Deciphering AKI in Burn Patients: Correlations between Clinical Clusters and Biomarkers.

Acute kidney injury (AKI) is a significant complication in burn patients, impacting outcomes substantially. This study explores the heterogeneity of AKI in burn patients by analyzing creatinine time-series data to identify distinct AKI clusters and evaluating routine biomarkers' predictive values. A retrospective cohort analysis was performed on 2608 adult burn patients admitted to Hangang Sacred Heart Hospital's Burn Intensive Care Unit (BICU) from July 2010 to December 2022. Patients were divided into four clusters based on creatinine trajectories, ranging from high-risk, severe cases to lower-risk, short-term care cases. Cluster A, characterized by high-risk, severe cases, showed the highest mortality and severity, with significant predictors being PT and TB. Cluster B, representing intermediate recovery cases, highlighted PT and albumin as useful predictors. Cluster C, a low-risk, high-resilience group, demonstrated predictive values for cystatin C and eGFR cys. Cluster D, comprising lower-risk, short-term care patients, indicated the importance of PT and lactate. Key biomarkers, including albumin, prothrombin time (PT), cystatin C, eGFR cys, and total bilirubin (TB), were identified as significant predictors of AKI development, varying across clusters. Diagnostic accuracy was assessed using area under the curve (AUC) metrics, reclassification metrics (NRI and IDI), and decision curve analysis. Cystatin C and eGFR cys consistently provided significant predictive value over creatinine, with AUC values significantly higher (p < 0.05) in each cluster. This study highlights the need for a tailored, biomarker-driven approach to AKI management in burn patients, advocating for the integration of diverse biomarkers in clinical practice to facilitate personalized treatment strategies. Future research should validate these biomarkers prospectively to confirm their clinical utility.

A deep dive into burn-mediated ARDS severity assessment: a retrospective study on hematological markers.

Acute Respiratory Distress Syndrome (ARDS) is a critical form of Acute Lung Injury (ALI), challenging clinical diagnosis and severity assessment. This study evaluates the potential utility of various hematological markers in burn-mediated ARDS, including Neutrophil-to-Lymphocyte Ratio (NLR), Mean Platelet Volume (MPV), MPV-to-Lymphocyte Ratio (MPVLR), Platelet count, and Platelet Distribution Width (PDW). Employing a retrospective analysis of data collected over 12 years, this study focuses on the relationship between these hematological markers and ARDS diagnosis and severity in hospitalized patients. The study establishes NLR as a reliable systemic inflammation marker associated with ARDS severity. Elevated MPV and MPVLR also emerged as significant markers correlating with adverse outcomes. These findings suggest these economical, routinely measured markers can enhance traditional clinical criteria, offering a more objective approach to ARDS diagnosis and severity assessment. Hematological markers such as NLR, MPV, MPVLR, Platelet count, and PDW could be invaluable in clinical settings for diagnosing and assessing ARDS severity. They offer a cost-effective, accessible means to improve diagnostic accuracy and patient stratification in ARDS. However, further prospective studies are necessary to confirm these findings and investigate their integration with other diagnostic tools in diverse clinical settings.

Big data insights into the diagnostic values of CBC parameters for sepsis and septic shock in burn patients: a retrospective study.

Sepsis and septic shock are prevalent and life-threatening complications in burn patients. Despite their severity, existing diagnostic methods are limited. This study aims to evaluate the efficacy of Complete Blood Count (CBC) and CBC ratio markers in diagnosing sepsis and septic shock, and in predicting mortality among burn patients. A cohort of 2757 burn patients was examined to ascertain the correlation between various CBC parameters, their ratios, and the incidence of sepsis and related mortality. Key markers analyzed included Red Cell Distribution Width (RDW), Mean Platelet Volume (MPV), Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), and Mean Platelet Volume-to-Platelet Ratio (MPVPR). Our findings indicate that 65.5% of the patients developed sepsis, and 24.3% succumbed to their conditions. The CBC parameters RDW, MPV, NLR, MPVPR, and MPV-to-Lymphocyte Ratio (MPVLR) were significantly associated with sepsis and mortality. These markers showed considerable temporal variation and yielded an Area Under the Curve (AUC) of over 0.65 in an unadjusted Generalized Estimating Equations (GEE) model. This study underscores the potential of RDW, MPV, NLR, MPVPR, and MPVLR as vital prognostic tools for diagnosing sepsis, septic shock, and predicting mortality in burn patients. Although based on a single-center dataset, our results contribute to the enhancement of sepsis management by facilitating earlier, more precise diagnosis and treatment strategies. Further multi-center research is necessary to confirm these findings and broaden their applicability, establishing a solid base for future explorations in this crucial field.

