Advances in wound care最新文献

Significance: Chronic diabetic wounds on the lower extremities (diabetic foot ulcers, DFU) are one of the most prevalent and life-threatening complications of diabetes, responsible for significant loss of quality of life and cost to the health care system. Available pharmacologic treatments fail to achieve complete healing in many patients. Recent studies and investigational treatments have highlighted the potential of modulating wound pH in DFU. Recent Advances: Data from in vitro, preclinical, and clinical studies highlight the role of pH in the pathophysiology of DFU, and topical administration of pH-lowering agents have shown promise as a therapeutic strategy for diabetic wounds. In this critical review, we describe the role of pH in DFU pathophysiology and present selected low-molecular-weight and hydrogel-based pH-modulating systems for wound healing and infection control in diabetic wounds. Critical Issues: The molecular mechanisms leading to pH alterations in diabetic wounds are complex and may differ between in vitro models, animal models of diabetes, and the human pathophysiology. Wound pH-lowering bandages for DFU therapy must be tested in established animal models of diabetic wound healing and patients with diabetes to establish a comprehensive benefit-risk profile. Future Directions: As our understanding of the role of pH in the pathophysiology of diabetic wounds is deepening, new treatments for this therapeutic target are being developed and will be tested in preclinical and clinical studies. These therapeutic systems will establish a target product profile for pH-lowering treatments such as an optimal pH profile for each wound healing stage. Thus, controlling wound bed pH could become a powerful tool to accelerate chronic diabetic wound healing.

Introduction: 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. Innovation: Currently there are no therapeutic RNAs approved for use in DFUs. Use of dressings containing novel layer-by-layer (LbL)-formulated therapeutic RNAs that inhibit PHD2 and miR-210 can significantly improve diabetic wound healing. These dressings provide sustained release of therapeutic RNAs to the wounds locally without systemic side effects. Clinical Problem Addressed: Diabetic foot wounds are difficult to heal and often result in significant patient morbidity and mortality. Materials and Methods: We used the diabetic neuroischemic rabbit model of impaired wound healing. Diabetes was induced in the rabbits with alloxan, and neuroischemia was induced by ligating the central neurovascular bundle of each ear. Four 6-mm full-thickness wounds were created on each ear. A LbL technique was used to conformally coat the wound dressings with chemically modified RNAs, including an antisense oligonucleotide (antimiR) targeting microRNA-210 (miR-210), an short synthetic hairpin RNA (sshRNA) targeting PHD2, or both. Results: Wound healing was improved by the antimiR-210 but not the PHD2-sshRNA. Specific knockdown of miR-210 in tissue as measured by RT-qPCR was ∼8 Ct greater than nonspecific controls, and this apparent level of knockdown (>99%) suggests that delivery to the tissue is highly efficient at the administered dose. Discussion: Healing of ischemic/neuropathic wounds in diabetic rabbits was accelerated upon inhibition of miR-210 by LbL delivery to the wound bed. miR-210 inhibition was achieved using a chemically modified antisense RNA.

Objectives: To identify proteins that are prognostic for diabetic foot ulcer (DFU) healing and may serve as biomarkers for its management, serum samples were analyzed from diabetic mellitus (DM) patients. Approach: The serum specimens that were evaluated in this study were obtained from DM patients with DFU who participated in a prospective study and were seen biweekly until they healed their ulcer or the exit visit at 12 weeks. The group was divided into Healers (who healed their DFU during the study) and Non-Healers. Results: Interleukin (IL)-10, IL-4, IL-5, IL-6, and IL-13 and interferon-gamma were higher in the Healers while Fractalkine, IL-8, and TNFα were higher in the Non-Healers. The trajectory of IL-10 levels remained stable over time within and across groups, resulting in a strong prognostic ability for the prospective DFU healing course. Classification and Regression Tree analysis created an 11-node decision tree with healing status as the categorical response. Innovation: Consecutive measurements of proteins associated with wound healing can identify biomarkers that can predict DFU healing over a 12-week period. IL-10 was the strongest candidate for prediction. Conclusion: Measurement of serum proteins can serve as a successful strategy in guiding clinical management of DFU. The data also indicate likely superior performance of building a multiprotein biomarker score instead of relying on single biomarkers.

