Advances in wound care最新文献

Objective: Keloids (KLs) and hypertrophic scars are common fibroproliferative disorders that cause significant functional and psychosocial distress. The lack of effective prevention and treatment strategies underscores the urgent clinical need to identify novel therapeutic targets and modifiable risk factors to improve patient outcomes. Approach: We conducted a comprehensive large-scale Mendelian randomization study to systematically assess the causal effects of 4,907 plasma proteins and 8,155 lifestyle and disease-related traits on KL risk. To validate our findings and explore the underlying cellular mechanisms, we analyzed the largest to-date single-cell RNA sequencing dataset for KLs, comprising 194,366 cells from 30 patients. Mediation analysis was used to dissect the pathways through which the identified proteins exert their effects. Results: Our proteome-wide analysis revealed R-spondin 3 (RSPO3) as a potent causal risk factor for KL development. These findings were corroborated at the tissue level, where RSPO3 expression was significantly upregulated specifically in KL-derived fibroblasts. Furthermore, our phenome-wide association screen revealed that several lifestyle and psychological factors, including alcohol intake, depression, and sleep disorders, are causally associated with an increased risk of KLs, whereas higher adult education status was identified as a protective factor. Innovation: This study establishes a pioneering multilayered causal inference framework by systematically integrating large-scale proteomics, phenomics, and single-cell transcriptomics. It moves beyond traditional association studies to first perform an unbiased, proteome-wide search for causal drivers of KL pathogenesis and then validate the top candidates at single-cell resolution. This "gene-cell-phenotype" strategy is the first to robustly link a genetically validated protein target (RSPO3) to its specific cellular origin (fibroblasts) in KLs. Conclusions: This study identifies RSPO3 as a promising, fibroblast-derived therapeutic target for KLs. In addition, we established a causal link between modifiable lifestyle factors and KL risk. These findings integrate genetic, proteomic, and single-cell data to significantly advance our understanding of KL pathogenesis.

Objective: The objective of this open-label, interventional, prospective clinical study was to evaluate the effectiveness of a multimodal wound matrix (MWM) in moving chronic, nonhealing wounds that had failed prior therapies onto a healing trajectory. The overall response rate was the proportion of subjects who had greater than 40% reduction in size after 4 weeks of treatment. Secondary objectives included the percentage area reduction (PAR) after 4 and 12 weeks, incidence of ulcer closing, and changes in quality of life. Approach: An open-label, interventional, prospective cohort, real-world evidence study was conducted following the STROBE criteria. Criteria included chronic nonhealing wounds of multiple etiologies in subjects with extensive comorbidities. Results were compared with data from the U.S. Wound Registry. Results: A total of 111 subjects entered the screening phase and 64 were treated. Fifty-three wounds were eligible for the dataset that included 18 diabetic foot ulcers, 19 venous leg ulcers, 2 pressure injuries, 1 surgical, 1 lower extremity wound, and 12 unclassified etiologies. The objective response rate was 42%. The 4-week PAR was 34%. The 12-week PAR was 66%. Eighteen wounds closed by week 12. Innovation: MWM is a formulation technology developed to address the major obstacles that prevent healing. Results were evaluated in a patient population with extensive comorbidities that had failed prior treatments and would be generally excluded from controlled trials. Conclusion: The results from this study support the contention that MWM achieves substantial clinical improvement in a complex patient population not enrolled in clinical trials and demonstrates an advancement in wound management.

Objective: SN514 is a thermolysin-like enzyme under development as a debrider. Preclinical and non-clinical studies supported a first in human healthy volunteer study to predict the need for protection of periwound skin. Approach: Pharmacologic activity testing compared in vitro digestion of collagen, fibrin, and elastin with relevant enzymes. A Yorkshire pig model of burn injury was used to evaluate debridement over 10 days and effects on intact skin. A human 21-day cumulative irritation study using Webril patches taped to the backs of 38 healthy adult volunteers compared four enzyme concentrations (0.10%, 0.20%, 0.40%, and 0.80% w/w) with the hydrogel vehicle, saline (low irritant control), and 0.2% sodium lauryl sulfate (positive irritant control) using randomized placements and blinded evaluation. Results: SN514 showed excellent digestion of fibrin, elastin, and collagen in vitro. Burn wound studies in Yorkshire pigs showed efficient eschar debridement with minimal periwound erythema. Direct treatment on intact porcine skin for 5 days produced no to limited erythema. The preclinical findings of minimal irritation with SN514 were verified by a Phase 1 first-in-human 21-day cumulative skin irritation test. Irritation was observed to increase stepwise by concentration, confirming formulation accuracy. Each enzyme concentration was found to be "possibly mild in use" (Berger and Bowman method). No treatment emergent adverse events were observed during the study. Innovation: A fast-acting enzyme with a favorable irritation profile, prepared as a stable, ready to use hydrogel formulation, overcomes many recognized shortcomings of enzyme debriders. Conclusion: The overall findings support clinical dose range testing for tolerance and preliminary efficacy.

