Umbilical cord-derived mesenchymal stem cells preconditioned with isorhamnetin:potential therapy for burn wounds

BACKGROUND Impaired wound healing can be associated with different pathological states.Burn wounds are the most common and detrimental injuries and remain a major health issue worldwide.Mesenchymal stem cells(MSCs)possess the ability to regenerate tissues by secreting factors involved in promoting cell migration,proliferation and differentiation,while suppressing immune reactions.Preconditioning of MSCs with small molecules having cytoprotective properties can enhance the potential of these cells for their use in cell-based therapeutics.AIM To enhance the therapeutic potential of MSCs by preconditioning them with isorhamnetin for second degree burn wounds in rats.METHODS Human umbilical cord MSCs(hU-MSCs)were isolated and characterized by surface markers,CD105,vimentin and CD90.For preconditioning,hU-MSCs were treated with isorhamnetin after selection of the optimized concentration(5μmol/L)by cytotoxicity analysis.The migration potential of these MSCs was analyzed by the in vitro scratch assay.The healing potential of normal,and preconditioned hU-MSCs was compared by transplanting these MSCs in a rat model of a second degree burn wound.Normal,and preconditioned MSCs(IH+MSCs)were transplanted after 72 h of burn injury and observed for 2 wk.Histological and gene expression analyses were performed on day 7 and 14 after cell transplantation to determine complete wound healing.RESULTS The scratch assay analysis showed a significant reduction in the scratch area in the case of IH+MSCs compared to the normal untreated MSCs at 24 h,while complete closure of the scratch area was observed at 48 h.Histological analysis showed reduced inflammation,completely remodeled epidermis and dermis without scar formation and regeneration of hair follicles in the group that received IH+MSCs.Gene expression analysis was time dependent and more pronounced in the case of IH+MSCs.Interleukin(IL)-1β,IL-6 and Bcl-2 associated X genes showed significant downregulation,while transforming growth factorβ,vascular endothelial growth factor,Bcl-2 and matrix metallopeptidase 9 showed significant upregulation compared to the burn wound,showing increased angiogenesis and reduced inflammation and apoptosis.CONCLUSION Preconditioning of hU-MSCs with isorhamnetin decreases wound progression by reducing inflammation,and improving tissue architecture and wound healing.The study outcome is expected to lead to an improved cell-based therapeutic approach for burn wounds.

Early burn wound excision in mass casualty events

Dear Editor,The aim of the letter is to stress the need of creating unified recommendations concerning early burn wound excision in cases of mass casualty burns exclusively.There are several triage methods,both for civilian and military circumstances,that govern burn casualty triage and evacuation from the incident site,as well as hospital referral up to 120 h from the disaster.

Transplantation of human induced pluripotent stem cell derived keratinocytes accelerates deep second-degree burn wound healing

BACKGROUND Current evidence shows that human induced pluripotent stem cells(hiPSCs)can effectively differentiate into keratinocytes(KCs),but its effect on skin burn healing has not been reported.AIM To observe the effects of hiPSCs-derived KCs transplantation on skin burn healing in mice and to preliminarily reveal the underlying mechanisms.METHODS An analysis of differentially expressed genes in burn wounds based on GEO datasets GSE140926,and GSE27186 was established.A differentiation medium containing retinoic acid and bone morphogenetic protein 4 was applied to induce hiPSCs to differentiate into KCs.The expression of KCs marker proteins was detected using immunofluorescence staining.A model of a C57BL/6 mouse with deep cutaneous second-degree burn was created,and then phosphate buffered saline(PBS),hiPSCs-KCs,or hiPSCs-KCs with knockdown of COL7A1 were injected around the wound surface.The wound healing,re-epithelialization,engraftment of hiPSCs-KCs into wounds,proinflammatory factor level,and the NF-κB pathway proteins were assessed by hematoxylin-eosin staining,carboxifluorescein diacetate succinimidyl ester(CFSE)fluorescence staining,enzyme linked immunosorbent assay,and Western blotting on days 3,7,and 14 after the injection,respectively.Moreover,the effects of COL7A1 knockdown on the proliferation and migration of hiPSCs-KCs were confirmed by immunohistochemistry,EdU,Transwell,and damage repair assays.RESULTS HiPSCs-KCs could express the hallmark proteins of KCs.COL7A1 was down-regulated in burn wound tissues and highly expressed in hiPSCs-KCs.Transplantation of hiPSCs-KCs into mice with burn wounds resulted in a significant decrease in wound area,an increase in wound re-epithelialization,a decrease in proinflammatory factors content,and an inhibition of NF-κB pathway activation compared to the PBS group.The in vitro assay showed that COL7A1 knockdown could rescue the inhibition of hiPSCs-KCs proliferation and migration,providing further evidence that COL7A1 speeds up burn wound healing by limiting cell proliferation and migration.CONCLUSION In deep,second-degree burn wounds,COL7A1 can promote KC proliferation and migration while also suppressing the inflammatory response.

