epidermal-growth-factor and Burns

The purpose of this meta-analysis was to assess the efficacy and safety of nano-silver dressing combined with recombinant human epidermal growth factor for deep second-degree burns.. PubMed, Web of Science, EMBASE, Cochrane Library and other databases were searched to identify relevant randomised controlled trials.. Twelve studies that assessed nano-silver dressing combined with recombinant human epidermal growth factor were identified. Nano-silver dressing combined with recombinant human epidermal growth factor for deep second-degree burns could significantly reduce the duration of wound healing (mean difference -5.68, 95% CI -7.38 - -3.99, P<0.00001), the wound healing rate (risk ratio [RR] 0.34, 95% CI 0.23-0.48, P<0.00001), the rate of scar hyperplasia (RR 0.67, 95% CI 0.54-0.84, P=0.0004), the wound bacterial positive rate (RR 0.50, 95% CI 0.28-0.89, P=0.02), and the adverse reactions rate (RR 0.31, 95% CI 0.16-0.58, P=0.0003).. This comprehensive meta-analysis of the available evidence suggest that the use of nano-silver dressing combined with recombinant human epidermal growth factor results in shorter duration of wound healing, reduced wound bacterial positive rates and adverse reactions rate, and improved wound healing rates.

Topics: Biological Dressings; Burns; Epidermal Growth Factor; Humans; Silver; Wound Healing

Mechanisms that drive wound repair are complex and have challenged wound-healing investigators for many years. In this review, we present four examples of new tools that are being utilized to discover events that drive wound repair and regeneration. Laser capture microdissection facilitates the focused collection of tissue for purposes of genomic or proteomic analysis from specific cell populations within the wound bed. Tissue profiling and protein imaging by matrix-assisted laser desorption ionization mass spectrometry are two proteomic-based tools that permit rapid analysis with spatial orientation and relative abundance of hundreds to thousands of molecules from intact tissues. Another approach uses an in vivo porcine model to harness a strategy of adenoviral-driven receptor overexpression. This biological model closely mimics the human setting and permits transient stimulation along a specific cytokine pathway to tip the balance in favor of accelerated repair. The advent of new approaches that collect cell samples from within their in vivo circumstance while preserving discrete cellular localizations is likely to move the field of wound repair forward.

Topics: Adenoviridae; Animals; Burns; Epidermal Growth Factor; ErbB Receptors; Humans; Microdissection; Receptor, ErbB-4; Regeneration; Signal Transduction; Skin Physiological Phenomena; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Wound Healing

To review the current condition of growth factors and their application to clinical treatment of acute and chronic wounds.. Data from the literature and Medline were analyzed according to their different uses in acute and chronic wounds. Their potential side-effects were studied.. All data showed that wound healing time in acute and chronic wounds was accelerated and wound healing quality was improved after treatment with growth factors. No side-effect was observed.. The efficacy and safety of growth factors in improving wound healing were confirmed. However, some reconsideration about potential problems of growth factors must be made to apply them clinically in the future.

Topics: Animals; Burns; Epidermal Growth Factor; Fibroblast Growth Factor 2; Growth Substances; Humans; Recombinant Proteins; Skin; Soft Tissue Injuries; Transforming Growth Factor beta; Vascular Endothelial Growth Factor A; Wound Healing

G-CSF, GM-CSF and EGF play an important role in wound healing as components of the cytokine network which regulates cooperation of cells in the repair processes. The first two cytokines have been registered as hematopoietic drugs under the names Neupogen (Roche) and Leucomax (Sandoz). Both G-CSF and GM-CSF stimulate phagocytosis in maturated leucocytes and enhance proliferation of endothelial cells. G-CSF, GM-CSF and EGF which is known as mitogenic agent were applied as topical drugs for wound care; the application resulted in acceleration of wound healing. Preliminary suggestions as to the topical dosage of the cytokines in the treatment of wounds are put forward.

Topics: Administration, Topical; Animals; Burns; Cytokines; Epidermal Growth Factor; Filgrastim; Granulocyte Colony-Stimulating Factor; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Recombinant Proteins; Skin; Wound Healing; Wounds and Injuries

Topics: Burns; Cell Division; Collagen; Culture Media; Epidermal Cells; Epidermal Growth Factor; Epidermis; Humans; In Vitro Techniques; Skin Transplantation; Surgical Flaps; Time Factors; Wound Healing

To explore the therapeutic effect of recombinant human epidermal growth factor (rhEGF) for burn wounds of degree II in the elderly patients.. From February 2003 to October 2008, 80 patients with burn wounds of degree II were treated and randomly divided into two groups (n=40). In treatment group, there were 24 males and 16 females with an average age of 70 years (60-86 years), including 20 cases of superficial II degree and 20 cases of deep II degree. Burn wounds were caused by flame in 23 cases, by hot liquid in 16 cases, and by electricity in 1 case. The mean time from injury to hospitalization was (2.87 +/- 2.57) hours. The wounds were treated with silver sulfadiazine (SD-Ag) and rhEGF. In control group, there were 18 males and 22 females with an average age of 69 years (61-83 years), including 19 cases of superficial II degree and 21 cases of deep II degree. Burn wounds were caused by flame in 23 cases, by hot liquid in 14 cases, by electricity in 2 cases, and by chemistry in 1 case. The mean time from injury to hospitalization was (3.39 +/- 3.33) hours. The wounds were treated with SD-Ag. The dressing was changed every day until wounds healing. There were no significant differences in general data between two groups (P > 0.05).. Wound did not heal in 1 case (deep II degree) of treatment group and in 5 cases (deep II degree) of control group over 40 days and free skin graft was used to repair wound. One case (superficial II degree) in control group gave up treatment. One case (deep II degree) died of pulmonary infection in treatment group. These cases were excluded and 72 cases were analysed. No other side reactions were observed in treatment group except for flash stabbing pain (4 cases) and pruritus (2 cases). Wound infection occurred in 5 cases of the control group and in 3 cases of the treatment group, and wound healed after symptomatic treatment. The healing time of burn wound was (14.30 +/- 1.26) days (superficial II degree) and (26.11 +/- 2.97) days (deep II degree) in the treatment group, was (16.22 +/- 1.40) days (superficial II degree) and (29.13 +/- 4.99) days (deep II degree) in control group, showing significant difference between two groups (P < 0.05).. In combined treatment, rhEGF can promote the healing of burn wounds of degree II in the elderly patients.

Topics: Aged; Aged, 80 and over; Burns; Combined Modality Therapy; Epidermal Growth Factor; Female; Humans; Male; Middle Aged; Recombinant Proteins; Skin Transplantation; Wound Healing

To evaluate the safety and long-term effect of recombinant human epithelial growth factor (rhEGF) on deep partial-thickness burn wounds.. Thirty-seven burn patients were enrolled in this study and were observed by randomized, double-blinded and placebo-controlled protocol. An area of deep partial-thickness burn wounds from each patient was divided into control (C) and treatment (T) portions. The wound in C was treated with normal saline while that in T with rhEGF. The patients were followed-up for 1 and 4 years after wound healing. The healed wounds were evaluated by modified Vancouver scar scale in terms of scar index (SI).. 1 year after wound healing, it was found that the SI in T group (7.19 +/- 1.67) was obviously lower than that in C group (8.92 +/- 1.78, P < 0.01). The SI in T group (6.12 +/- 1.54) was still evidently lower than that in C group (8.09 +/- 1.81, P < 0.01) four years after wound healing. There were no signs of development of tumor or cancer in all the tested burn wound areas.. External application of rhEGF might be beneficial to the healing quality of deep partial-thickness burn wound with less scar formation and better long-term effects, and it is safe.

Topics: Adult; Burns; Double-Blind Method; Epidermal Growth Factor; Female; Follow-Up Studies; Humans; Male; Recombinant Proteins; Treatment Outcome; Wound Healing; Young Adult

To investigate the efficiency of recombinant human epidermal growth factor (rhEGF) on burn wound healing and to explore the effective density of the ointments.. A total of 120 cases of burn in superficial II degree and profound II degree were randomly divided into 2 groups. In the first group of 15 cases of superficial II degree, the wounds were treated by rhEGF ointments of different density, 0.5 microgram/g, 10 micrograms/g and 50 micrograms/g, to screen out the effective density. And in the other 105 cases of the second group, optimal density of the ointments based on the result of the first group were employed to treat the burn wound in superficial II degree and profound II degree, with the self-corresponding wounds of the same degree as control, to study the efficiency of rhEGF on wound healing, according to the wound healing time, and adverse reaction of the ointment.. In the first group, the average healing time of superficial II wound treated by ointments of 10 micrograms/g and 50 micrograms/g significantly shortened when compared with that treated by ointments of 0.5 microgram/g(P < 0.01), but there was no obvious difference between the cases treated by ointments of 10 micrograms/g and 50 micrograms/g. In the second group, the healing time of superficial II wound treated by ointments of 10 micrograms/g was (8.39 +/- 2.25) days, (9.52 +/- 2.56) days in the control (P < 0.01); and healing time of profound II burn treated by ointments of 10 micrograms/g was (16.80 +/- 2.99) days, (18.27 +/- 3.17) days in the control (P < 0.01). And healing rates of burn wound at different periods were higher than those of the control.. The above results indicate that rhEGF ointments can enhance burn wound healing significantly, and the ointment of 10 micrograms/g is a good choice for clinical application.

Topics: Administration, Topical; Adolescent; Adult; Burns; Dosage Forms; Dose-Response Relationship, Drug; Epidermal Growth Factor; Female; Humans; Male; Middle Aged; Ointments; Recombinant Proteins; Wound Healing; Wound Infection

We evaluated the effect of topical epidermal growth factor treatment on healing of chronic wounds in a prospective, open-label, crossover trial. Five males and four females who ranged in age from 40 to 72 years (average 57 +/- 9 years) were enrolled. Four patients had adult-onset diabetes mellitus, two had rheumatoid arthritis, two had old burn scars, and one had a failed abdominal incision. The average duration of the ulcers prior to treatment with epidermal growth factor was 12 +/- 5 months (range 1 to 48 months). Following failure of the wounds to heal with conventional therapies, including debridement, skin graphs, and vascular reconstruction, wounds were treated twice daily with Silvadene alone for periods ranging from 3 weeks to 6 months. No evidence of healing was observed in any of the patients' wounds during Silvadene treatment, and patients were crossed over to twice a day treatment with Silvadene containing 10 micrograms epidermal growth factor per gram. Wounds of eight patients healed completely with epidermal growth factor-Silvadene treatment in an average of 34 +/- 26 days (mean +/- SD, range 12 to 92 days) and did not reoccur for periods ranging from 1 to 4 years. One patient failed therapy. These results suggest that topical treatment of chronic wounds with epidermal growth factor may stimulate healing.

