Advances in wound care最新文献

Significance: The rise of chronic nonhealing lower extremity wounds among aging, diabetic, obese, and cardiovascular patients has surged. Despite a decade of drug testing in preclinical animal models, few federally approved therapies have emerged. This translational gap raises concerns about the efficacy of current wound healing models and the need for improved research development. Recent Advances: To improve commonly used animal models of chronic wounds, researchers have made several animal model modifications to better mimic and understand the microbiota and immune-mediated wound healing processes that occur in humans. Critical Issues: Existing models do not fully account for the differences in skin architecture, healing processes, and immune system responses in wound healing between animal models and humans. Therefore, it is imperative to understand the limitations of a chosen model when designing experiments. As such, findings must be interpreted cautiously and validated in human contexts. Future Directions: Given the complexity of human wound healing, the use of several different animal models tailored to specific biological questions is necessary. Recent advancement in humanized mouse models and microbiota consideration offer a promising approach to study the human immune-mediated response in chronic wound healing.

Chronic wounds are a silent epidemic in the United States, affecting one in six Medicare beneficiaries-about 10.5 million people-and costing Medicare an estimated $22.5 billion annually. While outpatient wound care costs dropped from $10.5 billion in 2014 to $2.5 billion in 2019, physician office costs rose to $4.1 billion, reflecting a shift in care delivery. Globally, wound care expenditure reached a staggering $148.65 billion in 2022. Despite this burden, federal research funding remains disproportionately low. Chronic wounds often recur due to incomplete healing. Many wounds close by resurfacing without discharge but fail to restore the skin's barrier function-measured by transepidermal water loss at the site of closure-making them prone to reopening. Outcomes of recent patient-based studies advocate redefining wound closure endpoint to include full barrier restoration. The 2023 Wound Balance Framework promotes holistic, patient-centered care, while cutting-edge technologies are reshaping the field. Bioengineered skin therapies can reduce healing time. Machine learning tools, such as scanning electron microscopy-based trainable Weka (Waikato Environment for Knowledge Analysis) intelligent segmentation technology, detect biofilms, while other tools predict healing outcomes and amputation risks. Multiomics technologies identify biomarkers such as Fos-related antigen 1 (FOSL1), enabling precision therapies tailored to wound phase and patient biology. Telehealth is proving to be transformative for wound care. A 2023 meta-analysis of 2,397 patients showed it significantly reduced healing time, pain, and amputation rates. Policy is catching up: Centers for Medicare & Medicaid Services doubled allowable skin substitute applications (from four to eight) and extended treatment windows to 16 weeks. The Better Wound Care at Home Act established national payment for disposable negative pressure wound therapy, and the Lymphedema Treatment Act mandated Medicare coverage for compression garments, projected to save $1.3-$1.5 billion over 10 years. Together, these advances signal a shift toward proactive, personalized, and equitable wound care-driven by science, guided by ethics, supported by policy, and centered on patients.

Significance: The Wound Healing Foundation recognized the need for consensus-based unbiased recommendations for the treatment of wounds. Consensus statements on the treatment of chronic wounds and acute wounds have been developed and published previously. The current publication on diabetic wounds represents the next step in this process. Diabetic wounds constitute a major problem. Population-based and meta-analytic studies indicate that the presence of foot wounds in patients with diabetes increases their mortality risk by more than twofold. The management of diabetic wounds requires consistent and evidence-driven intervention to achieve optimal clinical outcomes. This consensus statement provides the clinician with the necessary foundational approaches to the causes, diagnosis, and therapeutic management of diabetic wounds. Presented in a structured format, this is a useful guide for clinicians and learners in all patient care settings. Recent Advances: Continuous glucose monitoring and other new tools have facilitated better diabetes management and the management of associated wounds. Diabetic limb salvage should focus on achieving and optimizing function for the patient with diabetes rather than preserving limb tissue at all costs. Critical Issues: Successful management of diabetic wounds requires a multidisciplinary approach encompassing comprehensive assessment, timely intervention, and collaborative care by the wound clinician with providers who can address critical aspects to achieve healing, including careful management of blood glucose levels, optimization of off-loading and physical therapy, assessment and treatment of limb ischemia, control and prevention of wound infection, and optimal pain management. Future Directions: Emerging treatments offer hope and promise, but the heterogenicity of diabetic wounds poses a challenge to performing good studies, which will be necessary to advance new treatments for diabetic wounds.