Clinical characteristics and treatment of burn wound sepsis in extensive burn patients: successful experience with eight cases

Eight burn wound sepsis patients, in which 6 cases were diagnosed as MODS and two as septic shock, were treated consecutively in our hospital from September 1997 to October 1998. The plasma concentration of IL-6, IL-8, TNFα and LPS were assayed before and after surgical intervention, as well as when the patients vital signs became stable. The results showed: ①The patients' conditions abruptly deteriorated when the burn wound sepsis emerged.

The effect of extensive excision of burn wound with invasive infection on hypermetabolism in burn patients with sepsis

To evaluate the effect of extensive excision of invasive burn wound infection on hypermeta-bolic response in burn patients with sepsis. Methods:Eight patients with major burn, complicated by invasive burn wound infection and sepsis were consecutively admitted to our hospital from September 1997 to October 1998. REEs were monitored by means of Cardiorespiratory Diagnostic System (Medical Graphics Corporation, USA) at patients bedside. Plasma concentration of IL-6、IL-8、TNF-α and LPS were assayed before an...

Remodeling of skin nerve fibers during burn wound healing

Burn wound healing involves a complex sequence of processes. Recent studies have revealed that skin reinnervation may have an impact on physiological wound repair. Few studies have addressed the process of reinnervation and morphological changes in regenerated nerve fibers. The regeneration of neurites during full-thickness burn wound healing was determined by immunofluorescent staining using an anti-neurofilament protein monoclonal antibody, and three-dimensional morphology was observed under a laser scanning confocal microscope. Morphology and the volume fraction of collagen and nerve fibers were measured. Skin reinnervation increased during wound healing, peaked during the proliferative scar stage, and then decreased to lower levels during the maturation period. The results from the skin nerve fibers correlated with those from collagen using semi-quantitative analysis. Disintegration and fragmentation were observed frequently in samples from the proliferative stage, and seldom occurred during the maturation stage. There was a remodeling process of regenerated nerve fibers during wound healing, which comprised changed innervation density and topical morphology. The mechanism of remodeling for nerve fibers requires further investigation.

Effect of Phyllanthus niruri.Linn on burn wound in rats

Objective:To evaluate the effect of ethanolic extract of Phyllanthus niruri.Linn(Euphorbiaceae) on experimentally induced burn wound model in rats and to evaluate whether it reverses the wound healing in steroid suppressed rats.Methods:Two models including burn wound model and dexamethasone suppressed bum wound model were used in the study.The formulations of ethanolic extract of Phyllanthus niruri were prepared in gum acacia at 8%and in ointment base at 10%and were administered orally(400 mg/kg) and externally respectively.The parameters studied were the wound contraction and the period of epithelialisation.Results:In bum wound model,oral and topical administration of Phyllanthus niruri did not show any significant effects in wound contraction and period of epithelialisation when compared to control.In dexamethasone suppressed burn wound model,wound contraction rate was increased significantly by topical(P 【 0.001) and oral(P 【 0.001) administrations of Phyllanthus niruri by about 47.57%and 26.16% respectively.Topical administration has shown significant(P 【 0.05) enhancement of wound contraction than oral dosage form.Dexamethasone depressed epithelialisation period was reversed significanUy by topical(P 【 0.0001) and oral(P 【0.001) administrations of Phyllanthus niruri by about 32.5%and 21.3%respectively.Conclusions:Both topical and oral administrations of ethanolic extract of Phyllanthus niruri are found to reverse dexamethasone suppressed burn wound healing.