Topics: Administration, Cutaneous; Adult; Aged; Arthritis, Rheumatoid; Burns; Chronic Disease; Diabetes Mellitus, Type 2; Epidermal Growth Factor; Female; Humans; Male; Middle Aged; Pilot Projects; Postoperative Complications; Prospective Studies; Silver Sulfadiazine; Skin Ulcer; Wound Healing

Experimental studies in animals have demonstrated that the topical application of epidermal growth factor accelerates the rate of epidermal regeneration of partial-thickness wounds and second-degree burns. We conducted a prospective, randomized, double-blind clinical trial using skin-graft-donor sites to determine whether epidermal growth factor would accelerate the rate of epidermal regeneration in humans. Paired donor sites were created in 12 patients who required skin grafting for either burns or reconstructive surgery. One donor site from each patient was treated topically with silver sulfadiazine cream, and one was treated with silver sulfadiazine cream containing epidermal growth factor (10 micrograms per milliliter). The donor sites were photographed daily, and healing was measured with the use of planimetric analysis. The donor sites treated with silver sulfadiazine containing epidermal growth factor had an accelerated rate of epidermal regeneration in all 12 patients as compared with that in the paired donor sites treated with silver sulfadiazine alone. Treatment with epidermal growth factor significantly decreased the average length of time to 25 percent and 50 percent healing by approximately one day and that to 75 percent and 100 percent healing by approximately 1.5 days (P less than 0.02). Histologic evaluation of punch-biopsy specimens taken from the centers of donor sites three days after the onset of healing supported these results. We conclude that epidermal growth factor accelerates the rate of healing of partial-thickness skin wounds. Further studies are required to determine the clinical importance of this finding.

Topics: Administration, Topical; Adolescent; Adult; Aged; Burns; Clinical Trials as Topic; Double-Blind Method; Epidermal Growth Factor; Female; Humans; Male; Middle Aged; Prospective Studies; Random Allocation; Silver Sulfadiazine; Skin Transplantation; Stimulation, Chemical; Wound Healing

Human epidermal cell sheet (human-ECS) is a feasible treatment option for wound injury. Traditionally, researchers often use murine 3T3 fibroblast cells as feeder layer to support human epidermal cell sheet grafts, thus increase risk to deliver animal-borne infection. To overcome the potential risks involved with xenotransplantation, we develop human foreskin fibroblast cell as feeder layer culture system and investigate the effects of human-ECS on second-degree burn wound healing in mini-pig in order to develop more effective and safer therapies to enhance wound healing in human.. Human epidermal keratinocytes and fibroblasts were isolated from foreskin tissue and were co-cultured to manufacture human-ECS. The cell morphology was monitored with phase-contrast microscopy, the stem cell markers were assessed by flow cytometry, and by colony-forming efficiency (CFE) assay. The structure of human-ECS was observed by hematoxylin and eosin staining. Expression of cytokines in human-ECS was confirmed by enzyme-linked immunosorbent assay. Second-degree burn wounds were created on the dorsal of miniature pig to evaluate the effect of oil gauze, oil gauze combined with commercial epidermal growth factor (EGF) cream, and oil gauze combined with human-ECS. Wound healing rate, histological examination, and Masson staining were measured to observe the wound repair efficacy. Real-time PCR and Western blot were utilized to detect the expression level of EGF and interleukin 6 (IL-6).. Stratified human-ECS with 6-7 layers of epidermal cells was successfully cultivated with human-derived feeder cells, in which epidermal cell highly expressed CD49f and CFE was 3% ± 0.45%. Application of human-ECS induced a higher wound healing rate than commerical EGF cream and oil gauze control. The expression of EGF in human-ECS group was higher than those in the other groups; however, the expression of IL-6 was significantly decreased at day 14 by human-ECS treatment group.. Human-derived feeder cells are suitable for cultivation of human-ECS, avoiding pathogen transmission. Human-ECS could enhance second-degree burn wound healing, and its promoting effect involved secreting a variety of cytokines to regulate tissue reparative process.

Topics: Animals; Burns; Cytokines; Epidermal Cells; Epidermal Growth Factor; Feeder Cells; Humans; Interleukin-6; Mice; Swine; Swine, Miniature

Our aim in this study was to investigate the effect of Gallic acid (GA) on gingival tissue injury.. Twenty rats were categorized into two groups. In the burn group, an excisional wound area was created by removing a 4 mm diameter flap from the left molar region in the mucoperiosteal region of the gingiva. In the Burn+gallic acid group, 1.2 mg/ml GA was administered as irrigation for 1 week. Animals were sacrificed under anesthesia at the end of experiment. Malondialdehyde (MDA), myeloperoxidase (MPO) and glutathione (GSH) levels were measured. Hematoxylin Eosin, fibroblast growth factor (FGF) and epidermal growth factor (EGF) immunostaining was applied to tissues.. MDA and MPO levels increased, and GSH, epithelization, FGF and EGF expression levels were decreased. Gallic acid treatment improved these scores. Degenerated gingival epithelium, disintegrity in epithelial and connective tissue fibers, edema and inflammatory cells were observed in the burn group. Gallic acid treatment after burn improved the pathologies. After burn injury, FGF and EGF activity was increased in Gallic acid-treated groups.. We suggest that GA has the potential for better healing outcomes in oral wounds. GA seems to have promising therapeutic efficacy in enhancing oral wound healing.

Topics: Animals; Burns; Epidermal Growth Factor; Gallic Acid; Glutathione; Rats; Wound Healing

Scars are common and intractable consequences after scalded wound healing, while monotherapy of epidermal growth factors does not solve this problem. Maintaining the stability of epidermal growth factors and promoting scarless healing of wounds is paramount. In this study, engineering cellular nanovesicles overexpressing PD-L1 proteins, biomimetic nanocarriers with immunosuppressive efficacy, were successfully prepared to encapsulate epidermal growth factors for maintaining its bioactivity. Remarkably, PD-L1 cellular nanovesicles encapsulating epidermal growth factors (EGF@PDL1 NVs) exerted desired therapeutic effect by attenuating the overactivation of T cell immune response and promoting skin cells migration and proliferation. Hence, EGF@PD-L1 NVs promoted wound healing and prevented scarring in deep second-degree scald treatment, demonstrating a better effect than using individual PD-L1 NVs or EGF. This research proved that EGF@PD-L1 NVs is considered an innovative and thorough therapy of deep second-degree scald.

Topics: B7-H1 Antigen; Burns; Cicatrix; Epidermal Growth Factor; Humans; Skin; Wound Healing

Our previous study has demonstrated that epidermal growth factor (EGF) with tocotrienol-rich fraction (TRF) cream formulation accelerating postburn wound healing with deep partial-thickness burn in rats. Current study was conducted to determine the gene expression levels related to burn wound healing process. A total of 180 Sprague-Dawley rats were randomly divided into 6 groups: untreated control, treated with Silverdin cream, base cream, base cream with 0.00075% EGF, base cream with 3% TRF or base cream with 0.00075% EGF, and 3% TRF, respectively. Burn wounds were created and the above-mentioned creams were applied once daily. Six animals from each group were sacrificed on days 3, 7, 11, 14, and 21 postburn. RNA was extracted from wound tissues and quantitative real-time polymerase chain reaction was performed to analyze the 9 wound healing-related genes against time postburn. Results demonstrated that topically applied EGF + TRF formulation downregulated the expression levels of

Topics: Animals; Burns; Epidermal Growth Factor; Gene Expression; Rats; Rats, Sprague-Dawley; Tocotrienols; Vascular Endothelial Growth Factor A; Wound Healing

Intestinal mucosal injury is one of the most significant complications of burns. In our previous study, it was found that autophagy could alleviate burn-induced intestinal injury, but the underlying mechanisms are still unclear. Irregular expression of long noncoding RNAs (lncRNAs) is present in many diseases, including burns. However, the relationship between lncRNAs and intestinal mucosal injury requires further elucidation. In this study, we established a burn mice model and detected the expression level of autophagy-related proteins. Then, H19 content after autophagy intervention was tested in vitro and in vivo. The interaction of H19 with Let-7g and that of Let-7g with epidermal growth factor (EGF) were verified by dual-luciferase reporter assays. We found that the expression of the autophagy-associated proteins LC3-II and Beclin-1 was raised in the intestinal tract of the burn mice model. Similarly, the transfection of H19 raised autophagy levels. H19 was elevated after autophagy intervention in vitro and in vivo. H19 overexpression was able to promote IEC-6 cell migration and proliferation. Let-7g was suppressed by the overexpression of H19 and the combination of Let-7g mimic was able to abolish the physiological effect of H19. Moreover, the suppression of Let-7g increased the expression of EGF protein, which heightened IEC-6 cell migration and proliferation. Besides this, dual-luciferase assays revealed that Let-7g was a direct target of H19 as well as the EGF gene. Taken together, autophagy-mediated H19 increases in mouse intestinal tract after severe burn and functions as a sponge to Let-7g to regulate EGF, which suggests that H19 serves as a potential therapeutic target and biomarker for intestinal mucosal injury after burns.

Topics: Animals; Autophagy; Autophagy-Related Proteins; Burns; Cell Line; Cell Movement; Cell Proliferation; Disease Models, Animal; Epidermal Growth Factor; Gene Expression Regulation; Intestinal Mucosa; Mice, Inbred C57BL; MicroRNAs; Rats; RNA, Long Noncoding; Signal Transduction

Partial burn injury in older patients is associated with higher rates of morbidity, mortality, and conversion to full thickness burn (Finnerty et al., 2009; Pham et al., 2009). Both human and mouse models demonstrate an altered systemic immune response in older subjects, however less is known about the localized response (Jeschke et al., 2016; Farinas et al., 2018; Mohs et al., 2017). We hypothesized that a mouse model could demonstrate differences in the localized inflammatory response of the old.. Six old (66 weeks) and young (8 weeks) mice received partial thickness thermal burns. Localized and systemic expression of nine chemokines (TNFalpha, MCP-1, MIP-2, S100A9, EGF, IL-10, RANTES, G-CSF, and EOTAXIN) were evaluated at day 3 after burn using Luminex analysis. Vimentin immunostaining was used to evaluate injury depth.. Vimentin staining demonstrated increased burn depth in old mice (449±38μm) as compared to young (166±18μm) (p<0.05). Both groups exhibited increased localized expression of EOTAXIN after burn (p<0.05), however expression in old mice (83.6±6.1pg/ml) was lower than that of young (126.8±18.7pg/ml) (p<0.05). Systemically, however, old mice had increased baseline EOTAXIN expression (1332.40±110.78pg/ml) compared to young (666.12±45.8pg/ml) (p<0.005).. EOTAXIN is one of the primary chemoattractants for selective eosinophilic recruitment and activation. While eosinophils are important for wound healing, a hyperactive eosinophilic response can result in tissue damage. We hypothesize that the increased baseline serum EOTAXIN in the old may prime their hyperactive response, and may contribute to their worse clinical outcomes. Long-term eosinophil activation requires further study, however our findings indicate a role for EOTAXIN and eosinophils in burn response.

