Current understanding of thermo(dys)regulation in severe burn injury and the pathophysiological influence of hypermetabolism,adrenergic stress and hypothalamic regulation-a systematic review

Background:In this systematic review,we summarize the aetiology as well as the current knowl-edge regarding thermo(dys)regulation and hypothermia after severe burn trauma and aim to present key concepts of pathophysiology and treatment options.Severe burn injuries with>20%total body surface area(TBSA)affected commonly leave the patient requiring several surgical procedures,prolonged hospital stays and cause substantial changes to body composition and metabolism in the acute and long-term phase.Particularly in severely burned patients,the loss of intact skin and the dysregulation of peripheral and central thermoregulatory processes may lead to substantial complications.Methods:A systematic and protocol-based search for suitable publications was conducted fol-lowing the PRISMA guidelines.Articles were screened and included if deemed eligible.This encompasses animal-based in vivo studies as well as clinical studies examining the control-loops of thermoregulation and metabolic stability within burn patients Results:Both experimental animal studies and clinical studies examining thermoregulation and metabolic functions within burn patients have produced a general understanding of core concepts which are,nonetheless,lacking in detail.We describe the wide range of pathophysiological alterations observed after severe burn trauma and highlight the association between thermoregulation and hypermetabolism as well as the interactions between nearly all organ systems.Lastly,the current clinical standards of mitigating the negative effects of thermodysregulation and hypothermia are summarized,as a comprehensive understanding and implementation of the key concepts is critical for patient survival and long-term well-being.Conclusions:The available in vivo animal models have provided many insights into the interwoven pathophysiology of severe burn injury,especially concerning thermoregulation.We offer an outlook on concepts of altered central thermoregulation from non-burn research as potential areas of future research interest and aim to provide an overview of the clinical implications of temperature management in burn patients.

A comparison of burn related injuries following the natural disaster Super Storm Hurricane Sandy to the National Burn Repository of the American Burn Association

Background:Burn related injuries from natural disasters are not wel described and natural disasters are not identified as an etiology of burn injury in the National Burn Repository(NBR)of the American Burn Association.The natural disaster Super Storm Hurricane Sandy had devastating effects.Our goal was to detail the burn related injuries fol owing this natural disaster and to compare the data to the NBR.Methods:This was a retrospective chart review of thirty four patients who sustained burn related injuries following Super Storm Hurricane Sandy(SSHS)and were managed at Staten Island University Hospital Burn Center.Institutional Review Board approval was obtained.Data variables included age,gender,race,past medical history(PMHx),burn type,percentage total body surface area(%TBSA),hospital length of stay(HLOS),and mortality.We compared data from SSHS to the 2003-2013 NBR.Categorical data were summarized using frequency counts,percentages and Clopper-Pearson 95%confidence interval for proportion.Continuous outcome data were summarized by descriptive statistics.Data analyses performed with SAS?System Version 9.3(SAS Institute Inc.,Cary,NC)and p<0.05 was significant.Results:In the SSHS group,average age was 36+24 years,range 1-80 years,and 44.1%were males(15/34,95%CI:27.2-62.1).Caucasians comprised 58.8%,(20/34,95%CI:40.7,75.4)and 73.5%had no PMHx(25/34,95%CI:55.6,87.1).The most common burn type was scald,55.9%,(19/34,95%CI:37.9,72.8)and%TBSA ranged 1%–47%,average of 7%+12%.The average HLOS was 13+26 days,range of 1–113 days.Mortality was 2.9%(1/34,95%CI:0.07–15).In comparison,the NBR reported an average age of 32 years and 69%were males.Caucasians comprised 59.1%.The most common burn type was flame,43.2%and the%TBSA ranged 1%–9.9%.HLOS ranged 8.4–10.2 days and mortality was 3.4%.Conclusion:We conclude that burn related injuries following a natural disaster differ as compared to those most commonly reported in the NBR.