The Effect of Oral <i>Melissa officinalis</i>on Serum Oxidative Stress and Second Degree Burn Wounds Healing

For this aim, this study conducted in order to assess the effect of lemon balm as an antioxidant on second degree wound healing and oxidative stress serum of burning patients. To meet the aim, 60 patients with 15 to 50 burn percent with the age range of 18 to 50 were invited after considering to inclusion criteria by the researchers. First they have been put by non-probable method and then random method in two groups of experiment (30 people) and control (30 people). After that, experiment group in addition to ordinary treatment has been used Melissa officinalis (lemon balm) plant two times a day for two weeks (1.5 g in 100 cc). Oxidative stress parameters included serum total antioxidant and the rate of malondialdehyde (MDA) that is one of total production of lipid peroxidation have been measured in patients’ blood sample in first and last parts of the study. The wound position has been studied by using standard wound BATES-JENSEN assessment tool in first, seventh and fifteenth days of study. In order to analyze data, independent sample t-test, paired sample t-test and repeated measurement variance have been used. These results indicated that the state of wound healing in experimental group was better than that in control group. Results indicated that mean of serum total antioxidant had been increased in both groups. The index of lipid peroxidation at the end of period has been increased in experiment group than control group, whether this index is significantly decreased at the end of 15 days in experimental group. According to the results of this study, the effect of Melissa officinalis (lemon balm) plant was effective in increasing lipid peroxideative in better states of second degree burn wound healing.

Time Course of Histomorphologic Features during Chronic Burn Wound Healing

In forensic pathology, it is always indispensable to determine burn wound vitality or age to accurately assess the relationship between death and any burn wounds. Subsequently, the determination of wound age is a definitive and still cutting-edge subject in forensic pathology. Therefore, deep second-degree burn injuries were induced in a group of mice. At 7, 12, 17, 21 and 28 days post-burn, burn wound specimens were histomorphologically differentiated and compared with normal intact skin using H&E stain. The study revealed that the burn wound during healing process was usually incorporated of infiltration of inflammatory cells, granulation tissue formation and epithelialization within 7 - 12 days post-burn. Then, the surface of burn wound was partially ulcerated in association with epidermal necrosis, dermal disorganization and degeneration of the sebaceous gland 17 - 21 days post-burn. Finally, the regenerated skin retained the structure of normal skin at 28th day post-burn. Our study demonstrated that the histopathological changes of burn wounds involved deep dermis, and the pathological changes occurred at distinctive time phases were almost different in comparing to regular intact skin. Such age estimation of burn wounds is important when a cadaver or a burnt body has many burns of diverse times, especially in criminal cases.

Negative Pressure Wound Therapy—An Effective, Minimally Invasive Therapeutic Modality in Burn Wound Management

Despite the advancement in burn therapy in the last decades the treatment of burn wounds still remains a challenging task. Infection is still a common complication;while sepsis remains the leading cause of death in severe burns. The research guided integration of new and effective techniques in burn wound management is mandatory. Negative pressure wound therapy (NPWT) is an effective and widely used technique in the management of problematic wounds. Previously existing indications include soft tissue traumas and chronic wounds such as diabetic, arterial, venous and pressure ulcers. The characteristics and challenges of these wounds have a lot in common with burns. Since the early 2000’s there are experiences with the use of NPWT for the healing of second degree burn wounds. Our clinical experience shows that it is a minimally invasive and effective way of improving burn wound management. In this article we give a review of the literature showing the mechanisms, unmapped future opportunities, financial issues, and possible adverse effects of NPWT in burn therapy.

Injectable chitosan hydrogels loaded with antioxidant agent as first-aid dressings for second-degree burn wounds

Burn wounds are destructive skin traumas typically of irregular shape and large area. Prone to infection, they require frequent dressing replacement, and painless removal of dressings from burn wounds remains a major challenge. This study focuses on the dynamic characteristics and treatment difficulty of burn wounds. Hydrogel dressings based on glycol chitosan and propionaldehyde-or benzaldehyde-terminated 4-arm poly(ethylene glycol) were designed on the basis of Schiff base cross-linking networks. The hydrogels exhibited shape-adaptability, self-healing and fast-degradation properties, which makes these hydrogels suitable for burn wounds. Salvianolic acid B(SaB)-loaded hydrogel exhibited good antioxidant properties in vitro. In a rat model of deep second-degree burn wounds, the SaB-loaded hydrogel could quickly reduce wound temperature, regulate wound oxidant microenvironment, promote angiogenesis, and accelerate wound healing. Thus, the drug-loaded hydrogel shows significant potential as a first-aid dressing for treatment of burn wounds.

