Citrus pectin protects mice from burn injury by modulating intestinal microbiota, GLP-1 secretion and immune response.

Water-soluble rhamnogalacturonan-I enriched citrus pectin (WRP) has promising effect on antimicrobial defense. We aim to determine whether the modified acidic (A) or neutral (B) WRP solutions can improve intestinal microbial dysbiosis in burn-injured mice. Male Balb/c mice were gavaged with WRPs at 80, 160, 320 mg/kg. Body weight daily for 21 days before exposed to thermal injury of 15 % total body surface area and mortality was monitored. Mice with 80 mg/kg WRPs were also subjected to fecal DNAs and T cell metabonomics analysis, intestinal and plasma glucagon-like peptide 1 (GLP-1) detection, plasma defensin, immunoglobin and intestinal barrier examinations at 1 and 3d postburn (p.b.). Burn-induced mortality was only improved by low dose WRP-A (P = 0.039). Both WRPs could prevent the dysbiosis of gut microbiota in burn injury by reducing the expansion of inflammation-promoting bacteria. Both WRPs suppressed ileum GLP-1 production at 1d p.b. (P = 0.002) and plasma GLP-1 levels at 3d p.b. (P = 0.013). Plasma GLP-1 level correlated closely with ileum GLP-1 production (P = 0.019) but negatively with microbiota diversity at 1d p.b. (P = 0.003). Intestinal T cell number was increased by both WRPs in jejunum at 3d p.b. However, the exaggerated splenic T cell metabolism in burn injury was reversed by both WRPs at 1d p.b. The burn-increased plasma defensin ß1 level was only reduced by WRP-B. Similarly, the intestinal barrier permeability was only rescued by WRP-B at 1d p.b. WRP-A rather than WRP-B could reduce burn-induced mortality in mice by suppressing intestinal GLP-1 secretion, restoring gut microbiota dysbiosis and improving adaptive immune response.

Dietary supplementation with inulin improves burn-induced skeletal muscle atrophy by regulating gut microbiota disorders.

Inulin, as a prebiotic, could modulate the gut microbiota. Burn injury leads to gut microbiota disorders and skeletal muscle catabolism. Therefore, whether inulin can improve burn-induced muscle atrophy by regulating microbiota disorders remains unknown. This study aimed to clarify that inulin intake alleviates gut microbiota disorders and skeletal muscle atrophy in burned rats. Rats were divided into the sham group, burn group, prebiotic inulin intervention group, and pseudo-aseptic validation group. A 30% total body surface area (TBSA) third-degree burn wound on dorsal skin was evaluated in all groups except the sham group. Animals in the intervention group received 7 g/L inulin. Animals in the validation group received antibiotic cocktail and inulin treatment. In our study inulin intervention could significantly alleviate the burn-induced skeletal muscle mass decrease and skeletal myoblast cell apoptosis. Inulin intake increased the abundances of Firmicutes and Actinobacteria but decreased the abundance of Proteobacteria. The biosynthesis of amino acids was the most meaningful metabolic pathway distinguishing the inulin intervention group from the burn group, and further mechanistic studies have shown that inulin can promote the phosphorylation of the myogenesis-related proteins PI3K, AKT and P70S6K and activate PI3K/AKT signaling for protein synthesis. In conclusion, inulin alleviated burn induced muscle atrophy through PI3K/AKT signaling and regulated gut microbiota dysbiosis.

Glutamine alleviates intestinal injury in a murine burn sepsis model by maintaining intestinal intraepithelial lymphocyte homeostasis.

Intestinal intraepithelial lymphocytes (IELs) play a sentinel role in the mucosal immune system because of their unique anatomical location in the epithelial layer. The disruption of IEL homeostasis is implicated in driving the intestinal injury of many typical inflammatory disorders, such as inflammatory bowel disease (IBD) and sepsis. Therefore, it is meaningful to alleviate intestinal injury by restoring IEL homeostasis in disease conditions. This study explores the effects of glutamine on intestinal IEL homeostasis in a murine model of burn sepsis. We report that glutamine inhibits inflammatory response and reduces injury in the small intestine of burn septic mice. This effect is attributed to the maintaining of IEL homeostasis by suppressing apoptosis and restoring the disrupted subpopulation balance induced by burn sepsis. Mechanistically, we show that glutamine does not affect the IL-15 dependent mechanisms that drive the maintenance and differentiation of IELs. Instead, glutamine sustains IEL homeostasis by upregulate aryl hydrocarbon receptor (AHR) and interleukin (IL)-22 transcription and expression. Consistently, the protective roles of glutamine in burn septic mice were repressed by further supplement with an AHR antagonist CH-223191. Collectively, our study reveals a new role of glutamine to maintain IEL homeostasis by activating the AHR signaling pathway, which in turn ameliorates intestinal injury in burn sepsis.

