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.

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.

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.

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.

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.

The Burns Menace: Antibiotics for the Fight against Burns Bacterial Infection, a Systemic Review

Burn wound infection delays wound healing, leading to varying degrees of morbidity and mortality. Various antibiotics are administered to burn patients in burn wound management. The emergence of antibiotic resistance is a menace that costs families and the country. This review seeks to expound on infections related to burn wounds, common bacteria of burn wound infections and choice of antibiotics in burns treatment. Words such as burns, wound infection, burns injury and antibiotics were put into the Google search engine. Only articles related to the subject of burns, burn wound infection and antibiotics were used to write the review. Articles obtained included case reports on burns, research articles, review articles, short notes, briefs, literatures and other articles relating to burns. We found that the choice of antibiotics in the management of burns is an issue of major concern due to the evolution of pathogens causing these infections. The challenge of antibiotic resistance still persists in burns wound management. The commonly used topical antimicrobials included silver sulphadiazine, silver nitrate solution, silver impregnated dressings and mafenide acetate. Mafenide acetate has a wide antibacterial activity and also acts against the usual wound pathogens that were identified: Pseudomonas aeruginosa and Staphylococcus aureus. The role of antibiotic resistance is of major concern. Antibiotics must be administered after culture evidence in order to reduce the chance of increasing evolution of resistant strains of bacteria.

Detection of Pathogenic Microorganisms from Burn Patients Admitted in Tertiary Medical College Hospital and Their Antimicrobial Patterns

Object: To isolate and identify the microorganisms from the burn patients admitted to the National Institute of Burn and Plastic Surgery Unit in Tertiary Medical College Hospital, Bangladesh. A total number of fifty wound surface swab samples of first and second-degree burn patients were collected and the microbial analysis as well as the study of antibacterial susceptibility was conducted. The study showed the bacterial isolates were found. 45 (90%) of wound swab were positive among 50 and only 5 samples (10%) were negative in bacterial growth, which presented invasive burn wound infection from both sex age groups marked 12 - 60 years. The total viable count TVC-11651 CFU/plate was found and the highest amount in the second-degree burn patients. The results showed that Pseudomonas aeruginosa was common in all positive samples 6636 CFU/plate (57%) followed by Staphylococcus aureus 4070 CFU/plate (35%), Klebsiella spp. 450 CFU/plate (5%), Proteus spp. 243 CFU/plate (2%), and E. coli 162 CFU/plate (1%). Most of the pathogens were found to be drug-resistant while several isolates were noted to be multi-drug resistant. The growth of multidrug-resistant organisms should be considered as a serious risk factor in a burn unit. Aggressive infection control measures should be applied to limit the emergence and spread of multidrug-resistant pathogens.

Tracking of Labelled Stem Cells Using Molecular MR Imaging in a Mouse Burn Model <i>in Vivo</i>as an Approach to Regenerative Medicine

Therapies based on stem cell transplants offer significant potential in the field of regenerative medicine. Monitoring the fate of the transplanted stem cells in a timely manner is considered one of the main limitations for long-standing success of stem cell transplants. Imaging methods that visualize and track stem cells in vivo non-invasively in real time are helpful towards the development of successful cell transplantation techniques. Novel molecular imaging methods which are non-invasive particularly such as MRI have been of great recent interest. Hence, mouse models which are of clinical relevance have been studied by injecting contrast agents used for labelling cells such as super-paramagnetic iron-oxide (SPIO) nanoparticles for cellular imaging. The MR techniques which can be used to generate positive contrast images have been of much relevance recently for tracking of the labelled cells. Particularly when the off-resonance region in the vicinity of the labeled cells is selectively excited while suppressing the signals from the non-labeled regions by the method of spectral dephasing. Thus, tracking of magnetically labelled cells employing positive contrast in vivo MR imaging methods in a burn mouse model in a non-invasive way has been the scope of this study. The consequences have direct implications for monitoring labeled stem cells at some stage in wound healing. We suggest that our approach can be used in clinical trials in molecular and regenerative medicine.

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...

Synthesis and characterization of polymeric responsive CMC/Pectin hydrogel films loaded with Tamarix aphylla extract as potential wound dressings

The fourth most predominant overwhelming type of trauma is burn injuries worldwide.Ideal wound healing dressings help in the wound healing process in a lower time with less pain.Commonly used dry wound dressing,like absorbent gauze or absorbent cotton,possess limited therapeutic effects and require repeated use,which further exaggerates patients’suffering.In contrast,hydrogels films present a promising alternative to improve healing by guaranteeing a moisture balance at the wound site.The aim of the current study was to synthesize Tamarix aphylla(T.aphylla)extract-loaded hydrogel film with Na-CMC and pectin and to study their wound healing properties.The Na-CMC/Pectin hydrogels films were synthesized and characterized for HPLC analysis,FTIR,surface morphology,rheology,tensile strength,swelling behavior,drug release kinetics,and in vivo wound healing in an animal model.FTIR confirmed the existence of strong interaction between both polymers but no interaction with the extract.SEM photographs showed successful embedding of extract in small pores of hydrogel film and showed smooth and homogenous morphology.Rheological and texture profiles indicated that hydrogels behaved as strong gels.Swelling and erosion were dependent on the amount of the CMC.HPLC showed drug content of three selected formulation(A3,E3 and S3)as 85±0.1%,82.5±0.4%and 80±0.3%,respectively.The release of the drug from the hydrogel was controlled by a Fickian diffusion mechanism.In vivo wound healing activity of hydrogel film confirmed that T.aphylla extract successfully promoted healing rate by significantly reducing(P<0.05)the size of wound closure compared to the control group,evidenced by intensive collagen formation in histopathological and biochemical analysis.The capability of these hydrogels for burn wounds could be valuable for medical uses as a new window of safe and effective medication.

