Split-thickness skin grafts are essential for managing burns and non-healing wounds, but donor site complications such as dyspigmentation and hypertrophic features can impair long-term donor site appearance. Evidence on risk factors for donor site morbidity in large, diverse populations is limited. This retrospective study reviewed medical records of 1,021 patients who underwent split-thickness skin graft procedures at a regional burn center from 2015 to 2024, including 559 patients with at least one postoperative follow-up visit documenting donor site appearance. Patient demographics, surgical characteristics, and donor site appearances were analyzed to identify risk factors. Fitzpatrick skin types IV, V, and VI accounted for 46.6% of patients presenting with hypertrophic features (P < .001), despite comprising 14.7% of the patient population. Older age (OR = 1.017 per year, P < .001) and a Body Mass Index ≥ 25 (OR = 2.00, P < .001) were associated with higher odds of dyspigmented donor sites. Diabetes and hypertension together elevated dyspigmentation risk (OR = 2.71, P < .001), with hypertension alone nearly doubling the risk (OR = 1.92, P < .001). Calcium alginate and silver dressings were associated with lower odds of dyspigmentation (OR = 0.368, P < .001), whereas film-only dressings more than doubled the risk (OR = 2.31, P < .001). Graft thickness and healing time were not statistically significant. These findings highlight the need for individualized care strategies that account for patient-specific risk factors to minimize donor site morbidity and improve long-term donor site outcomes after split-thickness skin grafts.
Opioids and benzodiazepines provide the foundation for procedural sedation during wound care following burn injury. Ketamine has been used as an adjunct and may limit exposure to opioids. Few data are published describing the use of oral ketamine in this population. This study was performed to compare the effects of oral ketamine on opioid and benzodiazepine requirements during wound care following burn injury. This was a retrospective, single center cohort study (August 2022-2024). The electronic medical record was queried for adult (≥18 years) patients admitted to the burn intensive care unit who received oral ketamine as a premedication for wound care. The primary outcome was oral morphine equivalents (OMEs) before (pre) and after (post) initiation of oral ketamine. Only medications used during wound care were recorded. Descriptive statistics were utilized for analysis. A total of 52 patients were included. The median percent total body surface area (%TBSA) burned was 31 (IQR 20-48). The median ketamine dose received during wound care was 100 mg (IQR 100-125). All patients received IV fentanyl and 47 (90%) received IV midazolam. Patients received a median of 225 mg (IQR 150-300) vs 180 mg (IQR 120-240) (P=0.008) of OMEs in the pre- and post-groups, respectively. There was no difference in midazolam received (6 mg [IQR 4-8] vs 5 mg [IQR 3-8]; P = 0.21). Oral ketamine may be an effective adjunct to wound care following burn injury and may reduce exposure to opioids.
Neighborhood disadvantage, measured by the Area Deprivation Index (ADI), is associated with long-term outcomes in burn survivors. However, prior work has relied on global scores, which may obscure domain-specific pathways linking neighborhood context to recovery. This secondary analysis of a randomized controlled trial examined whether specific ADI domains are associated, in separate adjusted models, with pain and functional outcomes in 74 adult burn survivors. Baseline addresses were linked to nationally referenced ADI scores calculated across 239,780 U.S. block groups. Three ADI-3 domains, Financial Strength, Economic Hardship, and Educational Attainment, were tested in hierarchical regressions predicting BPI Pain Severity, PROMIS Pain Interference, and BSHS Functional Abilities, controlling for demographics. The global ADI was associated with functional abilities (ΔR2 = .085, p = .012) but not pain outcomes. Domain-specific analyses revealed that both Financial Strength (β = 2.55, p-FDR = .012) and Economic Hardship (β = -2.22, p-FDR = .031) were each associated with functional abilities after multiple comparison correction, remaining robust in sensitivity analyses. A suggestive trend was observed between Financial Strength and pain severity (β = -0.52, p-FDR = .057), but this did not survive multiple comparison correction. No associations were observed for pain interference or Educational Attainment. These findings suggest that Financial Strength and Economic Hardship were domain-specific contextual correlates of functional abilities not apparent in the global index. The null pain findings alongside significant functional associations suggest neighborhood context may be more closely associated with daily functioning than with pain perception.
