Biofilm

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Wounds typically heal in four sequential but overlapping phases — hemostasis, inflammatory, proliferative and remodeling — ultimately leading to tissue regeneration. Healing sometimes stalls for various reasons, a key one being extensive inflammation, which disrupts the normal cascade of healing and leads to chronic and hard-to-heal wounds. A vicious cycle of ongoing inflammation, pain and poor quality of life often follows. Understanding how to break this cycle is essential for wound care clinicians who want to optimize healing outcomes and patient quality of life.

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Wound healing can stall for a number of reasons. Wounds that have not healed or significantly reduced in size after four to six weeks are considered chronic. They are characterized by a multitude of impeding factors including biofilm, excess matrix metalloproteinases (MMPs) and extracellular matrix degradation, inflammation, fibrosis, unresponsive keratinocytes and fibroblasts, and atypical growth factor signaling.

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Biofilm: Colonies of multiphenotype, free-floating bacteria that secrete a polysaccharide matrix that protects the bacteria from immune response and antibiotics.

Chronic wounds: Wounds that stall in the inflammation phase and fail to progress toward healing within 3 months are considered chronic or hard to heal.

Continuous inflammation: When wound healing becomes stalled in the inflammatory phase because of the presence of bacteria and their endotoxins, the wound is unable to move out of the inflammatory phase and into the repair phase.

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As scientists and researchers have delved deeper into the causes of wounds and wound chronicity, matrix metalloproteinases, or MMPs, have come into sharper focus. MMPs are not just present in chronic wounds — they also play an essential role in acute wounds.

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An injury to the human body initiates a wound healing chain reaction that occurs in four sequential but overlapping phases: hemostasis, inflammatory, proliferative and maturation. This post focuses on the second (inflammatory) phase, which begins after blood flow stops (i.e., hemostasis) and defender white blood cells, or leukocytes, migrate to the site of the injury — a process known as chemotaxis.

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Anoxia: A condition marked by the absence of oxygen reaching the tissues. It differs from hypoxia, in which there is a decrease in the oxygen levels to tissue.

Biocide tolerance: Demonstrating a tolerance to substances that destroy living things, such as bacteria. The initial stage in the life of biofilm can become biocide tolerant within 12 hours.

Calcium alginate: A water-insoluble, gelatinous substance that is highly absorbent. Dressings with calcium alginate can help to maintain a moist healing environment.

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Wound healing is often accompanied by bacterial infection. Many clinicians use antibiotics to treat wound infections. However, the overreliance on antibiotics is becoming an increasing concern for many global health organizations because it contributes to widespread antibiotic resistance. Excessive use of synthetic antibiotics leads to drug resistance, which poses a substantial threat to human health.

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Angiogenesis: The complex process in which the growth of normal, stable, and functional vessels is critically dependent on the coordinated interplay in space and time of different cell types and growth factors. This process involves the forming of new blood vessels from preexisting vessels by invading the wound clot to organize in a microvascular network throughout granulation tissue.

Autologous cell therapy: A therapeutic intervention that uses an individual’s cells, which are cultured and expanded outside of the body and reintroduced into the donor as a bioengineered skin substitute to aid in wound closure.

Immunomodulation: Therapeutic interventions aimed at modifying the immune response. Healing in chronic and complex wounds can be enhanced with immunomodulating agents.

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By Temple University School of Podiatric Medicine Journal Review Club

Chronic wounds require an increased amount of oxygen to help with cellular function and growth. They often manifest with biofilm, slough, and necrotic tissue, all of which deprive cells of the oxygen they need to perform vital functions. Various forms of debridement are commonly employed to rid wounds of pathological tissues that negatively affect cellular communication and growth. Sharp surgical debridement is most frequently performed by physicians. Continuous diffusion of oxygen (CDO) involves the use of humidified, purified air at 3mL/hour in conjunction with moist wound therapy (MWT) dressing. A previous paper by Niederauer et al. published in 2018 in the Journal of Wound Care, described using CDO for healing DFUs. This study showed that CDO improved the healing rate of DFUs in terms of time, chronicity, and weight-bearing ability when compared to a placebo. Additionally, the previous paper described wound size, chronicity, and adverse events.

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Bioburden: Bioburden is the number of microorganisms in a wound, and a high bioburden can cause delayed wound healing.

Biofilm: Biofilms are usually composed of mixed strains of bacteria, fungi, yeasts, algae, microbes, and other cellular debris that adhere to the wound surface.

Epibole: Epibole refers to rolled or curled-under closed wound edges. These rolled edges are thickened epidermis that may be callused, dry, scaly, and/or hyperkeratotic. When epibole is present in a wound, it signals to the body that the wound has healed, even though the wound remains open. Epibole must be resolved to allow the wound to close.