Pioneering predictions of AKI and AKIN severity in burn patients: a comprehensive CBC approach.

This study aims to evaluate the utility of complete blood count (CBC) markers, in conjunction with the acute kidney injury network (AKIN) criteria, for the early detection, severity assessment, and prediction of mortality outcomes of acute kidney injury (AKI) in burn patients. The research seeks to fill existing gaps in knowledge and validate the cost-effectiveness of using CBC as a routine diagnostic tool for better management of AKI. The study was conducted at Hangang Sacred Heart Hospital. We performed a large-scale retrospective analysis of 2758 adult patients admitted to the burn intensive care unit over a 12-year period. Among these patients, AKI occurred in 1554 patients (56.3%). Based on the AKIN stage classification, 794 patients (28.8%) were categorized as AKIN 1, 494 patients (17.9%) as AKIN 2, and 266 patients (9.6%) as AKIN 3. We defined several ratio markers, including the Neutrophil-to-lymphocyte ratio (NLR), Platelet-to-lymphocyte ratio (PLR), Monocyte-to-lymphocyte ratio (MLR), systemic immune-inflammation index (SII), and various mean platelet volume (MPV) ratios. Our statistical analyses, conducted using the R programming language, revealed significant correlations between these markers and AKI severity. The AUC values for neutrophil count and WBC count were 0.790 and 0.793, respectively, followed by immature granulocyte count with an AUC of 0.727. For red blood cell (RBC)-related parameters, the AUC values for hematocrit (Hct), hemoglobin (Hb), and RBC count were 0.725, 0.713, and 0.713, respectively. Among the platelet-related parameters, only platelet distribution width (PDW) had an AUC of 0.677. Among the ratio markers, the NLR had the highest AUC at 0.772, followed by MPVNR and SII with AUC values of 0.700 and 0.680, respectively. The findings underscore the potential of CBC as an economical, routine test for AKI, thereby paving the way for enhanced patient outcomes. Our study suggests the utility of routine CBC tests, specifically WBC count and PLR, for predicting AKI and platelet, MPV, and NLR for mortality assessment in burn patients. These findings underscore the potential of easily accessible CBC tests in enhancing AKI management. However, further multicenter studies are needed for validation.

The clinical differentiation of blood culture-positive and -negative sepsis in burn patients: a retrospective cohort study.

Background: Sepsis is a potentially life-threatening condition that occurs when the body's response to infection leads to widespread inflammation and tissue damage. Negative cultures can make it difficult for clinicians to make a diagnosis and may raise questions about the validity of the definition of sepsis. In addition, the clinical distinctions between burn patients with blood culture-positive and -negative sepsis are also poorly understood. Therefore, this study aimed to examine the clinical differences between blood culture-positive and -negative sepsis in burn patients in order to improve the understanding of the pathophysiology and epidemiology of sepsis in this population. Methods: This study had a retrospective design, and the participants were adults aged ≥18 years. Patients diagnosed with sepsis were divided into two groups based on their blood culture results within 1 week of sepsis diagnosis. Results: We enrolled 1643 patients admitted to our institution's burn intensive care unit between January 2010 and December 2021. pH, platelet count, bicarbonate and haematocrit were significant in both the positive and negative groups. However, lymphocyte, red cell distribution width and blood urea nitrogen were significant only in the positive group, whereas lactate dehydrogenase was significant only in the negative group. Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumonia are common gram-negative bacterial species, and Staphylococcus aureus and Staphylococcus epidermidis are common gram-positive bacterial species seen in burn patients with positive blood cultures. Carbapenem resistance was found to be associated with an unfavourable prognosis in gram-negative bacteria, with the exception of P. aeruginosa. Conclusions: pH, platelet count, bicarbonate and haematocrit were routine biomarkers that demonstrated statistical significance in both groups. Lactate dehydrogenase was significant in the blood-negative group, while red cell distribution width, blood urea nitrogen and lymphocyte count were significant in the positive group. Furthermore, the most common causes of sepsis are gram-negative bacteria, including A. baumannii, K. pneumoniae and P. aeruginosa. Additionally, resistance to carbapenems is associated with unfavourable outcomes.

Tracking longitudinal biomarkers in burn patients with sepsis and acute kidney injury: an unsupervised clustering approach.