Hypertrophic scar (HTS) is a fibrotic skin disease characterized by excessive extracellular matrix accumulation and chronic inflammation. This study aimed to investigate cellular heterogeneity, immune alterations, and nucleotide metabolism-related biomarkers in HTS and to explore their potential mechanisms. Single-cell RNA sequencing data were analyzed using Seurat for cell clustering and annotation. Nucleotide metabolism activity was evaluated to identify key cell populations and candidate genes. Bulk transcriptomic datasets from the Gene Expression Omnibus (GEO) were used for differential expression analysis, and machine learning algorithms were applied to develop a diagnostic model. Sixteen cell clusters were identified, with macrophages showing prominent activation of nucleotide metabolism pathways and immune-related signaling. The optimal Enet + svmLinear model achieved strong predictive performance (AUC = 0.934), and SHAP analysis identified NCF1 and GPR34 as key predictive genes. These genes were also associated with immune cell infiltration. In vitro validation using THP-1-derived M2 macrophages showed that NCF1 and GPR34 promoted TGF-β1 secretion and enhanced fibroblast activation, while their knockdown reduced α-SMA and collagen I expression. Collectively, this study reveals the important role of macrophage-associated nucleotide metabolism in HTS and identifies NCF1 and GPR34 as potential biomarkers and therapeutic targets.
The federal government recently passed legislation that will significantly reduce Medicaid spending through work requirements. Burns disproportionately affect the Medicaid population and are one of the most costly injuries with some admissions incurring multimillion dollar hospital stays. All admissions with a primary burn diagnosis were extracted from the National Inpatient Sample, 2017-2022. Cost-to-charge ratios were applied and adjusted for inflation to 2025 US dollars. Facilities were stratified by burn center and safety-net status. Reductions in Medicaid enrollment were modeled using US Congressional Budget Office estimates. Projections of burn care and burn center losses over a 6-year period with 95% confidence intervals (CIs) were derived from Monte Carlo simulations using bootstrap resampling distributions. Of 178,545 weighted burn encounters, 39,575 under 18 years old were excluded as children will not be affected by the new law. The frequency of burn encounters covered by Medicaid has increased by 7.0% over the past 6 years. The total annual cost of burn care is estimated at $3,190,265,497, 28.4% of which is costs to Medicaid. Burn center costs to Medicaid increased by 18.9% over the past 6 years. Assuming the current trajectory of inpatient admissions, the overall reduction in Medicaid payments from burn care is estimated at $525,645,056-$717,992,704. 33.1% of Medicaid encounters were treated at safety-net hospitals, which will incur a 2.70% reduction in burn center funding. Non-safety-net hospitals will incur a 2.39% reduction. Revenue-generating strategies and cost containment may be insufficient for financial solvency in some burn centers.
Burn injuries during pregnancy are associated with significant maternal and fetal morbidity and mortality; however, available evidence is fragmented and largely based on small observational studies. To estimate pooled maternal and fetal mortality among pregnant women with burn injuries and explore the impact of burn severity. A systematic review and meta-analysis of proportions was conducted following PRISMA 2020 guidelines. PubMed/MEDLINE, Scopus, Web of Science, and LILACS were searched from inception to March 2026. Observational studies and case series reporting maternal and/or fetal outcomes were included. Risk of bias was assessed using NOS and JBI tools, and certainty of evidence using GRADE. Random-effects models with Freeman-Tukey double arcsine transformation were applied. Results: Twenty-two studies including 1,162 pregnant women were analyzed. Most studies were case series (n=15), followed by cohort studies (n=5) one cross-sectional study, and one case report. Maternal mortality ranged from 0% to 70%. The pooled maternal mortality proportion was 0.43 (95% CI: 0.36.0.50), with substantial heterogeneity (I2=72.9%). Fetal mortality ranged from 31.3% to 90.5%, with a pooled estimate of 0.57 (95% CI: 0.49.0.65; I2=78.6%). Burn severity, particularly TBSA burned .50%, was consistently associated with worse outcomes. Funnel plots suggested possible publication bias. The overall certainty of evidence was low. Burn injuries during pregnancy are associated with high maternal and fetal mortality, strongly influenced by burn severity. Despite consistent findings, the low certainty of evidence highlights the need for high-quality prospective studies.
