Significance: A 2018 retrospective analysis of Medicare beneficiaries identified that ∼8.2 million people had wounds with or without infections. Medicare cost estimates for acute and chronic wound treatments ranged from $28.1 billion to $96.8 billion. Highest expenses were for surgical wounds followed by diabetic foot ulcers, with a higher trend toward costs associated with outpatient wound care compared with inpatient. Increasing costs of health care, an aging population, recognition of difficult-to-treat infection threats such as biofilms, and the continued threat of diabetes and obesity worldwide make chronic wounds a substantial clinical, social, and economic challenge. Recent Advances: Chronic wounds are not a problem in an otherwise healthy population. Underlying conditions ranging from malnutrition, to stress, to metabolic syndrome, predispose patients to chronic, nonhealing wounds. From an economic point of view, the annual wound care products market is expected to reach $15-22 billion by 2024. The National Institutes of Health's (NIH) Research Portfolio Online Reporting Tool (RePORT) now lists wounds as a category. Future Directions: A continued rise in the economic, clinical, and social impact of wounds warrants a more structured approach and proportionate investment in wound care, education, and related research.

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Human Wounds and Its Burden: An Updated Compendium of Estimates.

Significance: Chronic wounds impact the quality of life (QoL) of nearly 2.5% of the total population in the United States and the management of wounds has a significant economic impact on health care. Given the aging population, the continued threat of diabetes and obesity worldwide, and the persistent problem of infection, it is expected that chronic wounds will continue to be a substantial clinical, social, and economic challenge. In 2020, the coronavirus disease (COVID) pandemic dramatically disrupted health care worldwide, including wound care. A chronic nonhealing wound (CNHW) is typically correlated with comorbidities such as diabetes, vascular deficits, hypertension, and chronic kidney disease. These risk factors make persons with CNHW at high risk for severe, sometimes lethal outcomes if infected with severe acute respiratory syndrome coronavirus 2 (pathogen causing COVID-19). The COVID-19 pandemic has impacted several aspects of the wound care continuum, including compliance with wound care visits, prompting alternative approaches (use of telemedicine and creation of videos to help with wound dressing changes among others), and encouraging a do-it-yourself wound dressing protocol and use of homemade remedies/substitutions. Recent Advances: There is a developing interest in understanding how the social determinants of health impact the QoL and outcomes of wound care patients. Furthermore, addressing wound care in the light of the COVID-19 pandemic has highlighted the importance of telemedicine options in the continuum of care. Future Directions: The economic, clinical, and social impact of wounds continues to rise and requires appropriate investment and a structured approach to wound care, education, and related research.

Human Wound and Its Burden: Updated 2020 Compendium of Estimates.

Human Wounds and Its Burden: An Updated Compendium of Estimates

Objective The objective of this work was to causatively link biofilm properties of bacterial infection to specific pathogenic mechanisms in wound healing. Background Staphylococcus aureus is one of the four most prevalent bacterial species identified in chronic wounds. Causatively linking wound pathology to biofilm properties of bacterial infection is challenging. Thus, isogenic mutant stains of S. aureus with varying degree of biofilm formation ability was studied in an established preclinical porcine model of wound biofilm infection. Methods Isogenic mutant strains of S. aureus with varying degree (ΔrexB > USA300 > ΔsarA) of biofilm-forming ability were used to infect full-thickness porcine cutaneous wounds. Results Compared with that of ΔsarA infection, wound biofilm burden was significantly higher in response to ΔrexB or USA300 infection. Biofilm infection caused degradation of cutaneous collagen, specifically collagen 1 (Col1), with ΔrexB being most pathogenic in that regard. Biofilm infection of the wound repressed wound-edge miR-143 causing upregulation of its downstream target gene matrix metalloproteinase-2. Pathogenic rise of collagenolytic matrix metalloproteinase-2 in biofilm-infected wound-edge tissue sharply decreased collagen 1/collagen 3 ratio compromising the biomechanical properties of the repaired skin. Tensile strength of the biofilm infected skin was compromised supporting the notion that healed wounds with a history of biofilm infection are likely to recur. Conclusion This study provides maiden evidence that chronic S. aureus biofilm infection in wounds results in impaired granulation tissue collagen leading to compromised wound tissue biomechanics. Clinically, such compromise in tissue repair is likely to increase wound recidivism.