Topics: Aging; Animals; Burns; Calgranulin B; Chemokine CCL11; Chemokine CCL2; Chemokine CCL24; Chemokine CCL26; Chemokine CCL5; Chemokine CXCL2; Eosinophils; Epidermal Growth Factor; Granulocyte Colony-Stimulating Factor; Inflammation; Interleukin-10; Mice; Tumor Necrosis Factor-alpha

After burns, protecting tissues by medicines in the zone of stasis reduces the width and depth of injury. This study's goal was to reduce burned tissue damage in the zone of stasis using epidermal growth factor (EGF). Forty-eight Wistar rats were separated into three groups. In all groups, the burn procedure was applied following the comb burn model. In Group 1, no postburn treatment was administered. In Group 2, physiological saline solution (0.3 cc) was injected intradermally and in Group 3, EGF (0.3 cc) was injected intradermally into stasis zone tissues after the burn procedure. Surviving tissue rates were 24.0% in Group 1, 25.3% in Group 2, and 70.2% in Group 3. The average numbers of cells stained with Nrf2, HO-1, and the number of apoptotic cells were 230, 150, and 17.5 in Group 1, 230, 145, and 15.0 in Group 2, and 370, 230, and 0 in Group 3, respectively. Values in Group 3 were found to be statistically significantly different than those of Groups 1 and 2; there was no difference between Groups 1 and 2. This study shows that EGF protects zone of stasis tissue from burn damage.

Topics: Animals; Burns; Disease Models, Animal; Disease Progression; Epidermal Growth Factor; Female; Injections, Intradermal; Rats; Rats, Wistar; Skin; Treatment Outcome; Wound Healing

In this study, the effects of miR-27b on angiogenesis in skin repair procedure in rats with deep II degree scald were explored. The rat model of deep II scald was established. miR-27b mimics and inhibitor were injected daily at the wound site for 3 weeks. The healing of scald was observed at 0, 3, 7, 14, and 21 days after the model was established, and the pathological changes of skin were observed by HE and Masson's trichrome stains. Skin tissues were taken 14 days after the operation; CD31 and Ki-67 immunohistochemistry was exerted to evaluate neovascularization and proliferation. Human microvascular endothelial cells (HMEC-1) cells were cultured in vitro. miR-27b mimics or inhibitor was transfected to construct over-expression or inhibition cell lines. MTT assay, scratch test, and angiogenesis test were used to evaluate cell proliferation, migration, and vascular regeneration. Finally, RT-PCR and Western blot were exerted to determine the expression of vascular endothelial growth factor C (VEGF-C), epidermal growth factor (EGF) mRNAs, and protein, respectively. Control, inhibitor, mi-NC, VEGF-C, inhibitor + si-NC, and inhibitor + VEGF-C siRNA groups were used to further analyze the mechanism of miR-27b on VEGF-C; the above experiments were repeated. In contrast to model group, miR-27b inhibitor could significantly promote the healing of scalded skin, alleviate the pathological status of scalded, and promote the angiogenesis and proliferation (p < 0.05). In vitro, miR-27b inhibitor evidently promoted cell proliferation, migration, and angiogenesis and increased the expression of VEGF-C, EGF genes, and protein, while miR-27b mimics significantly reversed the above trends. Further studies shown that downregulation of miR-27b expression can promote the proliferation, migration, and angiogenesis of HMEC-1 cells by promoting the expression of VEGF-C. miR-27b promotes angiogenesis and skin repair in scalded rats through regulating VEGF-C expression.

Topics: Animals; Base Sequence; Burns; Cell Movement; Cell Proliferation; Collagen; Disease Models, Animal; Down-Regulation; Endothelial Cells; Epidermal Growth Factor; Gene Expression Regulation; Humans; Ki-67 Antigen; Male; MicroRNAs; Microvessels; Neovascularization, Physiologic; Rats, Sprague-Dawley; Skin; Vascular Endothelial Growth Factor C; Wound Healing

To investigate the regulation of epidermal growth factor (EGF) by autophagy-mediated long non-coding RNA (lncRNA) H19 in the intestinal tracts of severely burned mice. C57BL/6J mice received third-degree burns to 30% of the total body surface area. Rapamycin and 3-methyladenine (3-MA) were used to activate and inhibit autophagy, and the changes in LC3 and Beclin1 levels were assessed by Western blotting. The effect of autophagy on lncRNA H19 was detected by qRT-PCR. Adenovirus-mediated overexpression of lncRNA H19 in IEC-6 cells was used to assess the effects of lncRNA H19 on EGF and let-7g via bioinformatics analysis, Western blotting and qRT-PCR. let-7g mimic/inhibitor was used to overexpress/inhibit let-7g, and qRT-PCR and Western blotting were used to detect the effects of let-7g on EGF. The expression levels of LC3-II, Beclin1 and lncRNA H19 were increased in intestinal tissues and IEC-6 cells after rapamycin treatment but were reversed after 3-MA treatment. LC3-II, Beclin1 and lncRNA H19 levels increased in intestinal tissues after the burn, and these increases were more significant after rapamycin treatment but decreased after 3-MA treatment. The lncRNA H19 overexpression in IEC-6 cells resulted in increased and decreased expression levels of EGF and let-7g, respectively. Furthermore, overexpression and inhibition of let-7g resulted in decreased and increased expression of EGF, respectively. Taken together, intestinal autophagy is activated after a serious burn, which can increase the transcription level of lncRNA H19. lncRNA H19 may regulate the repair of EGF via let-7g following intestinal mucosa injury after a burn.

Topics: Animals; Autophagy; Beclin-1; Burns; Cell Line; Epidermal Growth Factor; Gene Expression Regulation; Intestines; Mice, Inbred C57BL; MicroRNAs; Microtubule-Associated Proteins; Rats; RNA, Long Noncoding; Transcription, Genetic

An ointment containing retinoic acid deformable liposomes (TRA DLs) and epidermal growth factor cationic deformable liposomes (EGF CDLs) was prepared for the treatment of deep partial-thickness burns. The characterization tests confirmed both liposomes featured small particle sizes, high drug entrapment efficiencies and sustained drug release behavior. Compared with the free drug, TRA DLs and EGF CDLs exhibited superior skin permeation and remarkably increased drug deposition by 2.9 and 18.8 folds, respectively. Results on HaCaT cells indicated the combined application of two liposomes exerted a synergistic effect and prominently promoted cell proliferation and migration. Application of the dual liposomal ointment on a deep partial-thickness burn model stimulated wound closure (p < 0.001), promoted skin appendage formation and increased collagen production, thus improving healing quality. Finally, it was demonstrated that TRA significantly up-regulated the expression of EGFR and HB-EGF to enhance the therapeutic effect of EGF. Therefore, the dual liposomal ointment is a promising topical therapeutic for burn treatment.

Topics: Animals; Burns; Cell Line; Cell Movement; Cell Proliferation; Epidermal Growth Factor; Humans; Liposomes; Mechanical Phenomena; Permeability; Rats; Skin; Tretinoin; Wound Healing

The use of artificial dermis as a skin substitute is a field of active study, as acellular dermal matrices from cadavers are susceptible to infection owing to their human origin. One such alternative dermal replacement scaffold, INSUREGRAF

Topics: Animals; Burns; Cell Movement; Cell Proliferation; Collagen; Epidermal Growth Factor; Extracellular Matrix; Female; Fibroblasts; Humans; Keratinocytes; Neuregulin-1; Rats; Rats, Sprague-Dawley; Regeneration; Skin; Skin, Artificial; Stress, Mechanical; Tissue Engineering; Tissue Scaffolds; Wound Healing

Individuals in the geriatric age range are more prone than younger individuals to convert their partial thickness thermal burns into full thickness injuries. We hypothesized that this often observed clinical phenomenon is strongly related to differential local injury responses mediated by the immune system.. Skin samples from areas with partial thickness thermal burns were obtained during routine excision and grafting procedures between post burn days 2-6. Tissue samples were grouped by age ranges with young patients defined as <30 years of age or aged patients defined as >65. Formalin fixed samples were used to confirm depth of burn injury and companion sections were homogenized for multiplex analysis using a Luminex platform. Immunohistochemical staining was used to quantify total macrophage numbers as well as the M1 and M2 subpopulations.. Our analysis includes samples derived from 11 young subjects (mean age=23) and 3 aged subjects (mean age=79.2). Our initial survey of analytes examined 31 cytokines/chemokines. Twelve were excluded from consideration as they were present in concentrations either above or below the optimal detection range. Two analytes emerged as candidate molecules with significant differences between the young and the aged patient responses to burn injury. EGF levels were on average 21.69pg/ml in young vs 14.87pg/ml in aged (p=0.032). RANTES/CCL5 levels were on average 14.86pg/ml in young vs 4.26pg/ml in aged (p=0.026). Elevated macrophage numbers were present within wounds of younger patients compared to the old (p<0.01), with a higher concentration of the M1 type in the elderly (p>0.05).. Our study has identified at least 2 well known cytokines, CCL5 (RANTES) and EGF, which are differentially regulated in response to burn injury by young versus aged burn victims. Evidence suggests that a proinflammatory environment can explain the high conversion rate from partial to full thickness burns. Our data suggest the need for future studies at the point of injury (cutaneous targets) that may be modulated by post burn release of cytokines/chemokines.

Topics: Age Factors; Aged; Burns; Chemokine CCL5; Cytokines; Epidermal Growth Factor; Female; Humans; Macrophages; Male; Young Adult

A multitude of topical wound treatments are used today. Although it is well established that the micro-environment of healing wounds can be altered to improve healing, it is difficult to measure the subtle differences in outcome where therapies are compared.. We compared wound healing properties between four different topical agents in surgically incised wounds in a pig model. The four topical agents, 5% Povidone-Iodine cream, 1% Silver-Sulphadiazine, 2% Mupirocin, and 1% Silver-Sulphadiazine plus 1mg/100g recombinant-human epithelial growth factor (EGF) were randomly assigned to four test animals each. Test agents were compared to each other and to untreated controls. We investigated existing and new methodologies of measurement of wound healing: clinical and histological visual scoring systems, immuno-histochemistry, and computerized image analysis of the wounds on days 3, 7, and 28.. All agents were found to have improved healing rates with better cellular architecture. Healing was faster, histological appearance resembled normal architecture sooner, clinical appearance improved, mitotic activity was stimulated and more collagen was deposited in comparison to the wounds with no agents. EGF-treated wounds showed an increased rate of epithelisation, but the rate of healing did not correlate well with evaluation of cosmetic outcome.. Topical agents improve all aspects of wound healing. The addition of a human recombinant EGF to Silver-Sulphadiazine increases epithelial growth and amounts of collagen in the regenerating wounds at day 7.

Topics: Administration, Cutaneous; Animals; Anti-Infective Agents; Burns; Cell Proliferation; Dermis; Epidermal Growth Factor; Epidermis; Female; Humans; Image Processing, Computer-Assisted; Immunohistochemistry; Mupirocin; Povidone-Iodine; Re-Epithelialization; Recombinant Proteins; Silver Sulfadiazine; Skin; Swine; Trauma Severity Indices; Wound Healing

In the present study chitosan based gel formulations containing Egg Yolk Oil (EYO) and Epidermal Growth Factor (EGF) were formulated successfully aiming at enhanced topical treatment of dermal burns the combination of traditional approaches with modern drug delivery systems. Physicochemical properties of the formulations were analyzed and efficacy of the formulations prepared were evaluated versus a commercial product; Silverdin (1% silver sulfadiazine) in vivo on Wistar rats. Burns were generated on the back of the rats and at predetermined time intervals tissue samples were collected and evaluated histologically. The analyses showed that chitosan based gel formulations containing Egg Yolk Oil (E1) and chitosan based gel formulations containing EYO and EGF (M1) formulations seem to be better alternatives for Silverdin with a significant difference (p < 0.05) considering healing ranks of tissue samples.

