Search

Significance: Chronic wounds fail to heal in a timely manner and exhibit sustained inflammation with slow tissue repair and remodelling. They decrease mobility and quality of life, and remain a major clinical challenge in the long-term care of many patients, affecting 6.5 million individuals annually in the U.S., decreasing mobility and quality of life. Treatment costs are a major burden on the U.S. healthcare system, totalling between $25 and $100 billion annually. Chronic wound severity depends upon several factors such as comorbidities, severity of tissue damage, infection and presence of necrosis and vary greatly in their healing mechanisms. In vivo animal models are critical for studying healing pathways of chronic wounds and seek to replicate clinical factors for trials of topical, systemic, and device-based therapeutics. This comprehensive review discusses murine, rat, lapine, canine, feline and porcine models of chronic wounds., Recent Advances: Foundational chronic wound models for several species are discussed together with refinements and advances in the time period between 2015 and 2020 which have the potential for broad utility in investigating biological and device-based wound treatment therapies for human health., Critical Issues: Chronic wounds fail to heal in a timely manner and have differing aetiologies, rendering no single in vivo animal model universally applicable., Future Directions: Further studies are required to develop clinically relevant chronic wound animal model which reflect the clinical reality of the various influences of age, disease, comorbidities and gender on delayed healing and enhance understanding of the biological processes of human wound healing., (Copyright © 2021 Tissue Viability Society. Published by Elsevier Ltd. All rights reserved.)

Background: Infected wounds are painful and cannot heal, with antibiotics showing reduced efficacy. Appropriate wound electrotherapy may limit incident planktonic and polymicrobial colonization, inhibit biofilm formation and accelerate healing., Methods: The Modular Adaptive Electrotherapy Delivery System (MAEDS) is a lightweight, flexible, battery-powered disposable bandage which delivers controlled reliable electrotherapy to the wound for up to 7 days. Large full-thickness excisional wounds (6 cm diameter) were created in a porcine model and freshly cultured 0.5 McFarland green fluorescent protein-labeled Pseudomonas aeruginosa evenly applied to the wound bed. Control wounds received standard wound care, Tegaderm HP Transparent Dressing (3 M Health Care, St. Paul, MN, USA) applied in a sterile fashion. Treatment wounds received MAEDS electrotherapy for up to 28 days or until healed. Onboard Bluetooth facilitated remote real-time monitoring of MAEDS function. Dressing changes occurred on postoperative day (POD) 1, 3, 5, 7, 10, 14, 21, and 28. Punch biopsies were taken at the wound margin and center. Bacterial samples were processed to determine infection status., Results: Acute infected wounds treated with MAEDS electrotherapy were 92% smaller than baseline by POD21. Healing rate was significantly faster (p < 0.01) and infection significantly decreased (p < 0.0001) at POD10, relative to control wounds., Conclusion: The MAEDS electrotherapy can significantly inhibit infection and enhance healing rate in acute infected wounds., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2019.)

Ideally, all chronic wounds would be prevented as they can become life threatening complications. The concept that a wound produces a 'current of injury' due to the discontinuity in the electrical field of intact skin provides the basis for the concept that electrical stimulation (ES) may provide an effective treatment for chronic wounds. The optimal stimulation waveform parameters are unknown, limiting the reliability of achieving a successful clinical therapeutic outcome. In order to gain a more thorough understanding of ES for chronic wound therapy, systematic evaluation using a valid in vivo model is required. The focus of the current paper is development of the flexible modular surface stimulation (MSS) device by our group. This device can be programed to deliver a variety of clinically relevant stimulation paradigms and is essential to facilitate systematic in vivo studies. The MSS version 2.0 for small animal use provides all components of a single-channel, programmable current-controlled ES system within a lightweight, flexible, independently-powered portable device. Benchtop testing and validation indicates that custom electronics and control algorithms support the generation of high-voltage, low duty-cycle current pulses in a power-efficient manner, extending battery life and allowing ES therapy to be delivered for up to 7 days without needing to replace or disturb the wound dressing.

Study Aim: Stereophotogrammetric digital imaging enables rapid and accurate detailed 3D wound monitoring. This rich data source was used to develop a statistically validated model to provide personalized predictive healing information for chronic wounds., Materials: 147 valid wound images were obtained from a sample of 13 category III/IV pressure ulcers from 10 individuals with spinal cord injury., Methods: Statistical comparison of several models indicated the best fit for the clinical data was a personalized mixed-effects exponential model (pMEE), with initial wound size and time as predictors and observed wound size as the response variable. Random effects capture personalized differences., Results: Other models are only valid when wound size constantly decreases. This is often not achieved for clinical wounds. Our model accommodates this reality. Two criteria to determine effective healing time outcomes are proposed: r-fold wound size reduction time, t(r-fold), is defined as the time when wound size reduces to 1/r of initial size. t(δ) is defined as the time when the rate of the wound healing/size change reduces to a predetermined threshold δ < 0. Healing rate differs from patient to patient. Model development and validation indicates that accurate monitoring of wound geometry can adaptively predict healing progression and that larger wounds heal more rapidly. Accuracy of the prediction curve in the current model improves with each additional evaluation., Conclusion: Routine assessment of wounds using detailed stereophotogrammetric imaging can provide personalized predictions of wound healing time. Application of a valid model will help the clinical team to determine wound management care pathways., (Published by Elsevier Ltd.)

Reference genes are often used in RT-quantitative PCR (qPCR) analysis to normalize gene expression levels to a gene that is expressed stably across study groups. They ultimately serve as a control in RT-qPCR analysis, producing more accurate interpretation of results. Whereas many reference genes have been used in various wound-healing studies, the most stable reference gene for ischemic wound-healing analysis has yet to be identified. The goal of this study was to determine systematically the most stable reference gene for studying gene expression in a rat ischemic wound-healing model using RT-qPCR. Twelve commonly used reference genes were analyzed using RT-qPCR and geNorm data analysis to determine stability across normal and ischemic skin tissue. It was ultimately determined that Ubiquitin C (UBC) and β-2 Microglobulin (B2M) are the most stably conserved reference genes across normal and ischemic skin tissue. UBC and B2M represent reliable reference genes for RT-qPCR studies in the rat ischemic wound model and are unaffected by sustained tissue ischemia. The geometric mean of these two stable genes provides an accurate normalization factor. These results provide insight on dependence of reference-gene stability on experimental parameters and the importance of such reference-gene investigations.

This paper reviews applications of therapeutic electrical stimulation (ES) specific to wound healing and pressure sore prevention. The application of ES for wound healing has been found to increase the rate of healing by more than 50%. Furthermore, the total number of wounds healed is also increased. However, optimal delivery techniques for ES therapy have not been established to date. A study of stimulation current effects on wound healing in a pig model has shown that direct current (DC) stimulation is most effective in wound area reduction and alternating current (AC) stimulation for wound volume reduction at current densities of 127 microA/cm2 and 1,125 microA/cm2, respectively. Preliminary studies have been carried out at two research centers to assess the role of ES in pressure sore prevention. Surface stimulation studies have shown that ES can produce positive short-term changes in tissue health variables such as regional blood flow and pressure distribution. The use of an implanted stimulation system consisting of intramuscular electrodes with percutaneous leads has been found to produce additional long-term changes. Specifically, gluteal muscle thickness increased by 50% with regular long-term ES application concurrent with a 20% decrease in regional interface pressures and increased tissue oxygen levels. These findings indicate that an implantable ES system may have great potential for pressure sore prevention, particularly for individuals who lack sensation or who are physically unable to perform regular independent pressure relief.