Corticosteroid-loaded chitosan-based in-situ forming gel combined with microneedle technology for improvement of burn eschar wound healing.

Burn is one of the most common skin injuries and accounts for 300,000 deaths annually. Debridement and antibiotic therapy are major burn treatments, however, as debridement is not always possible and many drugs have poor penetration into necrotic tissue, permeation enhancement is acquired. Another challenge is the short duration of topically applied drugs. This study aims to address both problems by combining in-situ forming gels and microneedles. A chitosan-based in-situ forming gel of hydrocortisone was applied to human burn eschar using microneedles. The formulation was optimized using Design-Expert software. Formulation characterization was done in terms of gelling time and temperature, thermal analysis, release phenomenon, rheology, texture analysis, and stability. Finally, animal studies on mice burn wound treatment were conducted. Results showed that optimized formulation controlled the drug release, and wherever microneedle was used, drug permeation and flux increased (P-value < 0.05). In all ex-vivo and in-vivo stages, gel plus microneedle (length of 1.5 mm and application mode of 2) produced the best results concerning increased flux and faster recovery of burn eschar. In conclusion, the in-situ forming gel with appropriate texture, quality, and stability in combination with microneedle can be a good candidate for the controlled release of drugs in third-degree burn eschars.

Development of a Novel Covalently Bonded Conjugate of Caprylic Acid Tripeptide (Isoleucine-Leucine-Aspartic Acid) for Wound-Compatible and Injectable Hydrogel to Accelerate Healing.

Third-degree burn injuries pose a significant health threat. Safer, easier-to-use, and more effective techniques are urgently needed for their treatment. We hypothesized that covalently bonded conjugates of fatty acids and tripeptides can form wound-compatible hydrogels that can accelerate healing. We first designed conjugated structures as fatty acid-aminoacid1-amonoacid2-aspartate amphiphiles (Cn acid-AA1-AA2-D), which were potentially capable of self-assembling into hydrogels according to the structure and properties of each moiety. We then generated 14 novel conjugates based on this design by using two Fmoc/tBu solid-phase peptide synthesis techniques; we verified their structures and purities through liquid chromatography with tandem mass spectrometry and nuclear magnetic resonance spectroscopy. Of them, 13 conjugates formed hydrogels at low concentrations (≥0.25% w/v), but C8 acid-ILD-NH2 showed the best hydrogelation and was investigated further. Scanning electron microscopy revealed that C8 acid-ILD-NH2 formed fibrous network structures and rapidly formed hydrogels that were stable in phosphate-buffered saline (pH 2-8, 37 °C), a typical pathophysiological condition. Injection and rheological studies revealed that the hydrogels manifested important wound treatment properties, including injectability, shear thinning, rapid re-gelation, and wound-compatible mechanics (e.g., moduli G″ and G', ~0.5-15 kPa). The C8 acid-ILD-NH2(2) hydrogel markedly accelerated the healing of third-degree burn wounds on C57BL/6J mice. Taken together, our findings demonstrated the potential of the Cn fatty acid-AA1-AA2-D molecular template to form hydrogels capable of promoting the wound healing of third-degree burns.

Complete Salvage of Third-degree Burn of Ear by Repairing Gel-PRP-Fibrin Glue, A Case Report.

The ear is a very important facial feature and enhances the overall look of the face. Usually, patients with entire ear burns also have large areas of burn in their bodies. To save the patient, skin grafting to reduce the injured body surface area is prioritized and the treatment of the ears may be inevitably delayed, which results in minor to very severe cosmetic deformity. This has a deep effect on the life quality of a patient who survives a burn injury. Therefore, any step that decreases ear deformity or loss is very crucial for the patient. There are different challenging procedures for ear reconstruction which are very tedious works. In this study, for one patient, repairing gel-platelet-rich plasma-fibrin glue was applied for the treatment of a deep dermal burned ear as a novel, non-invasive, and simple approach to give a normal shape to the ear to prevent extensive morbidity during the acute phase and deformities later as a consequence of burns. No keloid is observed after treatment.

20(R)-ginsenoside Rg3-loaded polyurethane/marine polysaccharide based nanofiber dressings improved burn wound healing potentials.

