Preclinical assessment procedures for wound dressings have been established with the clinical situation in mind, taking into account the important parameters of tensile mechanical properties, conformability to body surfaces, water vapour transmission rate (WVTR) and gaseous transmission (GTR) to 0₂ and CO₂. The mechanical (tensile) properties, the WVTR and the GTR's are measured by modified international standards. These are ASTM D882-81, ASTM E96-81 and BS 2782 respectively. The mechanical test is basically a uniaxial test taken to failure, from which the stress-strain characteristics and the ultimate strength of the material are determined. The WVTR is determined by measuring the rate of water loss from a container, covered with the dressing being evaluated, under controlled humidity conditions. Gaseous transmission, to both oxygen and carbon dioxide, is determined by the British Standard Vacuum technique. This method was used only for the assessment of the hydrophobic dressings. A liquid to gas technique was employed to assess the hydrophilic (water containing) dressings in respect to their transmission characteristics. Conformability is measured by an inflation test. At a pressure of 40 mmHg, a radius of curvature is calculated from the incremental change in height of the central point of a disc of the material under test. Viscoelastic tests were carried out to determine if any of the materials showed viscoelastic behaviour. These properties are of importance in the application of pretensioned dressings. A series of commercial and experimental materials were evaluated using the techniques described above. Some of the materials were assessed as a bi-laminate form, with a Mefix (adhesive bandage) top layer. Such a layer generally proved beneficial with regard to their possible clinical performance. Clinical studies were carried out for both in situ water vapour transmission and conformability. Such studies were carried out to provide a correlation between the laboratory and clinical situations. By providing an indication of possible clinical problems, preclinical assessment is of importance to clinicians and manufacturers.

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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.

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.

Complications during the healing process of skin wounds often arise due to infection by pathogenic bacteria. Bacterial hydrolytic enzymes degrade the host tissue while biofilms can shield the bacterial cells from the host's immune response. Wound dressings with bacteriostatic or bactericidal properties are a promising solution. This study investigated the potential of surface acetylated bacterial cellulose as a novel antibacterial wound dressing. Hydroxyl groups on the surface of bacterial cellulose were substituted with acetyl groups using acetic anhydride in a citric acid-catalyzed reaction. The resulting ester linkages between the acetyl groups and bacterial cellulose surface were hypothesized to be cleaved by bacterial esterases or other hydrolytic enzymes such that acetic acid, a well-known antibacterial compound, will be produced leading to the death of the bacterial cells. Surface acetylation was confirmed via FTIR and its effect on the morphology of bacterial cellulose was analyzed with FESEM and XRD while the degree of substitution was determined by HPLC-UV. Indirect contact human cell cytotoxicity assays using extracts from surface acetylated bacterial cellulose showed no cytotoxic effect on human umbilical vein endothelial cells. Two types of antibacterial assays were performed in which surface acetylated bacterial cellulose was exposed to Staphylococcus epidermidis, Escherichia coli, and Pseudomonas aeruginosa which were selected as model bacteria for Gram-positive, Gram-negative, and pathogenic bacterial species, respectively. Neither assay showed a reduction of bacterial cell viability. Further research is needed to determine if the acetyl ester linkages on the surface of bacterial cellulose are susceptible to cleavage by bacterial esterase enzymes. / Master of Science / The healing of skin wounds is frequently complicated by infection of the wound with harmful bacteria. A potential remedy could be wound dressings that kill such bacteria. Bacterial cellulose is a naturally occurring biomaterial with multiple properties that make it an ideal material for wound dressings. Pure bacterial cellulose has no inherent antibacterial properties but can be chemically modified with a separate substance that is antibacterial such as acetic acid. This study investigates the potential of chemically modified bacterial cellulose in antibacterial wound dressing applications. The material may release acetic acid in the presence of bacteria and cause cell death. A series of human cell and antibacterial assays were carried out to test the ability of the modified bacterial cellulose to inhibit bacterial growth as well as any potential harmful effect on human cells. While it showed no adverse effects on human cells, the modified bacterial cellulose did not reduce bacterial cell viability.

A novel dendritic wound dressing was designed and characterized for its potential to treat chronic wounds. Comprised of gelatin, dendrimer, synthetic polymer and antibiotics, the dressing was electrospun to mimic the natural extracellular matrix (ECM). Gelatin is biocompatible, biodegradable, non-toxic, and easily available. The antibiotic, doxycycline, has the ability to inhibit matrix metalloproteinases. Matrix metalloproteinases, which occur in excess in chronic wounds, degrade the reconstituted ECM. Starburst™ polyamidoamine (PAMAM) dendrimer G3.5, which provides a versatile and structurally controlled architecture to construct nanomedicine, was covalently bonded to the gelatin backbone and electrospun into nanofibers with gelatin, doxycycline and stabilizing polymers. The proposed gelatin/dendrimer hybrid provides a bacterial free environment and mimics the ECM to promote wound healing. The development of this new polymeric matrix is an important step in advancing the use of bioactive nanofibers with targeted and controlled drug delivery as a wound dressing.

