Saudi Cultural Missions Theses & Dissertations

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    Understanding the Therapeutic Role of Mesenchymal Stem Cells in Bacterial Skin Infections
    (Saudi Digital Library, 2025) Aljohani, Roaa; Morse, Daniel; Still, Karen
    Chronic wounds are a significant clinical problem due to persistent bacterial infections and slow tissue healing, which increase the burden on patients and healthcare systems. Conventional treatments, such as wound cleaning and antibiotics, often show limited effectiveness, especially with the rise of antibiotic-resistant strains of Staphylococcus aureus. This emphasizes the need for alternative biological approaches that can both limit infection and support tissue repair. This study examined the potential of bone marrow-derived mesenchymal stem cell-conditioned medium (MSC-CM) to inhibit bacterial growth and promote tissue regeneration. Various concentrations of MSC-CM were applied to S. aureus, including the JE2 strain, using growth inhibition assays, and Gene expression was also analyzed in human mesenchymal stem cells (MSCs), human dermal fibroblasts (HDFs), and bacterial virulence genes. For MSCs and HDFs, qPCR was used to evaluate cellular responses related to metabolism and tissue repair. For the virulence genes, qPCR was performed to assess whether the conditioned media resulted in a decrease in their expression. Results demonstrated that higher concentrations of MSC-CM substantially reduced the growth of S. aureus across all tested media, while the JE2 strain showed a decrease in lower concentrations. Expression of bacterial virulence genes, agr and mecA, decreased significantly under higher treatment. MSCs showed increased expression of PDK4 and EFNA3, indicating significant activation of these genes. Fibroblast responses were more variable and less consistent. These findings indicate that MSC-CM may have a dual role by contributing to the reduction of bacterial growth while also influencing cellular pathways associated with tissue repair. This highlights MSC-CM as a promising multifunctional approach for treating chronic wounds. Future studies should aim to identify the most active components of MSC-CM, investigate its effects on bacterial properties such as biofilm formation and strength, and evaluate its efficacy in animal models to advance clinical applications.
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    Decoding the Human Skin Ulcer Niche using Spatial Transcriptomics and Bioinformatics
    (Saudi Digital Library., 2025) Khawaja, Roseanne; Cash, Jenna
    What is already known about this subject? Venous leg ulcers (VLUs) are the most common form of chronic wounds and often arise from lipodermatosclerosis (LDS), a fibrotic pre-ulcer condition caused by chronic venous insufficiency. Despite their prevalence and burden, the molecular mechanisms driving the transition from LDS to VLU remain poorly defined. Most previous studies have relied on bulk transcriptomics or single-cell approaches, which lose critical spatial context and therefore cannot fully capture the architecture and heterogeneity of chronic wounds. What are the new findings? This study provides the first spatial transcriptomic comparison of LDS and VLU tissue using the high-resolution Visium HD platform. LDS tissue was characterized by uniform extracellular matrix producing fibroblasts and terminally differentiating keratinocytes, reflecting a fibrotic dermal state. In contrast, VLUs exhibited marked heterogeneity, with epidermal clusters showing both hyperproliferative and terminal keratinocyte states, dermal infiltrates dominated by plasma cells, and fibroblast subtypes spanning fibrotic, vascular, inflammatory, and endothelial-like programs. These findings reveal distinct cellular niches that underpin fibrotic stability in LDS versus disrupted repair in VLUs. How might it impact on the field in the foreseeable future? By providing a spatially resolved map of chronic venous disease progression, this study identifies fibroblast and immune subtypes as potential therapeutic targets and highlights biological programs that may drive wound progression. These insights lay the foundation for translational strategies to stratify patients according to fibrotic (LDS) or inflammatory/heterogeneous (VLU) phenotypes, with potential to inform more precise and effective management of chronic wounds.
