Water-powered, electronics-free dressings that electrically stimulate wounds for rapid wound closure.

Chronic wounds affect ~2% of the U.S. population and increase risks of amputation and mortality.

Adhesive anti-fibrotic interfaces on diverse organs.

Implanted biomaterials and devices face compromised functionality and efficacy in the long term owing to foreign body reactions and subsequent formation of fibrous capsules at the implant-tissue interfaces. Here we demonstrate that an adhesive implant-tissue interface can mitigate fibrous capsule formation in diverse animal models, including rats, mice, humanized mice and pigs, by reducing the level of infiltration of inflammatory cells into the adhesive implant-tissue interface compared to the non-adhesive implant-tissue interface. Histological analysis shows that the adhesive implant-tissue interface does not form observable fibrous capsules on diverse organs, including the abdominal wall, colon, stomach, lung and heart, over 12 weeks in vivo.

Effects of Age and Sex on Systemic Inflammation and Cardiometabolic Function in Individuals with Type 2 Diabetes.

Objective: Systemic inflammation, aging, and type 2 diabetes (T2DM) all contribute to the development of cardiovascular dysfunction and impaired aerobic exercise capacity but their interplay remains unclear. This study evaluates the impact of age, sex, and inflammation on coronary and peripheral vascular function and exercise capacity in elderly individuals with and without type 2 diabetes (T2DM).

Research Design And Methods: Elderly individuals (age ≥65 years) underwent biochemical and tissue inflammatory phenotyping, cardiopulmonary exercise testing (CPET), cardiovascular magnetic resonance (CMR) imaging, and vascular reactivity testing.

Use of Therapeutic RNAs to Accelerate Wound Healing in Diabetic Rabbit Wounds.

Diabetes mellitus (DM) affects over 422 million people globally. Patients with DM are subject to a myriad of complications, of which diabetic foot ulcers (DFUs) are the most common with ∼25% chance of developing these wounds throughout their lifetime. Currently there are no therapeutic RNAs approved for use in DFUs.

A Miniaturized, Battery-Free, Wireless Wound Monitor That Predicts Wound Closure Rate Early.

Diabetic foot ulcers are chronic wounds that affect millions and increase the risk of amputation and mortality, highlighting the critical need for their early detection. Recent demonstrations of wearable sensors enable real-time wound assessment, but they rely on bulky electronics, making them difficult to interface with wounds. Herein, a miniaturized, wireless, battery-free wound monitor that measures lactate in real-time and seamlessly integrates with bandages for conformal attachment to the wound bed is introduced.

Protocol for xenotransplantation of human skin and streptozotocin diabetes induction in immunodeficient mice to study impaired wound healing.

Here, we present a protocol for the integration of human skin onto the backs of diabetic immunodeficient mice, providing a versatile in vivo model for mimicking and studying mechanisms involved in impaired cutaneous wound healing. This protocol includes instructions for the grafting of human skin, induction of diabetes using streptozotocin and wounding/post-wounding care of immunodeficient mice, as well as suggested downstream tissue analyses. This preclinical mouse model can be used to validate the efficacy of newly developed wound dressings.

Experimental treatments in clinical trials for diabetic foot ulcers: wound healers in the pipeline.

Introduction: Diabetes affects 400 million people globally and patients and causes nephropathy, neuropathy, and vascular disease. Amongst these complications, diabetic foot ulcers remain a substantial problem for patients and clinicians. Aggressive wound care and antibiotics remain important for the healing of these chronic wounds, but even when treated these chronic ulcers can lead to infection and amputations.

Use of hyperspectral imaging to predict healing of diabetic foot ulceration.

Our main objective was to validate that hyperspectral imaging via a new portable camera carries the potential to provide a reliable clinical biomarker that can predict DFU healing. We recruited patients with diabetic foot ulceration (DFU) without peripheral arterial disease, infection or other serious illness. Using an hyperspectral imaging (HSI) apparatus, post-debridement hyperspectral images were taken evaluating the ulcer size, periwound oxyhemoglobin (OxyHb), deoxyhemoglobin level (DeoxyHb) and oxygen saturation (O Sat) for four consecutive visits.

Future Directions in Research in Transcriptomics in the Healing of Diabetic Foot Ulcers.

Diabetic foot ulcers are a health crisis that affect millions of individuals worldwide. Current standard of care involves diligent wound care with adjunctive antibiotics and surgical debridement. However, despite this, the majority will still become infected and fail to heal.

The NIDDK Diabetic Foot Consortium.

The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Diabetic Foot Consortium (DFC) was established in September 2018 by the NIDDK to build an organization to facilitate the highest quality of clinical research on diabetic foot ulcers (DFUs) that will answer clinically significant questions to improve DFU healing and prevent amputations. The initial focus of the DFC is to develop and validate biomarkers for DFUs that can be used in clinical care and research. The DFC consists of a data coordinating center (DCC) for operational oversight and statistical analysis, clinical sites for participant recruitment and evaluation, and biomarker analysis units (BAUs).