In this study, it was aimed to produce sericine/collagen composite membranes and to investigate their properties as a wound dressing. Different membrane compositions were prepared by casting and solvent evaporation method. After initial studies for optimization of ratios, membrane groups at two different thicknesses were prepared for each selected ratio and cross-linked with 3 % (w/v) glutaraldehyde (GTA). Considering the wound dressing requirements, equilibrium degree of swelling (EDS), water vapor transmission rate (WVTR), oxygen permeability, mechanical properties, in situ degradation, microbial penetration and cytotoxicity of membranes were examined. The EDS of membranes had a range of 14.91 to 4.37 (g/g) and increased significantly with the presence of sericin. There was no obvious relationship between the sericin ratio of membranes and WVTR, but the increase in membrane thickness decreased WVTR significantly. Thin and sericin containing membranes had statistically better oxygen permeabilities. Sericin deteriorated the tensile strength and elongation of membranes statistically. Cross-linked groups were resistant to hydrolytic degradation through 4 weeks of incubations. None of the membranes were penetrable to bacteria owing to their dense structure. For cytotoxicity studies, 3T3 fibroblasts and keratinocytes were seeded on membranes separately, and analyzed with MTT assays, and light microscopy and scanning electron microscopy (SEM). As regards to MTT assay, keratinocytes proliferated significantly on membranes and reached to high confluence within 7 days. Similarly, fibroblasts also showed high proliferation on membranes. Light microscopy and SEM analysis showed that both cells could attach, grow and spread on membranes. Also, cells gained their characteristic morphology after 1 day and formed flattened structure within 7 days.

The treatment of epidermal wounds, particularly chronic wounds, is one of the most ubiquitous medical challenges and has imposed a considerable financial burden on the global health care system. Several factors in epidermal wounds lead to severe medical conditions among which infection comprises a large number of mortalities. To tackle this issue, great efforts have been made in the last decades to incorporate antimicrobial agents into wound dressings in order to inhibit microorganism colonization. Additionally, various wound monitoring systems have been developed to detect and track infections using different indicators such as bacterial by-products. However, the integration of these infection sensors with wound dressings – most of which have benefited from electrochemical detectors – has been a major bottleneck due to the electrode failure in the wound environment and the need for electrical power supply. Other approaches have focused on the development of point-of-care devices that simplify the detection of infection. This study aims to address the aforementioned challenge by developing a multifunctional hydrogel-based wound dressing – made of alginate 1.5% (w/v) – for on-site infection monitoring via colourimetric and image processing methods. Taking advantage of wound acidity as an indicator of bacterial infection, the developed wound dressing was composed of an array of pH sensors, fabricated by 3-dimensional (3D) bioprinting. Brilliant Yellow and cabbage juice as two pH-responsive dyes were immobilized in the pH sensors to facilitate a wireless wound monitoring. In this system, Brilliant Yellow afforded a higher accuracy in image processing while cabbage juice provided a better visual observation of the wound condition. The functionality of the developed dressing in detecting bacterial infection was evaluated via an ex-vivo test on pig skin samples, infected by Pseudomonas aeruginosa, and the presence of bacteria was detected within 30 minutes after the placement of the dressings on the skin samples. Moreover, the inclusion of gentamicin-loaded components into the wound dressing facilitated the inhibition of bacterial growth, which was evaluated in vitro on the same strain of bacteria. In this experiment, 2 mg/ml of gentamicin in the hydrogel led to the eradication of P. aeruginosa. This incorporation of antibiotic delivery along with the simple colourimetric infection detection holds a great promise for managing acute and chronic wounds by inhibition of bacterial growth and monitoring infection in real-time without a need for dressing removal. / Graduate / 2018-08-16

No / Knowledge of clinically and cost-effective wound management is an obvious requirement for surgeons, yet wound care education rarely features within the medical curriculum. As a result surgical trainees are often poorly placed to join in multidisciplinary wound management and may feel threatened when asked to manage wound complications. A vast range of dressing products exists yet robust evidence of the function and effectiveness of individual products is often lacking. An understanding of wound pathophysiology, a defined treatment goal and regular wound assessment combined with knowledge of basic wound dressing categories will provide guidance on product selection for different clinical situations and wound types.

No / Knowledge of clinically and cost-effective wound management is an obvious requirement for surgeons, yet wound care education rarely features within the medical curriculum. As a result surgical trainees are often poorly placed to join in multidisciplinary wound management and may feel threatened when asked to manage wound complications. A vast range of dressing products exists yet robust evidence of the function and effectiveness of individual products is often lacking. An understanding of wound pathophysiology, a defined treatment goal and regular wound assessment combined with knowledge of basic wound dressing categories will provide guidance on product selection for different clinical situations and wound types.