BACKGROUND: Sepsis is a grave medical disorder characterized by a systemic inflammatory response to infection. Furthermore, it is a leading cause of morbidity and mortality, especially in hospitalized patients. Acute kidney injury (AKI) is a common complication of sepsis and is associated with increased morbidity and mortality. Patients with burns are particularly vulnerable to developing sepsis and AKI due to the extensive tissue damage and immune suppression resulting from burn injury. In this study, unsupervised clustering algorithms were used to track longitudinal biomarkers in patients with burns and assess their impact on mortality. METHODS: This retrospective study included adult patients with burns aged ≥ 18 years, who were admitted to the burn intensive care unit of Hallym University and Hangang Sacred Heart Hospital between July 2010 and December 2021. The patients were divided into two subgroups: those with sepsis (538 patients) and those without sepsis (826 patients). The longitudinal biomarkers were grouped into three clusters using the k-means clustering algorithm. Each cluster was assigned a letter from A to C according to its mortality rate. RESULTS: The odds ratio (OR) of pH was 9.992 in the positive group and 31.745 in the negative group in cluster C. The OR for lactate dehydrogenase (LD) was 3.704 in the positive group and 6.631 in the negative group in cluster C. The OR for creatinine was 2.784 in the positive group and 8.796 in the negative group in cluster C. The OR for blood urea nitrogen (BUN) in the negative group was 0.348, indicating a negative predictor of mortality. Regarding the application of Continuous Renal Replacement Therapy (CRRT) and ventilation, ventilation was significant in both groups. In contrast, CRRT application was not significant in the sepsis-positive group. Furthermore, it was not selected as a variable in the negative group. CONCLUSIONS: The pH, LD, and creatinine were significant in both groups, while lactate and platelets were significant in the sepsis-positive group. In addition, albumin, glucose, and BUN were significant in the sepsis-negative group. Continuous renal replacement therapy was not significant in either group. However, the use of a ventilator was associated with poor prognosis.

Evaluating clinical heterogeneity and predicting mortality in severely burned patients through unsupervised clustering and latent class analysis.

Burn injuries often result in a high level of clinical heterogeneity and poor prognosis in patients with severe burns. Clustering algorithms, which are unsupervised methods that can identify groups with similar trajectories in patients with heterogeneous diseases, can provide insights into the mechanisms of the disease pathogenesis. This study aimed to analyze routinely collected biomarkers to understand their mortality prediction power, identify the clinical meanings or subtypes, and inform treatment decisions to improve the outcomes of patients with burns. This retrospective cohort study included patients aged ≥ 18 years who were admitted between January 2010 and December 2021. The patients were divided into four subgroups based on the time period of their admission: week 1, 2, 3, and 4. The study revealed that 22 biomarkers were evaluated, and the red blood cell distribution width, bicarbonate level, pH, platelets, and lymphocytes were significantly associated with the mortality risk. Latent class analysis further demonstrated that the pH, platelets, lymphocytes, lactate, and albumin demonstrated the lowest levels in the cluster with the highest risk of mortality, with the lowest levels of pH and lactate being particularly noteworthy in week 1 of the study. During the week 2, the pH and lymphocyte levels were demonstrated to be significant predictors of the mortality risk, whereas the lymphocyte and platelet counts were meaningful predictors in week 3. During week 4, pH, platelet count, and albumin level were important predictors of mortality risk. Analysis of routinely collected biomarkers using clustering algorithms and latent class analysis can provide valuable insights into the heterogeneity of burn injuries and improve the ability to predict disease progression and mortality. Our findings suggest that lactate levels are a better indicator of cellular hypoxia in the early stages of burn shock, whereas platelet and lymphocyte levels are more indicative of infections such as sepsis. Albumin levels are considered a better indicator of reduced nutritional loss with decrease in unhealed burn wounds; however, the pH levels reflect the overall condition of the patient throughout the study period. These findings can be used to inform treatment decisions and improve the outcomes of burn patients.

Differentiation of Adipose-Derived Stem Cells into Smooth Muscle Cells in an Internal Anal Sphincter-Targeting Anal Incontinence Rat Model.