Epidemiology of foot burns in a Dutch burn centre

Background:Although the feet involve a small percentage of the total body surface area,they can have major effects in daily life,caused by prolonged bed rest,hospitalization and high risk of both early and late complications.The aim of this study was to define the aetiology,treatment and outcomes of foot burns,with special interest in paediatric patients,patients with diabetic disease and burns acquired at the workplace.Methods:This is a retrospective cohort study of 82 patients who were admitted to one of the three burn centres in the Netherlands during the period 2004 to 2013.The patients had a median age of 43.5 years(range 0.01–85.9),and included 14 children and 8 diabetics.Data were collected from the hospital records.Results:Scalding was the most common cause of the injury.Almost all patients required surgical management.It is notable that most of hospitalized patients(82%)were not admitted on the day of injury.Children had a significantly shorter length of stay compared to adults(p=0.01).The eight patients with diabetes had a significantly longer length of hospital stay,more complications and more often residual defects compared to the non-diabetic patients.In 13 patients,the injury took place at work.Half of these burns were caused by scalding,and foot burns caused by chemicals at work were rare(two patients).Conclusions:Although the incidence of foot burns is low,there is a significant morbidity due to complications and long hospital stay.The following three points are suggested.Immediate referral to a burn centre is essential.It is important to educate diabetic patients on the risk of complications and adverse outcomes after burn injury.Preventative measures at the workplace are worth considering.

Mesenchymal stromal cells-exosomes:a promising cell-free therapeutic tool for wound healing and cutaneous regeneration

Cutaneous regeneration at the wound site involves several intricate and dynamic processes which require a series of coordinated interactions implicating various cell types,growth factors,extracellular matrix(ECM),nerves,and blood vessels.Mesenchymal stromal cells(MSCs)take part in all the skin wound healing stages playing active and beneficial roles in animal models and humans.Exosomes,which are among the key products MSCs release,mimic the effects of parental MSCs.They can shuttle various effector proteins,messenger RNA(mRNA)and microRNAs(miRNAs)to modulate the activity of recipient cells,playing important roles in wound healing.Moreover,using exosomes avoids many risks associated with cell transplantation.Therefore,as a novel type of cell-free therapy,MSC-exosome-mediated administration may be safer and more efficient than whole cell.In this review,we provide a comprehensive understanding of the latest studies and observations on the role of MSC-exosome therapy in wound healing and cutaneous regeneration.In addition,we address the hypothesis of MSCs microenvironment extracellular vesicles(MSCs-MEVs)or MSCs microenvironment exosomes(MSCs-MExos)that need to take stock of and solved urgently in the related research about MSC-exosomes therapeutic applications.This review can inspire investigators to explore new research directions of MSC-exosome therapy in cutaneous repair and regeneration.

Considerations for pediatric burn sedation and analgesia

Burn patients experience anxiety and pain in the course of their injury, treatment, and recovery. Hence, treatment of anxiety and pain is paramount after burn injury. Children, in particular, pose challenges in anxiety and pain management due to their unique physiologic, psychologic, and anatomic status. Burn injuries further complicate pain management and sedation as such injuries can have effects on medication response and elimination. Burn injuries further complicate pain management and sedation as such injuries can have effects on medication response and elimination. The purpose of this review is to describe the challenges associated with management of anxiety, pain, and sedation in burned children and to describe the different options for treatment of anxiety and pain in burned children.