Burn injuries are challenging to treat due to wound progression and long-term scarring. Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) have regenerative and immunomodulatory properties that may mitigate these complications. In this Phase 1/2a, first-in-human, open-label study, a 47-year-old man with deep second-degree burns received a single topical dose of allogeneic bone marrow MSC-derived EVs within 48 hours of injury. The treated wound achieved >99% closure within one week, with durable healing for over one year. Scar outcomes improved over 52 weeks, with POSAS scores indicating early resolution of pain and pruritus and minimal residual scarring. No adverse events occurred. Laser Doppler imaging showed improved perfusion within one week, suggesting prevention of burn wound conversion. These findings support the potential of MSC-derived EVs to accelerate burn healing and reduce scar-related morbidity.
BACKGROUND:Severe burn injury induces gastrointestinal dysfunction and bacterial dysbiosis, yet the systemic impact of altered bacterial metabolites remains poorly understood. We assessed whether changes in plasma levels of trimethylamine N-oxide (TMAO), a gut-derived metabolite, have a relationship with changes in the whole blood transcriptomic profile following burn injury. METHODS:Using previously harvested plasma from 67 burn patients, we quantified circulatory levels of TMAO via ELISA. To assess TMAO's impact on the blood transcriptome, we applied a linear model to previously published whole blood microarray data from a subset of these patients (n = 22) with paired TMAO measurements. RESULTS:While initial TMAO levels were comparable across small and larger burns, concentrations significantly increased 24 to 36 hours post admission in patients with >10% total body surface area (TBSA) burns, independent of age or sex. Elevated TMAO positively correlated with both burn size and Baux score. Furthermore, transcriptomic analysis revealed that high TMAO levels were strongly associated with the enrichment of inflammatory and leukocyte activation pathways, despite a lack of association between TMAO levels and imputed fractions of immune cells. CONCLUSION:Burn injury is associated with a delayed, severity-dependent elevation in circulating TMAO. This increase in TMAO correlates with transcriptomic signatures of robust immune activation and systemic inflammation, suggesting that targeting the gut microbiome and its metabolites may offer a novel therapeutic avenue to address post burn inflammatory complications.
Diabetes mellitus causes vascular dysfunction, immune dysregulation, and cellular abnormalities. Prior studies suggest worse outcomes in burn patients with diabetes mellitus but are limited by single- institution studies and small sample sizes. National databases like the Burn Care Quality Platform (BCQP) can provide higher-powered multi-institutional datasets to determine outcomes otherwise unseen. Using the BCQP, adult burn patients admitted for burn care from 2016 to 2018 were retrospectively reviewed for diabetes status. Primary outcomes were time to 95% wound closure. Secondary outcomes were hospital and intensive care unit (ICU) length of stay (LOS), rates of acute respiratory distress syndrome (ARDS), ventilator-associated pneumonia (VAP), central line-associated bloodstream infection (CLABS), operative intervention rates, and in-hospital mortality. Diabetic patients had longer wound closure time (25 versus 22 days, p = 0.0006) and more operative procedures (15.8 versus 1.3, p < 0.0001) than non-diabetic patients. Diabetic patients also had longer hospital LOS (8 versus 5 days, p < 0.0001) and higher mortality (5.7% vs. 4.1%, p = 0.045) than non-diabetic patients, with no differences in ARDS, VAP, or CLABSI. On multivariable analysis, diabetes mellitus itself was not an independent predictor of complications or mortality, but early hyperglycemia was the strongest modifiable predictor of ARDS, VAP, and CLABSI. Overall, diabetes mellitus was associated with delayed wound healing, longer hospital LOS, and ICU LOS. Acute complications were driven by early hyperglycemia following admission and injury severity, highlighting early glycemic optimization in burn care.