OBJECTIVE: Studies on development of an anal incontinence (AI) model targeting smooth muscle cells (SMCs) of the internal anal sphincter (IAS) have not been reported. The differentiation of implanted human adipose-derived stem cells (hADScs) into SMCs in an IAS-targeting AI model has also not been demonstrated. We aimed to develop an IAS-targeting AI animal model and to determine the differentiation of hADScs into SMCs in an established model. MATERIALS AND METHODS: The IAS-targeting AI model was developed by inducing cryoinjury at the inner side of the muscular layer via posterior intersphincteric dissection in Sprague-Dawley rats. Dil-stained hADScs were implanted at the IAS injury site. Multiple markers for SMCs were used to confirm molecular changes before and after cell implantation. Analyses were performed using H&E, immunofluorescence, Masson's trichrome staining, and quantitative RT-PCR. RESULTS: Impaired smooth muscle layers accompanying other intact layers were identified in the cryoinjury group. Specific SMC markers, including SM22α, calponin, caldesmon, SMMHC, smoothelin, and SDF-1 were significantly decreased in the cryoinjured group compared with levels in the control group. However, CoL1A1 was increased significantly in the cryoinjured group. In the hADSc-treated group, higher levels of SMMHC, smoothelin, SM22α, and α-SMA were observed at two weeks after implantation than at one week after implantation. Cell tracking revealed that Dil-stained cells were located at the site of augmented SMCs. CONCLUSIONS: This study first demonstrated that implanted hADSc restored impaired SMCs at the injury site, showing stem cell fate corresponding to the established IAS-specific AI model.

Longitudinal profile of routine biomarkers for mortality prediction using unsupervised clustering algorithm in severely burned patients: a retrospective cohort study with prospectively collected data.

Purpose: Burn injury has high clinical heterogeneity and worse prognosis in severely burned patients. Clustering algorithms using unsupervised methods to identify groups with similar trajectories in heterogeneous disease patients can provide insight into mechanisms of disease pathogenesis. This study analyzed routinely collected biomarkers to evaluate mortality prediction, find clinical meanings for these or their subtypes, and evaluate patterns. Methods: This retrospective cohort study included patients aged >18 years, between July 2012 and June 2021. All eligible patients received fluid resuscitation and survived for at least 7 days. Characteristics of clinical interest to the physician at 4 clinically important time points were evaluated. Results: Eligible patients were divided into 4 subgroups according to these time points: from 1st week to 4th week. Total of 1,249 patients admitted within 2 days after burns and receiving fluid resuscitation were included. Mean Harrell's C-index of pH was the highest (0.816), followed by platelets (0.807), creatinine (0.796), red cell distribution width (RDW, 0.778), and lactate (0.759). Longitudinal profiles among biomarkers were different. Conclusion: The main predictors were pH, platelets, creatinine, RDW, and lactate. Creatinine and RDW showed consistent patterns. The other markers varied according to patient condition. Thus, these markers could provide clues into underlying mechanisms and predict mortality.

Validation of Sepsis-3 using survival analysis and clinical evaluation of quick SOFA, SIRS, and burn-specific SIRS for sepsis in burn patients with suspected infection.

PURPOSE: Sepsis-3 is a life-threatening organ dysfunction caused by dysregulated host responses to infection; and defined using the Sepsis-3 criteria, introduced in 2016, however, the criteria need to be validated in specific clinical fields. We investigated mortality prediction and compared the diagnostic performance of quick Sequential Organ Failure Assessment (qSOFA), systemic inflammatory response syndrome (SIRS), and burn-specific SIRS (bSIRS) in burn patients. METHODS: This single-center retrospective cohort study examined burn patients in Seoul, Korea during January 2010-December 2020. Overall, 1,391 patients with suspected infection were divided into four sepsis groups using SOFA, qSOFA, SIRS, and burn-specific SIRS. RESULTS: Hazard ratios (HRs) of all unadjusted models were statistically significant; however, the HR (0.726, p = 0.0080.001) in the SIRS ≥2 group is below 1. In the adjusted model, HRs of the SOFA ≥2 (2.426, <0.001), qSOFA ≥2 (7.198, p<0.001), and SIRS ≥2 (0.575, p<0.001) groups were significant. The diagnostic performance of dichotomized qSOFA, SIRS, and bSIRS for sepsis was defined by the Sepsis-3 criteria. The mean onset day was 4.13±2.97 according to Sepsis-3. The sensitivity of SIRS (0.989, 95% confidence interval [CI]: 0.982-0.994) was higher than that of qSOFA (0.841, 95% CI: 0.819-0.861) and bSIRS (0.803, 95% CI: 0.779-0.825). Specificities of qSOFA (0.929, 95% CI: 0.876-0.964) and bSIRS (0.922, 95% CI: 0.868-0.959) were higher than those of SIRS (0.461, 95% CI: 0.381-0.543). CONCLUSION: Sepsis-3 is a good alternative diagnostic tool because it reflects sepsis severity without delaying diagnosis. SIRS showed higher sensitivity than qSOFA and bSIRS and may therefore more adequately diagnose sepsis.

