Dermal Wound Research Articles

Hancornia speciosa serum latex fraction: a non-allergenic biomaterial.

Plant-derived products can assist in the healing process of dermal wounds. It has been demonstrated that Hancornia speciosa latex present angiogenic, osteogenic, anti-inflammatory, and antioxidant activities. Then, it could contribute to the wound healing process. However, natural products in contact with skin may cause dermatitis. The objective of this work was to evaluate the allergic and irritant potential of H. speciosa serum fraction latex using in vitro assays. The obtained results showed that the H. speciosa serum fraction latex has a slightly irritant potential and is not cytotoxic neither allergenic for human cells. Moreover, we identified a remarkable low amount of proteins in this material in comparison to Hevea brasiliensis latex. This result could explain the non-allergenic potential of H. speciosa serum fraction latex because proteins present in latex are the main responsible for allergy. This biomaterial could be used as a non-allergenic source for development of new medicines.

Withania somnifera-derived carbon dots protect human epidermal cells against UVB-induced cell death and support growth factor-mediated wound healing.

Solar radiation comprising UVA and UVB regions is considered a skin-damaging factor inducing inflammation, oxidative stress, hyperpigmentation, and photo-aging. Photoluminescent carbon dots (CDs) were synthesized from the root extract of a Withania somnifera (L.) Dunal plant and urea, using a one-step microwave method. These Withania somnifera CDs (wsCDs) were 14.4 ± 0.18 d nm in diameter and presented photoluminescence. UV absorbance showed the presence of π-π* (C[double bond, length as m-dash]C) and n-π* (C[double bond, length as m-dash]O) transition regions in wsCDs. FTIR analysis indicated the presence of nitrogen and carboxylic functional groups on the surface of wsCDs. HPLC analysis of wsCDs showed the presence of withanoside IV, withanoside V, and withanolide A. The wsCDs were found to be biocompatible in human skin epidermal (A431) cells and hindered UVB irradiation-induced loss of metabolic activity and oxidative stress. The wsCDs supported rapid dermal wound healing through augmented TGF-β1 and EGF gene expression levels in A431 cells. Finally, wsCDs were found to be biodegradable through a myeloperoxidase-catalyzed peroxidation reaction. The study concluded that under in vitro conditions, Withania somnifera root extract-derived biocompatible carbon dots provided photo-protection against UVB-stimulated epidermal cell damage and supported rapid wound healing.

S-Nitrosylation-mediated coupling of DJ-1 with PTEN induces PI3K/AKT/mTOR pathway-dependent keloid formation.

Keloids are aberrant dermal wound healing characterized by invasive growth, extracellular matrix deposition, cytokine overexpression and easy recurrence. Many factors have been implicated as pathological causes of keloids, particularly hyperactive inflammation, tension alignment and genetic predisposition. S-Nitrosylation (SNO), a unique form of protein modification, is associated with the local inflammatory response but its function in excessive fibrosis and keloid formation remains unknown. We aimed to discover the association between protein SNO and keloid formation. Normal and keloid fibroblasts were isolated from collected normal skin and keloid tissues. The obtained fibroblasts were cultured in DMEM supplemented with 10% fetal bovine serum and 1% penicillin/streptomycin. The effects of DJ-1 on cell proliferation, apoptosis, migration and invasion, and on the expression of proteins were assayed. TurboID-based proximity labelling and liquid chromatography-mass spectrometry were conducted to explore the potential targets of DJ-1. Biotin-switch assays and transnitrosylation reactions were used to detect protein SNO. Quantitative data were compared by two-tailed Student's t test. We found that DJ-1 served as an essential positive modulator to facilitate keloid cell proliferation, migration and invasion. A higher S-nitrosylated DJ-1 (SNO-DJ-1) level was observed in keloids, and the effect of DJ-1 on keloids was dependent on SNO of the Cys106 residue of the DJ-1 protein. SNO-DJ-1 was found to increase the level of phosphatase and tensin homolog (PTEN) S-nitrosylated at its Cys136 residue via transnitrosylation in keloids, thus diminishing the phosphatase activity of PTEN and activating the PI3K/AKT/mTOR pathway. Furthermore, Cys106-mutant DJ-1 is refractory to SNO and abrogates DJ-1-PTEN coupling and the SNO of the PTEN protein, thus repressing the PI3K/AKT/mTOR pathway and alleviating keloid formation. Importantly, the biological effect of DJ-1 in keloids is dependent on the SNO-DJ-1/SNO-PTEN/PI3K/AKT/mTOR axis. For the first time, this study demonstrated the effect of transnitrosylation from DJ-1 to PTEN on promoting keloid formation via the PI3K/AKT/mTOR signaling pathway, suggesting that SNO of DJ-1 may be a novel therapeutic target for keloid treatment.