The management of deep burn injuries is extremely challenging, ascribed to their delayed wound healing rate, susceptibility for bacterial infections, pain, and increased risk of hypertrophic scarring. In our current investigation, a series of composite nanofiber dressings (NFDs) based on polyurethane (PU) and marine polysaccharides (i.e., hydroxypropyl trimethyl ammonium chloride chitosan, HACC and sodium alginate, SA) were accomplished by electrospinning and freeze-drying protocols. The 20(R)-ginsenoside Rg3 (Rg3) was further loaded into these NFDs to inhibit the formation of excessive wound scars. The PU/HACC/SA/Rg3 dressings showed a sandwich-like structure. The Rg3 was encapsulated in the middle layers of these NFDs and slowly released over 30 days. The PU/HACC/SA and PU/HACC/SA/Rg3 composite dressings demonstrated superior wound healing potentials over other NFDs. These dressings also displayed favorable cytocompatibility with keratinocytes and fibroblasts and could dramatically accelerate epidermal wound closure rate following 21 days of the treatment of a deep burn wound animal model. Interestingly, the PU/HACC/SA/Rg3 obviously reduced the excessive scar formation, with a collagen type I/III ratio closer to the normal skin. Overall, this study represented PU/HACC/SA/Rg3 as a promising multifunctional wound dressing, which promoted the regeneration of burn skins and attenuated scar formation.

Efficacy of bioabsorbable dressing combined with antibacterial spray for treatment of third-degree burns.

OBJECTIVE: To evaluate the clinical efficacy of a bioabsorbable dressing in combination with antibacterial spray in treating third-degree burns. METHOD: Patients with third-degree burns in our hospital from February 2019 to February 2020 were enrolled and divided into an experimental group and a control group. In all patients, two wound repair surgeries were performed. During the first surgery, bioabsorbable dressing (PELNAC, Gunze Medical Equipment (Shenzhen) Co. Ltd., China) was used for wound treatment. During the second surgery, autologous split-thickness skin graft was performed. For patients in the experimental group, bioabsorbable dressings (PELNAC) were uniformly applied with antibacterial spray during the operation and during postoperative dressing. For patients in the control group, antibacterial spray was not used. RESULTS: A total of 68 patients took part in the study (experimental group n=36; control group n=32). Infection rate in the experimental group was significantly lower than that in the control group (2.8% versus 21.9%, respectively; p<0.05). The mean wound healing time in the experimental group was shorter by 3.2 days and the wound healing rate of the experimental group was significantly higher than that in the control group (p<0.05). Vancouver Scar Scale (VSS) scores at specific postoperative time intervals were significantly reduced in the experimental group compared with those in the control group (p<0.05). CONCLUSION: Bioabsorbable dressing combined with antibacterial spray could reduce infection rate, shorten wound healing time and reduce scar formation in repairing third-degree burns.

Unleashing the healing potential: Exploring next-generation regenerative protein nanoscaffolds for burn wound recovery.

Burn injury is a serious public health problem and scientists are continuously aiming to develop promising biomimetic dressings for effective burn wound management. In this study, a greater efficacy in burn wound healing and the associated mechanisms of α-lactalbumin (ALA) based electrospun nanofibrous scaffolds (ENs) as compared to other regenerative protein scaffolds were established. Bovine serum albumin (BSA), collagen type I (COL), lysozyme (LZM) and ALA were separately blended with poly(ε-caprolactone) (PCL) to fabricate four different composite ENs (LZM/PCL, BSA/PCL, COL/PCL and ALA/PCL ENs). The hydrophilic composite scaffolds exhibited an enhanced wettability and variable mechanical properties. The ALA/PCL ENs demonstrated higher levels of fibroblast proliferation and adhesion than the other composite ENs. As compared to PCL ENs and other composite scaffolds, the ALA/PCL ENs also promoted a better maturity of the regenerative skin tissues and showed a comparable wound healing effect to Collagen spongeⓇ on third-degree burn model. The enhanced wound healing activity of ALA/PCL ENs compared to other ENs could be attributed to their ability to promote serotonin production at wound sites. Collectively, this investigation demonstrated that ALA is a unique protein with a greater potential for burn wound healing as compared to other regenerative proteins when loaded in the nanofibrous scaffolds.

The effect of mesenchymal stem cell-conditioned medium gel on burn wound healing in rat.

Background and Aim: Stem cells are cells that can proliferate to form a new tissue, leading to its use in regenerative therapy. Stem cells will secrete biological factors, such as growth factors, cytokines, and other proteins to their surroundings and culture medium/conditioned medium (CM), altering tissue physiology. These factors can help wound healing, but their effect on third-degree burns is poorly understood. This research aimed to study the activity of mesenchymal stem cell-conditioned medium gel in healing and repairing third-degree burns on rats skin. Materials and Methods: Twenty-four Sprague-Dawley rats with burn wounds on the dorsal area were divided into four groups; the first group was treated with CM gel, with a concentration equivalent to 0.05% protein, the second group was treated with a placebo gel, the third group with silver sulfadiazine (SSD) cream (SSD-Burnazin contain 10 mg/g SSD), and the fourth group was not given any treatment, for 21 days, and on the final day, the rats were sacrificed, and the skins were taken. All topical treatments completely cover the wound area. Results: Wound healing process indicators observed include wound diameter, scabs' formation, blister formation, and hair growth every day. The skins taken were processed with hematoxylin-eosin and Masson's trichrome staining. The indicators studied include neutrophil infiltration, mononuclear cell infiltration, neovascularization, collagen area, and re-epithelization ratio. Conclusion: CM shows better wound healing than other groups and faster hair growth.