Topics: Administration, Cutaneous; Animals; Anti-Infective Agents; Burns; Chemistry, Pharmaceutical; Chitosan; Drug Stability; Egg Yolk; Epidermal Growth Factor; Female; Gels; Hydrogen-Ion Concentration; Rats; Rats, Wistar; Rheology; Sulfadiazine; Wound Healing

The effect of recombinant human epidermal growth factor (rhEGF) on innate immunity and cellular composition of the destruction focus in the third-degree (IIIA) burn (skin contact with an object heated to 100°C; 4% body surface) was studied in experiments on outbred albino rats. On days 7-28 after burn, blood count of phagocytes and their absorbing capacity and oxygen-dependent metabolism increased, which correlated with the increase in serum IL-1β level and neutrophil count in the destruction focus. Local application of rhEGF led to earlier (on day 14) normalization of the count and functional activity of blood phagocytes and decrease in serum IL-1β level and accelerated neutrophil and lymphocyte replacement with fibroblasts in the focus of injury.

Topics: Animals; Animals, Outbred Strains; Burns; Drug Evaluation, Preclinical; Epidermal Growth Factor; Fibroblasts; Histiocytes; Humans; Immunity, Innate; Immunologic Factors; Lymphocytes; Male; Neutrophils; Rats; Wound Healing

This study aimed to investigate the efficacy of an artificial dermis composed of hyaluronic acid (HA) and collagen (Col) with or without epidermal growth factor (EGF), both in in vitro and in vivo. The cross-linked high molecular weight HA spongy sheet was prepared by freeze-drying. The spongy sheet was immersed in a mixed solution of high molecular weight HA, low molecular weight HA, and heat-denatured Col, and then lyophilized to obtain a two-layered spongy sheet. Cross-linking among Col molecules was induced by ultraviolet irradiation to prepare the artificial dermis (Type I). In a similar manner, a two-layered artificial dermis containing EGF (Type II) was prepared using a similar mixed solution containing EGF. The in vitro experiments demonstrated that EGF released from the Type II artificial dermis stimulates fibroblasts to produce increased amounts of vascular endothelial growth factor and hepatocyte growth factor. The therapeutic efficacy of artificial dermis was evaluated in animal tests using Sprague Dawley (SD) rats. The dorsal skin of the SD rat was shaved and then exposed to boiling water for 3 s to induce a deep dermal burn. The necrotic tissue was then excised 3 days later. Each artificial dermis was applied to the skin defect for 7 days and assessed for its ability to generate a wound bed. The in vivo experiments demonstrated that the Type II artificial dermis promotes angiogenesis to a greater extent at an early stage (within 3 days), and also suppresses the inflammatory reaction more successfully compared with the Type I artificial dermis. In further animal tests, an autologous skin graft was performed by excising a piece of skin from the abdominal region and then grafting it onto the wound bed prepared using each artificial dermis for 7 days. Although the Type II artificial dermis had the highest potential to promote angiogenesis, in this animal study, each artificial dermis induced excellent wound bed formation acceptable for autologous skin grafting.

Topics: Animals; Burns; Cells, Cultured; Collagen; Epidermal Growth Factor; Fibroblasts; Freeze Drying; Humans; Hyaluronic Acid; Male; Neovascularization, Physiologic; Porosity; Rats; Rats, Sprague-Dawley; Skin; Skin Transplantation; Skin, Artificial; Wound Healing

We evaluated the laser induced burn wound healing efficacy of a recombinant low-molecular-weight protamine conjugated epidermal growth factor (rLMWP-EGF). rLMWP-EGF was prepared by genetically combining LMWP with the N-terminal sequence of EGF; we obtained a homogeneous modified EGF without reduced biological activity. Because of the protein transduction domain of LMWP, rLMWP-EGF showed enhanced drug penetration across artificial skin constructs and excised mouse skin layers versus EGF and showed significantly improved burn wound healing efficacy, with accelerated wound closure and minimized eschar and scar formation, compared with EGF or no treatment. Histological examination also revealed that rLMWP-EGF permeated through the intact skin around the wound and facilitated residual epithelial cell proliferation in an integrated manner to reform an intact epidermis. Radiofrequency microwound formation was effective for reducing large hypertrophic scars formed after severe laser burning by collagen remodeling but rLMWP-EGF did not show a meaningful synergistic effect in burn scar reduction. However, rLMWP-EGF was helpful for forming skin with a more normal appearance and texture. Thus, rLMWP-EGF demonstrated therapeutic potential as a novel topical burn wound healing drug with no obvious toxic effect.

Topics: Animals; Burns; Cell Proliferation; Epidermal Growth Factor; Female; Humans; Male; Mice; Mice, Inbred BALB C; Protamines; Rabbits; Recombinant Fusion Proteins; Skin; Skin Absorption; Wound Healing

This study was designed to investigate the effect of a wound dressing composed of hyaluronic acid (HA) and collagen (Col) sponge containing epidermal growth factor (EGF) on various parameters of wound healing in vitro and in vivo. High-molecular-weight (HMW) HA solution, hydrolyzed low-molecular-weight (LMW) HA solution and heat-denatured Col solution were mixed, followed by freeze-drying to obtain a spongy sheet. Cross-linkage between Col molecules was induced by UV irradiation to the spongy sheet (Type-I dressing). In a similar manner, a spongy sheet containing EGF was prepared (Type-II dressing). The efficacy of these products was firstly evaluated in vitro. Fibroblast proliferation was assessed in culture medium in the presence or absence of a piece of each wound dressing. EGF stimulated cell proliferation after UV irradiation and dry sterilization at 110°C for 1 h. In the second experiment, fibroblasts-embedded Col gels were elevated to the air-liquid interface to create a wound surface model, on which wound dressings were placed and cultured for 1 week. Cell proliferation and the production of vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) were investigated. With Type-II dressings, the amounts of VEGF and HGF released from fibroblasts in the Col gel were significantly increased compared with Type-I dressing. Next, the efficacy of these products was evaluated in vivo using Sprague-Dawley (SD) rats. Wound conditions after 1 and 2 weeks of treatment with the wound dressings were evaluated based on the gross and histological appearances. Type-II dressings promoted a decrease in wound size, re-epithelialization and granulation tissue formation associated with angiogenesis. These findings indicate that the combination of HA, Col and EGF promotes wound healing by stimulating fibroblast function.

Topics: Animals; Bandages; Burns; Cell Proliferation; Cells, Cultured; Collagen; Epidermal Growth Factor; Humans; Hyaluronic Acid; Male; Molecular Weight; Rats; Rats, Sprague-Dawley; Skin, Artificial; Wound Healing

This study aimed to investigate the feasibility of using an immortal keratinocyte cell line, HaCaT cells, to effectively deliver epidermal growth factor (EGF) in a skin substitute to treat burn wounds. The skin equivalent was constructed with human EGF (hEGF) gene modified HaCaT cells obtained through stable gene transfection; these were applied to full thickness burn wounds in a rat model. The results showed that the hEGF gene modified HaCaT cells produced more than 390ng/l of bioactive hEGF in the culture supernatant. K19 and integrin-β1 as keratinocyte differentiation markers were elevated in the hEGF gene modified HaCaT cells which were shown to be non-tumorigenic. The skin equivalent constructed with hEGF gene modified HaCaT cells demonstrated improved epidermal morphogenesis with a thick and compact epidermis. Wound healing was accelerated noticeably when applied with this skin substitute seeded with hEGF gene modified HaCaT cells in vivo. The results suggest that HaCaT cells modified with hEGF gene might be promising seed cells for construction of genetically modified skin substitute which can effectively secrete hEGF to accelerate wound repair and regeneration.

Topics: Animals; Burns; Cells, Cultured; Disease Models, Animal; Epidermal Growth Factor; Epidermis; Feasibility Studies; Gene Transfer Techniques; Humans; Keratinocytes; Male; Mice; Mice, Nude; Rats; Rats, Sprague-Dawley; Real-Time Polymerase Chain Reaction; RNA, Messenger; Tissue Engineering

The objective of this study is to develop a chitosan gel formulation containing liposomes loaded with epidermal growth factor (EGF) and to evaluate their effects on the healing of second-degree burn wounds in rats by immunohistochemical, histochemical and histological methods. EGF-containing multilamellar liposomes which were carried in chitosan gel, EGF gel and EGF-loaded liposome formulations were prepared. The in vivo experiments were performed on female Sprague Dawley rats. Second-degree standard burn wounds were formed on rats and liposomes containing 10 µg/ml EGF in 2% chitosan gel, EGF-chitosan gel and EGF-loaded liposome formulations were applied daily to the burn wounds and biopsies were taken at the 3rd, 7th and 14th day of the treatment. When the results were evaluated immunohistochemically, there were significant increases in cell proliferation observed in the EGF-containing liposome in chitosan gel (ELJ) formulation applied group (P < 0·001). The histochemical results showed that the epithelisation rate in the ELJ group was the highest compared with the other group results (P < 0·001). The histological results indicated and supported these findings and faster epithelisation was observed in the ELJ group compared with the other groups.

Topics: Administration, Topical; Animals; Biocompatible Materials; Biopsy; Burns; Chitosan; Disease Models, Animal; Epidermal Growth Factor; Epidermis; Female; Follow-Up Studies; Gels; Humans; Liposomes; Rats; Rats, Sprague-Dawley; Skin; Treatment Outcome; Wound Healing

β-lapachone is a quinone of lapachol extracted from the bark of lapacho tree. Recent findings demonstrated that punched skin wounds of mice healed faster with β-lapachone treatment. The present study investigates the effects of β-lapachone on burn-wound skin of C57BL/6 mice injured by a 100 °C iron stick. Our results indicated that wounds treated with β-lapachone recovered faster than those treated with control ointment containing no β-lapachone. On the third day after burning, the area of β-lapachone treated-wound was 30% smaller than wound treated with control ointment. H&E and immunohistochemistry staining showed that burn-wound skin treated with ointment containing β-lapachone healed faster in its epidermis, dermis, and underlying connective tissues with more macrophages appeared than those treated with control ointment alone. RAW264.7 cell, a macrophage-like cell line derived from BALB/C mice, was used as a model for scrutinizing the effect of β-lapachone on macrophages. We found that the proliferation and the secretion of EGF and VEGF by macrophages were higher in cultures treated with β-lapachone and that ß-lapachone can also increase the release of EGF with TNF-α pretreatment. We conclude that β-lapachone plays an important role in accelerating burn wound healing, and that β-lapachone not only can raise the proliferation of macrophages but also increase the release of VEGF from macrophages.

Topics: Animals; Burns; Cell Line; Cell Proliferation; Cell Survival; Epidermal Growth Factor; Macrophages; Male; Mice; Mice, Inbred C57BL; Naphthoquinones; Ointments; Petrolatum; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor A; Wound Healing

Clinical efficacy of preparation REGEN-D 150 for local treatment of burns was analyzed. In accordance to the data obtained, the preparation application for the burns treatment have secured the local inflammatory reaction reduction in the affection zone, reparative processes optimization in the burn wound and saving the functional possibilities of phagocytic cells on optimal level.

