Advances in wound care最新文献

Significance: Autologous adipose tissue grafting (AAG) can provide soft tissue reconstruction in congenital defects, traumatic injuries, cancer care, or cosmetic procedures; over 94,000 AAG procedures are performed in the United States every year. Despite its effectiveness, the efficiency of AAG is limited by unpredictable adipocyte survival, impacting graft volume retention (26-83%). Recent Advances: Acellular adipose matrices (AAMs) have emerged as a potential alternative to AAG. AAMs include adipose tissue-derived extracellular matrix (ECM) and growth factors (GFs), but not cells. When grafted, AAMs serve as scaffolds with biochemical and biophysical cues for local cell (especially adipocytes) proliferation, regenerating soft tissue, and restoring volume. Being acellular, the AAM is not limited by adipocyte necrosis/apoptosis. Critical Issues: Research on AAM has mostly been conducted on small animal models and with small grafts. Clinically relevant AAM research (large animal models and/or clinical trials) is sparse and limited. To address this gap, we conducted a systematic review of clinically relevant AAM literature to assess AAM's clinical efficacy and safety. Across 11 human and 1 porcine study involving reconstructive or cosmetic procedures, we found that AAMs resulted in significant volume retention, adipogenesis, and angiogenesis, without notable adverse effects. Future Directions: Available quantitative and qualitative data suggest that AAM is an effective and safe alternative to AAG. Yet, the current literature is still limited; more robustly designed studies with standardized methods to assess outcomes will help validate these positive preliminary findings, and possibly pave the way for a broader clinical adoption of AAM. [Figure: see text].

Objective: In a complex environment such as that in a diabetic foot ulcer (DFU), multiple factors, including cross talk between distinct cell types of the affected tissue, play a significant role. We identified a transcription factor (TF) cocktail that induces a transition from nonhealing to healing states across multiple cell types. Approach: Thirty-three skin and wound single-cell RNA-sequencing samples (85,928 cells) from patients with diabetes with healing or nonhealing DFU were analyzed (GSE165816). The relative activity of cell type-specific TF in healing versus nonhealing DFU was compared, and the cumulative additive effect of different TF cocktails was assessed. Results: We used a cumulative additive-effect approach to identify five transcription factors, FOS Like 2, AP-1 Transcription Factor Subunit (FOSL2), CAMP Responsive Element Binding Protein 3 Like 1, RELB Proto-Oncogene, NF-KB Subunit, ETS Proto-Oncogene 1 (ETS1), and X-Box Binding Protein 1, whose targets include 66.5% of pro-healing genes and only 12.5% of anti-healing genes across all cell types. In vascular endothelial cells, this TF panel accounted for 95% of vasculature-development genes; in myeloid cells, it regulated 85% of antimicrobial-response genes. In silico knockout of ETS1 or FOSL2 shifted cells toward nonhealing states, whereas Nuclear Receptor Subfamily 3 Group C Member 1 knockout shifted endothelial cells, fibroblasts, and myeloid cells toward healing-associated state. Innovation: This work recognizes a TF panel that is likely to have therapeutic value in promoting healing in nonhealing DFU. Conclusion: In this work, we identified a set of candidate TFs with the potential to induce a cell state transition favoring a switch from nonhealing to healing outcomes in patients with nonhealing DFU. Overall, our gene regulatory network-driven TF cocktail provides a rational blueprint for reprogramming DFU cell states and paves the way toward targeted regenerative therapies.

Significance: Recognized for its role in energy storage and thermal insulation, white adipose tissue (WAT) has garnered increasing attention given its functions beyond metabolism. In particular, dermal and subcutaneous WATs have been shown to play critical roles in wound healing and scarring. This review proposes that dermal and subcutaneous adipose tissues are not passive bystanders but active regulators of wound healing and fibrosis. Recent Advances: Significant advances in wound healing biology have identified critical roles and signaling pathways that immune cells and fibroblasts are involved with in wound healing; however, fewer investigations have studied adipocytes in this context. This review focuses on the roles of WAT and specifically white adipocytes at different stages of wound healing: inflammation, proliferation, and remodeling. We also discuss applications of WAT and its derivatives as therapeutic strategies for improved wound healing. Critical Issues and Future Directions: With multiple fibrotic conditions associated with decreased adipose tissue, understanding the different ways by which adipocyte subpopulations and WAT participate in repair and fibrotic processes will help shed light on how we can modulate cellular response for future therapeutic applications.