CD14 Involvement in Third-degree Skin Burn-induced Myocardial Injury via the MAPK Signaling Pathway.

This study investigated the potential genes and related pathways in burn-induced myocardial injury. Rat myocardial injury induced by third-degree burn and the histopathological structures, apoptosis, and cardiac injury markers were then identified using hematoxylin & eosin staining, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining, and enzyme-linked immunosorbent assay. Next, differentially expressed mRNAs were screened through next-generation sequencing (NGS), followed by functional annotation and key gene validation through quantitative reverse transcription-polymerase chain reaction. Subsequently, CD14 was screened out, and small interfering RNAs against CD14 were transfected to H9C2 cells to further verify the role of CD14 in burn-induced injury. The results showed that third-degree burn could markedly damage the structure of myocardial tissue, induce the apoptosis of myocardial cells, and increase the levels of myocardial injury-related markers, suggesting that burns could induce myocardial injury in rats. Besides, NGS data discovered that third-degree burn could result in 416 differentially upregulated mRNAs and 285 differentially downregulated mRNAs in myocardial tissue. It was also disclosed that differentially expressed mRNAs were mainly enriched in the phosphatidylinositol 3-kinase/Akt, mitogen-activated protein kinase (MAPK), and tumor necrosis factor signaling pathways. Furthermore, cell viability was significantly decreased in H9C2 cells treated with 10% rat burn serum. CD14 was significantly differentially expressed and screened out for further studies. Treatment with burn serum can significantly upregulate the phosphorylation level of extracellular signal-regulated kinase, p38, and c-Jun N-terminal kinase and the expression of cleaved caspase-3 and downregulate the expression of Bcl2 when compared with those in negative control of small interfering RNA transfected H9C2 cells, whereas interfering with CD14 expression reversed the effects of burn serum. The study demonstrated that burn serum treatment could activate the MAPK signaling pathway to promote cell apoptosis, and it can be reversed by interfering with the expression of CD14.

Measurement of Hansen Solubility Parameters of third-degree burn eschar.

Topical drug therapy is one of the most effective approaches in third-degree burn wound treatments. To optimize and enhance drug permeation through burn eschar, we need to characterize this barrier, most importantly, its affinity to drugs; the subject of this investigation. Hansen Solubility Parameters (HSP), as polarity and affinity scale, were measured here for human third-degree burn eschar through uptake studies using 19 solvents at 25 °C and 32 °C and two hydration levels by gravimetric method combined with thermal analysis and Karl Fischer titration. HSP parameters of dispersion (δD), bipolar (δP), and hydrogen bonding (δH) were calculated by HSPiP software. Results showed δD, δP, and δH of 17.0, 12.5, 14.6 and 16.8, 12.4, 14.4 at 25 and 32 °C respectively for normally-hydrated samples. Full hydration increased HSP values to 17.2, 12.9, 15.3 (25 °C) and 17.1, 12.8, 15.1 (32 °C). Good correlations between solvents uptakes and HSP values were observed for all parameters; higher for δP. Increased temperature decreased them with more changes in δH. Relative Energy Differences (RED) were calculated and shown to be a good parameter for predicting drug-eschar affinity. The obtained information is useful for drug selection and carrier design in drug delivery through burn eschar.

Hyperdry human amniotic membrane application as a wound dressing for a full-thickness skin excision after a third-degree burn injury.