Split-thickness skin grafting remains central to definitive wound closure in burn surgery. Although the biology of successful engraftment is well established, less attention has been paid to the geometric and mechanical determinants of graft behaviour. Broader grafts often appear more stable and require fewer peripheral fixation points per unit area than surfaces reconstructed from multiple narrow pieces. We propose a clinically grounded framework in which graft geometry defines boundary, interior, seams, and epithelialization gaps. Larger grafts have a lower perimeter-to-area ratio and proportionally more interior, whereas multiple graft pieces create internal seams and additional interface length. These principles apply to unmeshed sheet and meshed grafts. Geometry is not an isolated determinant: central fixation, fibrin adhesion, bolsters, wraps, splints, and negative-pressure wound therapy improve coupling and reduce displacement, but do not remove physical edges, seams, or gap geometry. Seam orientation is clinically consequential. Straight seams should be avoided across flexion creases, joints, and concavities when an alternative is available; unavoidable seams should be reoriented, staggered, interrupted, or constructed nonlinearly. In donor-limited grafting, the objective changes. At comparable high expansion ratios of 3:1 or greater, widely meshed grafts and Meek micrografts distribute epithelial fronts and migration distances differently. This conditional framework translates common operative observations into a vocabulary for planning, teaching, and research. It identifies practical decisions under the surgeon's control and generates testable hypotheses regarding interface length, stabilization, seam orientation, and epithelialization distance.
Acute kidney injury (AKI) is a common early complication in critically ill burn patients, but its risk factors remain incompletely understood. This study aimed to identify independent risk factors for early AKI in this population. A retrospective study enrolled 98 critically ill burn patients admitted to the participating medical center from January 2016 to September 2025. Patients were divided into AKI and non-AKI groups based on AKI occurrence within 3 days post-injury. Admission data (demographics, laboratory parameters, inflammatory indices) were analyzed. Independent risk factors were identified via univariate analysis, multicollinearity diagnosis, and multivariate logistic regression; a prediction model was constructed and evaluated using ROC curve analysis. The incidence of early AKI in critically ill burn patients was 28.6%. The multivariate logistic regression analysis revealed that blood urea nitrogen (BUN; OR = 1.519; 95% CI: 1.042 ~ 2.214; p = 0.030), cystatin C (CYS; OR = 12.142; 95% CI: 1.240 ~ 118.858; p = 0.032), and D-dimer (OR = 1.136; 95% CI: 1.006 ~ 1.283; p = 0.040) levels were independent risk factors for early AKI. The prediction model equation was Logit(P) = -9.159 + 0.418 × BUN (mmol/L) + 2.497 × CYS (mg/L) + 0.127 × D-dimer (mg/L). The area under the ROC curve (AUC) for this model was 0.887 (95% CI: 0.816 ~ 0.958; p < 0.001), and the optimal cut-off value was determined by the maximum Youden index, which was 0.235. According to the prediction equation, a calculated probability p ≥ .235 indicates a high risk of early AKI. Elevated BUN, CYS, and D-dimer levels increase early AKI risk in critically ill burn patients.
