Wound-related pain is complex, integrating the experience of noncyclic acute wound pain, cyclic acute wound pain, and chronic wound pain (Krasner 1995). More than 80% of chronic wound patients report pain during wound dressing change. A constellation of physical and psychological factors may be involved in the mediation of pain during wound dressing change. A burgeoning body of evidence suggests the intricate relationship between anxiety and pain. In this study, the attachment framework was examined to determine how personal views of self (attachment anxiety) and others (attachment avoidance) may affect pain during dressing change. Attachment styles are systematic patterns of expectations, emotional reactivity, strategies for distress management and social behaviour that are based on an individual’s belief about the self and others. Internal working models are cognitive-affective schemas that guide the attachment patterns. Purpose: The purpose of this study was to explore the relationship of attachment style and pain during dressing change in an older population. In particular the study focussed on the role that anxiety, anticipatory self reported pain, and behavioural expression of pain play in this relationships. Method: A questionnaire was used in this cross-sectional study to classify 96 older subjects into four different categories of attachment styles. Subjects were asked to rate their levels of anticipatory pain and actual pain levels at different times during wound care using a numerical rating scale. Results: The results indicated that subjects experienced more pain during dressing change than at baseline. Secure subjects reported less pain and anxiety than subjects with other attachment styles. Results of regression analysis indicated that anxiety mediated the relationship between attachment and pain. Conclusion: The results of this study also support the role that attachment plays in the experience of pain in older adults. Clinicians must be cognizant of the impact of personality, anxiety, and anticipation of pain on the actual pain experience.

A new design of dual-functional polyurea microcapsules was proposed for chronic wound dressings to provide both non-leaching infection control and sustained topical drug delivery functionalities. Quaternary ammonium functionalized polyurea microcapsules (MCQs) were synthesized under mild conditions through an interfacial crosslinking reaction between branched polyethylenimine (PEI) and 2,4-toluene diisocyanate (TDI) in a dimethylformamide/cyclohexane emulsion. An in-situ modification method was developed to endow non-leaching surface antimicrobial properties to MCQs via bonding antimicrobial surfactants to surface isocyanate residues on the polyurea shells. The resultant robust MCQs with both non-leaching antimicrobial properties and sustained drug releasing properties have potential applications in medical textiles, such as chronic wound dressings, for infection control and drug delivery.

Wound-related pain is complex, integrating the experience of noncyclic acute wound pain, cyclic acute wound pain, and chronic wound pain (Krasner 1995). More than 80% of chronic wound patients report pain during wound dressing change. A constellation of physical and psychological factors may be involved in the mediation of pain during wound dressing change. A burgeoning body of evidence suggests the intricate relationship between anxiety and pain. In this study, the attachment framework was examined to determine how personal views of self (attachment anxiety) and others (attachment avoidance) may affect pain during dressing change. Attachment styles are systematic patterns of expectations, emotional reactivity, strategies for distress management and social behaviour that are based on an individual’s belief about the self and others. Internal working models are cognitive-affective schemas that guide the attachment patterns. Purpose: The purpose of this study was to explore the relationship of attachment style and pain during dressing change in an older population. In particular the study focussed on the role that anxiety, anticipatory self reported pain, and behavioural expression of pain play in this relationships. Method: A questionnaire was used in this cross-sectional study to classify 96 older subjects into four different categories of attachment styles. Subjects were asked to rate their levels of anticipatory pain and actual pain levels at different times during wound care using a numerical rating scale. Results: The results indicated that subjects experienced more pain during dressing change than at baseline. Secure subjects reported less pain and anxiety than subjects with other attachment styles. Results of regression analysis indicated that anxiety mediated the relationship between attachment and pain. Conclusion: The results of this study also support the role that attachment plays in the experience of pain in older adults. Clinicians must be cognizant of the impact of personality, anxiety, and anticipation of pain on the actual pain experience.

A new design of dual-functional polyurea microcapsules was proposed for chronic wound dressings to provide both non-leaching infection control and sustained topical drug delivery functionalities. Quaternary ammonium functionalized polyurea microcapsules (MCQs) were synthesized under mild conditions through an interfacial crosslinking reaction between branched polyethylenimine (PEI) and 2,4-toluene diisocyanate (TDI) in a dimethylformamide/cyclohexane emulsion. An in-situ modification method was developed to endow non-leaching surface antimicrobial properties to MCQs via bonding antimicrobial surfactants to surface isocyanate residues on the polyurea shells. The resultant robust MCQs with both non-leaching antimicrobial properties and sustained drug releasing properties have potential applications in medical textiles, such as chronic wound dressings, for infection control and drug delivery.