Murine macrophages or their secretome delivered in alginate dressings enhance impaired wound healing in diabetic mice.

Diabetic foot ulceration is a devastating diabetic complication with unmet needs. We explored the efficacy of calcium-crosslinked alginate dressings in topically delivering primary macrophages and their secretome to diabetic wounds. The alginate bandages had a microporous structure that enabled even cell loading with prolonged cell survival and egress following wound placement.

A strain-programmed patch for the healing of diabetic wounds.

Diabetic foot ulcers and other chronic wounds with impaired healing can be treated with bioengineered skin or with growth factors. However, most patients do not benefit from these treatments. Here we report the development and preclinical therapeutic performance of a strain-programmed patch that rapidly and robustly adheres to diabetic wounds, and promotes wound closure and re-epithelialization.

Single-cell transcriptomics in human skin research: available technologies, technical considerations and disease applications.

Single-cell technologies have revolutionized research in the last decade, including for skin biology. Single-cell RNA sequencing has emerged as a powerful tool allowing the dissection of human disease pathophysiology at unprecedented resolution by assessing cell-to-cell variation, facilitating identification of rare cell populations and elucidating cellular heterogeneity. In dermatology, this technology has been widely applied to inflammatory skin disorders, fibrotic skin diseases, wound healing complications and cutaneous neoplasms.

Exosomes Derived from Epidermal Stem Cells Improve Diabetic Wound Healing.

Diabetic foot ulceration is a major diabetic complication with unmet needs. We investigated the efficacy of epidermal stem cells and epidermal stem cells-derived exosomes (ESCs-Exo) in improving impaired diabetic wound healing and their mechanisms of action. In vitro experiments showed that ESCs-Exo enhanced the proliferation and migration of diabetic fibroblasts and macrophages and promoted alternative or M2 macrophage polarization.

Phase 2a randomized controlled study investigating the safety and efficacy of PDA-002 in diabetic peripheral neuropathy.

Neuropathy is a major cause of morbidity and mortality in individuals with diabetes, with no effective therapy to alter the inevitable progression of nerve damage. We hypothesized that mesenchymal stroma cell-like populations, that are characterized as immune modulators also have the potential of inducing angiogenesis and neurite outgrowth, might be useful in treating diabetic peripheral neuropathy (DPN). The aims of this study were to investigate the efficacy and safety of mesenchymal stem cell-like product (PDA-002) in treating DPN.

Development and validation of a clinical prediction rule for development of diabetic foot ulceration: an analysis of data from five cohort studies.

Introduction: The aim of the study was to develop and validate a clinical prediction rule (CPR) for foot ulceration in people with diabetes.

Research Design And Methods: Development of a CPR using individual participant data from four international cohort studies identified by systematic review, with validation in a fifth study. Development cohorts were from primary and secondary care foot clinics in Europe and the USA (n=8255, adults over 18 years old, with diabetes, ulcer free at recruitment).

Advanced bandages for diabetic wound healing.

Current treatment options for foot ulcers, a serious and prevalent complication of diabetes, remain nonspecific. In this Perspective, we present recent advances in understanding the pathophysiology of diabetic wound healing and the emergence of previously unidentified targets. We discuss wound dressings tailored to the diabetic wound environment currently under development.

A Novel Three-Dimensional Skin Disease Model to Assess Macrophage Function in Diabetes.

A major challenge in the management of patients suffering from diabetes is the risk of developing nonhealing foot ulcers. Most methods to screen drugs for wound healing therapies rely on conventional 2D cell cultures that do not closely mimic the complexity of the diabetic wound environment. In addition, while three-dimensional (3D) skin tissue models of human skin exist, they have not previously been adapted to incorporate patient-derived macrophages to model inflammation from these wounds.

Macro- and microvascular reactivity during repetitive exposure to shortened sleep: sex differences.

Epidemiological studies have reported strong association between sleep loss and hypertension with unknown mechanisms. This study investigated macrovascular and microcirculation changes and inflammatory markers during repetitive sleep restriction. Sex differences were also explored.

Mast Cells in Diabetes and Diabetic Wound Healing.

Mast cells (MCs) are granulated, immune cells of the myeloid lineage that are present in connective tissues. Apart from their classical role in allergies, MCs also mediate various inflammatory responses due to the nature of their secretory products. They are involved in important physiological and pathophysiological responses related to inflammation, chronic wounds, and autoimmune diseases.

Integrated Skin Transcriptomics and Serum Multiplex Assays Reveal Novel Mechanisms of Wound Healing in Diabetic Foot Ulcers.

Nonhealing diabetic foot ulcers (DFUs) are characterized by low-grade chronic inflammation, both locally and systemically. We prospectively followed a group of patients who either healed or developed nonhealing chronic DFUs. Serum and forearm skin analysis, both at the protein expression and the transcriptomic level, indicated that increased expression of factors such as interferon-γ (IFN-γ), vascular endothelial growth factor, and soluble vascular cell adhesion molecule-1 were associated with DFU healing.