Identification of factors predicting scar outcome after burn injury in children:a prospective case-control study

Background:There is a lack of rigorous research investigating the factors that influence scar outcome in children. Improved clinical decision-making to reduce the health burden due to post-burn scarring in children will be guided by evidence on risk factors and risk stratification. This study aimed to examine the association between selected patient, injury and clinical factors and the development of raised scar after burn injury. Novel patient factors were investigated including selected immunological co-morbidities (asthma, eczema and diabetes type 1 and type 2) and skin pigmentation (Fitzpatrick skin type). Methods:A prospective case-control study was conducted among 186 children who sustained a burn injury in Western Australia. Logistic regression was used to explore the relationship between explanatory variables and a defined outcome measure:scar height measured by a modified Vancouver Scar Scale (mVSS). Results:The overall correct prediction rate of the model was 80.6%;80.9%for children with raised scars (>1 mm) and 80.4%for children without raised scars (≤1 mm). After adjustment for other variables, each 1%increase in%total body surface area (%TBSA) of burn increased the odds of raised scar by 15.8%(95%CI=4.4-28.5%). Raised scar was also predicted by time to healing of longer than 14 days (OR=11.621;95%CI=3.727-36.234) and multiple surgical procedures (OR=11.521;1.994-66.566). Conclusions:Greater burn surface area, time to healing of longer than 14 days, and multiple operations are independently associated with raised scar in children after burn injury. Scar prevention strategies should be targeted to children with these risk factors.

A biological membrane-based novel excisional wound-splinting model in mice (With video)

Rodents have robust wound healing mechanism compared to other animal species.The major mechanisms of wound healing diff er between rodents and humans.In humans,wound healing primarily depends on re-epithelialization and granulation tissue(GT)formation,whereas wound contraction is more important during rodent wound closure.In this study,we described a novel excisional wound-splinting model in mice with a new biological membrane to imitate wound healing in humans.In this model,wound contraction can be eff ectually prevented,and the extent of re-epithelialization and the amount of granulation tissue can be determined easily.Furthermore,the harvested tissues can be analyzed with diff erent methods according to the research aim.In conclusion,we have developed a biological membrane-based,novel,excisional wound-splinting model in mice that has unique advantages for wound healing research compared with the conventional animal model.

Myocardial injury:where inflammation and autophagy meet

Autophagy is a highly conserved bulk degradation mechanism that degrades damaged organelles,aged proteins and intracellular contents to maintain the homeostasis of the intracellular microenvironment.Activation of autophagy can be observed during myocardial injury,during which inflammatory responses are strongly triggered.Autophagy can inhibit the inflammatory response and regulate the inflammatory microenvironment by removing invading pathogens and damaged mitochondria.In addition,autophagy may enhance the clearance of apoptotic and necrotic cells to promote the repair of damaged tissue.In this paper,we briefly review the role of autophagy in different cell types in the inflammatory microenvironment of myocardial injury and discuss the molecular mechanism of autophagy in regulating the inflammatory response in a series of myocardial injury conditions,including myocardial ischemia,ischemia/reperfusion injury and sepsis cardiomyopathy.

Skin biomechanics:a potential therapeutic intervention target to reduce scarring

Pathological scarring imposes a major clinical and social burden worldwide.Human cutaneous wounds are responsive to mechanical forces and convert mechanical cues to biochemical signals that eventually promote scarring.To understand the mechanotransduction pathways in cutaneous scarring and develop new mechanotherapy approaches to achieve optimal scarring,the current study highlights the mechanical behavior of unwounded and scarred skin as well as intra-and extracellular mechanisms behind keloid and hypertrophic scars.Additionally,the therapeutic interventions that promote optimal scar healing by mechanical means at the molecular,cellular or tissue level are extensively reviewed.The current literature highlights the significant role of fibroblasts in wound contraction and scar formation via differentiation intomyofibroblasts.Thus,understanding myofibroblasts and their responses to mechanical loading allows the development of new scar therapeutics.A review of the current clinical and preclinical studies suggests that existing treatment strategies only reduce scarring on a small scale after wound closure and result in poor functional and aesthetic outcomes.Therefore,the perspective of mechanotherapies needs to consider the application of both mechanical forces and biochemical cues to achieve optimal scarring.Moreover,early intervention is critical in wound management;thus,mechanoregulation should be conducted during the healing process to avoid scar maturation.Future studies should either consider combining mechanical loading(pressure)therapies with tension offloading approaches for scar management or developing more effective early therapies based on contraction-blocking biomaterials for the prevention of pathological scarring.