Significance: Refractory wounds are complicated multistep biological processes that can lead to severe complications in patients. Selective autophagy plays a crucial role in precisely controlling the quality of intracellular components and regulating biological behavior. This review explores the features and underlying mechanisms of various types of selective autophagy and highlights their implications in burn injury and wound healing. Recent Advances: In-depth studies have underscored the critical role of selective autophagy, including mitophagy, endoplasmic reticulum (ER)-phagy, pexophagy, xenophagy, lysophagy, ferritinophagy, and lipophagy, in effectively controlling the quality of intracellular components and regulating biological behavior, which may enhance wound-healing process. Critical Issues: Autophagy is a housekeeping and self-renewal process that utilizes lysosomal machinery to degrade and recycle cellular components, thereby enhancing cellular adaptability to stressful conditions. In addition to nonselective bulk degradation, autophagy selectively recycles specific cell constituents, including mitochondria, ER, peroxisomes, pathogens, lysosomes, lipid droplets, and ferritin. The effective management of the quality of cellular components during wound healing remains a challenge in clinical practice. Future Directions: Understanding the basic mechanisms and intricate crosstalk underlying selective autophagy may facilitate the development of comprehensive strategies and therapeutic targets for wound healing.

Objectives: Endogenous bioelectric signaling (including transepidermal potential [TEP] and the current of injury) plays a fundamental role in normal wound repair. Despite this, commonly used wound management frameworks do not consider this important driver of healing. The objectives of this review are to explore whether the patient characteristics/pathologies common in delayed healing are associated with weakened electrical properties of the skin and to consider whether compromised currents of injury are a barrier to healing that could be addressed with electrical stimulation therapy (EST) and incorporated into existing frameworks. Approach: This systematic review of PubMed was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and aimed to explore the impact of three characteristics associated with delayed healing (older age, diabetes, and chronic inflammation) on the electrical properties of skin/wounds. Results: Twelve relevant studies were identified, revealing that TEP in older or diabetic people is significantly lower, and the current of injury is approximately half that of young, healthy controls. Innovation: Lower currents of injury are associated with slower wound healing; therefore, the reduced current of injury/TEP identified here can be considered a barrier to healing. EST is designed to boost the weakened current of injury, back up to normal levels, stimulating a healing response. The incorporation of EST into existing wound management frameworks is therefore proposed. Conclusion: Endogenous bioelectrical signaling in the wound healing process appears to be compromised particularly in older people and those with diabetes. Patients may benefit from incorporating treatment with EST, which boosts bioelectrical signaling, into relevant wound treatment frameworks. [Figure: see text].

Significance: Wound healing is a complex, tightly regulated process involving a range of enzymes, growth factors, and cytokines that coordinate cellular activities essential for tissue repair and wound closure. However, in cases of extensive or severe injury, the intrinsic repair mechanisms are often insufficient, underscoring the need for advanced therapeutic strategies to accelerate healing and minimize scar formation. Recent Advances: Electrically conductive hydrogels (ECHs), combining the advantageous properties of hydrogels with the physiological and electrochemical characteristics of conductive materials, present a safer and more convenient alternative to traditional electrode-based electrical stimulation (ES) for treating chronic and nonhealing wounds. This review summarizes the various types of ECHs and their functional roles in facilitating wound healing. Critical Issues: Understanding the mechanisms by which ECHs interact with electrical signals in the skin, along with precise control of the synergy between these signals and other functional properties, is critical for achieving optimal wound healing outcomes. Future Directions: Future development of ECHs should focus on elucidating underlying mechanisms, standardizing ES parameters, validating efficacy in clinically relevant animal models, and integrating multifunctional systems. Additionally, material design must be optimized for biocompatibility, adaptability, and scalability to facilitate clinical translation in chronic and nonhealing wound treatment.

Objective: This study aimed to evaluate the location-specific and time-sensitive trajectories of pressure injuries (PrIs) stages using real-world electronic health record (EHR) datasets. Approach: Using a dataset of 29,475 patients with records of PrIs documented from 2015 to 2023, we developed four PrI patient sub-cohorts with common PrI locations, including coccyx, buttocks, sacrum and heel. We estimated transition intensities between three PrI states: stage 1, stage 2, and a severe stage in each group. Stages and transition paths were derived from domain knowledge provided by clinical experts and The National PrI Advisory Panel (NPIAP) guidelines. Results: The trajectory analysis suggested that stage 2 serves as a "gateway state" in all four locations, meaning that once a PrI reaches stage 2, the likelihood of transiting to severe stages increases significantly. The commonly used Braden Scale and its sub-components are more likely to be associated with transitions from stage 2 to severe stages, suggesting that manual risk assessment tools are suboptimal for predicting early-stage PrI transitions. Further, we observed race-dependent variations across injury location groups. Innovation: To our knowledge, this is the first study to introduce multi-state trajectory analysis in PrI research. Our model can investigate PrI status in a dynamic manner, which fills an important gap in the field. Conclusion: Our findings underscore the lack of time-sensitive information in existing PrI risk assessment tools, revealing a critical gap in their ability to capture the dynamic nature of PrI progression. Clinical decision support using time sensitive data is needed for delivering personalized, timely, and effective PrI prevention.