Click-hydrogel delivered aggregation-induced emissive nanovesicles for simultaneous remodeling and antibiosis of deep burn wounds

As a high-risk trauma,deep burns are always hindered in their repair process by decreased tissue regeneration capacity and persistent infections.In this study,we developed a simultaneous strategy for deep burn wounds treatment using functional nanovesicles with antibacterial and tissue remodeling properties,delivered via a click-chemistry hydrogel.An aggregation-induced emission photosensitizer of 4-(2-(5-(4-(diphenylamino)phenyl)thiophen-2-yl)vinyl)-1-(2-hydroxyethyl)pyridin-1-ium bromide(THB)with excellent photodynamic properties was first prepared,and then combined with readily accessible adipose stem cells-derived nanovesicles to generate the THB functionalized nanovesicles(THB@ANVs).The THB@ANVs showed strong antibacterial activity against Gram-positive bacteria(up to 100%killing rate),and also beneficial effects on tissue remodeling,including promoting cell migration,cell proliferation,and regulating immunity.In addition,we prepared a click-hydrogel of carboxymethyl chitosan for effective delivery of THB@ANVs on wounds.This hydrogel could be injected to conform to the wound morphology while responding to the acidic microenvironment.In vivo evaluations of wound healing revealed that the THB@ANVs hydrogel dressing efficiently accelerated the healing of second-degree burn wounds by reducing bacterial growth,regulating inflammation,promoting early angiogenesis,and collagen deposition.This study provides a promising candidate of wound dressing with diverse functions for deep burn wound repair.

Design of a biofluid-absorbing bioactive sandwich-structured Zn-Si bioceramic composite wound dressing for hair follicle regeneration and skin burn wound healing

The deep burn skin injures usually severely damage the dermis with the loss of hair follicle loss,which are difficult to regenerate.Furthermore,severe burns often accompanied with large amount of wound exudates making the wound moist,easily infected,and difficult to heal.Therefore,it is of great clinical significance to develop wound dressings to remove wound exudates and promote hair follicle regeneration.In this study,a sandwich-structured wound dressing(SWD)with Janus membrane property was fabricated by hot compression molding using hydrophilic zinc silicate bioceramics(Hardystonite,ZnCS)and hydrophobic polylactic acid(PLA).This unique organic/inorganic Janus membrane structure revealed excellent exudate absorption property and effectively created a dry wound environment.Meanwhile,the incorporation of ZnCS bioceramic particles endowed the dressing with the bioactivity to promote hair follicle regeneration and wound healing through the release of Zn^(2+)and SiO^(2-)_(3)ions,and this bioactivity of the wound dressing is mainly attributed to the synergistic effect of Zn^(2+)and SiO^(2-)_(3)to promote the recruitment,viability,and differentiation of hair follicle cells.Our study demonstrates that the utilization of the Janus membrane and synergistic effect of different type bioactive ions are effective approaches for the design of wound dressings for burn wound healing.

Recent advances in nanotherapeutics for the treatment of burn wounds

Moderate or severe burns are potentially devastating injuries that can even cause death,and many of them occur every year.Infection prevention,anti-inflammation,pain management and administration of growth factors play key roles in the treatment of burn wounds.Novel therapeutic strategies under development,such as nanotherapeutics,are promising prospects for burn wound treatment.Nanotherapeutics,including metallic and polymeric nanoformulations,have been extensively developed to manage various types of burns.Both human and animal studies have demonstrated that nanotherapeutics are biocompatible and effective in this application.Herein,we provide comprehensive knowledge of and an update on the progress of various nanoformulations for the treatment of burn wounds.

Antimicrobial hydrogel with multiple pH-responsiveness for infected burn wound healing

Burns are a common medical problem globally,and wound infection is one of the major causes of inducing related complications.Although antibiotics effectively prevent wound infections,the misuse of antibiotics has created a new problem of superbugs.Herein,we propose a new strategy to obtain pH-responsive antimicrobial P-ZIF(ZIF:zeolitic imidazolate framework)by loading polyhexamethylenebiguanide(PHMB)into the framework of ZIF-8 nanoparticles.This will enable PHMB to be released in the weak acid environment of an infected wound.To address burn infections,P-ZIF nanoparticles were loaded into a hydrogel system made of sodium alginate(SA)and 3-aminophenylboronic acid modified human-like collagen(H-A)through borate ester bonds.The resulting H-A/SA/P-ZIF(HASPZ)hydrogel dressing not only possesses antibacterial and wound healing properties but also has dual pH responsiveness to prevent the overuse of medication while effectively treat deep second-degree burns.Therefore,P-ZIF nanoparticles and the corresponding HASPZ hydrogel dressing are considered of significant importance in antimicrobial,drug delivery,and wound repair.