Antibacterial polysaccharide-based hydrogel dressing containing plant essential oil for burn wound healing

Background:Polysaccharide-based hydrogels have been developed for many years to treat burn wounds.Essential oils extracted from aromatic plants generally exhibit superior biological activity,especially antibacterial properties.Studies have shown that antibacterial hydrogels mixed with essential oils have great potential for burn wound healing.This study aimed to develop an antibacterial polysaccharide-based hydrogel with essential oil for burn skin repair.Methods:Eucalyptus essential oil(EEO),ginger essential oil(GEO)and cumin essential oil(CEO)were employed for the preparation of effective antibacterial hydrogels physically crosslinked by carboxymethyl chitosan(CMC)and carbomer 940(CBM).Composite hydrogels were prepared and characterized using antimicrobial activity studies,Fourier-transform infrared spectroscopy,X-ray diffraction,scanning electron microscopy,gas chromatography-mass spectrometery,rheological analysis,viscosity,swelling,water loss rate and water vapor transmission rate studies.In addition,the biocompatibility of hydrogels was evaluated in vivo by cytotoxicity and cell migration assays and the burn healing ability of hydrogels was tested in vivo using burn-induced wounds in mice.Results:The different essential oils exhibited different mixing abilities with the hydrogel matrix(CMC and CBM),which caused varying levels of reduction in essential oil hydrogel viscosity,swelling and water vapor transmission.Among the developed hydrogels,the CBM/CMC/EEO hydrogel exhibited optimal antibacterial activities of 46.26±2.22%and 63.05±0.99%against Staphylococcus aureus and Escherichia coli,respectively,along with cell viability(>92.37%)and migration activity.Furthermore,the CBM/CMC/EEO hydrogel accelerated wound healing in mouse burn models by promoting the recovery of dermis and epidermis as observed using a hematoxylin–eosin and Masson’s trichrome staining assay.The findings from an enzyme-linked immunosorbent assay demonstrated that the CBM/CMC/EEO hydrogel could repair wounds through interleukin-6 and tumor necrosis factor-αdownregulation and transforming growth factor-β,vascular endothelial growth factor(VEGF)and epidermal growth factor upregulation.Conclusions:This study successfully prepared a porous CBM/CMC/EEO hydrogel with high antibacterial activity,favorable swelling,optimal rheological properties,superiorwater retention andwater vapor transmission performance and a significant effect on skin repair in vitro and in vivo.The results indicate that the CBM/CMC/EEO hydrogel has the potential for use as a promising burn dressing material for skin burn repair.

Evaluation of optimized continuous venovenous hemodiafiltration therapy efficiency in severe burn patients with sepsis

As an initial factor,sepsis and multiple organ dysfunction syndrome(MODS)caused by sepsis are the principal causes of death in burned patients. In this report, we measured the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-8 in severely burned patients with sepsis after the initiation of continuous vein-vein hemodiafiltration (CVVHDF) to evaluate the clinical usefulness of CVVHDF on the removal of key mediators. The vital sign indices, such as the heart rate (HR), respiration (R) and central venous pressure (CVP), were recorded at 0 and 42 h in each group. Further, the laboratory examinations indexes, such as the white blood cel count, blood sugar, se-rum sodium, blood urea nitrogen and serum creatinine, were detected in venous blood samples. Twenty-two severely burned patients suffering from sepsis were randomized into the control group (A, n = 11) and the experimental group (B, n = 11). The patients in group A underwent conventional treatment, and those in group B received conventional+CVVHDF treatment. The vital signs, such as the HR, R, and CVP, and laboratory examination indices, such as the blood cel count, blood sugar, serum sodium, blood urea nitrogen, and serum creatinine, dropped significantly in group B compared with those in group A at 42 h (P < 0.05). The plasma levels of TNF-α, IL-6 and IL-8 were measured at 0, 12, 18, 24, 36 and 42 h after the start of CVVHDF and at the same time points after the patients were diagnosed with sepsis in group A. The plasma levels of TNF-α in group B decreased by 32% at 18 h after the start of CVVHDF and decreased by 43%at 42 h after the start of CVVHDF;however, these levels were increased compared with the normal values (P < 0.01). The plasma levels of IL-6 decreased at 18 h after the start of CVVHDF (0.274 ± 0.137 ng/ml). Fol owing a brief increase at 24 h, the plasma levels of IL-6 again decreased continuously until the end of the investigation (0.192 ± 0.119 ng/ml). The plasma levels of IL-8 in group B decreased by 56% at 18 h after the start of CVVHDF, but they were increased compared with the normal values (P < 0.01). The plasma levels of IL-8 in group B decreased by 70% at 42 h after the start of CVVHDF, but they were increased compared with the normal values (P < 0.01). The MODS incident was 4 of 11 in group A compared with 1 of 11 in group B (P < 0.01). In conclusion, CVVHDF can effectively reduce the levels of TNF-α, IL-6 and IL-8 as wel as the MODS incidence in patients with serious burns.