Burn-wound progression contributes to early deterioration of burn severity and is closely associated with oxidative stress-induced inflammation in the zone of stasis, where mitochondria play a central role in regulating inflammatory responses and tissue damage. Melatonin is known to exert antioxidant and anti-inflammatory effects and to protect organelles from injury, suggesting a potential role in mitigating ischemia-related tissue damage. In this study, a "comb" scald rat model was used to investigate whether melatonin could prevent early burn-wound progression and to elucidate the underlying mechanisms. Melatonin was administered intraperitoneally at different doses immediately after injury, and wound conversion was assessed by histological analysis. Oxidative stress markers, inflammatory cytokines, and autophagy/mitophagy-related signals were evaluated using ELISA, immunostaining, qRT-PCR, and western blotting, with additional pharmacological modulation of autophagy and mitophagy to clarify mechanistic involvement. The results showed that melatonin significantly attenuated burn-induced activation of the HMGB1-NLRP3 inflammasome and reduced inflammatory cytokine release, while also alleviating oxidative stress, as indicated by decreased malondialdehyde (MDA) levels and restored superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities. These protective effects were closely associated with preservation of mitochondrial integrity and regulation of reactive oxygen species (ROS) through autophagy, particularly PINK1-PARKIN-dependent mitophagy. Importantly, the autophagy inhibitor 3-MA abolished the beneficial effects of melatonin, confirming the essential role of autophagy-related pathways. Together, these findings demonstrate that melatonin prevents early burn-wound progression by promoting mitophagy-mediated mitochondrial repair and suppressing downstream inflammatory responses.
Burn injuries vary widely in clinical severity, operative complexity, and physiologic burden. Although scoring systems exist for predicting morbidity and mortality in burn patients, a standardized framework for coordinating burn case acuity with anesthesia expertise has yet to be implemented in clinical practice. In this retrospective, single-center study, we analyzed 132 operative burn cases performed over a one-year period to evaluate a novel tiered classification system that stratifies anticipated anesthesia requirements by clinical severity. Cases were categorized as Green (low risk), Yellow (moderate risk), or Red (high risk) based on physiologic risk factors, including burn extent as percentage of total body surface area (TBSA), hemodynamic instability, and vasopressor dependence. Patient demographics and clinical variables, including age, mechanism of injury, TBSA, and intraoperative transfusion requirements were collected and statistically analyzed. Results showed that the pediatric cohort (<18 years old) demonstrated significantly greater mean TBSA burns (43.3% vs. 21.8%, p=0.0017, 95% CI [-33.70, -9.00]) and represented a higher proportion of Red-tier (high-risk) cases than adult patients (p=0.0011), with a similar mechanism of injury observed across cohorts (p=0.50). A statistically significant difference was observed in the distribution of intraoperative blood product administration across severity tiers (p<0.001). The findings of this study suggest that the proposed tiered system identifies clinically distinct groups of operative burn cases based on injury severity and physiologic instability. We propose that implementing this framework in clinical practice may improve outcomes for patients with acute burns, facilitate more efficient allocation of anesthesia resources, and guide standardized educational structures for management of acute burn injuries.
Burn injuries present significant public health and economic challenges in the United States. This study aimed to evaluate the key drivers of burn care costs by assessing relative changes in variable direct costs (VDC). A retrospective review of burn patients treated between 2022 and 2023 was conducted using cost and clinical data from hospital financial records. Patient demographics and clinical variables, including age, total body surface area, length of hospital stay, number of days on a ventilator, number of procedures, number of complications, number of comorbidities, and presence of inhalation injury, were analyzed. Univariate and multivariate quantile regression analyses were performed at the 25th, 50th, and 75th percentiles of VDC to examine how clinical factors influence cost variation across the cost distribution. The median age of patients was 39 years, with 66.2% being male. The median total body surface area affected was 3.7 percent, and the median length of hospital stay was 5 days. Length of stay and number of procedures were consistent predictors of increased VDC across all cost percentiles, demonstrating proportional increases in cost with greater resource utilization. At higher cost percentiles, prolonged ventilator use of four or more days demonstrated amplified effects on VDC, while procedural burden remained the strongest independent driver of increased costs after adjustment. The primary drivers of increased VDC included length of hospital stay, number of procedures, ventilator use, and overall clinical severity, particularly among high-cost patients. Targeted strategies aimed at reducing hospital length of stay and optimizing procedural utilization may help mitigate variable direct costs. Evaluating cost drivers across the VDC distribution provides critical insight for improving cost prediction, guiding resource allocation, and maintaining high-quality burn care.