Topics: Administration, Topical; Adult; Burns; Epidermal Growth Factor; Female; Humans; Male; Middle Aged; Recombinant Proteins; Trauma Severity Indices; Treatment Outcome; Wound Healing; Young Adult

To investigate the effect of topical external administration of recombinant human epidermal growth factor (rhEGF) when controlling blood sugar on expression of epidermal growth factor receptor (EGFR) and EGFR mRNA of wound in diabetes mellitus (DM) combined with scald.. A total of 136 male Wistar rats weighing (188.57 +/- 6.59) g were randomly divided into 4 groups (groups A, B, C, and D, n=34). The rats was made DM model by intraperitoneal injected 60 mg/kg streptozocin in groups A, B, and C; rats were injected buffer alone in group D as control group. After 8 weeks, the rats of 4 groups were placed in 80 degrees C hot water for 6 seconds for preparation of the back deep II degree scald model. In group A, the blood sugar level was controlled at the level of group D 1 week before scald model; within 24 hours after models preparation, rhEGF was sprayed on wound at 150 U/cm2. In group B, the rats were given the same treatment as group A except not controlling blood sugar. In group C, the blood sugar was controlled as group A and wound was suture fixation with 1% silver sulfadiazine cream at 24 hours after the model. In group D, the same treatment as group A was given after injury. The healing rate of the wound was detected at 3, 7, 11, 15, and 21 days after injury; the EGFR mRNA expression was determined by mRNA hybridization in situ, and the EGFR protein expression was determined by immunohistochemistry and Western blot at 1, 3, 5, 7, 11, 15, and 21 days.. All the rats survived at the end of experiment. There was no significant difference in the healing rate of the wound among the 4 groups at 3 days (P > 0.05). The healing rate of the wound was significantly higher in groups A and D than in groups B and C (P < 0.05) at 7, 11, 15, and 21 days. The expression of EGFR mRNA in 4 groups was observed by hybridization in situ, which mainly distributed in the dermal fibroblasts, capillary endothelial cells and remnants of skin and wound edge epithelium of the subsidiary; the expressions reached the peak at 5 days in group A, at 7 days in groups B and C, and at 11 days in group D; and the peak level was significantly higher in groups A and D than in groups B and C (P < 0.05). Immunohistochemistry and Western blot showed that the expression of EGFR protein was observed in 4 groups and reached the peak level at 7 days in groups A and B, and at 11 days in groups C and D; showing significant difference between groups B, C and groups A, D (P < 0.05).. External application of rhEGF when controlling blood sugar can accelerate obviously the wound healing in DM combined with scald. After controlling blood sugar, external application of rhEGF can boost obviously the expressions of EGFR mRNA, EGFR, and the extending process of signal conduction.

Topics: Animals; Burns; Diabetes Mellitus, Experimental; Epidermal Growth Factor; ErbB Receptors; Humans; Male; Rats; Rats, Wistar; Recombinant Proteins; RNA, Messenger; Wound Healing

It was aimed to develop liposome formulations containing epidermal growth factor (EGF) and to investigate the healing effects of these formulations on second-degree burn wounds in rats. Multilamellar type liposomes containing EGF were prepared by film formation method. In vitro releases of EGF from liposome formulations were determined using spectrofluorometer. Second-degree standard burn wounds were formed on rats and liposome formulations containing 10 microg/mL EGF (ELP group), EGF solution (ES group), liposome without containing EGF (LP group), and Silverdine ointment (SIL group) were applied daily. Untreated control groups [unburned (S) and untreated (Y) rats] were also evaluated. Biopsies were taken at the 3rd, 7th, and 14th day of the treatment from the wounds and histological observations were performed under transmission electron microscope. Bromodeoxyuridine (BrdU) staining technique was used for immunohistochemical analysis. After trichrome stainings, the thicknesses of the epidermis and the areas of the fibroblast nucleus were measured using a light microscope and Vision Screening Analysis Program. It was observed that the healing in the ELP group was the fastest among all groups (p < 0.05) at the 14th day of therapy. The healing effect in order from highest to lowest efficacy was found to be ELP>SIL>ES groups, respectively, at the 14th day. All results indicated that the EGF-liposome formulation is effective and can be used for the treatment of burn wounds.

Topics: Animals; Burns; Drug Delivery Systems; Epidermal Growth Factor; Female; Humans; Liposomes; Ointments; Rats; Rats, Sprague-Dawley; Wound Healing

Topics: Adolescent; Adult; Aged; Burns; Epidermal Growth Factor; Humans; Middle Aged; Recombinant Proteins; Wound Healing; Young Adult

Various studies have shown that chitosan is effective in promoting wound healing. In this study, we aimed to develop an effective chitosan gel formulation containing epidermal growth factor (EGF), and to determine the effect on healing of second-degree burn wounds in rats. Ten micrograms per millilitre EGF in 2% chitosan gel was prepared. In an in vitro study to investigate release of EGF from the formulations, the release rate was 97.3% after 24 h. In in vivo studies, animals were divided into six groups as follows: silver sulfadiazine [Silverdin cream (SIL)], chitosan gel with and without EGF (EJ, J), EGF solution (ES) and untreated control groups [unburned (S) and untreated (Y) rats] applied groups, respectively. A uniform deep second-degree burn of the backskin was performed with water heated to 94+/-1 degrees C during a 15-s exposure. The EGF formulations were repeatedly applied on the burned areas with a dose of 0.160 microg/cm2 for 14 days (one application per day). Healing of the wounds was evaluated immunohistochemically, histochemically and histologically on the tissue samples. When the results were evaluated immunohistochemically, there were significant increases in cell proliferation observed in the EGF containing gel applied group (p<0.001). The histochemical results showed that the epithelization rate in the EJ group was the highest compared to the ES group results (p<0.001). The histological results indicated and supported these findings. It can be concluded that a better and faster epithelization was observed in the EJ group compared to the other groups.

Topics: Animals; Biocompatible Materials; Burns; Chitosan; Epidermal Growth Factor; Female; Gels; Immunohistochemistry; Rats; Rats, Sprague-Dawley; Treatment Outcome; Wound Healing

To better define the relationship between dermal regeneration and wound contraction and scar formation, the effects of epidermal growth factor (EGF) loaded in collagen sponge matrix on the fibroblast cell proliferation rate and the dermal mechanical strength were investigated. Collagen sponges with acid-soluble fraction of pig skin were prepared and incorporated with EGF at 0, 4, and 8 microg/1.7 cm2. Dermal fibroblasts were cultured to 80% confluence using DMEM, treated with the samples submerged, and the cell viability was estimated using MTT assay. A deep, 2nd degree- burn of diameter 1cm was prepared on the rabbit ear and the tested dressings were applied twice during the 15-day, post burn period. The processes of re-epithelialization and dermal regeneration were investigated until the complete wound closure day and histological analysis was performed with H-E staining. EGF increased the fibroblast cell proliferation rate. The histology showed well developed, weave-like collagen bundles and fibroblasts in EGF-treated wounds while open wounds showed irregular collagen bundles and impaired fibroblast growth. The breaking strength (944.1 +/- 35.6 vs. 411.5 +/- 57.0 Fmax, gmm(-2)) and skin resilience (11.3 +/- 1.4 vs. 6.5 +/- 0.6 mJ/mm2) were significantly increased with EGF-treated wounds as compared with open wounds, suggesting that EGF enhanced the dermal matrix formation and improved the wound mechanical strength. In conclusion, EGF-improved dermal matrix formation is related with a lower wound contraction rate. The impaired dermal regeneration observed in the open wounds could contribute to the formation of wound contraction and scar tissue development. An extraneous supply of EGF in the collagen dressing on deep, 2nd degree-burns enhanced the dermal matrix formation.

Topics: Animals; Biological Dressings; Biomechanical Phenomena; Burns; Cell Survival; Cells, Cultured; Collagen; Epidermal Growth Factor; Fibroblasts; Rabbits; Regeneration; Skin; Wound Healing

To study an early comprehensive prevention and treatment of sepsis in severely burned patients with delayed fluid resuscitation.. From January 1990 to December 2001, 72 cases of patients with delayed fluid resuscitation were admitted to our burn department. Two different periods were divided and analyzed retrospectively. The first period was from January 1990 to December 2001 and the span of the second period was from January 1995 to December 2001.. (1)The mortality rate and incidence of sepsis in the second period (6.5 percent and 17.4 percent) were significantly lower than those of the first period (23.0 percent and 57.7 percent, P<0.05 and P<0.01). (2)The time of wound healing in the second period was (1.9+/-0.9) hours, it was lower than that of the first period (6.6+/-2.5) hours. (3)The serum contents of tumor necrosis factor (TNF) and blood lactic acid (BLA) were increased at all times in two periods and were markedly increased in the first period (all P<0.01).. Our data demonstrated that measures adopted in the second period for patients with delayed fluid resuscitation, including early excision, early rapid adequate resuscitation, early enteral feeding, increased immunity function, early applying antibactials, xenotransfusion of ultraviolet-irradiated blood, application of recombinant human-growth factor (rh-GH), epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), are beneficial to the prevention and treatment of sepsis in severely burned patients with delayed fluid resuscitation.

Topics: Adult; Anti-Bacterial Agents; Burns; Epidermal Growth Factor; Female; Fibroblast Growth Factor 2; Fibroblast Growth Factors; Fluid Therapy; Human Growth Hormone; Humans; Lactic Acid; Male; Middle Aged; Nutrition Therapy; Prognosis; Sepsis; Time Factors; Trauma Severity Indices; Treatment Outcome; Tumor Necrosis Factor-alpha

Local skin trauma induces inflammatory responses resulting in local tissue and distant organ injury. EGF, a polypeptide hormone, mainly produced in saliva, is one of the major accelerators in wound healing. Wistar albino rats of both sexes received either bovine serum albumin or EGF (10 microg/kg) subcutaneously before a circular (18 mm diameter) partial thickness burn was induced. Afterwards, some rats were placed in separate cages to prevent licking, while the others were caged together to allow wound-licking. Treatments were continued for 5 more days and on the 5th day animals were decapitated. Histopathological analysis of skin damage and dermal myeloperoxidase (MPO) activity, as an index for neutrophil activity, were evaluated. Oxidant injury to the liver and intestines was determined by measuring glutathione (GSH) and malondialdehyde (MDA) levels, as well as MPO activity. The results demonstrate that healing of the burn wound on the skin is accelerated by both wound-licking and EGF administration, which also attenuated tissue neutrophil accumulation, suggesting the role of neutrophils as the source of mediators involved in delayed epithelial regeneration. Moreover, local dermal burn results in oxidant injury to the liver, concomitant with significant elevations in hepatic and intestinal GSH levels. Exogenous administration of EGF at physiological doses had no effect on inflammatory responses of the distant organs, while allowing the rats to lick the wound reduced the oxidant injury to the liver. Since saliva or EGF enhances skin wound healing, topical use of EGF-rich artificial saliva merits consideration for its use in burn patients.