A systematic review of translation and experimental studies on internal anal sphincter for fecal incontinence.

The complexity in the molecular mechanism of the internal anal sphincter (IAS) limits preclinical or clinical outcomes of fecal incontinence (FI) treatment. So far, there are no systematic reviews of IAS translation and experimental studies that have been reported. This systematic review aims to provide a comprehensive understanding of IAS critical role in FI. Previous studies revealed the key pathway for basal tone and relaxation of IAS in different properties as follows; calcium, Rho-associated, coiled-coil containing serine/threonine kinase, aging-associated IAS dysfunction, oxidative stress, renin-angiotensin-aldosterone, cyclooxygenase, and inhibitory neurotransmitters. Previous studies have reported improved functional outcomes of cellular treatment for regeneration of dysfunctional IAS, using various stem cells, but did not demonstrate the interrelationship between those results and basal tone or relaxation-related molecular pathway of IAS. Furthermore, these results have lower specificity for IAS-incontinence due to the included external anal sphincter or nerve injury regardless of the cell type. An acellular approach using bioengineered IAS showed a physiologic response of basal tone and relaxation response similar to human IAS. However, in both cellular and acellular approaches, the lack of human IAS data still hampers clinical application. Therefore, the IAS regeneration presents more challenges and warrants more advances.

Wound healing ability of acellular fish skin and bovine collagen grafts for split-thickness donor sites in burn patients: Characterization of acellular grafts and clinical application.

Due to its high polyunsaturated fatty acid content, acellular fish skin has emerged as a dermal substitute for the promotion of wound healing as it decreases scar formation while providing pain relief. However, various systematic studies on acellular fish skin, such as its biophysical analysis, in vitro activities, and clinical application, have not been sufficiently investigated. In this study, we conducted a comparative study to evaluate the wound-healing ability of acellular fish skin graft (Kerecis®) with that of the widely used bovine collagen skin graft (ProHeal®). The skin grafts were evaluated not only in terms of their biophysical properties, but also their in vitro cellular activities, using fibroblasts, keratinocytes, and human endothelial cells. The clinical study evaluated wound healing in 52 patients with acute burns who underwent skin grafting on donor sites from January 2019 to December 2020. The study was conducted with two groups; while only Kerecis® was tested in one group, Kerecis® and ProHeal® were compared in the other. In both groups, the application time of the dressing material was one to two days after split-thickness skin grafting to the donor sites. The Kerecis®-treatment group experienced faster healing than the other treatment group. In particular, the average wound healing time using the Kerecis® treatment and the ProHeal® treatment was 10.7 ± 1.5 days and 13.1 ± 1.4 days, respectively. We believe that the faster healing of the Kerecis® treatment, compared to that of the ProHeal® treatment, maybe due to the synergistic effect of the unique biophysical structure and the bioactive components of acellular fish skin.

Angiogenic factors secreted from human ASC spheroids entrapped in an alginate-based hierarchical structure via combined 3D printing/electrospinning system.

Human adipose-derived stem cell spheroids have been widely used in the treatment or regeneration of damaged skin tissues, and their success is believed to be due in part to angiogenic factors released from the spheroids. To achieve the sustained release of bioactive components from implanted spheroids within a defective area, the use of a biocompatible scaffolding biomaterial is required. In this study, we developed an alginate-based scaffolding structure, which was processed using three-dimensional printing and electrospinning for use as a spheroid-entrapping structure. A micro-sized alginate strut and electrospun alginate nanofibers functioned not only to firmly entrap the spheroids, but also to enable the stable release of various angiogenic and wound healing-related factors. We also demonstrated the function of these factors using a tube-forming assay and found that conditioned media from the spheroid-scaffold group improved capillary-like structure formation in human umbilical vein endothelial cells compared to the single cell-scaffold group. Our results suggest that this spheroid-entrapping alginate hybrid structure could represent a new platform for stem cell therapy using spheroid transplantation.

A clinical trial with a novel collagen dermal substitute for wound healing in burn patients.