Significance: Alginate, sourced from seaweed, holds significant importance in industrial and biomedical domains due to its versatile properties. Its chemical composition, primarily comprising β-D-mannuronic acid and α-L-guluronic acid, governs its physical and biological attributes. This polysaccharide, extracted from brown algae and bacteria, offers diverse compositions impacting key factors such as molecular weight, flexibility, solubility, and stability. Recent Advances: Commercial extraction methods yield soluble sodium alginate essential for various biomedical applications. Extraction processes involve chemical treatments converting insoluble alginic acid salts into soluble forms. While biosynthesis pathways in bacteria and algae share similarities, differences in enzyme utilization and product characteristics are noted. Critical Issues: Despite its widespread applicability, challenges persist regarding alginate's stability, biodegradability, and bioactivity. Further understanding of its interactions in complex biological environments and the optimization of extraction and synthesis processes are imperative. Additionally, concerns regarding immune responses to alginate-based implants necessitate thorough investigation. Future Directions: Future research endeavors aim to enhance alginate's stability and bioactivity, facilitating its broader utilization in regenerative medicine and therapeutic interventions. Novel approaches focusing on tailored hydrogel formations, advanced drug delivery systems, and optimized cellular encapsulation techniques hold promise. Continued exploration of alginate's potential in tissue engineering and wound healing, alongside efforts to address critical issues, will drive advancements in biomedical applications.

Objective: The mechanisms of structured exercise therapy (SET) in peripheral artery disease (PAD) are not clear. We have developed an SET module for our large animal model of ischemic myopathy. We hypothesized that SET would increase muscle strength and walking distance in this model. The objective was to discover the SET-dependent mechanisms involved in this process. Approach: After induction of unilateral hind limb ischemia, three animals were exposed to standard environmental enrichment (sedentary or SED) and four animals underwent SET thrice weekly for 4 weeks postoperatively. Walking, hind limb pressure indices, and strength testing were performed weekly. Terminal muscle samples were used for skeletal muscle testing. Results: SET animals increased walking distance over time. SET increased muscle strength in both the ischemic and nonischemic limb. When comparing the ischemic SED hind limb muscle with that of ischemic + SET, the SET group has improved respiration and decreased oxidative stress. Markers of cell death and impaired functional regeneration were increased in SED ischemic muscles but returned toward baseline in the SET ischemic muscle. Innovation: This study uses a validated, large animal model of ischemic myopathy similar to that seen in humans with PAD. The effects of exercise on limb function, strength, and skeletal muscle health are reported in this model. Conclusion: SET increases muscle strength and regeneration by increasing endogenous antioxidants and mitochondrial respiration, resulting in favorable muscle health despite ongoing ischemia. This model may assist in preclinical testing of PAD therapies designed to improve muscle health.

Objective: Diabetes and smoking are frequently co-morbid conditions leading to arterial insufficiency, significantly increasing the risk of non-healing wounds and subsequent major amputation. Autologous patient-specific mesenchymal stem cells (MSCs) present a novel tool for regenerative therapy to treat advanced stages of arterial insufficiency. The regenerative performance of cells from diabetics with impaired arterial perfusion is known to be reduced, but the impact of additional patient factors such as smoking remains poorly understood. Approach: MSCs were harvested from amputees under IRB approval. Mitochondria were evaluated for mitophagy and bioenergetic function. MSC growth, reactive oxygen species (ROS), and synthetic function were measured. Exogenous nicotine was used to mimic smoking byproducts. Data were analyzed by one-way analysis of variance with p < 0.05 considered statistically significant. Results: Four MSC patient lines were from smokers and four were from non-smokers. All were male, diabetic, and matched for age. Mitochondrial turnover, ROS production, proliferation, and doubling time were comparable between groups. Smoking status significantly decreased glycolytic capacity, maximal mitochondrial respiration, and the synthetic function of MSCs compared with non-smokers (p < 0.05). Acute nicotine exposure in non-smoker MSCs significantly increased mitochondrial function, an effect that incompletely resolved with nicotine withdrawal (p < 0.001). Innovation: This study implicates mitochondrial dysfunction in smoking-mediated impairment of MSC synthetic function. Conclusion: Smoking alters mitochondrial bioenergetics and synthetic function of MSCs from diabetic patients with arterial insufficiency. Restoring mitochondrial function may improve synthetic function and therapeutic capabilities of smoker MSCs. Targeted rejuvenation strategies may be required based on smoking status for autologous MSC therapies for patients with arterial insufficiency.