Plasma medicine offers an innovative and advanced physical approach to wound care that uniquely combines wound antimicrobial effects (primary goal) and accelerated regeneration of injured tissue (secondary goal). This review explores its transformative potential in modern medicine, demonstrating how this technology can enhance wound healing, reduce microbial load, and improve clinical outcomes. A certified plasma device provides an add-on technology that has the potential to improve current wound care medical procedures by integrating findings from basic research, preclinical models, and clinical applications. This review underscores the significant role of plasma medicine in transforming wound care practices by bridging fundamental research, preclinical validation, regulatory compliance, and clinical application, paving the way for safer, more effective, and minimally invasive treatment strategies.

Significance: Skin lipids are essential for various skin functions including maintaining barrier integrity, regulating hydration, and providing protection against microbes and inflammatory irritants. Along with skin health, the role of lipids in the etiology of macroangiopathic diseases, such as atherosclerosis of arteries, is well recognized. Recent Advances: In diabetes, lipid dysregulation is evident and may contribute to the diverse complications of the disease. Diabetic vasculopathy primarily reflects the dysfunction and deterioration of existing blood vessels, as their preservation is key in preventing the progression of vascular disease and reducing the need for compensatory angiogenesis. In the peripheral diabetic skin of the limbs, diabetic vasculopathy runs alongside peripheral neuropathy. Although a causative link between the two is plausible, direct evidence in support of such claim is scanty. Critical Issues: Diabetic skin is known to be compromised in many ways, including weakened barrier functionality and diabetes-induced alterations in the extracellular matrix, likely stemming from chronic inflammation, which may directly affect vascular integrity and nerve health. Both, in the compromised skin and within wounds, microbial pathogens and their enzymes may metabolize host lipids, driving inflammatory reactions and exacerbating the pathogenesis of diabetic vasculopathy and related neuropathy. Future Directions: This review focuses on lipid mediators such as sphingolipids, resolvins, oxidized low-density lipoproteins and their specific downstream signaling pathways to obtain a comprehensive understanding of diabetic complications relevant to wound healing. Through lipid-based strategies, this review hopes to inspire the development and utilization of individualized, precision-based approaches to manage diabetic vasculopathy and neuropathy.

Objective: This post hoc analysis determined the correlation between wound bed preparation (WBP), defined as complete debridement of nonviable tissue and complete granulation tissue coverage, and wound closure, using data from a published, Consolidated Standards of Reporting Trials (CONSORT)-compliant randomized controlled trial that evaluated bromelain-based enzymatic debridement (BBD) compared with a placebo gel vehicle (GV) or nonsurgical standard of care (NSSOC) in patients with chronic venous leg ulcers (VLUs). Approach: Patients with chronic VLUs were randomized (3:3:2 ratio) to daily treatment with BBD, GV, or NSSOC for up to 2 weeks and followed up weekly with NSSOC for 12 weeks. Wound closure incidence was compared between those who did and did not achieve WBP by 14 days or anytime during the study. Results: Data were analyzed from 119 VLUs. Among 80 wounds that achieved WBP anytime during the study, 42% healed; among 39 wounds without WBP, only 10.3% healed (relative risk [RR] = 4.1, p = 0.0004, negative predictive value [NPV] = 90%). Among 37 wounds that achieved WBP by 14 days, 54% healed; among 78 wounds that did not achieve WBP by 14 days, only 22% healed (NPV = 78%). Wounds were 2.4 times more likely to achieve closure anytime during the study, if they achieved WBP by 14 days (RR = 2.4, p = 0.0005). Innovation: This landmark analysis confirms that WBP status is an early predictive variable of wound closure. Conclusion: WBP of chronic VLUs significantly increased the likelihood of wound closure and is a critical, though not sufficient, condition for healing.

Objective: To evaluate the clinical efficacy of negative pressure wound therapy (NPWT) combined with topical oxygen therapy (TOT) for chronic refractory wounds (CRWs), addressing potential hypoxia limitation of NPWT through oxygen supplementation, thereby offering an innovative therapeutic approach for CRWs. Approach: The study was performed according to the 2015 Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols statement. A comprehensive search was conducted in PubMed, Cochrane, Embase, Web of Science, CNKI, VIP, and Wanfang databases for randomized controlled trials (RCTs) on the treatment of CRWs with NPWT combined with TOT (inception to October 2024). Studies were screened based on predefined criteria, and data were extracted and assessed using RevMan 5.4. Meta-analysis, sensitivity analysis, and publication bias assessment were performed using Stata 15.0. Results: Eleven RCTs (844 patients) were included. Compared with NPWT, the combination therapy was associated with the following outcomes: increased healing rate (risk ratio [RR] = 1.51, 95% confidence interval [CI]: 1.36-1.69, I² = 18.1%), reduced time from debridement to skin grafting (mean difference [MD] = -2.82 days, 95% CI: -3.15 to -2.50, I² = 4%), shortened healing time (MD = -9.09 days, 95% CI: -11.98 to -6.20, I² = 91.2%), enhanced granulation coverage (MD = 7.56%, 95% CI: 6.09-9.03, I² = 0.0%), and decreased bacterial positivity (RR = 0.27, 95% CI: 0.18-0.41, I² = 0.0%). Innovation: This study provides evidence-based medical research supporting NPWT plus TOT as a synergistic strategy for CRWs. Conclusion: Combined therapy may offer benefits over NPWT alone in CRW treatment, suggesting a promising approach to improve healing outcomes.