Topics: Animals; Burns; Epidermal Growth Factor; Female; Glutathione; Intestines; Liver; Male; Malondialdehyde; Neutrophils; Oxidants; Peroxidase; Rats; Rats, Wistar; Saliva; Skin; Wound Healing

Many cutaneous laser devices incorporate a temperature-based epidermal protection system to minimize surface damage while continuing to affect targeted tissue. The use of cold air is a new technique to aid in epidermal protection during the application of cutaneous lasers. This study investigates the efficacy of cold air versus chilled sapphire in regards to epidermal preservation when used with an 810 nm diode laser.. White-haired pink piglets and dark-haired pigmented piglets were treated using the 810 nm diode laser in conjunction with either (1) no cryogen protection; (2) cold air alone; (3) chilled sapphire window alone; (4) cold air with water/gel; or (5) chilled sapphire window with water/gel. Laser fluence was varied by adjusting laser duration time while maintaining the intensity at 60 W. Biopsies were obtained from the sacrificed animals, stained with Masson's trichrome, and analyzed for extent of epidermal damage.. Among white-haired pink pigs, the cold air afforded the same degree of epidermal preservation as the chilled sapphire window. Epidermal protection was further enhanced with the addition of either gel or water. Among dark-haired pigmented pigs, the chilled sapphire window alone likewise provided significant epidermal protection, although the cold air alone did not. However, with the addition of water/gel, epidermal preservation was demonstrated in both.. Cold air is an effective means in promoting epidermal preservation, though slightly inferior to the chilled sapphire window on darkly pigmented subjects. Combining either method with water or gel further enhances surface protection, enabling safe use of higher fluences.

Topics: Air Movements; Animals; Burns; Cryotherapy; Data Interpretation, Statistical; Epidermal Growth Factor; Epidermis; Gels; Insulin-Like Growth Factor I; Low-Level Light Therapy; Models, Animal; Skin Temperature; Swine; Water

Mutant strain WYBS2001 of B. subtilis with strong anti-pathogenic activity was obtained by mutagenic ultraviolet rays. The gene fragment of Human Epidermal Growth Factor(hegf) of 175 bp was synthesized by PCR and the restriction sites Pst I and Hind III, original code and the signal sequence CTTAGA of secreting vector pUS186 were induced in the fragment. The DNA sequencing result revealed that the synthesized fragment was identical with that of human egf. Then the biological engineering strain WYBS2001T with human egf was obtained by transforming pUSE which was constructed by cloning egf into the secreting plasmid pUS186, into mutant strain WYBS2001. The result of RIA showed that hEGF can be found in the supernatant of the cultures and its content was 7.6 ng/ml. And the content can be increased if the proteinase inhibitor was added into the medium. After several generations' culturing, WYBS2001T positive engineering strain can still secrete and express hEGF steadily. The result of experiment showed hEGF had biological activity of proliferation and growth of human cell K562 in vitro. WYBS2001T engineering strain had obvious effect on healing the burned animals' models. This research showed microecological gene-engineering bacteria has good applying foreground.

Topics: Amino Acid Sequence; Animals; Bacillus subtilis; Base Sequence; Burns; Cell Division; Culture Media, Conditioned; DNA; Enzyme-Linked Immunosorbent Assay; Epidermal Growth Factor; Gene Expression; Genetic Vectors; Humans; K562 Cells; Mice; Molecular Sequence Data; Mutation; Recombinant Proteins; Sequence Analysis, DNA; Transformation, Genetic; Wound Healing

To explore an optimal method of recombinant human epidermal growth factor(rhEGF) application on the burn wounds of superficial II degree and profound II degree for accelerating its healing.. There were 180 burn wounds in 60 patients with the self-corresponding wound of the same degree as controls. The wounds of all patients were divided three regions(A, B, C). The wounds were treated once a day with 1% SD-Ag in region A as controls, with rhEGF(40 U/cm2) in region B, and with a combination of rhEGF(40 U/cm2) and Su Yu Ping (5 g) in region C. The wound healing time was recorded and compared.. In regions A, B and C, the healing time of superficial II degree wound was (13.20 +/- 2.40) days, (10.20 +/- 2.20) days and (8.72 +/- 2.31) days (P < 0.01); that of profound II degree wound was (20.10 +/- 3.40) days, (17.20 +/- 3.12) days and (15.10 +/- 3.81) days respectively (P < 0.01, P < 0.05). The healed wound of profound II degree was elastic and tough in regions B and C, while that was not elastic and tough, and congestive in region A.. The above results indicate that rhEGF can enhance burn wound healing markedly and that a combination rhEGF and Su Yu Ping has more significant effect than rhEGF alone and is recommended for clinical application.

Topics: Administration, Topical; Adolescent; Adult; Burns; Cell Division; Drug Therapy, Combination; Epidermal Growth Factor; Epithelial Cells; Female; Humans; Liposomes; Male; Middle Aged; Recombinant Proteins; Wound Healing

To observe the effects of recombinant human epidermal growth factor (rhEGF) on deep partial thickness burn wound healing.. The rats were inflicted with deep partial thickness burn. The wounds were either treated with rhEGF, rhEGF with heparin or isotonic saline, respectively. Wound healing time was observed. Wound healing rate, water content and hydroxyproline (OHP) content and type I/III collagen ratio in the wound tissue were determined. Cellular DNA cycle analysis and histological examination were processed.. After the application of rhEGF, burn wound healing time was shortened by two days and wound content of OHP was increased (P < 0.05), with decreased collagen type I/III ratio (P < 0.05). As a result, granulation was enhanced and cellular DNA replication was accelerated (P < 0.05). Heparin addition could augment the effects of rhEGF, especially on wound healing time (2 days shorter) and granulation.. The wound healing time of the deep partial thickness burn could be accelerated markedly by topical application of rhEGF, but early application did not show obvious effects. The addition of heparin might further accelerate wound healing.

Topics: Animals; Burns; Epidermal Growth Factor; Epithelial Cells; Female; Heparin; Humans; Male; Rats; Rats, Sprague-Dawley; Recombinant Proteins; Wound Healing

Major burns are associated with multiple internal organ damages, including necrosis of the gastrointestinal mucosa. Failure of the intestinal barrier is a serious complication in burned patients. Epidermal growth factor (EGF) is a mitogenic polypeptide that stimulates wound repair and affords protection to the gastric mucosa. We examined whether a single systemic intervention with EGF prevents organ systems damages, following full-thickness scalds (25-30%) in rodents. Animals were randomly assigned to receive an intraperitoneal injection of EGF (30 microg/kg in mice, 10 microg/kg in rats) or saline solution, 30 min prior thermal injury in mice or after the cutaneous injury in rats. General clinical condition and mortality during 24h were recorded. Animals were autopsied and histopathological and histomorphometric studies were conducted. Mice treated with EGF exhibited a milder clinical evolution and acute lethality was significantly reduced as compared to saline counterparts (P<0.01). Histopathological and morphometric analysis showed that EGF significantly reduced intestinal necrosis and contributed to preserve jejunoileal architecture in mice (P<0.05) and rats (P<0.01). The onset of renal hemorrhagic foci was significantly reduced in EGF-treated groups (P<0.01). Lung damages appeared attenuated in EGF-treated animals. These data indicate the salutary effects of EGF by attenuating internal complications associated to thermal injuries. Further studies are warranted to fully elucidate the usefulness of this therapy.

Topics: Animals; Burns; Digestive System; Disease Models, Animal; Epidermal Growth Factor; Injections, Intraperitoneal; Male; Mice; Mice, Inbred BALB C; Multiple Organ Failure; Random Allocation; Rats; Rats, Sprague-Dawley; Time Factors; Trauma Severity Indices

To investigate the effect of nerve growth factor(NGF) on the burn wound healing and to study the mechanism of burn wound healing.. Six domestic pigs weighting around 20 kg were used as experimental animals. Twenty-four burn wound, each 2.5 cm in diameter, were induced on every pigs by scalding. Three different concentrations of NGF, 1 microgram/ml, 2.5 micrograms/ml, 5 micrograms/ml were topically applied after thermal injury, and saline solution used as control group. Biopsy specimens were taken at 3, 5 and 9 days following treatment and immunohistochemistry method was used to detect the epidermal growth factor(EGF), EGF receptor (EGF-R), NGF, NGF receptor (NGF-R), NGF, NGF-R, CD68 and CD3.. The expression of EGF, EGF-R, NGF, NGF-R CD68 and CD3 were observed in the experimental group, especially at 5 and 9 days, no expression of those six items in the control group.. NGF can not only act directly on burn wound, but also modulate other growth factors on the burn wound to accelerate the healing of burn wound.

Topics: Animals; Burns; Epidermal Growth Factor; ErbB Receptors; Nerve Growth Factor; Receptor, Nerve Growth Factor; Swine, Miniature; Wound Healing

Topics: Burns; Epidermal Growth Factor; Honey; Humans; Randomized Controlled Trials as Topic; Sensitivity and Specificity; Skin; Treatment Outcome; Wound Healing

To explore the effects of endogenous growth factors on the formation of scars and ulcers after trauma or burn.. The amounts of endogenous epidermal growth factor (EGF), tumor necrosis factor(TNF) and nitric oxide (NO) in scar and the developing granulation tissues after trauma or burn were determined and their relation with the wound healing were studied.. The results showed that EGF, TNF and NO could be found in all scars and the granulation tissues, but their concentration varied with different tissues, sex and age of patients. In male patients or youngsters, the amounts of EGF, TNF and NO in scars were much greater than those in granulation tissues.. The results indicated that the growth factors are necessary for wound healing, but insufficiency or overproduction of the endogenous growth factors may lead to the development of chronic ulcers or scar formation after trauma or burn.

Topics: Adult; Burns; Cicatrix; Epidermal Growth Factor; Female; Humans; Male; Nitric Oxide; Tumor Necrosis Factor-alpha; Wound Healing

Topics: Burns; Epidermal Growth Factor; Fibroblast Growth Factors; Humans; Recombinant Proteins; Wound Healing

To investigate the role of growth factors and their receptors in partial-thickness burn wound healing.. SD rats were used. After 10% total body surface area partial-thickness burn, wound tissues were harvested on postburn days (PBDs) 0(normal control), 1, 3, 5, 7, 10 and 14 respectively. The gene expressions of growth factors and their receptors were determined in wound by in situ hybridization and slot blotting hybridization. At the same time, the process of the wound healing was observed histologically, and the regeneration cycle of epidermal cells and the temporal change in inflammatory cells were measured.. Inflammatory cells infiltrated into wound surface were neutrophils, followed by macrophages and lastly lymphocytes. Epidermal cells proliferated most actively on PBD 3 and the mitoses of them increased significantly on day 7 after burn. The gene expression of PDGF, PDGFR and EGFR reached peaks on PBD 1 and the gene expression of EGF and TGF beta-R2 were highest on PBD 3. In addition, the gene expression of TGF beta-R1 and TGF beta 1 increased significantly on PBDs 5 and 7 respectively.. The data suggested that burn can induce gene expression of EGF, PDGF, TGF-beta 1 and their receptors temporally, spatially, and reversibility, which might play a major role in burn wound healing, and the mutual regulation may exist in the gene expression and the cell cycle.