Knockdown of CPEB1 and CPEB4 Inhibits Scar Formation via Modulation of TAK1 and SMAD Signaling.

Cytoplasmic polyadenylation element binding (CPEB) proteins are sequence-specific RNA-binding proteins that control translation via cytoplasmic polyadenylation. We previously reported that CPEB1 or CPEB4 knockdown suppresses TAK1 and SMAD signaling in an in vitro study. This study aimed to investigate whether suppression of CPEB1 or CPEB4 expression inhibits scar formation in a mice model of acute dermal wound healing. CPEB1 and CPEB4 expression levels were suppressed by siRNA treatment. Skin wounds were created by pressure-induced ulcers in mice. Images of the wound healing were obtained using a digital camera and contraction was measured by ImageJ. mRNA and protein expression was analyzed using quantitative real time polymerase chain reaction and western blotting, respectively. Wound contraction was significantly decreased by pre-treatment with CPEB1 or CPEB4 siRNA compared to the control. Suppression of CPEB1 or CPEB4 expression decreased TAK1 signaling by reducing the levels of TLR4 and TNF-α, phosphorylated TAK1, p38, ERK, JNK, and NF-κB-p65. Decreased levels of phosphorylated SMAD2 and SMAD3 indicated a reduction in SMAD signaling as well. Consequently, the expression of α-SMA, fibronectin, and type I collagen decreased. CPEB1 siRNA or CPEB4 siRNA inhibit scar formation by modulating the TAK1 and SMAD signaling pathways. Our study highlights CPEB1 and CPEB4 as potential therapeutic targets for the treatment of scar formation.

Evaluation of two fungal exopolysaccharides as potential biomaterials for wound healing applications

Microbial exopolysaccharides (EPSs) are mostly produced by bacteria and fungi and have potentialuse in the production of biomedical productssuch asnutraceuticalsandin tissue engineering applications. The present study investigated the in vitro biological activities and in vivo wound healing effects of EPSs produced from a Sclerotium-forming fungus (Sclerotium glucanicum DSM 2159) and a yeast (Rhodosporidium babjevae), denoted as scleroglucan (Scl) and EPS-R, respectively. EPS yields of 0.9 ± 0.07g/L and 1.11 ± 0.4g/L were obtained from S. glucanicum and R. babjevae, respectively. The physicochemical properties of the EPSs were characterized using infrared spectroscopy and scanning electron microscopy. Further investigations of thebiological properties showed thatboth EPSs were cytocompatible toward the human fibroblast cell line and demonstrated hemocompatibility. Favorablewound healing capacities of the EPSs (10mg/mL) were also established via in vivotests.The present study therefore showed that theEPSs produced by S. glucanicum and R. babjevae have the potential useas biocompatible components for the promotion ofdermal wound healing.

Experimental study of the effects of nitroglycerin, botulinum toxin A, and clopidogrel on bipedicled superficial inferior epigastric artery flap survival

Beneficial effects could be achieved by various agents such as nitroglycerin, botulinum toxin A (BoTA), and clopidogrel to improve skin flap ischaemia and venous congestion injuries. Eighty rats were subjected to either arterial ischaemia or venous congestion and applied to a bipedicled U-shaped superficial inferior epigastric artery (SIEA) flap with the administration of nitroglycerin, BoTA, or clopidogrel treatments. After 7 days, all rats were sacrificed for flap evaluation. Necrotic area percentage was significantly minimized in flaps treated with clopidogrel (24.49%) versus the ischemic flaps (34.78%); while nitroglycerin (19.22%) versus flaps with venous congestion (43.26%). With ischemia, light and electron microscopic assessments revealed that nitroglycerin produced degeneration of keratinocytes and disorganization of collagen fibers. At the same time, with clopidogrel administration, there was an improvement in the integrity of these structures. With venous congestion, nitroglycerin and BoTA treatments mitigated the epidermal and dermal injury; and clopidogrel caused coagulative necrosis. There was a significant increase in tissue gene expression and serum levels of vascular endothelial growth factor (VEGF) in ischemic flaps with BoTA and clopidogrel, nitroglycerin, and BoTA clopidogrel in flaps with venous congestion. With the 3 treatment agents, gene expression levels of tumor necrosis factor-α (TNF-α) were up-regulated in the flaps with ischemia and venous congestion. With all treatment modalities, its serum levels were significantly increased in flaps with venous congestion and significantly decreased in ischemic flaps. Our analyses suggest that the best treatment option for ischemic flaps is clopidogrel, while for flaps with venous congestion are nitroglycerin and BoTA.