The purpose of this review is to provide verified data on the current knowledge acquired from preclinical and clinical studies regarding topically used antimicrobial peptides (AMPs) with diabetic wound healing activity. The electronic databases were searched for articles published from 2012 to 2022. The 20 articles comparing topically used AMPs in diabetic wound healing treatment versus control treatments (placebo or active therapy) were selected. AMPs have several unique advantages in diabetic wound healing, such as a broad spectrum of antimicrobial activity even against antibiotic-resistant strains, and the capability to modulate the host's immune response and affect wound healing processes through various mechanisms of action. AMPs through antioxidant activity, stimulation of angiogenesis, keratinocytes, and fibroblast migration and proliferation may be considered an important support during conventional therapy used for diabetic wound treatment.

Objective: Wound closure is skin reepithelialization confirmed at two consecutive clinical visits 2 weeks apart. Our objective was to identify participant characteristics, including transepidermal water loss (TEWL), associated with complete wound closure of diabetic foot ulcers (DFUs) and reopening of a DFU within 2 weeks after initial closure in the National Institute of Diabetes and Digestive and Kidney Diseases-sponsored Diabetic Foot Consortium TEWL prospective observational cohort study of wound recurrence. At the site of wound closure, TEWL measures restoration of skin barrier function and functional wound closure. Approach: Four hundred and sixty-six eligible participants had physician-assessed wound closure at baseline. Of which, 418 (90%) had confirmed closure 2 weeks later and remained in the study, whereas 29 had their DFU reopen 2 weeks later and were not eligible for follow-up (i.e., screen failures). We compared baseline characteristics of 418 enrolled and 29 screen fail individuals using Wilcoxon rank sum and Fisher's exact tests p value for continuous and categorical outcomes, respectively. Results: There were no statistically significant differences in demographics, including age, sex, race, education, employment status, social support, or dressing change requirements between groups. The failure to maintain closure group had longer median duration of index DFU before initial closure (25.8 vs. 14 weeks, p = 0.003), higher frequency of prior total contact casting use (37% vs. 14%, p = 0.003), and a higher median initial TEWL measurement at the healed ulcer midpoint (27.1 vs. 21.0 g/m^2/h, p = 0.006). Innovation: TEWL measurement at the site of wound closure can assess functional capacity of the skin in conjunction with current standards of wound closure end point in DFU and has significant potential to add quantitative measurement to assist in clinical assessment of healing wounds. Conclusion: Individuals with DFU who did not maintain wound closure had higher TEWL values at baseline, longer DFU wound duration, and more prior off-loading use. These findings are clinically relevant as a higher TEWL measurement demonstrates incomplete functional wound closure, supporting the use of TEWL to identify a healed DFU.

Objective: To investigate the association between the Prognostic Nutritional Index (PNI) and mortality risk in intensive care unit (ICU) patients with pressure injuries (PIs) to provide a basis for early risk stratification and clinical decision-making. Approach: This retrospective cohort study used data from the Medical Information Mart for Intensive Care IV database, which included 972 ICU patients diagnosed with PI. Patients were stratified by median PNI levels, and Kaplan-Meier survival analysis, Cox regression, logistic regression, restricted cubic splines, and propensity score matching (PSM) were performed to assess the relationship between PNI and 28-day, 90-day, and ICU mortality. Results: A higher PNI was significantly associated with lower 28-day (hazard ratio [HR] = 0.702, 95% confidence interval [CI] 0.551-0.895), 90-day (HR = 0.722, 95% CI: 0.576-0.905), and ICU mortality (odds ratio [OR] = 0.644, 95% CI: 0.474-0.872). An L-shaped relationship between the PNI and all-cause mortality was observed. This association remained robust after multivariate adjustment, subgroup analysis, and PSM. Innovation: This study is the first to evaluate the prognostic significance of the PNI in ICU patients with PIs, addressing the gap in current research by identifying a simple and accessible marker associated with mortality risk in this vulnerable population. Conclusion: PNI can be calculated from routine laboratory results and may guide early nutritional or wound care interventions in ICU patients with PI. A PNI value below 19.02 is associated with an increased risk of mortality (i.e., PNI <19.02 = high risk) and serves as a critical threshold for identifying patients at elevated risk.