Overexpression of TRPM7 promotes the therapeutic effect of curcumin in wound healing through the STAT3/SMAD3 signaling pathway in human fibroblasts.

OBJECTIVE: Curcumin, a natural extract from the rhizomes of Curcuma longa, is also known as a curcuminoid. Curcumin has been studied as a therapeutic drug for wound healing because of its anti-inflammatory, anti-oxidant, and anti-bacterial activities. However, the detailed mechanism of curcumin in wound healing is not clear. It is well-known that the skin is the largest organ in humans and prevents tissues from damage, including infection, radiation, and mechanical damage. Wound healing of the skin is a complex physiological regulation process requiring various cell types and cytokines; hence, wound healing, including surgery and care, incurs a huge expenditure each year. Transient receptor potential cation channel subfamily M member 7 (TRPM7) regulates multiple physiological and pharmacological processes through its channel and kinase activities. In addition, TRPM7 regulates cell adhesion, migration, and anti-oxidative activity, thereby playing a regulatory role in the wound healing process. This study aimed to explore the function of curcumin in the wound healing process. METHODS: We first established TRPM7 overexpression and knockdown models in fibroblasts using lentivirus. CCK-8 and wound healing assays were used to clarify whether overexpression of TRPM7 promoted proliferation and migration in fibroblasts. Expression of target genes and proteins was detected using qPCR and western blotting. Concentrations of migration-related cytokines were measured using ELISA. RESULTS: Proliferation and migration of fibroblasts increased after curcumin treatment and was further enhanced after overexpression of TRPM7. In addition, expression of proliferation-related genes and proteins was elevated after TRPM7 overexpression. Further, the secretion of migration-related cytokines was elevated after TRPM7 overexpression. CONCLUSION: Curcumin treatment promoted proliferation and migration of fibroblasts, and these effects were mediated by the signal transducer and activator of transcription 3 (STAT3)/SMAD family member 3/hypoxia-inducible factor 1 subunit alpha signaling pathway. Thus, we conclude that overexpression of TRPM7 might contribute to wound healing.

A multifunctional black phosphorus-based adhesive patch intrinsically induces partial EMT for effective burn wound healing.

The ultimate goal of cutaneous wound healing is to reform a stratified epithelium to restore the normal epidermal barrier, which involves the epithelial-to-mesenchymal transition (EMT) process. However, healing strategies based on EMT induction are immature and ambiguous to date. Excessive induction of EMT may cause fibrosis, hypertrophic scarring, and increased risk of malignancy. Here, we present a new EMT-inducing strategy for eliciting partial EMT to facilitate proper epithelial cell migration. The new EMT-inducing system integrates black phosphorus nanosheets (BPNSs), catechol-modified chitosan (CA-CS), and oxidized dextran (Odex) to engineer an adhesive hydrogel patch (C&BP-Patch) with remarkable efficacy on infectious burn wound healing. The C&BP-Patch can orchestrate key early skin wound healing processes including hemostasis, inflammation, and proliferation, which enable fast partial EMT induction to restore an intact epithelial barrier. The C&BP-Patch acts initially as a high-performance bio-sealant to create a moist and stable microenvironment for EMT. Moreover, the photothermal effects of the C&BP-Patch can eliminate bacteria, accelerate microcirculation and reduce inflammation to maintain a proper EMT. Most importantly, the BPNSs can intrinsically induce partial EMT of epithelial cells via a Snail1-mediated signaling pathway. Therefore, our study proposes a new strategy for effective infectious burn wound healing based on inducing partial EMT.