Objective: Hard-to-heal diabetic foot ulcers (DFUs) are associated with higher mortality rates and an increased medical burden for patients. ON101, a new topical cream, exhibited better healing efficacy than the control dressing in a Phase III trial. In this post hoc analysis, we further identify whether ON101 can improve the healing of ulcers with hard-to-heal risk factors in this cohort of DFU patients. Approach: To compare the efficacy of ON101 with absorbent dressing among various hard-to-heal wounds in patients with DFU, a post hoc analysis of a randomized Phase III trial that included 276 DFU patients was performed by subgrouping those patients based on ulcer depth, location, size, duration, and patients' glycated hemoglobin (HbA1c) levels and body mass index (BMI). Results: In the full analysis set, the proportion of patients achieving healing was 61.7% in the ON101 group and 37.0% in the comparator (p = 0.0001). In subgroup analysis according to risk factors, ON101 demonstrated superior healing capacity on Wagner grade 2 ulcers (p < 0.0001); plantar ulcers (p = 0.0016), ulcer size ≥5 cm² (p = 0.0122), ulcer duration ≥3 months (p = 0.0043); for patients with HbA1c ≥9% (p = 0.0285); and patients with BMI ≥25 (p = 0.0005). Innovation: ON101, a novel therapeutic drug, can modulate the functions of macrophages and demonstrate superior healing rates to conventional absorbent dressing in patients with hard-to-heal DFUs. Conclusions: The results of this post hoc study suggest that ON101 is a better therapeutic option than conventional dressing used in treatment for DFU patients with higher HbA1c, BMI, or ulcers with complex conditions such as longer duration, deeper wounds, larger size, and plantar location.

Objective: To develop scanning electron microscopy-based Trainable Weka (Waikato Environment for Knowledge Analysis) Intelligent Segmentation Technology (SEMTWIST), an open-source software tool, for structural detection and rigorous quantification of wound biofilm aggregates in complex human wound tissue matrix. Approach: SEMTWIST model was standardized to quantify biofilm infection (BFI) abundance in 240 distinct SEM images from 60 human chronic wound-edge biospecimens (four technical replicates of each specimen). Results from SEMTWIST were compared against human expert assessments and the gold standard for molecular BFI detection, that is, peptide nucleic acid fluorescence in situ hybridization (PNA-FISH). Results: Correlation and Bland-Altman plot demonstrated a robust correlation (r = 0.82, p < 0.01), with a mean bias of 1.25, and 95% limit of agreement ranging from -43.40 to 47.11, between SEMTWIST result and the average scores assigned by trained human experts. While interexpert variability highlighted potential bias in manual assessments, SEMTWIST provided consistent results. Bacterial culture detected infection but not biofilm aggregates. Whereas the wheat germ agglutinin staining exhibited nonspecific staining of host tissue components and failed to provide a specific identification of BFI. The molecular identification of biofilm aggregates using PNA-FISH was comparable with SEMTWIST, highlighting the robustness of the developed approach. Innovation: This study introduces a novel approach "SEMTWIST" for in-depth analysis and precise differentiation of biofilm aggregates from host tissue elements, enabling accurate quantification of BFI in chronic wound SEM images. Conclusion: Open-source SEMTWIST offers a reliable and robust framework for standardized quantification of BFI burden in human chronic wound-edge tissues, supporting clinical diagnosis and guiding treatment.

Significance: It has long been hypothesized that naturally occurring electric fields (EFs) aid wound healing by guiding cell migration. Consequently, the application of EFs has significant potential for promoting wound healing. However, the mechanisms underlying the cellular response to EFs remain unclear. Recent Advances: Although the directed migration of isolated single cells under EFs has been studied for decades, only recently has experimental evidence demonstrated the distinct collective migration of large sheets of keratinocytes and corneal epithelial cells in response to applied EFs. Accumulating evidence suggests that the emergent properties of cell groups in response to EF guidance offer new opportunities for EF-assisted directional migration. Critical Issues: In this review, we provide an overview of the field of collective electrotaxis, highlighting key advances made in recent years. We also discuss advanced engineering strategies utilized to manipulate collective electrotaxis. Future Directions: We outline a series of unanswered questions in this field and propose potential applications of collective electrotaxis in developing electrical stimulation technologies for wound healing.