Successful treatment of invasive burn wound infection with sepsis in patients with major burns

To investigate the clinical characteristics of invasive burn wound infection with sepsis in patients with major burns and to summarize the successful experiences in the treatment of such patients Methods Eight patients with major burns, complicated by invasive burn wound infection and sepsis were consecutively admitted to our hospital from September 1997 to October 1998 Among them, 6 patients developed multiple organ dysfunction syndrome (MODS) and 2 developed septic shock The plasma concentrations of IL 6, IL 8, TNFα and lypopolysaccharide (LPS) were assayed before and after surgical intervention, as well as when the patient's vital signs became stable Results The patients' conditions usually deteriorated abruptly when extensive invasive burn wound infection emerged While multi microbial infection was usually found, Pseudomonas aeruginosa was the predominant bacteria isolated from the subeschar tissue The plasma concentrations of IL 6, IL 8, TNFα and LPS before surgical intervention were significantly higher than those after surgical intervention ( P <0 05) The lowest levels of the inflammatory mediators were observed when the patients' conditions became stable, and the values were significantly lower than those before surgical intervention ( P <0 001) Conclusion Since the main cause of burn wound sepsis is the presence of a large area of infected burn wound, they should be excised and covered as early as possible LPS and pro inflammatory mediators play an important role in the pathogenesis of burn sepsis Although favorable results should be attributed to comprehensive treatment, we believe that early, aggressive and thorough surgical excision of infected burn wounds, followed by sound and complete coverage of the area, play a crucial role

Macrophage metabolism reprogramming EGCG-Cu coordination capsules delivered in polyzwitterionic hydrogel for burn wound healing and regeneration

Excessive reactive oxygen species(ROS)at severe burn injury sites may promote metabolic reprogramming of macrophages to induce a deteriorative and uncontrolled inflammation cycle,leading to delayed wound healing and regeneration.Here,a novel bioactive,anti-fouling,flexible polyzwitterionic hydrogel encapsulated with epigallocatechin gallate(EGCG)-copper(Cu)capsules(termed as EGCG-Cu@CBgel)is engineered for burn wound management,which is dedicated to synergistically exerting ROS-scavenging,immune metabolic regulation and pro-angiogenic effects.EGCG-Cu@CBgel can scavenge ROS to normalize intracellular redox homeostasis,effectively relieving oxidative damages and blocking proinflammatory signal transduction.Importantly,EGCG-Cu can inhibit the activity of hexokinase and phosphofructokinase,alleviate accumulation of pyruvate and convert it to acetyl coenzyme A(CoA),whereby inhibits glycolysis and normalizes tricarboxylic acid(TCA)cycle.Additionally,metabolic reprogramming of macrophages by EGCG-Cu downregulates M1-type polarization and the expression of proinflammatory cytokines both in vitro and in vivo.Meanwhile,copper ions(Cu^(2+))released from the hydrogel facilitate angiogenesis.EGCG-Cu@CBgel significantly accelerates the healing of severe burn wound via promoting wound closure,weakening tissue-damaging inflammatory responses and enhancing the remodeling of pathological structure.Overall,this study demonstrates the great potential of bioactive hydrogel dressing in treating burn wounds without unnecessary secondary damage to newly formed skin,and highlights the importance of immunometabolism modulation in tissue repair and regeneration.

Wnt4 increases the thickness of the epidermis in burn wounds by activating canonical Wnt signalling and decreasing the cell junctions between epidermal cells