Human skin incurs damage in various ways; a few of the recognizable factors are electric burns, chemical burns, scalding burns, surgery, and physical injuries, such as automobile accidents. If skin damage is extensive and severe enough [second degree and total body surface area (TBSA) involvement of >20%], the skin will lose the ability to regenerate itself. Burn wounds are treated in various ways. For full-thickness skin defects, the mainstay of treatment is an autologous split-thickness skin graft. However, there are some limitations due to scars, poor elasticity, and limitations in the joint movements due to contractures. Recently, artificial dermis has been widely used to minimize contractures. The use of dermal replacements for the treatment of burns brings new hope in maintaining the characteristics of the normal dermis. Herein, Insuregraf® was used for skin regeneration in patients who had burn injury from flames, electricity, heat, or steam. The mean take-rate values at 7 and 14 days after operation were 94.55 ± 3.02% and 97.40 ± 2.57%, respectively. Furthermore, areas covered by Insuregraf® showed higher mean values of trans-epidermal water loss (24.6 ± 3.9 g h-1 m-2), gross elasticity (Ua/Uf = 0.76 ± 0.24), and biological elasticity (Ur/Uf = 0.55 ± 0.1). These values were much better than those of the control where Insuregraf® was not used (p = 0.030, p = 0.040, and p = 0.013, respectively). Furthermore, the biomechanical scar properties of Insuregraf® and Matriderm were very similar. Hence, we suggest that Insuregraf® can be used in the medical field.

Enhancement of wound healing efficiency mediated by artificial dermis functionalized with EGF or NRG1.

The use of artificial dermis as a skin substitute is a field of active study, as acellular dermal matrices from cadavers are susceptible to infection owing to their human origin. One such alternative dermal replacement scaffold, INSUREGRAF®, is derived primarily from extracellular matrix proteins such as collagen and elastin and has been clinically used to treat severe skin wounds such as burns. This scaffold has proven to be useful to minimize wound contraction and scar formation owing to its biocompatibility, interconnected pore structure, sufficient biodegradability, and suitable mechanical properties. However, INSUREGRAF® does not provide scar-free wound healing in cases of severe skin damage such as full-thickness (FT) excision. Considering that the efficient recruitment of fibroblasts and keratinocytes into a wound site represents a critical step in the regeneration of damaged skin, we attempted to enhance the efficiency for wound healing by fabricating growth factor-functionalized INSUREGRAF®. In particular, we utilized epidermal growth factor (EGF) and an EGF family member, neuregulin-1 (NRG1), not previously studied in the context of wound healing, whose cellular role is to promote proliferation and migration in fibroblasts and keratinocytes. Both artificial dermis-growth factor combinations led to efficient recruitment of fibroblasts and keratinocytes into a wound site during the early steps of skin regeneration. Notably, EGF- or NRG1-functionalized INSUREGRAF® induced rapid proliferation of skin cells in an ERK pathway-dependent manner and exhibited efficient wound healing in a Sprague-Dawley rat FT excision and grafting model. These results provide the foundation for expanding the use of growth factor-functionalized INSUREGRAF® to clinical application in cases of severe skin injury.

Accelerated Wound Healing by Fibroblasts Differentiated from Human Embryonic Stem Cell-Derived Mesenchymal Stem Cells in a Pressure Ulcer Animal Model.

Fibroblasts synthesize and secrete dermal collagen, matrix proteins, growth factors, and cytokines. These characteristics of fibroblasts provide a potential way for fibroblast therapy to treat skin ulcers more effectively than conventional therapies such as cytokine therapy and negative pressure wound therapy. However, the obstacle to the commercialization of fibroblast therapy is the limited supply of cells with consistent quality. In this study, we tested whether human embryonic stem cell-derived mesenchymal stem cells (hESC-MSCs) could be differentiated into fibroblasts considering that they have characteristics of high differentiation rates, unlimited proliferation possibility from a single colony, and homogeneity. As a result, hESC-MSC-derived fibroblasts (hESC-MSC-Fbs) showed a significant increase in the expression of type I and III collagen, fibronectin, and fibroblast-specific protein-1 (FSP-1). Besides, vessel formation and wound healing were enhanced in hESC-MSC-Fb-treated skin tissues compared to PBS- or hESC-MSC-treated skin tissues, along with decreased IL-6 expression at 4 days after the formation of pressure ulcer wound in a mouse model. In view of the limited available cell sources for fibroblast therapy, hESC-MSC-Fbs show a promising potential as a commercial cell therapy source to treat skin ulcers.