Topics: Animals; Burns; Epidermal Growth Factor; ErbB Receptors; Gene Expression; Platelet-Derived Growth Factor; Rats; Rats, Sprague-Dawley; Receptors, Platelet-Derived Growth Factor; Wound Healing

Fluids that accumulate at wound sites may be an important reservoir of growth factors that promote the normal wound healing response. The presence of heparin-binding growth factors was studied in burn wound fluid (BWF) from 45 pediatric patients who had sustained partial thickness burns. One of the growth factors present was similar to platelet-derived growth factor (PDGF) based on its heparin affinity, inhibition of bioactivity by a PDGF antiserum, and detection in a PDGF-AB enzyme-linked immunosorbent assay. A second growth factor was identified as heparin-binding epidermal growth factor-like growth factor (HB-EGF) based on its heparin affinity, competition with 125I-labeled epidermal growth factor (EGF) for EGF receptor binding, and recognition in biological assays and Western blots by two HB-EGF antisera. Amino acid sequence analysis of one form of this second growth factor verified its identity as an N-terminally truncated form of HB-EGF. Immunohistochemical analysis of partial thickness burns demonstrated the presence of HB-EGF in the advancing epithelial margin, islands of regenerating epithelium within the burn wound, and in the duct and proximal tubules of eccrine sweat glands. HB-EGF in the surface epithelium of burn wounds was uniformally distributed, whereas it was restricted to the basal epithelium in nonburned skin. These data support a role for PDGF and HB-EGF in burn wound healing and suggest that the response to injury includes deposition of HB-EGF and PDGF into blister fluid and a redistribution of HB-EGF in the surface epithelium near the wound site.

Topics: Adolescent; Body Fluids; Burns; Child; Child, Preschool; Epidermal Growth Factor; Heparin; Heparin-binding EGF-like Growth Factor; Humans; Immunohistochemistry; Infant; Intercellular Signaling Peptides and Proteins; Platelet-Derived Growth Factor; Reference Values; Tissue Distribution

Wound healing is a complex biologic process in which peptide growth factors play a very important role. The object of this research was to study the effects of recombinant human epidermal growth factors (rh-EGF) and acidic fibroblast growth factor (aFGF), basic fibroblast growth factor (bFGF) and bovine brain extract (bBE) on porcine partial-thickness burn wound healing. The biopsies were taken for determination of DNA contents and cell DNA cycle with the aid of flow cytometry and histological observation. The results showed that more extensive reepithelization and greater thickness of epidermis exhibited in growth factor treated wounds, and DNA contents and percent of S phase of cell DNA cycle were also higher in those groups treated with growth factors. The results suggested that repeated topical application of rh-EGF, aFGF, bFGF and bBE accelerated epithelial healing of burn wounds, and it may be helpful in clinical practice.

Topics: Animals; Burns; DNA; Epidermal Growth Factor; Fibroblast Growth Factor 1; Fibroblast Growth Factor 2; Recombinant Proteins; Swine; Tissue Extracts; Wound Healing

The topical application of recombinant growth factors such as epidermal growth factor, platelet-derived growth factor-BB homodimer (rPDGF-BB), keratinocyte growth factor (rKGF), and neu differentiation factor has resulted in significant acceleration of healing in several animal models of wound repair. In this study, we established highly reproducible and quantifiable full and deep partial thickness porcine burn models in which burns were escharectomized 4 or 5 days postburn and covered with an occlusive dressing to replicate the standard treatment in human burn patients. We then applied these growth factors to assess their efficacy on several parameters of wound repair: extracellular matrix and granulation tissue production, percent reepithelialization, and new epithelial area. In full thickness burns, only rPDGF-BB and the combination of rPDGF-BB and rKGF induced significant changes in burn repair. rPDGF-BB induced marked extracellular matrix and granulation tissue production (P = 0.013) such that the burn defect was filled within several days of escharectomy, but had no effect on new epithelial area or reepithelialization. The combination of rPDGF-BB and rKGF in full thickness burns resulted in a highly significant increase in extracellular matrix and granulation tissue area (P = 0.0009) and a significant increase in new epithelial area (P = 0.007), but had no effect on reepithelialization. In deep partial thickness burns, rKGF induced the most consistent changes. Daily application of rKGF induced a highly significant increase in new epithelial area (P < 0.0001) but induced only a modest increase in reepithelialization (83.7% rKGF-treated versus 70.2% control; P = 0.016) 12 days postburn. rKGF also doubled the number of fully reepithelialized burns (P = 0.02) at 13 days postburn, at least partially because of marked stimulation of both epidermal and follicular proliferation as assessed by proliferating cell nuclear antigen expression. In situ hybridization for KGFR in porcine burns revealed strong expression of KGFR on hair follicles and basal epidermis, confirming direct rKGF action on follicular as well as epidermal keratinocytes. Although the epithelial proliferation induced by rKGF resulted in marked neoepidermal psoriasiform hyperplasia with exaggerated rete ridges and neoepidermal and follicular maturation as assessed by expression of cytokeratin 10, a marker of keratinocyte terminal differentiation was not delayed and appeared to be accelerated i

Topics: Administration, Topical; Animals; Becaplermin; Burns; Cell Division; Epidermal Growth Factor; Epithelium; Fibroblast Growth Factor 10; Fibroblast Growth Factor 7; Fibroblast Growth Factors; Glycoproteins; Growth Substances; Hyperplasia; In Situ Hybridization; Integrins; Keratinocytes; Neuregulins; Platelet-Derived Growth Factor; Proto-Oncogene Proteins c-sis; Psoriasis; Recombinant Proteins; Swine; Wound Healing

This report indicates that retention fluid from blisters of partial skin thickness burns, which contains relatively large amounts of cytokines and growth factors, stimulates the wound healing process. Although epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) levels were low, relatively large amounts of cytokines including platelet derived growth factor (PDGF), interleukin (IL-6) and transforming growth factor (TGF) alpha were present and these exercised stimulatory effects on wound healing. TGF beta, which plays an important role in collagen metabolism and in scar formation, was also detected. Contrary to our expectations, IL-1 alpha and beta, both of which initiate inflammation, were detected at relatively low levels whereas IL-8 levels were rather high. Various cytokines were shown to coexist in a balanced state in the retention fluids, suggesting that epithelialization might be regulated via a cytokine network operating on the wound surface. The growth of keratinocytes in culture significantly increased with the addition of 1 per cent or more of blister fluid to the medium.

Topics: Blister; Burns; Cytokines; Epidermal Growth Factor; Exudates and Transudates; Fibroblast Growth Factor 2; Humans; Interleukins; Platelet-Derived Growth Factor; Transforming Growth Factors; Wound Healing

Evidence for epidermal growth factor (EGF) involvement in the physiological response to burns was sought from urinary levels of EGF, urea and creatinine in male rats using a standardized thermal skin injury model (25 per cent body surface) and treated with fluid resuscitation. Postmortem, the skin lesions were studied by microscopy to guarantee the absence of inflammatory complications. Statistically significant differences were observed in body weight, urea and creatinine excretion when compared to the basal values. When EGF excretion results were evaluated as raw data (expressed as ng/mg of creatinine or ng/day) compared to basal levels, no statistically significant differences were observed. However, when the results were expressed as percentage increases with respect to the basal values, a statistically significant increase was found over the first 7 days postinjury (P = 0.029).

Topics: Animals; Burns; Creatinine; Epidermal Growth Factor; Kidney Function Tests; Male; Rats; Rats, Sprague-Dawley

We quantified endogenous levels of multiple cytokines in skin graft donor site wounds in patients with small to moderate-sized burn injuries. Thirteen patients aged 11 months to 61 years with mean TBSA burn of 4 +/- 1 per cent underwent placement of occlusive wound dressings on partial skin thickness donor site wounds. Fluid was aspirated from beneath the dressing on postoperative day 1 and every subsequent 24 h until no further fluid could be obtained. Interleukin-1 alpha (IL-1) and tumour necrosis factor-alpha (TNF-alpha) levels were determined by enzyme-linked immunosorbent assay (ELISA). Epidermal growth factor (EGF), basic-fibroblast growth factor (bFGF), and platelet-derived growth factor (PDGF) were measured by an enzyme immunoassay (EIA). We found substantial levels of EGF and TNF-alpha in the donor site wound fluid in all 13 patients; detectable levels of bFGF in five patients; and elevated levels of IL-1 in three patients. There were no detectable levels of these cytokines in normal human serum. In contrast, there were no measurable levels of PDGF in any patient's wound fluid; the mean level in serum was 1.5 ng/ml +/- 0.2 s.e.m. Studies of cytokines in the normal wound healing environment may help in the design of future therapies to augment wound healing.

Topics: Adolescent; Adult; Burns; Child; Child, Preschool; Cytokines; Enzyme-Linked Immunosorbent Assay; Epidermal Growth Factor; Exudates and Transudates; Female; Fibroblast Growth Factor 2; Humans; Immunoenzyme Techniques; Infant; Infant, Newborn; Interleukin-1; Male; Middle Aged; Platelet-Derived Growth Factor; Skin Transplantation; Tumor Necrosis Factor-alpha; Wound Healing

When epidermal growth factor (EGF) ointment containing a protease inhibitor, nafamostat (NM), was applied to burn sites in rats, the superoxide dismutase (SOD) enzyme activity and protein content increased 45% and 60%, respectively, at these sites 1 d after the burns compared with the control ointment. Following treatment with EGF plus NM (EGF + NM) ointment, messenger RNA for SOD also increased, to about 1.6 times that of the control at 1 d after the burn, indicating that this ointment stimulates SOD synthesis at burn sites in vivo. In contrast, following treatment with EGF + NM ointment, the content of heat shock protein (HSP 70) in the burned tissue decreased to about 70% of the control value 1 d after the burn. These findings suggest that EGF + NM ointment alleviated tissue damage at burn sites at an early stage, and that this was related to the stimulation of SOD synthesis and reduced HSP 70 levels. We also examined the effects of SOD ointment on wound healing at burn sites. A dose-dependent increase in the dry weight of granulation tissue at wound sites 3 d after the burn was observed following the application of this ointment. These results suggest that SOD may play an important role in wound healing after burns.

Topics: Animals; Benzamidines; Blotting, Northern; Burns; Drug Combinations; Epidermal Growth Factor; Guanidines; Heat-Shock Proteins; Male; Molecular Weight; Ointments; Protease Inhibitors; Proteins; Rats; Rats, Wistar; RNA, Messenger; Skin; Superoxide Dismutase

The systemic effects of epidermal growth factor (EGF) ointment containing nafamostat (NM), gabexate, or gelatin was studied in rats with burns or open wounds. At 1 d after burn, plasma epinephrine, cortisol, and glutamic-oxalacetic transaminase (GOT) levels were elevated, but treatment with EGF plus NM (EGF+NM) ointment significantly suppressed the increase in these levels. Further, there was no loss of body weight in the open wound model following treatment with EGF+NM ointment, while loss of body weight occurred in animals in which EGF ointments without NM were applied. Increases in plasma epinephrine 1 d after open wound formation were also suppressed by the application of EGF+NM ointment. Treatment with EGF ointment containing gabexate (GX) or gelatin (GL) ameliorated changes in body weight that occurred after open wound formation, while loss of body weight in animals with open wounds occurred following the application of ointment base, EGF ointment, GX ointment, or GL ointment. The present study thus indicates that the topical application of EGF ointment containing a protease inhibitor has ameliorative systemic effects.