Glutamine relieves the hypermetabolic response and reduces organ damage in severe burn patients: A multicenter, randomized controlled clinical trial.

BACKGROUND: Severe burns can cause a hypermetabolic response and organ damage. Glutamine is a conditionally essential amino acid with various pharmacological effects. In this study, whether glutamine could alleviate the hypermetabolic response and maintain organ function after burn injury was analyzed. METHODS: A multicenter, randomized, single-blind, parallel controlled trial was conducted to evaluate the efficacy of glutamine in decreasing hypermetabolism after burn injury. Physiological and biochemical indexes, such as vital signs, metabolic hormones, metabolic rate, and organ damage, were recorded on the 7th and 14th days after treatment. RESULTS: In total, 55 adult burn patients with a total burn surface area (TBSA) of 30-70% were included in this study and randomly divided into the burn control (B, 28 patients) and burn+glutamine (B+G, 27 patients) groups. Except for the glutamine administration, the groups did not differ in the other treatments and nutrition supplements. The levels of diamine oxidase (DAO), lactulose/mannitol (L/M), ß2-microglobulin, lactate dehydrogenase (LDH), hydroxybutyrate dehydrogenase (HBD) and cardiac troponin l (cTnl) in the B+G group were significantly lower than those in the B group (p < 0.05 or 0.01). The levels of resting energy expenditure (REE), serum catecholamines, glucagon, lactate and Homeostasis model assessment (HOMA) in the B+G group were significantly lower than those in the B group (p < 0.05 or 0.01). No significant difference was found in the length of hospitalization or the mortality rate between the two groups (p > 0.05). CONCLUSIONS: Glutamine moderately alleviates the hypermetabolic response and reduces organ damage after severe burns. Therefore, the early application of glutamine, which is effective and safe, should be used as an active intervention as early as possible.

Tea polyphenol modified, photothermal responsive and ROS generative black phosphorus quantum dots as nanoplatforms for promoting MRSA infected wounds healing in diabetic rats.

BACKGROUND: Healing of MRSA (methicillin-resistant Staphylococcus aureus) infected deep burn wounds (MIDBW) in diabetic patients remains an obstacle but is a cutting-edge research problem in clinical science. Surgical debridement and continuous antibiotic use remain the primary clinical treatment for MIDBW. However, suboptimal pharmacokinetics and high doses of antibiotics often cause serious side effects such as fatal complications of drug-resistant bacterial infections. MRSA, which causes wound infection, is currently a bacterium of concern in diabetic wound healing. In more severe cases, it can even lead to amputation of the patient's limb. The development of bioactive nanomaterials that can promote infected wound healing is significant. RESULTS: The present work proposed a strategy of using EGCG (Epigallocatechin gallate) modified black phosphorus quantum dots (BPQDs) as therapeutic nanoplatforms for MIDBW to achieve the synergistic functions of NIR (near-infrared)-response, ROS-generation, sterilization, and promoting wound healing. The electron spin resonance results revealed that EGCG-BPQDs@H had a more vital photocatalytic ability to produce singlet oxygen than BPQDs@H. The inhibition results indicated an effective bactericidal rate of 88.6% against MRSA. Molecular biology analysis demonstrated that EGCG-BPQDs significantly upregulated CD31 nearly fourfold and basic fibroblast growth factor (bFGF) nearly twofold, which were beneficial for promoting the proliferation of vascular endothelial cells and skin epidermal cells. Under NIR irradiation, EGCG-BPQDs hydrogel (EGCG-BPQDs@H) treated MIDBW area could rapidly raise temperature up to 55 °C for sterilization. The MIBDW closure rate of rats after 21 days of treatment was 92.4%, much better than that of 61.1% of the control group. The engineered EGCG-BPQDs@H were found to promote MIDBW healing by triggering the PI3K/AKT and ERK1/2 signaling pathways, which could enhance cell proliferation and differentiation. In addition, intravenous circulation experiment showed good biocompatibility of EGCG-BPQDs@H. No significant damage to major organs was observed in rats. CONCLUSIONS: The obtained results demonstrated that EGCG-BPQDs@H achieved the synergistic functions of photocatalytic property, photothermal effects and promoted wound healing, and are promising multifunctional nanoplatforms for MIDBW healing in diabetics.