Decoding the molecular landscape of keloids:new insights from single-cell transcriptomics

Keloids are a fibrotic disease caused by an excessive accumulation of extracellular matrix in the dermis;they have neoplasia-like properties of aggressive growth and high posttreatment recurrence rates.Therefore,it is imperative to gain additional insight into the pathobiology of keloid formation.Single-cell RNA sequencing(scRNA-seq)technology has brought data-driven innovation to understanding the pathogenesis of keloids by breaking the limitations of traditional sequencing technologies to resolve cell composition and to distinguish functional cell subtypes at an unprecedented resolution.The present review aims to cover the application of scRNAseq technology in keloids and its exploratory findings,including the depiction of the cellular landscape of keloids,fibroblast heterogeneity,the lineage development of Schwann cells and the mesenchymal-activation phenomenon of endothelial cells.Furthermore,scRNA-seq records the transcriptional profiles of fibroblasts and immune cells in a more refined manner,and this gene expression information provides excellent material for inferring intercellular communication networks and lays an important theoretical foundation for future studies.

Autophagy-mediated regulation of neutrophils and clinical applications

Autophagy,an adaptive catabolic process,plays a cytoprotective role in enabling cellular homeostasis in the innate and adaptive immune systems.Neutrophils,the most abundant immune cells in circulation,are professional killers that orchestrate a series of events during acute inflammation.The recent literature indicates that autophagy has important roles in regulating neutrophil functions,including differentiation,degranulation,metabolism and neutrophil extracellular trap formation,that dictate neutrophil fate.It is also becoming increasingly clear that autophagy regulation is critical for neutrophils to exert their immunological activity.However,evidence regarding the systematic communication between neutrophils and autophagy is insufficient.Here,we provide an updated overview of the function of autophagy as a regulator of neutrophils and discuss its clinical relevance to provide novel insight into potentially relevant treatment strategies.

Topical antimicrobial agents for pediatric burns

While topical antimicrobial agents are indicated for most if not all burn wounds, the choice of a topical agent must consider many factors such as the wound depth, anticipated time to healing, need for surgical intervention, and the known cytotoxicity of the agent. Especially relevant to the pediatric burn patient are the antimicrobial agent's properties related to causing pain or irritation and the required frequency of application and dressings. This article will discuss the general principles surrounding the use of topical antimicrobials on burn wounds and will review the most common agents currently in use.