Topics: Animals; Aspartate Aminotransferases; Benzamidines; Body Weight; Burns; Drug Interactions; Drug Synergism; Epidermal Growth Factor; Epinephrine; Gabexate; Gelatin; Guanidines; Hydrocortisone; Male; Ointments; Protease Inhibitors; Rats; Rats, Wistar; Wounds and Injuries

Burn injury produces acute gastrointestinal derangements that may predispose to bacterial translocation (BT). We studied effects of recombinant human epidermal growth factor (r-HuEGF), a gastrointestinal trophic hormone, on gastrointestinal alterations and BT after murine burn injury.. r-HuEGF was administered 1 and 12 hours after burn injury in a dose of 4 micrograms per animal subcutaneously after 25% and 32% total body surface area (TBSA) scald burn. Small bowel and gastric weight and histologic factors were studied, and BT was measured by culturing mesenteric lymph nodes.. Mice treated with r-HuEGF maintained gastric and small intestine weight measured 24 hours after burn injury, and ileal mucosal height was preserved, whereas burned-untreated mice lost organ weight and mucosal height. BT was decreased significantly in mice with 32% TBSA burn injury treated with r-HuEGF after injury (burn, 64.2% of animals had BT; burn-r-HuEGF, 34.6% had BT; p < 0.05). After 25% TBSA burn injury, BT was also decreased in r-HuEGF-treated animals (burn, 31.4% of animals had BT; burn-r-HuEGF, 14.3% had BT), but the difference was not statistically significant (p < 0.1).. r-HuEGF improves intestinal and gastric structure in mice 24 hours after burn injury and decreases BT after 32% TBSA burn injury.

Topics: Absorption; Animals; Bacteria; Bacterial Physiological Phenomena; Burns; Digestive System; Epidermal Growth Factor; Female; Intestinal Mucosa; Mice; Organ Size; Recombinant Proteins

Epidermal growth factor (EGF) along with several related peptide growth factors has been shown both in vivo and in vitro to accelerate events associated with epidermal wound repair. EGF and transforming growth factor alpha act by binding to a common EGF receptor tyrosine kinase thereby initiating a series of events which ultimately regulate cell proliferation. This study examined the immunohistochemical localization of EGF receptor (EGF-R) in burn wound margins, adjacent proliferating epithelium, and closely associated sweat ducts, sebaceous glands, and hair follicles. Tissue specimens removed during surgical debridement were obtained from full and partial thickness burn wounds in 32 patients with total body surface area burns ranging from 2 to 88%. In the early postburn period (days 2-4), prominent staining for EGF-R was found in undifferentiated, marginal keratinocytes, adjacent proliferating, hypertrophic epithelium, and both marginal and nonmarginal hair follicles, sweat ducts, and sebaceous glands. During the late postburn period (days 5-16), EGF-R was depleted along leading epithelial margins; however, immunoreactive EGF-R remained intensely positive in the hypertrophic epithelium and all skin appendages. Increased detection of immunoreactive EGF-R and the presence of [125I]EGF binding in the hypertrophic epithelium correlated positively with proliferating cell nuclear antigen distributions. Thus, the presence of EGF-R in the appropriate keratinocyte populations suggests a functional role for this receptor during wound repair. Dynamic modulation in EGF receptor distribution during the temporal sequence of repair provides further evidence that an EGF/transforming growth factor alpha/EGF-R-mediated pathway is activated during human wound repair.

Topics: Burns; Cell Division; Epidermal Growth Factor; Epidermis; Epithelium; ErbB Receptors; Humans; Hypertrophy; Keratinocytes; Nuclear Proteins; Proliferating Cell Nuclear Antigen; Time Factors; Wound Healing

The healing effect of human epidermal growth factor (hEGF) on second degree burn was studied in rats. No improvement in wound healing was found on topical application of EGF alone to burn sites, but an ointment containing EGF and nafamostat mesilate (NM), a protease inhibitor, accelerated the healing rate of burns. The dry weight of the granulation tissue on the wound site in the group treated with EGF plus NM ointment did not change, although that in other groups decreased. After treatment with EGF ointment containing NM, the content of uronic acid, as an index of acid mucopolysaccharide, at 3 d after burn rapidly increased and had recovered to nearly normal levels at 7 d after burn. However, the uronic acid content in the other groups (control, EGF alone, and NM alone) showed a higher value at 7 d than at 3 d. When compared with the control values significant increases in hydroxyproline, as an index of collagen, in the wound site were observed at 7 d after treatment with EGF ointment containing NM. The degradation of [125I]EGF in burned tissue homogenate decreased significantly in a concentration-dependent manner in the presence of NM. Body weights did not change after treatment with EGF plus NM ointment, although the body weights of other treatment groups decreased after burn, suggesting that EGF ointment containing the protease inhibitor, NM, alleviated the effects of burn shock. These findings indicate that the stabilization of EGF at the wound site is an important factor for the expression of its healing effects.

Topics: Animals; Benzamidines; Burns; Drug Interactions; Drug Stability; Drug Therapy, Combination; Epidermal Growth Factor; Guanidines; Hydroxyproline; Male; Ointments; Rats; Rats, Inbred Strains; Serine Proteinase Inhibitors; Uronic Acids; Wound Healing

Topics: Burns; Cells, Cultured; Culture Media; Cytological Techniques; Epidermal Growth Factor; Humans; Keratinocytes; Skin Transplantation; Wound Healing

Epidermal regeneration following middermal injuries to skin requires both proliferation and migration of keratinocytes. Epidermal growth factor (EGF) stimulates the proliferation of keratinocytes in culture, and topical administration of EGF accelerates epidermal regeneration of partial thickness burns or split-thickness incisions in vivo. Transforming growth factor-alpha (TGF-alpha) and vaccinia growth factor (VGF) have substantial sequence homology with EGF, and all appear to bind to the same receptor protein. Whether TGF-alpha or VGF can affect epidermal wound healing in vivo is not known. The present studies show that topical administration of TGF-alpha or VGF in antibiotic cream to partial thickness burns (second degree) accelerated epidermal regeneration in comparison with untreated or vehicle-treated burns. Low levels of both TGF-alpha and VGF (0.1 microgram per milliliter) appeared to be more effective than EGF in stimulating epidermal regeneration. Regenerated epithelium from burns treated with TGF-alpha or VGF appeared normal histologically. This finding suggests that topical application of selected growth factors may be useful in accelerating healing of partial thickness injuries.

Topics: Animals; Burns; Dose-Response Relationship, Drug; Epidermal Growth Factor; Growth Substances; Intercellular Signaling Peptides and Proteins; Peptides; Regeneration; Skin; Skin Physiological Phenomena; Swine; Transforming Growth Factors; Vaccinia virus; Wound Healing

Epidermal regeneration depends on mitosis and migration of keratinocytes. Epidermal growth factor is known to stimulate growth of keratinocytes in vitro, thus it might be expected to promote wound healing. The results of this study show that topical application of biosynthetic human epidermal growth factor accelerates epidermal regeneration in split-thickness wounds and partial-thickness burns. The significant enhancement of epidermal regeneration suggests the potential for clinical use of epidermal growth factor for accelerating healing of burns, wounds from trauma, diabetic ulcers, skin graft donor sites, and others.

Topics: Animals; Burns; Epidermal Growth Factor; Epidermis; Recombinant Proteins; Regeneration; Swine; Wound Healing

Topics: Angiogenesis Inducing Agents; Animals; Antigens; Biocompatible Materials; Blood Platelets; Burns; Cicatrix; Collagen; Epidermal Growth Factor; Fibroblast Growth Factors; Fluorescent Antibody Technique; Granulocytes; Growth Substances; Humans; Hypertrophy; Inflammation; Laminin; Leukocytes; Macrophages; Pulmonary Fibrosis; Rabbits; Silicone Elastomers; Wound Healing; Wound Infection

The effects of the topical application and the intraperitoneal administration of epidermal growth factor (EGF) on the healing of epidermal wounds, and of partial-thickness scalds in rats and of corneal wounds in rabbits were evaluated. The parameters measured were the daily percentage body weight change, time to complete healing of the wounds, the evaporative water loss from the wound surface and the rate of new formation of epithelial cell layers on the epidermal and corneal wounds. Wounded animals treated with 0.9% NaCl were used as controls. After removal of the corneal epithelium the local application of EGF stimulated the regeneration process appreciably. No significant healing advantage from the treatment with EGF was observed, however, in epidermal wounds and partial-thickness scalds. The result does not warrant any clinical evaluation.

Topics: Animals; Body Water; Body Weight; Burns; Cell Division; Cornea; Corneal Injuries; Epidermal Growth Factor; Epidermis; Mice; Rabbits; Rats; Rats, Inbred Strains; Skin; Wound Healing

The effects of the topical application of epidermal growth factor (EGF) on the healing of partial-thickness scald burns in rats was evaluated. Time to complete healing, the rate of healing, daily percentage weight change, and cell growth were the measured parameters. We were able to demonstrate an insignificant healing advantage with the topical application of EGF, by itself or in combination with silver sulphadiazine. This insignificant healing advantage does not warrant clinical evaluation.

Topics: Administration, Topical; Animals; Burns; Drug Evaluation; Drug Therapy, Combination; Epidermal Growth Factor; Rats; Rats, Inbred Strains; Silver Sulfadiazine; Wound Healing

The cells from a small piece of epidermis can be grown into a large number of cultured epithelia. Such epithelia, generated from autologous skin, were grafted onto full-thickness burn wounds in two patients. The cultured epithelia acquired an epidermal structure resembling that achieved with conventional split-thickness skin grafts, and survived for the period of observation (up to 8 months). Since the method of cultivation can generate large amounts of epithelium, the procedure is applicable to the grafting of large areas, as in severe burns.

Topics: Adult; Burns; Burns, Electric; Cells, Cultured; Epidermal Cells; Epidermal Growth Factor; Epidermis; Epithelial Cells; Humans; Male; Middle Aged; Transplantation, Autologous

A radioreceptor assay for human epidermal growth factor-urogastrone (EGF-URO) employing mouse EGF-URO as tracer and calibration standards and human placental receptor as binding protein is compared with a radioimmunoassay for human EGF-URO. Results employing the receptor assay indicated similar values for urinary concentrations (1-16 nmol/l) for healthy control subjects and for patients with psoriasis. Lower values were obtained for bed-ridden patients with burns or patients recovering from orthopaedic surgery. The results obtained by radioimmunoassay were somewhat higher and correlated poorly (r = 0.5) with those obtained with the radioreceptor assay. The reason for this discrepancy is discussed.

Topics: Adult; Aged; Burns; Epidermal Growth Factor; Evaluation Studies as Topic; Humans; Immobilization; Male; Middle Aged; Psoriasis; Radioimmunoassay; Radioligand Assay