Lipid mediator profiles of burn wound healing: Acellular cod fish skin grafts promote the formation of EPA and DHA derived lipid mediators following seven days of treatment.

The use of acellular fish skin grafts (FSG) for the treatment of burn wounds is becoming more common due to its beneficial wound healing properties. In our previous study we demonstarted that FSG is a scaffold biomaterial that is rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) conjugated to phosphatidylcholines. Here we investigated whether EPA and DHA derived lipid mediators are influenced during the healing of burn wounds treated with FSG. Deep partial and full thickness burn wounds (DPT and FT, respectively) were created on Yorkshire pigs (n = 4). DPT were treated with either FSG or fetal bovine dermis while FT were treated either with FSG or cadaver skin initially and followed by a split thickness skin graft. Punch biopsies were collected on days 7, 14, 21, 28 and 60 and analyzed in respect of changes to approximately 45 derivatives of EPA, DHA, arachidonic acid (AA), and linoleic acid (LA) employing UPLC-MS/MS methodology. Nine EPA and DHA lipid mediators, principally mono-hydroxylated derivatives such as 18-HEPE and 17-HDHA, were significantly higher on day 7 in the DPT when treated with FSG. A similar but non-significant trend was observed for the FT. The results suggest that the use of FSG in burn wound treatment can alter the formation of EPA and DHA mono hydroxylated lipid mediators in comparison to other grafts of mammalian origin. The differences observed during the first seven days after treatment indicates that FSG affects the early stages of wound healing.

Accelerated burn wound healing with photobiomodulation therapy involves activation of endogenous latent TGF-ß1.

The severity of tissue injury in burn wounds from associated inflammatory and immune sequelae presents a significant clinical management challenge. Among various biophysical wound management approaches, low dose biophotonics treatments, termed Photobiomodulation (PBM) therapy, has gained recent attention. One of the PBM molecular mechanisms of PBM treatments involves photoactivation of latent TGF-ß1 that is capable of promoting tissue healing and regeneration. This work examined the efficacy of PBM treatments in a full-thickness burn wound healing in C57BL/6 mice. We first optimized the PBM protocol by monitoring tissue surface temperature and histology. We noted this dynamic irradiance surface temperature-monitored PBM protocol improved burn wound healing in mice with elevated TGF-ß signaling (phospho-Smad2) and reduced inflammation-associated gene expression. Next, we investigated the roles of individual cell types involved in burn wound healing following PBM treatments and noted discrete effects on epithelieum, fibroblasts, and macrophage functions. These responses appear to be mediated via both TGF-ß dependent and independent signaling pathways. Finally, to investigate specific contributions of TGF-ß1 signaling in these PBM-burn wound healing, we utilized a chimeric TGF-ß1/ß3 knock-in (TGF-ß1Lß3/Lß3) mice. PBM treatments failed to activate the chimeric TGF-ß1Lß3/Lß3 complex and failed to improve burn wound healing in these mice. These results suggest activation of endogenous latent TGF-ß1 following PBM treatments plays a key role in burn wound healing. These mechanistic insights can improve the safety and efficacy of clinical translation of PBM treatments for tissue healing and regeneration.

Astaxanthin protects against early acute kidney injury in severely burned rats by inactivating the TLR4/MyD88/NF-κB axis and upregulating heme oxygenase-1.

Early acute kidney injury (AKI) contributes to severe morbidity and mortality in critically burned patients. Renal inflammation plays a vital role in the progression of early AKI, acting as a therapeutic target. Astaxanthin (ATX) is a strong antioxidant widely distributed in marine organisms that exerts many biological effects in trauma and disease. ATX is also suggested to have anti-inflammatory activity. Hence, we attempted to explore the role of ATX in protecting against early postburn AKI via its anti-inflammatory effects and the related mechanisms. A severely burned model was established for histological and biochemical assessments based on adult male rats. We found that oxidative stress-induced tissue inflammation participated in the development of early AKI after burn injury and that the MyD88-dependent TLR4/NF-κB pathway was activated to regulate renal inflammation. The TLR4 and NF-κB inhibitors TAK242 and PDTC showed similar effects in attenuating burn-induced renal inflammation and early AKI. Upon ATX treatment, the release of inflammatory mediators in the kidneys was downregulated, while the TLR4/MyD88/NF-κB axis was inhibited in a dose-related manner. TAK242 and PDTC could enhance the anti-inflammatory effect of high-dose ATX, whereas lipopolysaccharide (LPS) reversed its action. Furthermore, the expression of heme oxygenase (HO)-1 was upregulated by ATX in a dose-related manner. Collectively, the above data suggest that ATX protects against renal inflammation in a dose-related manner by regulating the TLR4/MyD88/NF-κB axis and HO-1 and ultimately prevents early AKI following severe burns.

