Advances in wound care最新文献

Objective: Drugs regulating hypoxia-inducible factor (HIF)-1α have not been investigated for wound healing in lymphedema. Therefore, we examined the effects of drug modulation of HIF-1α activity for wound healing in our previously developed mouse model of nonirradiated hind limb lymphedema. Approach: Mouse hind limb lymphedema models (n = 17) and a sham group (n = 6) were created using 8- to 10-week-old male C57BL/6N mice. Mice with hind limb lymphedema were randomized into experimental groups receiving roxadustat, 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole (YC-1), or dimethyl sulfoxide and were given intraperitoneal injections every 2 days for up to 2 weeks. Four days after the surgery, an 8-mm diameter full-thickness skin wound was created in the hind limb. The number of days required for wound closure and the percentage of wounds closed were measured. Skin samples taken at wound creation were evaluated by histological and molecular analysis. Results: Administration of roxadustat accelerated wound healing, whereas YC-1 delayed it, with a significant decrease and increase in skin thickness, respectively. The relative mRNA expression of Hif1α, matrix metalloproteinase-3, and interleukin-6 was significantly higher in the roxadustat group and that of metalloproteinase-9 was significantly lower in the roxadustat group compared with the control group. Innovation: This study is the first to demonstrate delayed wound healing in a mouse model of hind limb lymphedema and the first to demonstrate the promotion of significant wound healing through the use of roxadustat. Conclusion: Roxadustat exerts wound-healing effects and may promote the regulation of extracellular matrix remodeling via gene expression in hind limb lymphedema wound models.

Significance: Although skin grafting is a basic surgical procedure, there are many sophisticated innovations that are used only by experienced surgeons. In-depth knowledge of new and old methods gives the opportunity to select the most appropriate technique in each case. Recent Advances: Most methods have been invented long ago, but some of them have been rediscovered and further refined. An improved understanding of wound healing and basic skin grafting techniques enable the development of new solutions. Critical Issues: Clinical randomized controlled trials in wound research are time consuming, expensive, and difficult to perform. This has given rise to many techniques that are not well proven. Recent strict regulations concerning all forms of cell therapy have further hindered the development of promising new ideas. Future Directions: Cell therapies to enhance epithelialization and promote wound healing are already available but far from everyday practice. Very strict regulations have halted many promising projects. An alternative approach to circumvent some of these regulatory hurdles is the grafting of uncultured, autologous cells or very small pieces of skin, which also offer very large expansion of the graft. The development and adoption of new bilayered skin substitutes are expected to be the most significant development in the near future, although they face similar regulatory challenges as cell therapies.

Objective: Lower-extremity diabetic ulcers (LEDUs) affect more than 500,000 U.S. Medicare beneficiaries each year. Dehydrated human amnionic and chorionic allografts (DHACAs) are clinically effective complements to standard of care (SoC; e.g., surgical debridement, offloading, infection, and moisture control) when treating LEDUs. However, Medicare and commercial payer coverage have restricted access to DHACAs. Our objective was to compare the effectiveness of DHACAs versus SoC among Medicare beneficiaries with LEDUs for reduction of adverse outcomes such as mortality, recurrency, and major amputation. Approach: We analyzed a retrospective cohort of U.S. Medicare claims for LEDUs between 2018 and 2022. LEDU claims were collapsed into episodes of care (EOC). Frequency distribution of characteristics was compared using univariate and bivariate statistics. Zero-inflated binomial regression with 1:1 nearest-neighbor propensity score matching evaluated six main outcome measures: mortality; wound recurrence; major amputation; minor amputation; emergency department (ED) utilization; and readmission. Results: There were 25,760 Medicare EOCs between 2018 and 2022 representing 12,880 matched samples in the DHACA and SoC cohorts. DHACAs were associated with a 20% reduction in 30-day mortality (95% confidence interval [CI]:10%, 29%), 28% reduction in risk of major amputation (95% CI: 19%, 36%), 9% reduction in ED utilization (95% CI: 3%,14%), and 8% reduction in 30-day readmission (95% CI: 2%, 13%). DHACAs were noninferior for minor amputation rates and wound recurrence compared to SoC cohort. Conclusion: Beneficiaries with LEDUs benefit significantly from DHACAs on multiple outcomes, including a lower risk of mortality. Providers should examine the appropriateness of DHACAs for patients with LEDU as part of wound management. Medicare and commercial payers should consider improved outcomes when defining coverage policies that restrict access to DHACAs given the observed benefits.

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.