No / The increasing prevalence of chronic wounds has significant financial implications for nations with advanced healthcare provision. Although the diseases that predispose to hard-to-heal wounds are recognized, their etiology is less well understood, partly because practitioners in wound management lack specialized diagnostic support. Prognostic indicators for healing may be inherent to wound biochemistry but remain invisible under routine clinical investigation; lactate is an example of this. In this study, lactate concentration in exudate obtained from 20 patients undergoing wound management in hospital was variable but in some cases approached or exceeded 20 mM. In vitro viability studies indicated that fibroblasts and endothelial cells tolerated low levels of lactate (1-10 mM), but cell viability was severely compromised by high lactate concentrations (=20 mM). Scratched monolayer experiments revealed that cell migration was affected earlier than viability in response to increasing lactate dose, and this was shown by immunocytochemistry to be associated with cytoskeletal disruption. A prototype enzyme-based colorimetric assay for lactate generating a color change that was rapid in the context of clinical practise, and capable of functioning within a gel vehicle, was developed with point-of-care dipstick applications in mind. A randomized single-blinded trial involving 30 volunteers and using a color chart to calibrate the assay demonstrated that lactate concentration could be reliably estimated with 5 mM precision; this suggesting that "physiological" and "pathological" lactate concentration could be distinguished. The present data suggest that a dipstick-type colorimetric assay could comprise a viable diagnostic tool for identifying patients at-risk from high-wound lactate.

Hyperbaric oxygen (HBO) therapy is the intermittent inhalation of 100% oxygen at a pressure greater than one atmosphere absolute. It is an effective treatment for various inflammatory conditions, including chronic wounds which are characterized by an excessive influx of neutrophils and their prolonged persistence at the wound site. Neutrophil apoptosis and clearance have been shown to be required for resolution of inflammation. The mechanisms by which HBO aids wound healing are well documented, but its effects on cellular inflammatory response are not well understood particularly with respect to neutrophils. The hypothesis presented in this thesis is that increased oxygenation via HBO assists chronic wound healing by enhancing non-inflammatory neutrophil defences and cell death through apoptosis. An investigation was carried out into the effects of HBO on neutrophil antimicrobial function and apoptosis using differentiated HL-60 cells as an in vitro neutrophil model. The data clearly showed that a single HBO treatment for 90 min caused an increase in the oxidative burst activity of neutrophil-like cells as shown by increased NBT staining, superoxide (cytochrome c reduction) and H2O2 production (Kruskal-Wallis, P < 0.05), and phagocytosis of Staphylococcus aureus. HBO treatment displayed a pro-apoptotic effect, enhancing caspase 3/7 activity both in the presence and absence of a TNF-α stimulus (Kruskal-Wallis, P < 0.05) and causing morphological changes (observed using Giemsa and SYBR® Safe staining) associated with apoptosis. Although no consistent pattern was observed, both hyperoxia and pressure alone seemed to contribute to both the increase in antimicrobial activity and the increase in apoptosis induced by HBO in these neutrophil-like cells (Chapters 4 and 5). HBO-enhanced neutrophil clearance by macrophages was investigated using bovine neutrophils and monocyte-derived macrophages (MDMФ). A single 90 min HBO exposure significantly increased the clearance of fresh and 22 h-aged neutrophils by MDMФ (two-way ANOVA, P < 0.05), suggesting an increase in phosphatidylserine (PS) exposure in apoptotic neutrophils after HBO treatment (Chapter 6). Importantly, a long-term repetitive exposure to HBO in patients with chronic wounds caused a significant decrease in the antioxidant enzyme defence system (one-way repeated measures ANOVA, P < 0.05), plasma TNF-α and IL-1β after 30 HBO sessions, with down regulation of expression of the anti-apoptotic factors, NF-B and Bcl-2 (Chapter 7). These findings may go some way towards explaining the effectiveness of HBO treatment not only for chronic wounds but also for other inflammatory conditions that may be affected by this treatment.

Abstract Chronic wounds afflict millions worldwide, incurring significant health care costs and chronic suffering. Clinicians are often unsure about treatment, resulting in poor outcomes. Objective To determine the scope of knowledge possessed by fifth year medical students, general practitioners (GP’s) and surgical registrars, concerning chronic wound management. Design Cross sectional study Methods Deans of eight South African medical schools received letters requesting information regarding time devoted to wound-care training. Knowledge-based questionnaires were distributed to final-year students at two universities, surgical registrars at three universities and general practitioners attending refresher courses. Result. Four medical schools replied, of whom only two offered formal teaching. 162 medical students, 45 GP’s and 47 surgical registrars completed questionnaires. The overall median (25th–75th percentiles) knowledge scores for registrars, GP’s and students were 65%;(55%–70%), 55%;(45%–65%) and 45%;(35%–50%) respectively. Whereas the scores of registrars and GP’s did not differ, the student scores were significantly less. Only 32% of registrars and 18% of GP’s attained scores of 70% or more. 96% considered training to be inadequate. Interest in wound-care was only mild to moderate, with more GP’s than registrars requesting literature. Conclusions Very little, if any training on chronic wounds is offered in South Africa. The levels of knowledge cannot be considered adequate for successful treatment, nor for teaching to undergraduates. This preliminary study cannot reflect the attitudes and knowledge throughout the country; however it is clear that there is a need for improved education about these conditions that have huge clinical and economic consequences.