The Notch pathway attenuates burn-induced acute lung injury in rats by repressing reactive oxygen species

Background:Acute lung injury(ALI)is a common complication following severe burns.The underlying mechanisms of ALI are incompletely understood;thus,available treatments are not sufficient to repair the lung tissue after ALI.Methods:To investigate the relationship between the Notch pathway and burn-induced lung injury,we established a rat burn injury model by scalding and verified lung injury via lung injury evaluations,including hematoxylin and eosin(H&E)staining,lung injury scoring,bronchoalveolar lavage fluid and wet/dry ratio analyses,myeloperoxidase immunohistochemical staining and reac-tive oxygen species(ROS)accumulation analysis.To explore whether burn injury affects Notch1 expression,we detected the expression of Notch1 and Hes1 after burn injury.Then,we extracted pulmonary microvascular endothelial cells(PMVECs)and conducted Notch pathway inhibition and activation experiments,via aγ-secretase inhibitor(GSI)and OP9-DLL1 coculture,respectively,to verify the regulatory effect of the Notch pathway on ROS accumulation and apoptosis in burn-serum-stimulated PMVECs.To investigate the regulatory effect of the Notch pathway on ROS accumulation,we detected the expression of oxidative-stress-related molecules such as superoxide dismutase,nicotinamide adenine dinucleotide phosphate(NADPH)oxidase(NOX)2,NOX4 and cleaved caspase-3.NOX4-specific small interfering RNA(siRNA)and the inhibitor GKT137831 were used to verify the regulatory effect of the Notch pathway on ROS via NOX4.Results:We successfully established a burn model and revealed that lung injury,excessive ROS accumulation and an inflammatory response occurred.Notch1 detection showed that the expression of Notch1 was significantly increased after burn injury.In PMVECs challenged with burn serum,ROS and cell death were elevated.Moreover,when the Notch pathway was suppressed by GSI,ROS and cell apoptosis levels were significantly increased.Conversely,these parameters were reduced when the Notch pathway was activated by OP9-DLL1.Mechanistically,the inhibition of NOX4 by siRNA and GKT137831 showed that the Notch pathway reduced ROS production and cell apoptosis by downregulating the expression of NOX4 in PMVECs.Conclusions:The Notch pathway reduced ROS production and apoptosis by downregulating the expression of NOX4 in burn-stimulated PMVECs.The Notch-NOX4 pathway may be a novel therapeutic target to treat burn-induced ALI.

Topical odour management in burn patients

Preventing microbial colonization or infections that cause offensive smells may lead to odor reduction.As both anaerobic and aerobic bacteria cause the release of malodor from wounds,the most direct way of avoiding or eliminating wound odor is to prevent or eradicate the responsible infection through the debridement of necrotic tissues.However,some burn patients with malodorous wounds are unable to undergo debridement due to systemic conditions,especially in the acute stage.Moreover,the optimal drug doses and dressings to ensure the efficacy and cost-effectiveness of odorous burn wound management is unclear.The purpose of this commentary is to outline the odor management options available for burn patients,focusing on topical strategies.Numerous potential therapies for treating odorous wounds after burn injuries are suggested.

A modified scar model with controlled tension on secondary wound healing in mice

Pathological scars might cause a distorted appearance and restricted mobility,and the study of scar pathophysiology has been hindered by the absence of a reliable model.In this study,we introduce a model with a modified device to induce controlled tension on a wound healing by secondary intention to overcome the shortcomings of the model generated by Aarabi et al.We investigated and recommend an induction of 0.1 N/mm^(2) tension on day 7 for 14 days to mimic the characteristics of human scars.A 3.5-fold increase in scar tissue and a 2-fold increase in collagen production were induced by the modified model.Histologically,the modified method increased scar thickness.However,no significant difference was found in cell density between the two groups.This modified procedure significantly increased scar tissue,which could be used for further cellular and biomolecular research.The mechanical force applied to the wound became measurable and controllable.This method is more convenient for researchers to observe in realtime and for providing timely adjustments of the tension used in this modified model.