Objective: This study compared the effect of two frequencies of direct cold atmospheric plasma (direct-CAP) treatment with standard of care (SOC) alone on healing of venous leg ulcers (VLUs). Approach: Open-label, randomized controlled trial (ClinicalTrials.gov NCT04922463) on chronic VLUs at two home care organizations in the Netherlands. All three groups received SOC for 12 weeks or until healing. In addition, treatment groups received direct-CAP once (1× direct-CAP) or twice (2× direct-CAP) a week, at specialized wound care facilities and the patients' residences. Primary outcome was percentage of wounds healed. Secondary outcomes included wound area reduction and adverse events. Results: In total, 46 patients were randomly allocated to receive SOC only (n = 15), SOC + direct-CAP once a week (n = 17), or SOC + direct-CAP twice a week (n = 14). A higher percentage of wounds healed within 12 weeks in the treatment groups 53.3% (1× direct-CAP, p = 0.16) and 61.5% (2× direct-CAP, p = 0.08) versus 25.0% (control). The largest wound area reduction was obtained with 2× direct-CAP (95.2%, p = 0.07), followed by 1× direct-CAP (63.9%, p = 0.58), versus control (52.8%). Absolute wound area reduced significantly compared with baseline in both treatment groups (p ≤ 0.001), not in control (p = 0.11). No device-related serious adverse events occurred. Innovation: Direct-CAP applied once or twice a week could substantially improve wound healing of VLUs in primary care. Conclusion: Together with other clinical safety and efficacy data, these results support the integration of direct-CAP as a valuable therapy for complex wounds.

Significance: Pathologic scarring occurs secondary to imbalances in the cellular mechanisms of wound healing and affects millions of people annually. This review article aims to provide a concise overview of the pathophysiology and management of pathologic scarring for clinicians and scientists alike. Recent Advances: Contemporary research in the field has identified aberrations in transforming growth factor-β/small mothers against decapentaplegic (TGF-β/SMAD) signaling pathways as key drivers of pathologic scar formation; indeed, this pathway is targeted by many treatment modalities and translational investigations currently underway. Although intralesional injection of corticosteroids has been the gold standard in the treatment of pathologic scarring, studies show greater treatment efficacy with the use of combination injections such as triamcinolone/5-fluorouracil and triamcinolone/botulinum toxin. Adjunctive therapies including ablative fractional carbon dioxide/erbium-doped yttrium aluminum garnet and non-ablative pulsed-dye lasers, microneedling, and carboxytherapy have shown encouraging results in small cohort studies. Translational investigations involving the use of nanogels, RNA interference, and small molecules targeting TGF-β/SMAD pathways are also currently underway and hold promise for the future. Critical Issues: The heterogeneous nature of hypertrophic scars and keloids poses significant challenges in formulating standardized treatment and assessment protocols, thereby limiting the conclusions that can be drawn. Future Directions: Rigorous clinical trials into the individual and synergistic effects of these therapies would be ideal before any definitive conclusions or evidence-based treatment recommendations can be made. Owing to the heterogeneity of the pathology and patient population, well-conducted cohort studies may be the next best option.

Significance: Negative pressure wound therapy (NPWT) has been in practice for decades, proving its utility in many applications, ranging from acutely infected wounds to complex combat wounds and skin grafting. It has been routinely demonstrated that NPWT has superior wound healing outcomes compared with previous standard-of-care therapies. However, the technique involves some challenges related to each of the components that comprise the therapy. The purpose of this article is to highlight the challenges, introduce the recent advancements, and discuss about the future directions in NPWT systems. Recent Advances: New techniques and materials have been developed to improve the currently used NPWT systems with promising results when utilized with appropriate indications. Many advancements have been introduced in modes of negative pressure delivery, pumps, interface dressings, adhesive dressings, and tubing technology. Critical Issues: An optimal NPWT system would avoid the common problems such as failure to deliver negative pressure due to loss of an airtight seal or tissue ingrowth into the interface dressing causing painful dressing changes and bleeding. Other challenges include infection control and patient pain and discomfort that may contribute to noncompliance. Future Directions: Many studies have been performed to evaluate the optimal combination of settings and components in various wounds; however, there is still no clear "best" answer for many specific patient-wound scenarios. Novel and emerging tissue engineering and regenerative medicine approaches could potentially be utilized in the future NPWT systems and thus, this review will discuss some novel ideas for future considerations.

Significance: Management of infection is a critical aspect of wound care. It involves the application of various interventions to treat the wound and prevent the infection from spreading to other parts of the body, which may lead to serious complications, including sepsis. Local treatment of skin wound infections is the favored route of administration, reducing the risk of adverse systemic effects while providing very high therapeutic concentrations at the target site. The purpose of this article was to review clinical trials from 2013 and onward, focusing on local treatment of acute wounds and burns as well as chronic wounds as their primary outcome measurement. Recent Advances: Based on our literature search, 49 clinical trials were focusing on treating infected chronic wounds, and 6 trials studied infection as their primary outcome in acute wounds during the last 10 years. Critical Issues: Currently commercially available local treatments do not prevent the onset of invasive infection. Therefore, there is a need for more effective local therapies. Future Directions: Despite multiple preclinical studies introducing novel and promising strategies in terms of novel antimicrobial agents and delivery methods to prevent and treat skin wound infections locally, many have yet to be tested in a clinical setting. These preclinically tested approaches could still be valuable additions to today's care of infected skin wounds.

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.