Tag: Wound Care

  • How microbes influence healing and infection risks

    How microbes influence healing and infection risks

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    In a recent Nature Reviews Microbiology study, researchers review how the wound microbiota interferes with skin repair processes and facilitates infection onset by modulating host immune responses.

    Study: The wound microbiota: microbial mechanisms of impaired wound healing and infection. Image Credit: A3pfamily / Shutterstock.com

    Background

    The skin protects the human body from the potentially harmful effects of invading pathogens and chemicals. Any injury or damage to the skin can lead to wound development; therefore, dressing and infection control are standard practices of wound care.

    The wound-healing process involves coagulation, hemostasis, inflammation, cell proliferation and migration, and tissue remodeling. Any alteration to these processes can lead to delayed wound healing and the development of a chronic wound.

    Non-healing and chronic wounds are associated with certain risk factors, including advanced age and the presence of specific comorbidities, such as diabetes, obesity, systemic diseases, immunosuppressive diseases, and autoimmune diseases.

    Microorganisms colonizing in wounds, collectively referred to as the wound microbiota, can significantly impact the healing process. While some microorganisms facilitate faster skin repair, some can acquire virulence factors and antibiotic resistance, thereby increasing the risk of infection.

    Both exogenous and endogenous microorganisms can contaminate an open wound. The wound can facilitate microbial growth by exposing subcutaneous tissues and nutrients, which can subsequently lead to the colonization of microorganisms in the wound. This type of colonization can cause local infection and biofilm formation, which has the potential to spread to other tissues and organs.

    Wound microbiota composition

    The most common microbial populations found in both acute and chronic wounds include Staphylococcus spp., Pseudomonas spp., Corynebacterium spp., Enterococcus spp., Streptococcus spp. and Cutibacterium spp, all of which are microorganisms that are also commonly found in healthy skin microbiota.

    Staphylococcus aureus

    A skin wound can significantly alter its surrounding environment through the secretion of molecules from damaged tissues to support the growth, invasion, adhesion, and migration of pathogens such as Staphylococcus aureus. High abundance of fibronectin- and collagen-binding proteins facilitates Staphylococcus aureus to easily invade broken skin and induce intracellular infection.

    Staphylococcus aureus also produces pore-forming toxins that disrupt the host cell membrane to prevent immune clearance. Furthermore, serine proteases produced by this bacterium act as enterotoxins that induce chronic inflammation and create severe, non-healing diabetic wounds.

    Staphylococcus aureus has multiple master regulators, including the accessory gene regulator quorum-sensing system and sarA, which help activate its virulence factors. Glucose transporters acquired by Staphylococcus aureus further induce the production of virulence factors under hyperglycemic conditions.

    Pseudomonas aeruginosa

    Pseudomonas aeruginosa is a pathogen that can be found in burn wounds, chronic surgical wounds, and diabetic wounds. High-level antibiotic resistance and robust ability to form biofilm allow Pseudomonas aeruginosa to create chronic and non-healing wounds. Pseudomonas aeruginosa also comprises a type III secretion system that controls the production of effector toxins, further facilitating the production of virulence factors.

    Streptococcus

    Streptococcus spp., including β-Hemolytic group A streptococci (GAS), group B streptococci (GBS), and group C streptococci, can be found in invasive and non-invasive wounds.

    GAS bacteria contain multiple adhesins that promote their access to diverse tissue surfaces. Virulence factors present in GAS bacteria work in synergy to bind to and activate host plasminogens and create a proteolytic environment that alters wound-site architecture.    

    Anaerobic bacteria

    Anaerobic bacteria commonly found in wound infections include Finegoldia magna, B. fragilis, and Clostridium perfringens. These bacteria can be introduced to the wound during injury, such as bite or abdominal penetrating wounds. In diabetic or other chronic wounds, these bacteria thrive in conditions of low tissue oxygenation and can exist in mixed facultative and obligate anaerobes communities.

    Fungi

    Candida albicans is a fungal species most commonly found in chronic, surgical, and burn wounds. These fungi can enter host cells by binding to E-cadherin and triggering endocytosis. The pathogenicity of C. albicans is dependent on its ability to switch between yeast and a highly invasive hyphal phenotype.

    Viruses

    Viruses can also impact wound healing and skin repair processes. Whereas specific bacteriophages can worsen wound infections by increasing the virulence of bacteria they have infected, other bacteriophages can improve wound healing by changing bacterial virulence.