Survival analysis and mortality predictors of hospitalized severe burn victims in a Malaysian burns intensive care unit

Background:Prognostic measures to determine burn mortality are essential in evaluating the severity of individual burn victims.This is an important process of triaging patients with high risk of mortality that may be nursed in the acute care setting.Malaysian burn research is lacking with only one publication identified which describes the epidemiology of burn victims.Therefore,the objective of this study was to go one step further and identify the predictors of burn mortality from a Malaysian burns intensive care unit(BICU)which may be used to triage patients at higher risk of death.Methods:This is a retrospective cohort study of all admissions to Hospital Sultan Ismail’s BICU from January 2010 till October 2015.Admission criteria were in accordance with the American Burn Association guidelines,and risk factors of interest were recorded.Data was analyzed using simple logistic regression to determine significant predictors of mortality.Survival analysis with time to death event was performed using the Kaplan-Meier survival curve with log-rank test.Results:Through the 6-year period,393 patients were admitted with a male preponderance of 73.8%.The mean age and length of stay were 35.6(±15.72)years and 15.3(±18.91)days.There were 48 mortalities with an overall mortality rate of 12.2%.Significant risk factors identified on simple logistic regression were total body surface area(TBSA)>20%(p<0.001),inhalation injury(p<0.001)and presence of early systemic inflammatory response syndrome(SIRS)(p<0.001).Survival analysis using Kaplan-Meier survival curve showed similar results with TBSA>20%,presence of SIRS,mechanical ventilation and inhalation injury which were associated with poorer survival(p<0.001).Conclusion:The predictors of mortality identified in a Malaysian BICU were TBSA>20%,early SIRS,mechanical ventilation and inhalation injury which were associated with poorer survival outcome.The immunological response differs from individual patients and influenced by the severity of burn injury.Early SIRS on admission is an important predictor of death and may represent the severity of burn injury.Patients who required mechanical ventilation were associated with mortality and it is likely related to the severity of pulmonary insults sustained by individual patients.This data is important for outcome prognostication and mortality risk counselling in severely burned patients.

The clinical effectiveness and safety of using epidermal growth factor,fibroblast growth factor and granulocyte-macrophage colony stimulating factor as therapeutics in acute skin wound healing:a systematic review and meta-analysis

Background:Promoting wound healing is crucial to restore the vital barrier function of injured skin.Growth factor products including epidermal growth factor(EGF),fibroblast growth factor(FGF)and granulocyte-macrophage colony stimulating factor(GM-CSF)have been used for decades although no systematic evaluation exists regarding their effectiveness and safety issues in treating acute skin wounds.This has resulted in a lack of guidelines and standards for proper application regimes.Therefore,this systematic review and meta-analysis was performed to critically evaluate the effectiveness and safety of these growth factors on skin acute wounds and provide guidelines for application regimes.Methods:We searched PubMed/Medline(1980-2020),Cochrane Library(1980-2020),Cochrane CENTRAL(from establishment to 2020),ClinicalTrials.gov(from establishment to 2020),Chinese Journal Full-text Database(CNKI,1994-2020),China Biology Medicine disc(CBM,1978-2019),Chinese Scientific Journal Database(VIP,1989-2020)andWanfang Database(WFDATA,1980-2019).Randomized controlled trials(RCTs),quasi-RCTs and controlled clinical trials treating patients with acute skin wounds from various causes and with those available growth factors were included.Results:A total of 7573 papers were identified through database searching;229 papers including 281 studies were kept after final screening.Administering growth factors significantly short-ened the healing time of acute skin wounds,including superficial burn injuries[mean differ-ence(MD)=−3.02;95%confidence interval(CI):−3.31∼−2.74;p<0.00001],deep burn injuries(MD=−5.63;95%CI:−7.10∼−4.17;p<0.00001),traumata and surgical wounds(MD=−4.50;95%CI:−5.55∼−3.44;p<0.00001).Growth factors increased the healing rate of acute skin wounds and decreased scar scores.The incidence of adverse reactions was lower in the growth factor treatment group than in the non-growth factor group.Conclusions:The studied growth factors not only are effective and safe for managing acute skin wounds,but also accelerate their healing with no severe adverse reactions.