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    Identifying the Therapeutic Application of Cold Atmospheric Plasma in Chronic Wound Healing: A Scoping Review
    (King's college london, 2024) Fallatah, Alaa; Dyson, Alex
    Background: Cold atmospheric plasma (CAP) is a plasma that is generated through the application of electric or electromagnetic fields to a gas operates at a low temperature and is produced under atmospheric pressure, making it suitable for medical applications. It has demonstrated beneficial effects in various medical fields, including oncology, dentistry, and dermatology. Chronic wounds are a type of wounds that are difficult to heal, which can negatively impact individual quality of life, different treatment modalities are used to treat chronic wounds. However, due to the complexity of chronic wounds new therapies are required to address these complexities. CAP therapy has shown promising results in promoting wound healing. This review aims to assess these existing data on the application of CAP therapy in chronic wound healing. Objective: Explore the mechanisms by which Cold Atmospheric Plasma (CAP) therapy promotes chronic wound healing, assess its effectiveness across various chronic wound types, and identify the optimal treatment duration to balance both efficacy and safety in chronic wound care. Methods: A scoping review was conducted of English language articles published from 2019 onward that focus on the application of cold plasma therapy in chronic wound healing. A comprehensive literature search was performed across four databases—PubMed, Embase, Google Scholar, and ClinicalTrials.gov. Both clinical and pre-clinical studies were included. Articles were assessed for inclusion, and data were extracted from those deemed relevant. A thematic analysis was then conducted to identify recurring themes within the data. Results: Following the initial broad screening of relevant articles, 36 studies were selected for detailed analysis. The thematic analysis revealed six key themes, including patient characteristics, treatment outcome, patients-reported outcome, CAP therapy protocol, mechanisms of wound healing, and correlations each theme offers an insight into the use of cold plasma therapy for chronic wound healing. The data indicates that cold plasma therapy lacks follow-up studies, a lack of standardization in the application of cold plasma therapy for chronic wound healing, and an underrepresentation of various types of chronic wounds in the research. Conclusion: This review highlights the promising potential of cold plasma therapy (CAP) for chronic wound healing while identifying critical research gaps. Future research should address these gaps to better gauge the full therapeutic potential of CAP therapy in healing chronic wounds.
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    The effect of components of electrospun material on S. aureus, P. aeruginosa and E. coli bacterial growth and biofilm formation
    (Saudi Digital Library, 2023-11-28) Alomair, Munirah; Powell, Lydia
    The prevalence of chronic wounds in immunocompromised patients has risen recently, leading to increased morbidity and mortality rates. The emergence of antibiotic resistance has necessitated novel technology for the treatment of these wounds. In order to provide a bespoke wound dressing for patients, Corryn Biotechnologies is developing an innovative device that electrospins a polymer solution directly onto a wound. The antibiotic activity of the electrospun components, namely dimethyl sulfoxide (DMSO), collagen 1, acetone and a non-disclosed polymer solution, were tested against gram-positive methicillin-resistant Staphylococcus aureus (MRSA 1004A) and gram-negative Pseudomonas aeruginosa PAO1 and Escherichia coli IR57 in both planktonic and biofilm assays to determine their effect on bacterial growth and biofilm formation. Minimum inhibitory concentration (MIC) assays were used to evaluate the effect of DMSO against MRSA 1004A, P. aeruginosa PAO1, and E. coli IR57, with resultant MICs of 25%, 6.25%, and 12.5%, respectively. The MICs of collagen 1 and acetone were >50% for both gram-positive and gram-negative bacteria. Confocal laser scanning microscopy (CLSM) revealed that DMSO significant inhibited the formation of MRSA 1004A biofilm biomass at both concentrations of 1/2 MIC DMSO (p<0.0001) and 1/4 MIC DMSO (p=0.0017), with increased cell death achieved with 1/2 MIC DMSO treatment (p=0.0003). The MRSA 1004A biofilm roughness significantly increased with 1/2 MIC DMSO (p=0.0008), but the average thickness area and average thickness biomass were significantly decreased (both p<0.0001) at 1/2 MIC DMSO treatment. The P. aeruginosa PAO1 biofilm biomass significantly increased with 1/2 MIC DMSO treatment (p=0.03), while cellular death decreased with 1/4 MIC DMSO treatment (p=0.038). The effects of the components of the electrospun solution against the most common strains of gram-positive and gram-negative bacteria in chronic wounds highlight the potential application of these components to form a bespoke wound dressing to reduce biofilm formation and aid in chronic wound healing.
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