Bakgrund: Kroniska sår innefattas av bensår, fotsår, trycksår, diabetessår, sårskada, tumörer, reumatiska sår och vårdskador vid komplikationer efter kirurgiska ingrepp, som inte har läkt inom 6 veckor. Forskning visar att trots att förebyggande strategier används, utvecklas det sår som kräver behandling. I mötet med vården är en god omvårdnad och en god vårdrelation viktig. Bristen på dessa leder ofta till ett lidande som individen måste kämpa emot med copingstrategier. Syfte: Syftet med denna litteraturstudie var att belysa personers erfarenhet av att leva med kroniska sår. Metod: En litteraturöversikt gjordes i denna studie med 15 vetenskapliga artiklar, som bestod av både kvantitativ och kvalitativ metod. Resultat: 3 huvudkategorier identifierades: begränsningar, lidande samt coping. Deltagarna ansåg att en brist på information samt begränsningar i vardagen påverkade individens sociala umgänge och fysiska aktivitet. Smärta, skam och rädsla ledde till depression. För att hantera detta använde individerna sig av familjen och stöd av vårdpersonalen Slutsats: Det framkom att individernas dagliga liv påverkades av det kroniska såret. Den konstanta smärtan orsakade sömnsvårigheter hos individen, vilket ytterligare försvårade hanteringen av smärtan och vardagen. Kontinuitet hos vårdpersonal och i behandlingen gav personerna en trygghet och en ökad förståelse för sitt tillstånd. Det belystes att det var viktigt att vårdpersonalen ser individen bakom såret, och inte bara lägger sitt fokus på sårläkningen och behandlingen. / Bakground: Chronic wound comprises of leg ulcer, foot ulcer, decubitus, diabetic ulcer, damaged ulcer, tumors, rheumatic wounds and care damage with complications after surgical intervention, which hasn't healed within six weeks. Research gives the results of showing that, even though prevention of strategies are used, the ulcer is still developing and needs treatment. In the meeting with the healthcare, it is important to have a good nursing and a good relationship care. Lack of this often leads to suffering that the individual must endure with the aid of coping strategies. Aim: The aim of this study was to explore the persons experience of living with a chronic ulcer. Method: In this study a literature review was done, with 15 scientific articles, which consisted of both quantitative and qualitative methods. Results: 3 main categories where identified: restriction, pain and coping. The participants felt that it was lack of information and limitations in everyday life which affected the individual's social life and physical activity. Pain, shame and fear led to depression. To get the capability to handle the situation, the individuals turned to their families and care provider for support. Conclusion: As it is stated, the individuals where affected in their everyday life due to the chronic ulcer. The constant pain which is caused the sleeping disturbances in the individual´s made coping the pain and everyday life harder. Continuity with the healthcare provider and treatment gave an understanding and safety for the individuals for their condition. It was important that the health professionals not only put their focus on the healing of the wound and the treatment, they must also put attention to the individual with the wound.

A characteristic feature of chronic wounds is a prolonged inflammatory response as well as susceptibility to infection. Studies have shown that during the inflammatory response, there is a significant increase in the levels of neutrophil-derived enzymes. The purpose of this work was to determine whether the anionic macromolecule polystyrene sulfonate (PSS) and five of its salt forms, namely PSS-calcium, PSS-chlorhexidine, PSS-doxycycline, PSS-glutathione and PSS-silver are able to inhibit the activity of three of the enzymes whose levels are elevated in chronic wounds: elastase, cathepsin G and myeloperoxidase. In addition to the enzyme inhibition study, the various formulations’ antimicrobial properties were analyzed by evaluating their ability to inhibit the growth of three common clinical isolates: Staphylococcus aureus, Pseudomonas aeruginosa and Acinetobacter baumanii. It is worthy to note that the structure of PSS makes it a very flexible platform to which other molecules can be added in order to address a variety of “targets” as well as tailor quantitative strength. The results from this project showed that purified PSS and the various salt derivatives were able to inhibit elastase and cathepsin G activity. In addition, three of the therapeutic cations attached to PSS: silver, doxycycline and chlorhexidine retained their intrinsic antimicrobial properties without having an adverse effect on healthy tissue. In summary, this study demonstrated that PSS possessed an intrinsic ability to inhibit a number of proteases and that it could also be used as a delivery vehicle for other compounds with potential therapeutic value.

Chronic diabetic foot ulcers, venous leg ulcers and pressure ulcers affect a large subset of the United State population yet they remain a challenge for physicians to treat. There are many different types of products on the market for the treatment of chronic wounds. Some use living cells but only two are FDA approved to heal chronic wounds. A new type of product recently garnered attention in the wound care market because it also contains living cells: hypothermically stored amniotic tissue products. Hypothermically stored amniotic tissue is unique because it maintains living cells and offers the benefits of containing signaling molecules and maintaining an intact extra cellular matrix. While there are other types of amniotic or placental tissue products in the wound care market, they are processed by dehydration or cryopreservation which limits their capacities for maintaining living cells. This thesis will explore the potential for hypothermically processed amniotic tissue products to treat chronic wounds.