Adult burn survivors are at risk for developing anxiety and reduced health-related quality of life. The purpose of the study was to investigate predictors of anxiety at one- and two-years post injury. Data from 266 patients were queried from the Burn Model System National Database between 2015-2020. Patient-reported outcomes at one- and two-years post injury were analyzed using the Patient-Reported Outcomes Measurement Information System (PROMIS-29) for anxiety severity, and the Mental Component Summary (MCS) and Physical Component Summary (PCS) for mental and physical health-related quality of life respectively. Logistic models were computed to determine predictors of anxiety at one- and two-years post injury. Results showed that at one-year post injury, burns to specific body regions and pre-existing diagnoses of mental health disorders predict high anxiety severity scores and low MCS scores, whereas burns at perineum area predict low PCS scores. At two-years post injury, younger age predicted low MCS scores, and burns to the leg area, older age, and pre-existing diagnosis of diabetes predict low PCS scores. Findings from this study showed that burns to visible areas, pre-existing mental health disorders, and younger age predict increased anxiety and lower mental-health related quality of life, whereas burns to the perineum and lower limbs, and older age predict lower physical-health related quality of life. Therefore, allocating mental and physical health-related resources to burn survivors based on burn area, age, and comorbidities is crucial for quality of life after burn injury.
Methicillin-resistant Staphylococcus aureus (MRSA) is consistently associated with more severe wound complications and worse outcomes in burn patients. Many burn centers who have implemented routine MRSA screening and decolonization protocols have reported reduced MRSA transmission, lower rates of device-associated infections such as CAUTI and CLABSI, and decreased LOS. At the Ohio State University, Wexner Medical Center (OSUWMC), we initiated a multidisciplinary quality improvement two-phase project to implement routine screening. Phase 1: all patients who screened positive for MRSA received a decolonization protocol consisting of intranasal mupirocin twice daily for 5 days and daily chlorhexidine gluconate baths; Phase 2: all patients were screened but no decolonization measures were taken. We aimed to determine if MRSA decolonization aids in decreasing incidence of MRSA, LOS, and incidence of wound infections. Phase 1: 45 patients were admitted in March 2025, with 93% compliance for admission MRSA screening (n = 36). 19 (49%) were negative, 10 (26%) were MSSA+, and 7 (18%) were MRSA+. All MRSA+ patients completed the decolonization protocol. Only 2 of the 45 patients (4%) developed MRSA wound infections requiring treatment. Phase 2: 103 patients from July-September 2025, with a 52.4% compliance rate for screening on admission (n = 54). 36 (66.7%) were negative, 5 (9.3%) were MRSA+, and 13 (24.1%) were MSSA+. 13 patients developed non-MRSA wound infections. No differences in length of stay, LOS/TBSA, incidence of infection by screened result or TBSA (once adjusted) or mortality were observed in either phase. The additional cost and resource utilization required for screening and decolonization did not appear to provide meaningful clinical advantage.