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.

natural polymer-based bilayer adhesive skin substitute for infected burned wound healing

Thermal wounds are complex and lethal with irregular shapes, risk of infection, slow healing, and large surface area. The mortality rate in patients with infected burns is twice that of non-infected burns. Developing multifunctional skin substitutes to augment the healing rate of infected burns is vital. Herein, we 3D printed a hydrogel scaffold comprising carboxymethyl chitosan (CMCs) and oxidized alginate grafted catechol (O-AlgCat) on a hydrophobic electrospun layer, forming a bilayer skin substitute (BSS). The functional layer (FL) was fabricated by physiochemical crosslinking to ensure favorable biodegradability. The gallium-containing hydrophobic electrospun layer or backing layer (BL) could mimic the epidermis of skin, avoiding fluid penetration and offering antibacterial activity. 3D printed FL contains catechol, gallium, and biologically active platelet rich fibrin (PRF) to adhere to both tissue and BL, show antibacterial activity, encourage angiogenesis, cell growth, and migration. The fabricated bioactive BSS exhibited noticeable adhesive properties (P ≤ 0.05), significant antibacterial activity (P ≤ 0.05), faster clot formation, and the potential to promote proliferation (P ≤ 0.05) and migration (P ≤ 0.05) of L929 cells. Furthermore, the angiogenesis was significantly higher (P ≤ 0.05) when evaluated in vivo and in ovo. The BSS-covered wounds healed faster due to low inflammation and high collagen density. Based on the obtained results, the fabricated bioactive BSS could be an effective treatment for infected 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

Obstruction of the formation of granulation tissue leads to delayed wound healing after scald burn injury in mice

Background:Delayed wound healing remains a common but challenging problem in patients with acute or chronic wound following accidental scald burn injury.However,the systematic and detailed evaluation of the scald burn injury,including second-degree deep scald(SDDS)and thirddegree scald(TDS),is still unclear.The present study aims to analyze the wound-healing speed,the formation of granulation tissue,and the healing quality after cutaneous damage.Methods:In order to assess SDDS and TDS,the models of SDDS and TDS were established using a scald instrument in C57BL/6 mice.Furthermore,an excisional wound was administered on the dorsal surface in mice(Cut group).The wound-healing rate was first analyzed at days 0,3,5,7,15 and 27,with the Cut group as a control.Then,on the full-thickness wounds,hematoxylin and eosin(H&E)staining,Masson staining,Sirius red staining,Victoria blue staining and immunohistochemistry were performed to examine re-epithelialization,the formation of granulation tissue,vascularization,inflammatory infiltration and the healing quality at different time points in the Cut,SDDS and TDS groups.Results:The presented data revealed that the wound-healing rate was higher in the Cut group,when compared with the SDDS and TDS groups.H&E staining showed that re-epithelialization,formation of granulation tissue and inflammatory infiltration were greater in the Cut group,when compared with the SDDS and TDS groups.Immunohistochemistry revealed that the number of CD31,vascular endothelial growth factor A,transforming growth factor-βandα-smooth muscle actin reached preferential peak in the Cut group,when compared with other groups.In addition,Masson staining,Sirius red staining,Victoria blue staining,Gordon-Sweets staining and stress analysis indicated that the ratio of collagen I to III,reticular fibers,failure stress,Young’s modulus and failure length in the SDDS group were similar to those in the normal group,suggesting that healing quality was better in the SDDS group,when compared with the Cut and TDS groups.Conclusion:Overall,the investigators first administered a comprehensive analysis in the Cut,SDDS and TDS groups through in vivo experiments,which further proved that the obstacle of the formation of granulation tissue leads to delayed wound healing after scald burn injury in mice.

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.

Doseeffect of dietary Larginine supplementation on burn woundhealing in rats

Objective To investigate the dose effect of dietary L arginine supplementation on burn wound healing in rats Methods 218 Sprague Dawley rats (weighing 200-250?g) were subjected to 10% deep partial thickness scald burns and were randomized into six groups Groups A, B, C, D, E and F received 800, 400, 200, 100, 50 and 0?mg·kg -1 ·d -1 L arginine in the form of L arginine solution, and 0, 727, 1090, 1272, 1364, and 1454?mg·kg -1 ·d 1 glycine, respectively Each solution was isonitrogenous The times of completing re epithelization were recorded The contents of hydroxyproline (OHP) in burn wound area (index of reparative collagen synthesis) and the ratios of type Ⅰ and type Ⅲ collagen were examined in all groups Results The times of completing re epithelization (day) in groups A, B, C, D, E, and F were 24 9±1 95, 22 5±2 0, 20 2±2 4, 23 5±2 6, 23 8±3 5, and 24 7±2 3, respectively The contents of hydroxyproline in groups B, C and D were higher than in groups A, E and F on PBD 7, 10 and 14 The ratios of typeⅠ and type Ⅲ collagen in groups B, C and D were lower than in groups A, E and F Conclusion Oral dietary L arginine supplementation from 100?mg·kg -1 ·d -1 to 400?mg·kg -1 ·d -1 shortened the times of re epithelization, increased amounts of hydroxyproline, and accelerated the synthesis of reparative collagen in burn rats