Phosphorylated chitosan accelerates dermal wound healing in diabetic wistar rats

Phosphorylated chitosan (PC), a water-soluble derivative of chitosan possesses several biological and chemical properties suitable for diabetic wound healing. In the present study, we report the synthesis and diabetic wound healing capabilities of PC. Elemental analysis, FT-IR, 13C-NMR and 31P-NMR techniques were employed for the chemical characterization of PC. In vitro, antioxidant properties of PC were determined in terms of Fe3+ reducing, metal chelating, lipid peroxidation and superoxide scavenging ability. The wound healing potential of PC was assessed in diabetic excisional wound rat model. PC exhibited good water solubility, and in vitro antioxidant capacity. Wound contraction was higher in PC-treated wounds (91.11%) as compared to untreated wounds (67.26%) on 14th-day post wound creation. Histopathology of PC-treated wounds revealed improved tissue morphology with higher number of fibroblasts, a thicker epithelial layer, enhanced collagen deposits and angiogenesis as compared to untreated wounds. An overall increase of 57% and 25% in hydroxylamine and hexosamine content respectively were noted as compared to untreated wounds. A significant (P ≤ 0.05) increase in SOD activity and a significant (P ≤ 0.05) decrease in lipid peroxides were recorded in PC-treated wounds as compared to untreated wounds. These observations demonstrated that PC can be used as an effective agent in diabetic wound healing.Graphical Illustration of phosphorylated chitosan (PC) synthesis and its wound healing potential: Chitosan was phosphorylated to impart diabetic wound healing properties. Chemical characterizations such as elemental analysis, FT-IR and NMR confirmed successful phosphorylation of chitosan. PC exhibited good in vitro antioxidant properties. To assess the diabetic wound healing potential, an excisional wound model was developed in diabetic rats. PC treatment demonstrated accelerated wound healing.

Recombinant Expression of Human IL-33 Protein and Its Effect on Skin Wound Healing in Diabetic Mice.

Chronic refractory wounds are one of the complications of diabetes mellitus that require effective therapy. The dermal-wound-healing property of IL-33 in diabetics is little understood. Therefore, this study aimed to express recombinant humanized mature IL-33 (rhmatIL-33) in Escherichia coli BL21 (DE3) and demonstrate its efficacy on dermal wounds in streptozotocin (STZ)-induced diabetic and nondiabetic mice by the dorsal incisional skin wound model. Results revealed that the rhmatIL-33 accelerated the scratch-healing of keratinocytes and fibroblasts at the cellular level. The wounds of diabetic mice (DM) showed more severe ulceration and inflammation than wild-type mice (WT), and the exogenous administration of rhmatIL-33 increased wound healing in both diabetic and wild-type mice. Compared with the up-regulation of endogenous IL-33 mRNA after injury in WT mice, the IL-33 mRNA decreased after injury in DM mice. Exogenous IL-33 administration increased the endogenous IL-33 mRNA in the DM group but decreased the IL-33 mRNA expression level of the WT group, indicating that IL-33 plays a balancing role in wound healing. IL-33 administration also elevated ILC2 cells in the wounds of diabetic and non-diabetic mice and improve the transcript levels of YM1, a marker of M2 macrophages. In conclusion, Hyperglycemia in diabetic mice inhibited the expression of IL-33 in the dermal wound. Exogenous addition of recombinant IL-33 promoted wound healing in diabetic mice by effectively increasing the level of IL-33 in wound tissue, increasing ILC2 cells, and accelerating the transformation of macrophage M1 to M2 phenotype.

Effect of deep dermal tissue dislocation injury on skin fibrosis in pig

Effect of deep dermal tissue dislocation injury on skin fibrosis in pig

591 Exploring the molecular basis for the dermal fibroblast state switch

The skin dermis evolves from a multipotent pool of fibroblasts, which differentiate into distinct subpopulations creating the different dermal layers and respective architecture. This dermal maturation process is governed by a tight balance of fibroblast proliferation, quiescence and extracellular matrix (ECM) deposition. During wound healing, quiescent fibroblasts restart proliferating, migrate into the wound bed and deposit ECM to regenerate the skin. Which signalling networks control the switch in fibroblast behaviour and how the fibroblast subpopulations organize themselves and influence each other during dermal maturation and wound healing is currently unknown.

Hyaluronic Acid-Based Antibacterial Hydrogels for Use as Wound Dressings.

Wound dressings have been shifting toward a more active role in the wound-healing process. Hydrated environments with additives to aid in the healing process are currently being explored through the application of hydrocolloid dressings. However, these moist healing environments are also ideal for bacterial growth, leading to the widespread use of antibiotics with concerns of antibiotic resistance and toxicity. To overcome this concern, we present a hydrogel wound dressing consisting of hyaluronic acid (HA) cross-linked with gentamicin. This hydrogel treats bacterial infection locally, lowering the effective dose and reducing the concerns of antibiotic resistance and systemic exposure. Changing the cross-linking density, by using varied amounts of a cross-linker, created gels that provided a sustained release of gentamicin for up to 9 days with a range of adhesive and cohesive properties. Overall, this HA hydrogel could provide an important solution in treating local infection in burns and other dermal injuries.