Significance: The incidence of diabetes continues to rise throughout the world in an alarming rate. Diabetic patients often develop diabetic foot ulcers (DFUs), many of which do not heal. Non-healing DFUs are a major cause of hospitalization, amputation, and increased morbidity. Understanding the underlying mechanisms of impaired healing in DFU is crucial for its management. Recent Advances: This review focuses on the recent advancements on macrophages and neutrophils in diabetic wounds and DFUs. In particular, we discuss diabetes-induced dysregulations and dysfunctions of macrophages and neutrophils. Critical Issues: It is well established that diabetic wounds are characterized by stalled inflammation that results in impaired healing. Recent findings in the field suggest that dysregulation of macrophages and neutrophils plays a critical role in impaired healing in DFUs. The delineation of mechanisms that restore macrophage and neutrophil function in diabetic wound healing is the focus of intense investigation. Future Directions: The breadth of recently generated knowledge on the activity of macrophages and neutrophils in diabetic wound healing is impressive. Experimental models have delineated pathways that hold promise for the treatment of diabetic wounds and DFUs. These pathways may be useful targets for further clinical investigation.

Significance: Release of extracellular vesicles (EVs) by various cell types has been shown to mediate the delivery of biologically active payloads from donor cells to recipient cells; however, it remains unclear what cell types these EVs come from. With a focus on fluorescent reporters to monitor the release of EVs, especially those under the control of cell type-specific promoters, we address the translational relevance of genetic tools in cultured cells, normal tissues, and in models of development, injury, cancer, and wound healing. Recent Advances: It is well established that EVs are released by many cell types in the body via fusion and release processes at the plasma membrane. Since there remains debate about what fraction of EVs are released through regulated endosomal trafficking pathways versus nonspecific mechanisms, the development and validation of novel molecular tools are important to address the cellular source of EVs. Critical Issues: There is a need to develop and characterize new cell type-specific reporter mouse models that build upon the examples detailed here to identify the cellular source of EVs with genetic approaches being useful in addressing these critical limitations. Future Directions: Advances in reporter systems will drive a better understanding of EV subsets to identify compartment-specific EV localization to guide the development of more translationally relevant models for the wound healing field.

Significance: Lower extremity traumatic wounds are associated with numerous perioperative challenges. Their etiologies determine the characteristics and extent of the injury. The timing of subsequent surgical intervention and wound healing optimization after lower extremity trauma are integral to successful perioperative lower extremity wound management. Recent Advances: Managing trauma to the lower extremities uses a multidisciplinary surgical approach. The objective of this review is to summarize lower limb trauma assessment, advancements in lower extremity trauma management, and the clinical applications of advanced wound care in lower limb traumatic wounds. The advent of lower limb reconstruction and the development of advanced wound care modalities have helped to improve the management of these complex injuries. Critical Issues: The extensive involvement of bone, soft tissues, nerves, and blood vessels of severe lower extremity trauma wounds presents a challenge for clinicians in both the acute care setting and during patient rehabilitation. If not properly managed, these injuries may be subject to a decline in limb function and may possibly result in limb loss. To reveal developing limb-threatening conditions, serial examinations should be performed. Future Directions: The majority of lower limb traumatic wound will benefit from the perioperative administration of an appropriate negative pressure wound therapy (NPWT)-based system, which can help to promote granulation tissue and remove wound exudate before definitive closure and/or reconstruction. NPWT should be included as an important adjunct in the surgical management of lower limb traumatic wounds.

