningarna gjordes i två olika databaser samt manuella sökningar och resultatet grundades på tolv artiklar som genomgick en kvalitetsgranskning. Resultat: Fem teman identifierades påverka patientens upplevelse av behandlingen. Behandlingen påverkar den fysiska förmågan att leva ett dagligt liv och tenderar att framkalla smärta vid omläggning. Behandlingen tenderar även att på ett psykiskt påfrestande sätt påverka både det allmänna välmåendet och det sociala livet. Kunskap och information, hos både personal och patient, visades ha en inverkan på patientens livskvalitet och hälsa. Slutsats: Denna avancerade sårbehandling påverkar patientens livskvalitet och hälsa. Behandlingen innebär en fysisk påfrestning där patienten behöver bära runt på en behandlingsmaskin samt uppleva smärta. Det innebär också en psykisk påfrestning som ger utryck i stress, oro och rädsla samt en risk för isolering i det sociala livet. Det är därför av största vikt att vårdpersonal införskaffar sig och tillgodoser patientens behov av information och kunskap för att förutsättningar för en optimal omvårdnad ska kunna skapas.

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Skin is a dynamic and complex organ that relies on the interaction of different cell types,biomacromolecules and signaling molecules. Upon injury, a cascade of events occurs to quickly restore the skin’s integrity. Depending on the size and severity of the wound, a dressing is used to provide a temporary barrier to protect from dehydration, microorganisms and debris. Current wound dressings however, cannot accelerate wound healing beyond the natural rate, require frequent dressing changes, and cannot be easily removed without triggering additional pain ortissue destruction. Insulin, a peptide used to treat Type 1 diabetes, has been reported to improve the recovery of severe burn wounds. Yet, no one has successfully demonstrated a convenient and effective insulin delivery vehicle that can be used to accelerate burn wound healing. Poly(lactic-co-glycolic acid) microparticles, were shown to release bioactive insulin for a period of 25 days, stimulating human keratinocyte migration in vitro. A wound dressing made from poly(ethylene glycol) and alginate was formulated incorporating the insulin-loaded poly(lactic-co-glycolic acid) microparticles. Bioactive insulin release was achieved for nearly 3 weeks, along with favourable water handling and physical properties conducive for wound healing. Finally, in vivo testing confirmed that a constant dose of insulin from alginate-PEG sponge dressings loaded with 0.125mg, or 0.04mg/cm2 insulin, with dressing changes every 3 days, was sufficient to significantly improve wound healing by 25%, as compared to an alginate- PEG sponge dressing without insulin. Insulin releasing alginate-PEG sponge dressings are therefore, an effective method of improving burn wound healing and may serve as a delivery vehicle platform to incorporate other therapeutic molecules in the future. / Thesis (Ph.D, Chemical Engineering) -- Queen's University, 2012-12-20 17:50:47.872

Wounding of the cornea generates lateral electric fields (EFs) and initiates the expression of hepatocyte growth factor (HGF) and keratinocyte growth factor (KGF; Chiang et al., 1992; Wilson et al., 1999a). Therefore, these biologically generated EFs and endogenous growth factors may be of particular significance during wound healing. In the presence of an EF (150 mV/mm) cultured corneal epithelial cells (CECs) oriented perpendicular, directed cathodally and migrated at an enhanced rate. The induction times, induction thresholds and response patterns for these behaviours in increasing field strengths, indicated that they may operate through separate and parallel pathways. The application of either HGF or KGF enhanced the rate of CEC migration but neither affected the extent of CEC orientation or directionality. The distribution of HGF receptors (HGFR) was found to be exclusive to the cell body in the presence of an EF, the receptors accumulated cathodally. Moreover, the asymmetrical accumulation of HGFR in the presence of an EF correlated with the direction of CEC migration. The application of both HGF and an EF activated extracellular-signal regulated kinase (ERK) a mitogen-activated protein kinase. Furthermore, in the presence of an EF the observed ERK activation was greater in the cathodal facing half of the CECs. Inhibition of ERK reduced the extent of HGF and EF-enhanced CEC migration rate but did not alter EF-induced CEC cathodal directionality or perpendicular orientation. The HGF- and EF-enhancement of CEC migration rate may involve the activation of ERK and with the downstream liberation of leukotrienes and phosphorylation of MLCK, would culminate in actin contraction and polymerisation respectively. The potential clinical relevance for this work would concern the topical application of HGF and exogenous application of EFs to corneal epithelial wounds in order to augment healing in patients where this process is slow or deficient.

