Restarting the Healing Process of Chronic Wounds Using a Novel Desiccant

A Prospective Case Series

Albert Cogo, PhD; Bert J. Quint, PhD; Carlo Alberto Bignozzi, PhD

Disclosures

Wounds. 2021;33(1):1-8. 

In This Article

Abstract and Introduction

Abstract

Introduction: Chronic skin wounds represent a major global health problem and financial burden. The blocked healing process of chronic wounds involves excess inflammatory proteins, persistent microbial burden, and often, drug-resistant biofilm on the wound bed. Wound-bed debridement is considered crucial to restart the healing process.

Objective: The authors developed a novel desiccant (desiccating agent A) to serve as a new form of chemical debridement. The objective is to establish the working mechanism of desiccating agent A.

Materials and Methods: Desiccating agent A was exposed to 7 pathogens in vitro and a prospective trial investigation was performed in vivo on 10 cases to establish a timeline to reach granulation.

Results: The growth of a pool of the 7 pathogens showed an inhibition ring at 24 hours was 54 mm ± 5 mm. The prospective trial investigating 10 cases (5 females, 5 males) had a median age of 72.5 years (range, 50–90 years). The duration of the ulcers ranged from 6 weeks to 52 weeks (interquartile range, 6–24 weeks). The wound bed (median area, 64 cm2) was rinsed and dried. Desiccating agent A was applied directly to the wound bed with a gloved finger; after 30 to 60 seconds, desiccating agent A was rinsed and the remaining desiccated material was mechanically removed with dry sterile gauze. The wound bed was dried and covered with sterile gauze soaked in fitostimoline; dressings were changed as needed. The only observed side effect, transient pain, graded on a visual analog scale. Pain intensity ranged from 1 to 7 on a scale from 0 to 10. No nodules, welts, or blisters were observed. Median time to full granulation was 20.5 days (range, 7–78 days).

Conclusions: These data support continued development of desiccating agent A as a chemical debridement agent.

Introduction

Chronic skin wounds represent a major global health problem and financial burden.[1,2] Their prevalence among the general population is approximately 1.5% and is higher among the elderly.[2] Because risk factors include increased age and comorbidities such as diabetes, which is occurring in increasingly younger populations, the incidence of chronic skin wounds is expected to rise in the next decade.[2,3] In particular populations, such as patients with diabetes, the prevalence of chronic ulcers ranges from 1.5% in Australia to 13% in North America and 16.6% in Belgium.[2,4]

Wounds that have failed to heal or reduce in size by 4 weeks to 12 weeks are considered to be chronic wounds.[3,5] The healing of chronic wounds is dependent on their size as well as the patient's health status, concurrent medications, and treatments.[6] The healing process of chronic wounds usually ranges from 6 weeks to more than 1 year, including wounds treated at specialized wound care clinics. Chronic wounds with different etiologies (venous insufficiency, peripheral arterial disease, diabetic neuropathy, pressure ulcers, and vasculitis) share several mechanisms that can halt the healing process: the presence of excessive inflammatory cells and proteins (cytokines and proteases),[7] persistent low-grade microbial burden, and often drug-resistant biofilm.[6] Excessive and prolonged presence of inflammatory mediators, proinflammatory macrophages, and neutrophils in the wound bed contribute to the development and persistence of chronic wounds.[7] These mechanisms can inhibit progression through the 3 steps of wound healing: removal of necrotic and nonvital material (autolytic debridement) by inflammation (eg, macrophages), neovascular growth, and proliferation of dermal/epidermal cells.

Biofilms consist of an extracellular polymeric matrix that shelters aggregates of bacteria and/or fungi so they are extremely tolerant to antimicrobial treatment and the host defense.[8,9] Chronic wounds vary in the extent of microbial burden and presence of biofilm, which has been observed microscopically in the chronic wounds of 60% to 100% of patients.[9,10] Chronic wound microbiota (top 30 species) from approximately 80% of patients (35/43) induced slough and exudate in a murine chronic wound model, indicating that microbiota from chronic wounds can play a major role in halting the healing process.[11] Interestingly, chronic diabetic foot ulcers examined with molecular diagnosis of biofilm followed with biofilm-based wound treatment management showed faster healing, displayed a higher response rate, and cost less per patient by 68% in a retrospective comparison to those treated with standard of care.[12]

Current chronic wound management often involves surgical debridement to remove nonvital and potentially infectious materials and is combined with appropriate dressings[13] that support the TIME framework (tissue, infection/inflammation, moisture balance, and edge of wound) for the individual situation.[9] Types of debridement include surgical, chemical, enzymatic, biologic (maggots), and autolytic. Although only sharp and surgical debridement effectively remove most slough, biofilm, and nonvital tissue in a single-step procedure,[9] surgical debridement requires special teams and access to operating rooms, which are associated with high costs. Sharp debridement can be performed in some physician offices or at the bedside, depending on the facility. Reinfection is a major concern, and patient compliance can decrease with need for multiple sessions. Other types of debridement that are currently available require several weeks to be effective. Because wound management is predominately performed by nurses in the real world,[14] the authors searched for an easily administered, nonsurgical, effective wound bed debridement treatment that would in many cases restart the wound healing process.

Because research has shown that biofilm can be removed from teeth by an aqueous phenolsulfonic/sulfuric acid solution with desiccating properties,[15,16] the authors postulated that a topical desiccating agent could be beneficial in terms of antibacterial effect, biofilm destruction, and inflammatory protein denaturation and removal. As support for use in chronic wounds, Wolcott has described 3 recalcitrant wound cases in which the healing process had restarted and was continued with weekly surgical debridement followed by local treatment with an aqueous phenolsulfonic/sulfuric acid solution with desiccating properties.[17] To reduce the caustic nature of the desiccant, the authors developed a novel hygroscopic gel (henceforth desiccating agent A) that contains 99% methane sulfonic acid, dry proton acceptors, and dimethyl sulfoxide, which acts as a biofilm penetration enhancer. Herein, the authors describe the in vitro antimicrobial activity of desiccating agent A against a pool of several bacteria common in biofilms on lower extremity wounds[18] and chronic osteomyelitis of the jaw.[19] This study also shows the agent's desiccating effect on the wound bed, its effect on progression to granulation, and its side-effect profile from an initial open-label prospective case trial with patients with chronic wounds in the lower extremity. A protocol for application of desiccating agent A is presented in detail.

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