BACKGROUND: Severe burn injuries create large skin defects that render the host susceptible to bacterial infections. Burn wound infection often causes systemic sepsis and severe septicemia, resulting in an increase in the mortality of patients with severe burn injuries. Therefore, appropriate wound care is important to prevent infection and improve patient outcomes. However, it is difficult to heal a third-degree burn injury. The aim of this study was to investigate whether hyperdry human amniotic membrane (HD-AM) could promote early granulation tissue formation after full-thickness skin excision in third-degree burn injury sites in mice. METHODS: After the development of HD-AM and creation of a third-degree burn injury model, the HD-AM was either placed or not placed on the wound area in the HD-AM group or HD-AM group, respectively. The groups were prepared for evaluation on postoperative days 1, 4 and 7. Azan staining was used for granulation tissue evaluation, and estimation of CD163, transforming growth factor beta-1 (TGF-ß1), vascular endothelial growth factor (VEGF), CD31, alpha-smooth muscle actin (α-SMA) and Iba1 expression was performed by immunohistochemical staining. Quantitative reverse-transcription polymerase chain reaction (PCR) was used to investigate gene expression of growth factors, cell migration chemokines and angiogenic and inflammatory markers. RESULTS: The HD-AM group showed significant early and qualitatively good growth of granulation tissue on the full-thickness skin excision site. HD-AM promoted early-phase inflammatory cell infiltration, fibroblast migration and angiogenesis in the granulation tissue. Additionally, the early infiltration of cells of the immune system was observed. CONCLUSIONS: HD-AM may be useful as a new wound dressing material for full-thickness skin excision sites after third-degree burn injuries, and may be a new therapeutic technique for improving the survival rate of patients with severe burn injuries.

A full-thickness chemical burn to the hand using formic acid-based anti-wart treatment: a case report and literature review.

INTRODUCTION: Chemical burns are comparably rare but often result in full-thickness skin defects with frequent involvement of underlying structures. Hands are the most commonly affected injury site and impaired functional outcome is common. We present a case of an unusual chemical burn to the dorsum of the hand of a child secondary to application of a topical anti-wart treatment containing formic acid. CASE REPORT: An 11-year-old girl was referred to our outpatient department with a full-thickness injury resulting from a chemical burn having used a topical formic acid solution in the treatment of common warts. On examination, a 20-mm circular full-thickness defect was noted to the dorsum of the hand. The extensor tendons were not involved and there were no signs of infection. She required surgical debridement and local flap coverage. The postoperative recovery was unremarkable. CONCLUSION: Through a comprehensive literature review, four common topical solutions used in anti-wart treatment were identified to be associated with burns. Together with our case, this highlights the importance of careful patient education in the usage of common topical over-the-counter treatments.

Thymol enriched bacterial cellulose hydrogel as effective material for third degree burn wound repair.

Bacterial cellulose is well known for its excellent contributions in biomedical applications due to its superior properties. However the lack of antimicrobial property restricts its use in wound healing. To address the complications in third degree burns, thymol enriched bacterial cellulose hydrogel (BCT) was developed in this study. The incorporation of thymol into bacterial cellulose along with its chemical and thermal changes were investigated by FTIR, TGA and DSC respectively. Antimicrobial studies revealed that BCT possess excellent biocidal activity against burn specific pathogens. The in vitro biocompatibility studies were carried out in mouse 3T3 fibroblast cells. The BCT hydrogel facilitated the growth of fibroblast cells, exhibiting low toxicity, and increased cell viability. The burn wound healing efficiency of the BCT hydrogel was examined in vivo using female albino Wistar rats. Histopathological studies reveal that the wound treated with BCT hydrogel showed faster wound closure than BC and control groups. All these findings, suggest that BCT hydrogel can be used as resourceful and natural burn wound dressing material.

Single dose eradication of extensively drug resistant Acinetobacter spp. In a mouse model of burn infection by melittin antimicrobial peptide.

Bacterial infections caused by antibiotic resistant bacteria are the leading cause of morbidity and mortality after burn injuries. This issue has driven the need for promising antimicrobial drugs to eradication of bacterial pathogens. Accordingly, we aimed to determine the therapeutic value of melittin, as a natural Antimicrobial peptide (AMP), in eradication of extensively drug-resistant (XDR) Acinetobacter spp. on a mouse model of third degree burn infection. Melittin killed all examined XDR isolates at 4 µg/mL up to 3 h. Melittin caused significant fluorescence release from XDR isolates at the minimum dose of 0.062 µg/mL. Vesicle formation on the membrane and squeezing of bacteria followed by cell lysis indicated the membranolytic effect of melittin. Melittin at 32 µg/mL completely eradicated the colonized XDR bacteria on infected burn mice during 2 h. No toxicity was observed on injured or healthy derma, as well as circulating Red Blood Cells (RBCs) in the examined mice. Potent promising antibacterial activity of melittin and the lack of toxicity at the therapeutic dose can clarify that melittin can be implemented as a topical drug lead in a preclinical trial of third degree burn infections.

Analysis of the effect of subcutaneous injection of omental-derived cells on the healing of third degree burns in rats: a preliminary study.