Artificial intelligence (AI) is rapidly transforming biomedical research and health care, offering new paradigms for discovery, diagnosis, and decision-making. This article provides a roadmap for researchers, clinicians, and reviewers seeking to understand and apply AI with rigor and relevance. It begins with a historical anchor: the birth of AI in health care at the University of Pittsburgh in the 1970s, where the INTERNIST-1 system pioneered diagnostic reasoning through symbolic logic, a milestone that laid the foundation for today's intelligent systems. Structured into three tiers-foundations, core techniques, and applications-the article addresses the full spectrum of biomedical AI. It introduces foundational concepts such as data engineering and preprocessing, knowledge representation and reasoning, and symbolic AI, which together enable structured, interpretable intelligence. Core techniques including expert systems, machine learning, deep learning, and explainable AI are presented with clinical examples, highlighting their role in wound care, image analysis, and predictive modeling. The applications tier showcases natural language processing, non-machine learning computer vision, robotics and automation, and distributed AI/multi-agent systems, demonstrating how AI integrates into real-world workflows. Ethical considerations and bias mitigation strategies are addressed with emphasis on Institutional Review Board oversight and fairness frameworks. Crucially, the article emphasizes that successful AI adoption begins not with technology, but with people. It outlines a systematic approach to building a biomedical AI workforce from within, empowering clinicians, researchers, and staff to become AI-literate contributors and leaders. With rigor checklists, practical guidance, and a vision for human-AI collaboration, this article invites readers to move beyond hype and toward responsible, transformative innovation in health care and biomedical science. [Figure: see text].

Significance: Volumetric muscle loss is defined as composite loss of muscle mass. Severe injuries result in permanent functional impairment. Treatment options are limited. Tissue engineering techniques utilizing scaffolds offer promise as a potential therapy. Recent Advances: Emerging strategies, including bioactive molecules and growth factors in biocompatible scaffolds, may promote muscle regeneration following severe injury. In this context, scaffolds can act as a drug-delivery device, provide guidance to cells as a supporting matrix, and slowly release growth factors to promote healing. Critical Issues: Scaffolds engraftment and ability to promote tissue regeneration in injured beds remain limited. Tuning and optimizing scaffold fiber diameter, alignment, cellular cues, growth factor delivery, and porosity will be important in reconstituting functional skeletal muscle following loss. Future Directions: Our mechanistic understanding of interactions between biomimetic scaffolds and host tissue is still evolving, and future research can identify factors to promote tissue regeneration.

Peripheral nerve injuries, especially those with complete transection of major nerves, create significant morbidity including debilitating pain, loss of protective haptic feedback, and impaired volitional control of musculature. The societal burden and cost of medical care for these injuries are enormous, with estimates in the United States alone in excess of $670 million per year. In clinical scenarios with a segmental nerve gap where end-to-end coaptation without tension is not possible, a "bridge" or scaffold must be interposed to facilitate communication between the proximal and distal stumps to facilitate organized growth following Wallerian degeneration. A multitude of constructs have been created and studied to facilitate this regeneration. Among the three overall types of bridge employed in contemporary clinical care-conduit/scaffold, allograft, and autograft-each has significant downsides ranging from limited successful nerve ingrowth to donor site morbidity. Despite the tremendous work over the last 150 years in nerve biology and medical technology for the treatment of peripheral nerve injury, the biological processes governing nerve regeneration remain incompletely understood. Especially in cases of long segmental gaps, there remains room for significant improvement. Ongoing studies have identified several promising modalities for nerve scaffolds to facilitate more efficient and effective neuronal outgrowth but still require further investigation. Here, we review contemporary paradigms in the treatment of segmental nerve injuries with interposing scaffolds and reexamine nerve physiology, regulatory programs in nerve regeneration, and strategic targets for neurogenic pathways that may facilitate novel treatment modalities.

Significance: Nonhealing or chronic wounds represent a significant and growing global health concern, imposing substantial burdens on individuals, health care systems, and economies worldwide. Although the standard-of-care treatment involves the application of wound dressings, most dressing materials are not specifically designed to address the pathological processes underlying chronic wounds. This review highlights recent advances in biomaterial design tailored to chronic wound healing. Recent Advances: Chronic wounds are characterized by persistent inflammation, impaired granulation tissue formation, and delayed re-epithelialization. Newly developed designer materials aim to manage reactive oxygen species and extracellular matrix degradation to suppress inflammation while promoting vascularization, cell proliferation, and epithelial migration to accelerate tissue repair. Critical Issues: Designing optimal materials for chronic wounds remains challenging due to the diverse etiology and a multitude of pathological mechanisms underlying chronic wound healing. While designer materials can target specific aberrations, designing a materials approach that restores all aberrant wound-healing processes remains the Holy Grail. Addressing these issues requires a deep understanding of how cells interact with the materials and the complex etiology of chronic wounds. Future Directions: New material approaches that target wound mechanics and senescence to improve chronic wound closure are under development. Layered materials combining the best properties of the approaches discussed in this review will pave the way for designer materials optimized for chronic wound healing.