Objective: Keloids are benign fibroproliferative disorders with invasive growth exceeding the wound boundary. Aurora kinase A (AURKA) is a serine/threonine kinase highly expressed in various tumors, facilitating tumor growth and invasion. Currently, the role of AURKA in keloid remains unclear. Approach: Fibroblasts were isolated from keloid and normal skin samples. AURKA was evaluated by qPCR, Western blot, and immunohistochemistry. Transcriptome sequencing and dual-luciferase reporter assays were applied to figure out targets of AURKA. Following expression alteration and MLN8237 (an AURKA kinase inhibitor, AKI) treatment, phenotypical experiments were conducted to clarify biological functions of AURKA along with its target, and to probe into the clinical potential of AURKA inhibition. Results: AURKA was upregulated in keloid tissues and fibroblasts. Forkhead box O 3a (FOXO3a) was verified as a downstream of AURKA. Further experiments demonstrated that AURKA transactivated FOXO3a by binding to FOXO3a, while FOXO3a directly transactivated AURKA. Functionally, AURKA and FOXO3a cooperated in enhancing the proliferation and migration of keloid fibroblasts via protein kinase B (AKT) phosphorylation. Although MLN8237 weakened the proliferation and migration in keloid fibroblasts, the transactivation of AURKA on FOXO3a was independent of kinase activity. Innovation: This study reveals that AURKA and FOXO3a compose a transactivation loop in enhancing the proliferative and migrative properties of keloid fibroblasts, and proposes AURKA as a promising target. Conclusion: AURKA/FOXO3a loop promotes the proliferation and migration of keloid fibroblasts via AKT signaling. Despite the anti-keloid effects of AKIs, AURKA acts as a transcription factor independently of kinase activity, deepening our understanding on AKI insensitivity.

Significance: The laparotomy is a common surgical procedure with a wide range of indications. Ideally, once the goals of surgery were achieved, the incision edges could then be approximated and the abdomen primarily closed. However, in some circumstances, it may be impossible to achieve primary closure, and instead the abdomen is intentionally left open. This review discusses the indications and objectives for the open abdomen (OA), summarizes the most common techniques for temporary abdominal closure, and illustrates treatment algorithms grounded in the current recommendations from specialty experts. Recent Advances: Still a relatively young technique, multiple strategies, and technologies have emerged to manage the OA. So too have the recommendations evolved, based on updated classifications that take wound characteristics into account. Recent studies have also brought greater clarity on recommendations for managing infection and malnutrition to support improved clinical outcomes. Critical Issues: The status of the OA can change rapidly depending on the patient's condition, the wound quality, and many other factors. Thus, there is a significant need for comprehensive treatment strategies that can be adapted to these developing circumstances. Future Directions: Treatment recommendations should be continuously updated as new technologies are introduced and old techniques fall out of use.

Significance: Burns result in irretrievable cell damage, which can occur upon exposure to hot surfaces, liquids, gases, ultraviolet or ionizing radiation, and through friction. Standard of care in burn management involves protecting the patient, limiting burn progression, and achieving wound closure. Negative pressure wound therapy (NPWT) and NPWT with instillation and dwell time (NPWTi-d) are two wound management options that have been shown to improve outcomes for burn patients in recent years. This work provides a general review of NPWT and NPWTi-d use in burn wound management. A literature search was performed using PubMed and Embase for peer-reviewed publications and conference abstracts written in English and reporting on burn management using NPWT and/or NPWTi-d from a single manufacturer between 2000 and 2021. All burn types were included. Recent Advances: Thirteen studies and 308 patients were available for assessment. Use of NPWT was reported in a majority of studies (n = 11). When conventional NPWT was applied, graft take of >90% was observed and consistent final wound closure was achieved. Two studies described NPWTi-d use for burn wound management. NPWTi-d use promoted granulation tissue development in burn wounds. Critical Issues: Limited high-level prospective evidence exists for use of NPWT and NPWTi-d in burn wound management. Future Directions: Available literature on the use of NPWT and/or NPWTi-d in burn care has reported improved outcomes in wound bed preparation, which can ultimately lead to final wound closure. The use of these modalities should be considered in management of burn care patients.

Significance: In trauma care, extensive surgical intervention may be required. Damage control surgery (DCS) is applicable to patients with life or limb-threatening conditions that are incapable of tolerating a traditional surgical approach. Recent Advances: The current resuscitation strategy for complex trauma patients includes limiting crystalloid fluids, balanced mass transfusion protocols, permissive hypotension, and damage control resuscitation. Recent technological advancements in surgical critical care have improved outcomes in these critically ill patients. Critical Issues: DCS, which is often required in patients with trauma injuries, is typically followed by surgical correction of the injury once the immediate patient survival procedures have been completed. However, DCS and the subsequent injury repair procedures have a high risk for postsurgical complication development. Future Directions: Negative pressure therapy modalities can offer clinicians additional adjunctive and cost-effective tools for the management of the trauma care patient, as these systems can be utilized during both the DCS and the postoperative injury management phases of trauma care.