Background:Burn wound healing is a complex process and the role of Wnt ligands varies in this process.Whether and how Wnt4 functions in burn wound healing is not well understood.In this study,we aim to reveal the effects and potential mechanisms of Wnt4 in burn wound healing.Methods:First,the expression of Wnt4 during burn wound healing was determined by immunoflu-orescence,Western blotting and qPCR.Then,Wnt4 was overexpressed in burn wounds.The healing rate and healing quality were analysed by gross photography and haematoxyline and eosin staining.Collagen secretion was observed by Masson staining.Vessel formation and fibroblast distribution were observed by immunostaining.Next,Wnt4 was knocked down in HaCaT cells.The migration of HaCaT cells was analysed by scratch healing and transwell assays.Next,the expression ofβ-catenin was detected by Western blotting and immunofluorescence.The binding of Frizzled2 and Wnt4 was detected by coimmunoprecipitation and immunofluorescence.Finally,the molecular changes induced by Wnt4 were analysed by RNA sequencing,immunofluorescence,Western blotting and qPCR in HaCaT cells and burn wound healing tissues.Results:The expression of Wnt4 was enhanced in burn wound skin.Overexpression of Wnt4 in burn wound skin increased the thickness of epidermis.Collagen secretion,vessel formation and fibroblast distribution were not significantly impacted by Wnt4 overexpression.When Wnt4 was knocked down in HaCaT cells,the ratio of proliferating cells decreased,the ratio of apoptotic cells increased and the ratio of the healing area in the scratch healing assay to the number of migrated cells in the transwell assay decreased.The nuclear translocation ofβ-catenin decreased in shRNA of Wnt4 mediated by lentivirus-treated HaCaT cells and increased in Wnt4-overexpressing epidermal cells.RNA-sequencing analysis revealed that cell junction-related signalling pathways were significantly impacted by Wnt4 knockdown.The expression of the cell junction proteins was decreased by the overexpression of Wnt4.Conclusions:Wnt4 promoted the migration of epidermal cells.Overexpression of Wnt4 increased the thickness of the burn wound.A potential mechanism for this effect is that Wnt4 binds with Frizzled2 and increases the nuclear translocation ofβ-catenin,thus activating the canonical Wnt signalling pathway and decreasing the cell junction between epidermal cells.

Effects of Nano-patterning Modification on the Cell Proliferation and Adhesion in Burn Wound Healing of Regenerated Silk Fibroin Membrane

Objective:To investigate the effect of nano-patterning modification on the cell proliferation and adhesion in burn wound healing of regenerated silk fibroin membrane.Methods:A total of 60 healthy SD mice were randomly divided into three groups:group A received treatment involving nano-patterning on the surface of regenerated silk fibroin membrane,group B received treatment with recombinant human epidermal growth factor gel,and group C received the same treatment with recombinant human epidermal growth factor gel,with 20 cases in each group.Wound healing,surface structure,protein adsorption,cell proliferation and adhesion were assessed at intervals of 5th,15th and 25th d after treatment.Results:The findings indicated that:(1)The duration and pace of wound healing in groups A and B surpassed those of group C,with group A exhibiting superior results compared to group B(P<0.05);(2)Histopathological analysis revealed a progressive increase in neovascularization and fibroblast count in wound tissue across the 5th,15th,and 25th days for all three groups,with group C exhibiting a higher count of neovascularization and fibroblasts in unhealed tissue compared to groups A and B.(3)The levels of basic calponin expression in group A and group B showed an increase on the 5th and 15th day,followed by stabilization on the 25th day.In group C,the expression of basic calponin was initially high on the 5th day,and then stabilized on the 15th and 25th day(P<0.05);(4)The expression of fibroblast proliferating cell nuclear antigen in the wound tissue of mice in all three groups peaked on the 15th day and subsequently declined.The expression of PCNA in group A and group B was higher than that in group C at each time point,with group A exhibiting higher levels than group B(P<0.05);(5)As wounds healed,there was a reduction in apoptotic cells within the wound tissues of mice across three groups,with group a exhibiting a lower count compared to groups B and C(P<0.05).Conclusion:Nanopatterning on the surface of regenerated silk fibroin membrane can enhance the biocompatibility of burn wound treatment and promote the proliferation and adhesion of reparative cells.

Burn blister fluids in the neovascularization stageof burn wound healing: A comparison betweensuperficial and deep partial-thickness burn wounds

Burn wound healing is a complex and dynamic process that involves the interaction between different cell types and mediators. Neovascularization is an imperative stage of wound healing and consists of not only angiogenesis but also adult vasculogenesis. A superficial partial-thickness burn (SPTB) heals within 2 weeks without scarring. A deep partial-thickness burn (DPTB), conversely, requires 2 weeks or longer to heal and requires an aggressive treatment to prevent hypertrophic scarring. Burn blisters on the skin are a hallmark of not only SPTB but also DPTB;however, the effect of burn blister fluids on the neovascularization in these types of burns has not been fully explored. To verify this effect, the role of different burn fluids and the angiogenic factors that modulate this process are currently under investigation.