    Risk factors for wound infection

    The outcomes of wound microbial infections primarily depend on microbial virulence, polymicrobial interactions, and complex crosstalk between microbes and the wound microenvironment.

    Multidrug-resistant pathogens, including methicillin-resistant Staphylococcus aureus (MRSA) or multidrug-resistant Pseudomonas aeruginosa, can complicate the treatment of wound infections. Likewise, a compromised immune system or certain genetic factors can further delay the wound-healing process and increase the risk of infection.

    Microbial virulence is also an important determinant of wound outcomes and treatment modalities. Wound bioburden, characterized by microbial load, microbial diversity, and the presence of pathogenic microbes, is a key contributor to delayed wound healing and infection onset.

    Journal reference:

    • Uberoi, A., McCready-Vangi, A., & Grice, E. A. (2024). The wound microbiota: microbial mechanisms of impaired wound healing and infection. Nature Reviews Microbiology. doi:10.1038/s41579-024-01035-z.

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  • SolasCure publishes phase IIa clinical trial report in leading wound care journal

    SolasCure publishes phase IIa clinical trial report in leading wound care journal

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    SOLASCURE Ltd (SolasCure), a biotechnology company developing a novel treatment to transform chronic wound care, has today announced the publication of its CLEANVLU Phase IIa clinical trial report in the International Wound Journal, a leading wound care journal. 

    SolasCure’s first investigational product, Aurase Wound Gel, is a hydrogel releasing tarumase (provisional INN), a recombinant enzyme derived from medical maggots, which aims to promote wound healing through debridement and wound bed preparation.

    The Phase IIa data, which demonstrates proof-of-concept and safety of Aurase Wound Gel in humans, has now been peer-reviewed and published, providing strong validation as SolasCure progresses into further clinical studies, and marks a significant milestone for the Company.

    Chronic wounds are a major healthcare challenge, with around 100 million people suffering from these wounds globally. This represents a significant unmet need as patients and healthcare systems lack safe, pain-free, and effective treatment solutions.

    Recent clinical data suggest that, after 20 weeks of the current standard of care treatment, complete wound closure is achieved in as little as 25%–50% of chronic or hard-to-heal wounds.2 Aurase Wound Gel aims to address this global challenge by being the first treatment to target all elements of wound bed preparation: debridement, moisture provision, infection control and overall promotion of healing.

    SolasCure’s CLEANVLU Phase IIa trial was performed in venous leg ulcer (VLU) patients across centers in the US, UK, and Hungary. The trial compared five escalating dose concentrations to baseline the use of tarumase for enzymatic debridement and wound bed preparation. Patients were treated three times per week, for four weeks.

    The study established proof-of-concept that tarumase successfully debrides wounds, with faster and more complete debridement and improved healing observed at increased enzyme concentrations. The trial also demonstrated a strong safety profile, with no indications of systemic absorption, antibody generation, or systemic effects on coagulation.

    Significantly, application of Aurase Wound Gel was shown to be pain-free, did not add to the patients’ existing pain burden, and had no evidence of local tolerability issues.

    Further Phase II studies plan to use randomized controlled groups over a longer period, with stratification for factors that may affect debridement and wound healing, to explore the efficacy of tarumase at higher concentrations.

    “The opportunity for Aurase Wound Gel to truly transform chronic wound care is very exciting, as no other treatment to date aims to target all elements of wound care management in a single product. The peer-review publication of our Phase IIa data not only provides important validation to enable further Phase II studies, but also highlights the clinical potential of Aurase Wound Gel to treat millions of patients globally safely and effectively, addressing an urgent and unmet medical need. With this excellent data we are now fundraising to support the next phase of SolasCure’s clinical and product development.”   

    Andy Weymann MD, MBA, Chairman of the Board, SolasCure

    Debridement is a key first step of successful wound bed preparation, itself a prerequisite for wound healing. Achieving timely complete and pain-free debridement which is agnostic of the patient setting is an urgent unmet medical need. SolasCure’s Aurase Wound Gel has shown in this publication positive safety and proof-of-concept results, which bring this product a significant step closer to providing relief to those suffering from chronic wounds worldwide.”

    Rob Kirsner, MD, Ph.D, Head of Medical Advisory Board at SolasCure, Chairman and Harvey Blank Professor of Dermatology at the University of Miami

    For more information about SolasCure, please visit: https://solascure.com/.

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