Wound-healing activity of glycoproteins from white jade snail (Achatina fulica) on experimentally burned mice.

Burns are a global public health problem and the treatment of burn wounds is a major medical and economic issue. White jade snails (Achatina fulica) are now widely distributed in Asia, and they have been used to treat burns in folk medicine of China. In this study, the glycoproteins from white jade snails were investigated and their effect on burn healing was evaluated by a mouse burn model. The results showed that the snail mucus was mainly composed of proteins and polysaccharides, and it had good adhesion. The main component of snail mucus was glycoprotein from the results of DEAE Sepharose FF ion exchange chromatography. The 2,2-Diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging effect of 1 mg/mL snail mucus reached 13.77%. The wound healing rate of the snail mucus group was higher than that of the control group (p < 0.0001). Histopathological results showed that mice in the snail mucus group had a faster healing than that of the control group. The biochemical analysis was in agreement with the histopathological findings. These results suggested that glycoproteins from snail mucus showed effective wound healing activities in the skin of experimentally burned mice.

Omega-7 oil increases telomerase activity and accelerates healing of grafted burn and donor site wounds.

This study investigated the efficacy of Omega-7 isolated from the sea buckthorn oil (Polyvit Co., Ltd, Gangar Holding, Ulaanbaatar, Mongolia) in ovine burn wound healing models. In vitro, proliferation (colony-forming rate) and migration (scratch) assays using cultured primary ovine keratinocytes were performed with or without 0.025% and 0.08% Omega-7, respectively. The colony-forming rate of keratinocytes in the Omega-7 group at 72 and 96 h were significantly higher than in the control (P < 0.05). The percentage of closure in scratch assay in the Omega-7 group was significantly higher than in the control at 17 h (P < 0.05). In vivo, efficacy of 4% Omega-7 isolated from buckthorn oil was assessed at 7 and 14 days in grafted ovine burn and donor site wounds. Telomerase activity, keratinocyte growth factor, and wound nitrotyrosine levels were measured at day 14. Grafted sites: Un-epithelialized raw surface area was significantly lower and blood flow was significantly higher in the Omega-7-treated sites than in control sites at 7 and 14 days (P < 0.05). Telomerase activity and levels of keratinocyte growth factors were significantly higher in the Omega-7-treated sites after 14 days compared to those of control (P < 0.05). The wound 3-nitrotyrosine levels were significantly reduced by Omega-7. Donor sites: the complete epithelialization time was significantly shorter and blood flow at day 7 was significantly higher in the Omega-7-treated sites compared to control sites (P < 0.05). In summary, topical application of Omega-7 accelerates healing of both grafted burn and donor site wounds. Omega-7 should be considered as a cost-efficient and effective supplement therapy for burn wound healing.

Effects of Carnosine, Ankaferd, and Silver Sulfadiazine on an Experimental Burn Model: Roles of Irisin and HSP70.

In this study, the effects of carnosine, ankaferd, and 1% silver sulfadiazine applied topically on second-degree burns were investigated and the roles of irisin and Heat shock protein 70 (HSP70) in this healing process were evaluated. Ninety male albino rats were used and divided into five groups. The groups were classified as control, burn, burn + carnosine (CAR), burn + ankaferd (ABS), and burn + silver sulfadiazine (SS). It was found that level of irisin increased in the first week and decreased in the second week in the burn and CAR groups. In the ABS and SS groups, the level of irisin was determined that started to increase in the first week and continued to increase in the second week. The level of HSP70 was found to increased in the first week in burn and CAR groups and decreased in the second week, but started to increase in the second week in ABS and SS groups. Both levels of irisin and HSP70 were observed to decreased in all treatment groups in the third week. In this study, it was shown that ankaferd and silver sülfadiazine treatments cause an increase in the irisin levels in the early period and a gradually increase in HSP70 levels in the later period in burns. The inflammatory response was observed to be limited in the early period in the ankaferd and sulfadiazin groups. It was concluded that these findings were effective in early wound healing in burns.

