Significance: Chronic wounds include, but are not limited, to diabetic foot ulcers, venous leg ulcers, and pressure ulcers. They are a challenge to wound care professionals and consume a great deal of healthcare resources around the globe. This review discusses the pathophysiology of complex chronic wounds and the means and modalities currently available to achieve healing in such patients.Recent Advances: Although often difficult to treat, an understanding of the underlying pathophysiology and specific attention toward managing these perturbations can often lead to successful healing.Critical Issues: Overcoming the factors that contribute to delayed healing are key components of a comprehensive approach to wound care and present the primary challenges to the treatment of chronic wounds. When wounds fail to achieve sufficient healing after 4 weeks of standard care, reassessment of underlying pathology and consideration of the need for advanced therapeutic agents should be undertaken. However, selection of an appropriate therapy is often not evidence based.Future Directions: Basic tenets of care need to be routinely followed, and a systematic evaluation of patients and their wounds will also facilitate appropriate care. Underlying pathologies, which result in the failure of these wounds to heal, differ among various types of chronic wounds. A better understanding of the differences between various types of chronic wounds at the molecular and cellular levels should improve our treatment approaches, leading to better healing rates, and facilitate the development of new more effective therapies. More evidence for the efficacy of current and future advanced wound therapies is required for their appropriate use.

Chronic nonhealing wounds are one of the major and rapidly growing clinical complications all over the world. Current therapies frequently require emergent surgical interventions, while abuse and misapplication of therapeutic drugs often lead to an increased morbidity and mortality rate. Here, we introduce a wearable bioelectronic system that wirelessly and continuously monitors the physiological conditions of the wound bed via a custom-developed multiplexed multimodal electrochemical biosensor array and performs noninvasive combination therapy through controlled anti-inflammatory antimicrobial treatment and electrically stimulated tissue regeneration. The wearable patch is fully biocompatible, mechanically flexible, stretchable, and can conformally adhere to the skin wound throughout the entire healing process. Real-time metabolic and inflammatory monitoring in a series of preclinical in vivo experiments showed high accuracy and electrochemical stability of the wearable patch for multiplexed spatial and temporal wound biomarker analysis. The combination therapy enabled substantially accelerated cutaneous chronic wound healing in a rodent model.

Background: The purpose of this study was to evaluate whether or not standard of care treatment of diabetic foot ulcers has improved over the past 20 years as measured by the percentage of ulcers healed within set periods of time. Previously reported percentages of wound healing were 24% at 12 weeks and 31% at 20 weeks. Methods: A meta-analysis was performed to review the control groups of randomized clinical trials in the treatment of diabetic foot ulcers. The mean percentage of ulcers healed at defined end points were then compared to percentages of ulcers healed at corresponding end points reported 20 years ago. A literature search was performed to identify articles published before December 30, 2019, to identify randomized controlled clinical trials that included human subjects with diabetic foot ulcers. The control arm was required to include wound debridement, dressing changes, and offloading. Results: The literature search yielded 16 randomized clinical trials that fit the selection criteria to be included in the meta-analysis. Analysis of the percentage of wounds healed with standard of care therapy alone yielded the following results: 6 weeks (14.9% ± 13.0%), 12 weeks (33.4% ± 18.2%), 20 weeks (43% ± 0%). Conclusions: The results of this meta-analysis of the available evidence suggest that the percentage of diabetic foot ulcers healed with standard of care therapies alone have improved over the past 20 years. However, the percentage of ulcers healed at each of these endpoints remains low and demonstrates continued challenges in healing diabetic foot ulcers. Disclosure V.E. Parks: None. P. Crisologo: None. L.A. Lavery: Advisory Panel; Self; Acelity, Bayer AG. Consultant; Self; Boehringer Ingelheim International GmbH. Research Support; Self; AstraZeneca, Cardinal Health, EO2 Concepts, Integra LifeSciences, MedImmune, Smith & Nephew. J. Banks: None. M.D. Liette: None. L. Johnson: None.

Background: Diabetic foot ulcers are complex and create a heavy financial burden to the health system. The purpose of this systematic review and meta-analysis is to assess the clinical effectiveness and safety of human amniotic membrane tissue products in diabetic foot ulcerations. Methods: A meta-analysis was performed to evaluate the clinical effectiveness of the use of amnion tissue products verses the standard of care in the management of diabetic foot ulcers. A literature search of PubMed/Medline, Cochrane Library, and ClinicalTrials.gov for articles published before December 30, 2019 was performed to identify randomized controlled clinical trials that included human subjects with diabetic foot ulcers treated with amnion tissue products. Results: The literature search revealed ten randomized clinical trials that fit the selection criteria to be included in the meta analysis. Analysis of the percent of wounds healed yielded the following results: 4 weeks (treatment group 64.2%, SOC 18.8%), 6 weeks (treatment group 60.9%, SOC 60.7%), 12 weeks (treatment group 70.8%, SOC 32.4%) with P <0.01. There was no significant difference in mean number of adverse events between groups with a p=0.71. Conclusions: The results of this meta-analysis of the available evidence suggest that the application of amniotic tissue products in diabetic foot ulcerations significantly increases the percent of diabetic foot ulcers healed as compared to stand of care alone. Disclosure V.E. Parks: None. J. Banks: None. L. Johnson: None. M.D. Liette: None. P. Crisologo: None. L.A. Lavery: Advisory Panel; Self; Acelity, Bayer AG. Consultant; Self; Boehringer Ingelheim International GmbH. Research Support; Self; AstraZeneca, Cardinal Health, EO2 Concepts, Integra LifeSciences, MedImmune, Smith & Nephew.