Staphylococcus aureus Biofilm Infection Compromises Wound Healing by Causing Deficiencies in Granulation Tissue Collagen.

The skin provides a protective barrier to the body against the environment. Ineffective healing of damaged skin can cause a chronic wound which would increase the risk of infection and associated complications. The use of wound dressings to protect the wound and provide an optimal environment for wound repair is a common practice in the burn clinic. While traditional wound healing dressings have substantially changed the wound outcome, wound healing complications are still a challenge to healthcare. Advancements in tissue engineering, biomaterial sciences, and stem cell biology led to the development of novel dressings that not only dress the wounds but also actively contribute to the process of healing. This review discusses the various properties of the emerging wound dressings that are designed in attempts to improve wound care upon skin injury.

Emerging Innovative Wound Dressings

Objective:This study was designed to employ electroceutical principles, as an alternative to pharmacological intervention, to manage wound biofilm infection. Mechanism of action of a United States Food and Drug Administration-cleared wireless electroceutical dressing (WED) was tested in an establish

Electric Field Based Dressing Disrupts Mixed-Species Bacterial Biofilm Infection and Restores Functional Wound Healing.

This work represents the first study employing non-invasive high-resolution harmonic ultrasound imaging to longitudinally characterize skin wound healing. Burn wounds (day 0-42), on the dorsum of a domestic Yorkshire white pig were studied non-invasively using tandem digital planimetry, laser speckle imaging and dual mode (B and Doppler) ultrasound imaging. Wound depth, as measured by B-mode imaging, progressively increased until day 21 and decreased thereafter. Initially, blood flow at the wound edge increased up to day 14 and subsequently regressed to baseline levels by day 21, when the wound was more than 90% closed. Coinciding with regression of blood flow at the wound edge, there was an increase in blood flow in the wound bed. This was observed to regress by day 42. Such changes in wound angiogenesis were corroborated histologically. Gated Doppler imaging quantitated the pulse pressure of the primary feeder artery supplying the wound site. This pulse pressure markedly increased with a bimodal pattern following wounding connecting it to the induction of wound angiogenesis. Finally, ultrasound elastography measured tissue stiffness and visualized growth of new tissue over time. These studies have elegantly captured the physiological sequence of events during the process of wound healing, much of which is anticipated based on certain dynamics in play, to provide the framework for future studies on molecular mechanisms driving these processes. We conclude that the tandem use of non-invasive imaging technologies has the power to provide unprecedented insight into the dynamics of the healing skin tissue.

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High-resolution harmonics ultrasound imaging for non-invasive characterization of wound healing in a pre-clinical swine model.

Biofilm has a complex architecture and show high tolerance to host immune responses and antimicrobial agents [1]. Biofilm infection of chronic wounds often makes them very resistant to treatment, and can be a severe health problem in patients with compromised immune systems. Despite the extensive study of biofilm in the past 15 years [2], the pathogenic biofilm structures remain to be characterized. DualBeam FIB/SEM tomography is a suitable tool to investigate three-dimensional (3D) structures of biological materials at intermediate to high resolution. In order to understand the biofilm architecture in animal model and clinical chronic wound, we have studied a porcine pre-clinical wound model involving single-species and multi-species infection as well as chronic wound from a patient using FIB/SEM tomography.

Kasturi Ganesh Barki

Papers

Electric Field Based Dressing Disrupts Mixed-Species Bacterial Biofilm Infection and Restores Functional Wound Healing.

High-resolution harmonics ultrasound imaging for non-invasive characterization of wound healing in a pre-clinical swine model.

FIB/SEM Tomography of Wound Biofilm