Repair function of essential oil from Crocodylus Siamensis (Schneider, 1801) on the burn wound healing via up-regulated growth factor expression and anti-inflammatory effect.

ETHNOPHARMACOLOGICAL RELEVANCE: Crocodile oil has been used by traditional physicians around the world to treat wound healing and inflammation. However, the scientific rationale and mechanism behind its use in vivo has not been fully researched. AIMS OF THE STUDY: We mainly investigated the mechanism during crocodile oil treatment of up-regulated growth factor expression and anti-inflammatory on burn wound healing in rats. MATERIALS AND METHODS: The moisture and nitric oxide (NO) levels in the skin of rats were analyzed in the first 14 days after burn and the changes of the structure of the skin tissues in the wound healing were studied by hematoxylin-eosin (H.E.) staining within 21 days after scald. The inflammatory factor on burn wound healing in rats was dected by ELISA kits and Q-PCR. the expression of a variety of growth factors (TGF-ß1, VEGE-α, EGF) and PCNA in the skin tissue after burns was evaluated using immunohistochemistry. The down-regulated phosphorylation of p38 MAPK in the wound healing was confirmed by Western-blot analysis. In addition, TEM was used to observe the ultrastructure of scalded skin. RESULTS: This study showed that crocodile oil could significantly reduce the protein and mRNA levels of TNF-α, IL-1ß and IL-6. And it was found that the phosphorylation of p38 MAPK was down-regulated in the wound healing (p < 0.05). Meanwhile, crocodile oil can promote the expression of a variety of growth factors (TGF-ß1, VEGE-α, EGF) and PCNA in the skin tissue after burns, and promote the repair of collagen fibers in the dermis, preventing the production of melanin and maintain the appearance of repaired skin.

Bioelements in the treatment of burn injuries - The complex review of metabolism and supplementation (copper, selenium, zinc, iron, manganese, chromium and magnesium).

Appropriate nutrition is a key component of burn treatment and should be regarded as an integral part of the therapeutic process in burn patients. A nutritional intervention plan should not only allow for adequate quantities of energy and protein but also carefully consider the supply of macro- and micronutrients. As a result of the severe inflammatory response, oxidative stress, and hypermetabolic state, accompanied by often extensive exudation in burn patients, there is a considerable loss of macro- and micronutrients, including essential trace elements. This leads to certain complications, involving e.g. more frequent infections and impaired wound healing. Our current body of knowledge is still insufficient, and the studies carried out to date focus for the most part on the imbalances in trace elements, such as copper (Cu), selenium (Se), and zinc (Zn). Nevertheless, there are many other trace elements involved in immune functions, regulating gene expression or antioxidant defense, and many of those have not been properly investigated in a clinical setting. Due to the insufficient amount of unambiguous literature data and relatively few, often dated, studies carried out with small patient groups, further evaluation of macro- and microelements in burn patients seems indispensable, e.g. to bring up to date local nutritional protocols.

Burns: modified metabolism and the nuances of nutrition therapy.

OBJECTIVE: To review the effects of burn injury on nutritional requirements and how this can best be supported in a healthcare setting. METHOD: A literature search for articles discussing nutrition and/or metabolism following burn injury was carried out. PubMed, Embase and Web of Science databases were searched using the key search terms 'nutrition' OR 'metabolism' AND 'burn injury' OR 'burns'. There was no limitation on the year of publication. RESULTS: A total of nine articles met the inclusion criteria, the contents of which are discussed in this manuscript. CONCLUSION: Thermal injury elicits the greatest metabolic response, among all traumatic events, in critically ill patients. In order to ensure burn patients can meet the demands of their increased metabolic rate and energy expenditure, adequate nutritional support is essential. Burn injury results in a unique pathophysiology, involving alterations in endocrine, inflammatory, metabolic and immune pathways and nutritional support needed during the inpatient stay varies depending on burn severity and idiosyncratic patient physiologic parameters.