Dermal wound healing involves a myriad of highly regulated and sophisticated mechanisms, which are coordinated and carried out via several specialized cell types. The dominant players involved in this process include platelets, neutrophils, macrophages and fibroblasts. These cells play a vital role in the repair of the wound by orchestrating tasks such as forming a fibrin clot to stanch blood flow, removing foreign organisms and cellular debris, depositing new collagen matrix and establishing the contractile forces which eventually bridge the void caused by the initial infraction.\\[5pt] \indent Our current understanding of these mechanisms has been primarily based upon animal models. Unfortunately, these models lack insight into pathologic conditions, which plague human beings, such as keloid scar or chronic ulcer formation. Consequently, investigators have proposed a number of {\it in vivo} techniques to study wound repair in humans in order to overcome this barrier. One approach, which has been devised to increase our level of understanding of these chronic conditions, involves the cutaneous placement of a small cylindrical structure within the appendage of a human test subject.\\[5pt] \indent Researches have designed a variety of these implantable structures to examine different aspects of wound healing in both healthy subjects and individuals that experience some trauma related condition. In each case, several implants are surgically positioned at multiple locations under sterile conditions. These structures are later removed at distinct time intervals at which point they are histologically analyzed and biochemically assayed to deduce the presence of biological markers involved in the repair process. Implantable structures used in this way are often referred to as Human Implantable Models or Systems.\\[5pt] \indent Clinical studies with implantable models open up tremendous opportunities in fields such as biomathematics because they provide an experimentally controlled setting that aids in the development and validation of mathematical models. Furthermore, experiments carried out with implants greatly simplify the mathematics required to describe the repair process because they minimize the modeling of complex features associated with healing such as wound geometry and the evolution of contractile forces.\\[5pt] \indent In this work, we present a notional mathematical model, which accounts for two fundamental processes involved in the repair of an acute dermal wound. These processes include the inflammatory response and fibroplasia. Our system describes each of these events through the time evolution of four primary species or variables. These include the density of initial damage, inflammatory cells, fibroblasts and deposition of new collagen matrix. Since it is difficult to populate the equations of our model with coefficients that have been empirically derived, we fit these constants by carrying out a large number of simulations until there is reasonable agreement between the time response of the variables of our system and those reported by the literature for normal healing. Once a suitable choice of parameters has been made, we then compare simulation results with data obtained from clinical investigations. While more data is desired, we have a promising first step toward describing the primary events of wound repair within the confines of an implantable system.

Macrophages are key cells during inflammation and repair. Their activity is highly varied and requires precise regulation. The characterisation of cues coordinating macrophage functions has focussed on chemical and biological soluble mediators. Little is known about their responses to physical stimuli, in particular electric fields (EF) that are generated naturally in wounded tissue and infected tissue. Importantly, EFs are known to accelerate wound healing and limit infection but the mechanisms of this remain poorly understood. To address this gap in understanding, this study tested how key properties of human monocyte-derived macrophages are regulated by applied EFs equivalent to physiological EF strengths generated naturally. Using live-cell video microscopy, we show macrophage migration is directed anodally by EFs as low as 5 mV/mm and is EF-strength dependent, with effects peaking around 300 mV/mm. In contrast, monocytes, as macrophage-precursors, migrate in the opposite, cathodal direction. Strikingly, we show for the first time that EFs significantly enhance macrophage phagocytic uptake of a variety of targets, including carboxylate beads, apoptotic neutrophils and the nominal opportunist pathogen Candida albicans, all of which engage different classes of surface receptors. These EF-induced functional changes are accompanied by clustering of phagocytic receptors, enhanced PI3K and ERK activation, mobilization of intracellular calcium and actin polarization. EFs also selectively modulate cytokine production and augment effects of conventional polarising stimuli on cytokine secretion. Taken together, electrical signals have been identified as major contributors to the co-ordination and regulation of important human macrophage functions, including those essential for microbial clearance and healing. Our results open up a new area of research into effects of naturally occurring and clinically-applied EFs in conditions where macrophage activity is crucial.

This project focuses on the stabilisation, modification, delivery and treatment of phospholipid based vesicles for applications in advanced wound care, with a focus on paediatric burns. Vesicles, commonly referred to as liposomes or nanocapsules, are attractive drug delivery composites, due to their biocompatible properties. They have the ability to entrap active compounds within their core, which can be released at the point of use, (in vivo or ex vivo) either through passive diffusion, or in response to local environmental stimulus.