There is an increasing population of geriatric burn patients, and burns in this population are more morbid. Autologous skin cell suspension is an adjunct to autografting, which uses an 80:1 expansion of skin cells. The purpose of this investigation was to evaluate the ability of autologous skin cell suspension to augment wound healing in burn patients 65 years or older. We performed a single-center retrospective review of geriatric burn patients who underwent surgical treatment between January 2020 and October 2024. We identified burn patients aged 65 or older who were treated with autografting and an autologous skin cell suspension and matched them to a group that received autografting alone based on age, gender, comorbidity index, total body surface area burn, and number of days on a ventilator. The primary outcome was the achievement of 95% re-epithelialization of the primary burn wound at 4 weeks. Secondary outcomes included time to wound healing, autograft mesh ratio, graft thickness, autograft area, recipient wound characteristics, and postoperative complications. Twenty-seven patients were included in each cohort. Most patients achieved 95% re-epithelialization at 4 weeks. Time to wound healing and the proportions of patients that healed by 4 weeks were the same between the groups. However, ASCS use was independently associated with utilization of higher mesh ratios (OR 6.37, 95% CI 1.61-25.15; p = 0.0082), and high mesh ratios (≥3:1) were used more frequently in the ASCS cohort (29.0% compared to 3.7%, p = 0.0142). Patients treated with ASCS also received significantly thinner split-thickness skin grafts (p < 0.001). Autograft area, recipient wound bed composition, anatomic wound location, and postoperative complication rates were similar between groups. Although ASCS was not associated with improved early wound healing in this cohort, its use was associated with thinner split-thickness skin grafts and higher autograft mesh ratios without prolonging time to healing. These findings suggest that ASCS may facilitate the use of thinner grafts and higher mesh ratios while maintaining comparable early wound healing geriatric burn patients.
Burn injuries impose significant healthcare and logistical burdens in both civilian and military settings. This includes infectious complications that are amplified in prolonged field care environments where surgical intervention is delayed. As such, there is a growing need for adjunctive therapies that mitigate infection and zwitterionic (ZW) hydrogels offer a promising solution for maintaining a moist wound environment and reducing bacterial colonization. This study evaluates the safety and efficacy of two ZW hydrogel products: CleraFlexTM and a ZW hydrogel loaded with polyhexamethylene biguanide (PHMB) in infected burns in swine under simulated prolonged field care conditions. Ten-5x5cm contact burns were created on the dorsum of Yorkshire-cross swine (n=3) and inoculated with Pseudomonas aeruginosa (ATCC #27853, 2.5 x 105 CFU). Wounds were treated with saline, triple antibiotic ointment (TAO), CleraFlex, or ZW + PHMB. Photographs and biopsies were obtained. On day 7 post-burn, wounds appeared infected due to greenish discoloration to varying degrees. Saline-treated wounds had the highest bacterial burden (9.38±0.40 log CFU/g). TAO treatment resulted in a non-significant reduction to 6.95±0.63 log CFU/g (p=0.078), whereas CleraFlex and ZW + PHMB achieved greater significant reductions (6.39±0.36 log CFU/g and 5.98±0.65 log CFU/g, respectively; (p<0.05 and p<0.01). Blinded histological analysis also showed reduced leukocyte extravasation, and potentiated removal of the necrotic eschar in burn wounds treated with ZW +/- PHMB. ZW formulations +/- PHMB significantly reduced bacterial burden in a porcine burn-infection model simulating prolonged field care, supporting their potential as effective adjuncts in managing infection during delayed evacuation in austere environments.
Burn wound healing remains a major clinical challenge. Mesenchymal stem cell-derived extracellular vesicles engineered to deliver defined microRNA cargo or modulate endogenous microRNA profiles have emerged as promising cell-free therapeutics, but native extracellular vesicle preparations remain constrained by low yield, heterogeneity, insufficient targeting, and incomplete cargo control. Moreover, much of the current evidence still comes from non-burn wound models. This review presents a burn-oriented framework that aligns upstream parental-cell programming, downstream vesicle modification, and biomaterial-assisted delivery with key burn-specific barriers, including burn depth, eschar, infection, hypoxia, systemic inflammation, inhalation injury, grafting requirements, and temporal immune dysregulation across the systemic inflammatory response syndrome-to-compensatory anti-inflammatory response syndrome transition. We also discuss translational requirements that are often underemphasized in general wound-healing reviews, including dose scaling for large total body surface area burns, repeat application, compatibility with debridement and grafting, storage and thawing in burn centers, sterility, use in infected wounds, and whether local extracellular vesicle delivery can mitigate systemic dysfunction. Overall, microRNA-engineered extracellular vesicles are a versatile platform for burn wound repair; however, clinical translation remains speculative without large-animal, infected-burn, grafting, long-term scar, and human safety data.