Mechanosensitive Aspects of Cell Biology in Manual Scar Therapy for Deep Dermal Defects.

Deep dermal defects can result from burns, necrotizing fasciitis and severe soft tissue trauma. Physiological scar restriction during wound healing becomes increasingly relevant in proportion to the affected area. This massively restricts the general mobility of patients. External mechanical influences (activity or immobilization in everyday life) can lead to the formation of marked scar strands and adhesions. Overloading results in a renewed inflammatory reaction and thus in further restriction. Appropriate mechanical stimuli can have a positive influence on the scar tissue. "Use determines function," and even minimal external forces are sufficient to cause functional alignment (mechanotransduction). The first and second remarkable increases in connective tissue resistance (R1 and R2) seem to be relevant clinical indications of adequate dosage in the proliferation and remodulation phase, making it possible to counteract potential overdosage in deep dermal defects. The current state of research does not allow a direct transfer to the clinical treatment of large scars. However, the continuous clinical implementation of study results with regard to the mechanosensitivity of isolated fibroblasts, and the constant adaptation of manual techniques, has nevertheless created an evidence-base for manual scar therapy. The manual dosages are adapted to tissue physiology and to respective wound healing phases. Clinical observations show improved mobility of the affected regions and fewer relapses into the inflammatory phase due to mechanical overload.

Effect of photobiomodulation associated with cell therapy in the process of cutaneous regeneration in third degree burns in rats.

Due to the complexity involved in the healing process of full thickness burns, the literature looks for alternatives to optimize tissue reconstruction. The objective of this study was to explore the action of photobiomodulation therapy associated with MSCs in the healing process of third degree burns. A total of 96 male Wistar rats were used, distributed in four groups with 24 animals each: Control Group, Laser Group, Cell Therapy Group, and Laser Group and Cell Therapy. The burn was performed with aluminum plate (150 °C). We performed analysis of wound contraction, histology, immunohistochemistry, birefringence analysis, and immunoenzymatic assay to evaluate tissue quality. Our results demonstrate that the association of the techniques is able to accelerate the repair process, modulating the inflammatory process, presenting a cutaneous tissue with better quality. Thus, we conclude that the use of photobiomodulation therapy associated with cell therapy is a promising treatment in the repair of total thickness burns.

The effect of a hydrolyzed collagen-based supplement on wound healing in patients with burn: A randomized double-blind pilot clinical trial.

INTRODUCTION: Burn is among the most severe forms of critical illness, associated with extensive and prolonged physical, metabolic and mental disorders. The aim of this study was to assess the effect of an oral, low-cost, and accessible collagen-based supplement on wound healing in patients with burn. METHODS: In this randomized double-blind controlled pilot clinical trial, 31 men, 18-60years, with 20-30% total body surface area burn were studied. Patients were randomly assigned to receive either a collagen-based supplement (1000kcal) or an isocaloric placebo, for 4 weeks. Serum pre-albumin, rate of wound healing, length of hospital stay, and anthropometries were assessed at baseline, and the end of week 2 and 4. RESULTS: Serum pre-albumin was significantly higher at week 2 (29.7±13.6 vs. 17.8±7.5mg/dL, P=0.006) and week 4 (35.1±7.6 vs. 28.3±8.2mg/dL, P=0.023) in collagen than control group. Changes in pre-albumin concentration were also significantly higher in collagen group at week 2 (13.9±9.8 vs. -1.9±10.3mg/dL, P<0.001) and week 4 (19.2±7.5 vs. 8.5±10.1mg/dL, P=0.002). The Hazard ratio of wound healing was 3.7 times in collagen compared to control group (95% CI: 1.434-9.519, P=0.007). Hospital stay was clinically, but not statistically, lower in collagen than control group (9.4±4.6 vs. 13.5±7 days, P=0.063). There were no significant differences in weight, body mass index, dietary energy and protein intakes between the two groups. CONCLUSION: The findings showed that a hydrolyzed collagen-based supplement could significantly improve wound healing and circulating pre-albumin, and clinically reduce hospital stay in patients with 20-30% burn.