Burn injury is considered a global health issue. Third degree burn wounds do not heal spontaneously and require skin grafts. Some factors could contribute to wound healing. In this study we assessed the effect of non-fatty omental cells in burn wound healing. Similar third degree burn wounds were induced on the back of 192 rats. Forty-eight of these rats were put in a control group that did not receive any treatment. The rest of the rats were put in 3 groups, each receiving a different treatment regime. Rats in group 2 had a daily application of silver sulfadiazine; group 3 rats were injected with omental cells, and group 4 rats were injected with phosphate buffer saline (PBS) once, followed by daily application of Vaseline to the burned region. Parameters such as open epidermis length, number of epidermal cell layers, granulation tissue thickness (GTT) and neutrophil density were evaluated in each group. The average open epidermis length in the omental cell group was less than in the other groups on days 10 and 20 (P<0.05). The thickness of epidermal cell layers in the group receiving cells was greater than in the other groups on all days. On the 20th day, there was a significant difference in GTT between the four groups (P<0.05). The injection of non-fatty omental cells has a positive effect on third degree burn wounds in rats.

Les brûlures sont un problème de santé publique. Celles du 3ème ne peuvent guérir spontanément et requièrent des greffes cutanées. Certains facteurs pourraient contribuer à la cicatrisation. Nous avons évalué l'effet des cellules épiploïques non adipocytaires sur la cicatrisation des brûlures. Des brûlures similaires, du 3ème degré au niveau du dos ont été infligées à 192 rats. Quatre vingt huit d'entre eux, contrôles (groupe 1), n'ont reçu aucun traitement. Les autres ont été répartis en 3 groupes recevant chacun un type de traitement. Le groupe 2 a reçu chaque jour une application de sulfadiazine argentique ; le groupe 3 a reçu une injection de cellules épiploïques ; le groupe 4 une injection de sérum salé suivis d'application journalière de vaseline. La longueur non épidermisée, le nombre de couches de cellules épidermiques, l'épaisseur du tissu de granulation et la densité de neutrophiles ont été évalués. La longueur non épidermisée à J10 et J20 était plus courte dans le groupe 3 (p<0,05). L'épaisseur des couches épidermiques était constamment supérieure dans ce groupe. À J20, les différences d'épaisseur du tissu de granulation étaient significatives entre tous les groupes. L'injection de cellules épiploïques non adipocytaires a un effet favorable sur l'évolution de brûlures du 3ème degré chez le rat.

Functional Reconstruction of Severely Burned Hand With Osseous Blood Flow Deficiency With Immediate Surgery Using an Abdominal Bipediceled Flap: A Case Report.

Objective: When hands suffer burns, the tendons and digital bones are rarely injured because of the quick withdrawal reflex away from the heat source. Hence, a consensus of opinion regarding the treatment of severe hand burns with osseous blood flow deficiency has not been reached among clinicians. Methods: The patient was a 28-year-old woman whose fingers were accidentally soaked in heated cooking oil (160°C-170°C) for approximately 1 minute. The result was fourth-degree (extending to the tendon) digital burns of the distal end of the proximal interphalangeal joint with blood flow deficiency to the skin, tendon, and bone. Results: We performed immediate reconstructive surgery using an abdominal bipediceled flap. Two weeks later, after the flap was separated, all fingers showed complete range of motion, restoration of the metacarpophalangeal joint, and a high range (0°-75°) of proximal interphalangeal joint mobility with an acceptable digital length. Conclusions: Our experience shows that immediate surgery is highly preferable for deep burns of the hand to avoid delayed intractable complications and to achieve better and faster results.

The Adipofascial V-Y Advancement Flap with Skin Graft for Coverage of the Full-Thickness Burns of the Gluteal Region

Any types of burn injury that involve more than deep dermis often require reconstructive treatment. In gluteal region, V-Y fasciocutaneous advancement flap is frequently used to cover the defect. However, in case of large burn wounds, this kind of flap cannot provide adequate coverage because of the lack of normal surrounding tissues. We suggest V-Y adipofascial flap using the surrounding superficially damaged tissue. We present the case of a patient who was referred for full-thickness burn on gluteal region. We performed serial debridement and applied vacuum-assisted closure device to defective area as wound preparation for coverage. When healthy granulation tissue grew adequately, we covered the defect with surrounding V-Y adipofascial flap and the raw surface of the flap was then covered with split-thickness skin graft. We think the use of subcutaneous fat as an adipofascial flap to cover the deeper defect adjacent to the flap is an excellent alternative especially in huge defect with uneven depth varying from subcutaneous fat to bone exposure in terms of minimal donor site morbidity and reliability of the flap. Even if the flap was not intact, it was reuse of the adjacent tissue of the injured area, so it is relatively safe and applicable.