Antibacterial Host-Guest Intercalated LDH-Adorned Polyurethane for Accelerated Dermal Wound Healing.

Curcumin has a limited clinical application because of its extremely poor accessibility. In the present study, improved curcumin bioavailability within a castor oil polyurethane/layered double hydroxide (LDH) wound cover was achieved by preparing a curcumin p-sulfonic acid calix[4]arene (SC4A) inclusion complex. Then, it was utilized to intercalate MgAl-layered double hydroxide (MgAl-LDH) nanosheets. The incorporation of the nanostructure into a PU/Cur-SC4A-LDH film provided bacteria-killing performance against both Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli bacteria. This finding is due to an increase in curcumin bioavailability in the PU matrix. Furthermore, all PU nanocomposites exhibited appropriate cytocompatibility based on an MTT assay. Mainly, the proliferation of L929 fibroblast cells in contact with the PU/Cur-SC4A-LDH sample was significantly further enhanced than that for other nanocomposites within 7 days. This observation can be related to the better availability of curcumin on the film's surface, which causes an improvement in the proliferation rate of cells. Regarding the histological results, the hematoxylin and eosin (H&E) images showed faster epidermal layer formation and a larger quantity of matured hair follicles for PU/Cur-SC4A-LDH-healed wounds in comparison with those for the negative control over a period of 28 days. Thus, this practical healing ability of the PU/Cur-SC4A-LDH nanocomposite makes it a promising candidate as a wound dressing film.

Risk single-nucleotide polymorphism-mediated enhancer-promoter interaction drives keloids through long noncoding RNA down expressed in keloids.

Keloids represent one extreme of aberrant dermal wound healing and are characterized by fibroblast hyperproliferation and excessive deposition of extracellular matrix. Genetics is a major factor for predisposition to keloids and genome-wide association study has identified a single-nucleotide polymorphism (SNP) rs873549 at 1q41 as a susceptibility locus. The SNP rs873549, and the SNPs in strong linkage disequilibrium (LD) with rs873549, may be involved in keloid development. However, the functional significance of these SNPs in keloid pathogenesis remains elusive. To investigate the function and mechanism of SNP rs873549 and the SNPs in strong LD with rs873549 in keloids. SNPs in strong LD with rs873549 were analysed using Haploview. The expression levels of the genes near the susceptibility locus were analysed using quantitative real-time polymerase chain reaction. The interaction between rs1348270-containing enhancer and the long noncoding RNA down expressed in keloids (DEIK) (formerly RP11-400N13.1) promoter in fibroblasts was investigated using chromosome conformation capture. The enhancer activity of the rs1348270 locus was evaluated using luciferase reporter assay. Knockdown experiments were used to explore the function of DEIK in keloids. RNA-Seq was performed to investigate the mechanism by which DEIK regulates the expression of collagens POSTN and COMP. rs1348270, an enhancer-located SNP in strong LD with rs873549, mediated looping with the promoter of DEIK. The risk variant was associated with decreased enhancer-promoter interaction and DEIK down-expression in keloids. Mechanistically, downregulation of DEIK increased the expression of collagens POSTN and COMP through upregulating BMP2. Furthermore, correlation analysis revealed that DEIK expression was inversely correlated with BMP2, POSTN and COMP expression in both keloid and normal fibroblasts. Our findings suggest that the risk variant rs1348270 is located in an enhancer and is associated with the downregulation of DEIK in keloids, and that downregulation of DEIK increases the expression of collagens POSTN and COMP through BMP2 in keloid fibroblasts. These findings will help to provide a more thorough understanding of the role played by genetic factors in keloid development and may lead to new strategies for screening and therapy in keloid-susceptible populations.

Understanding the approach to animals with thermal burns

Thermal burn injuries represent a spectrum of superficial to deep epidermal and dermal injury sustained after exposure to a liquid, solid or gaseous heat source. Severe thermal burns result in both local damage and systemic effects. In systemically compromised animals, managing major body system abnormalities takes priority over surgically managing the thermal burn. General principles of wound management are relevant to animals with thermal burns. The surgical approach will vary according to individual wound and patient factors. Adjunctive therapies, such as negative pressure wound therapy, are touched on. Further research into thermal burns in veterinary cases is warranted.

Development of chloramphenicol wound dressing protein-based microparticles in chitosan hydrogel system for improved effectiveness of dermal wound therapy

Skin wounds have been reported to increase the number of microbial colonies susceptible to infection. Treatments using oral antibiotics have been limited due to their toxicity and hydrophobic characteristics. In this study, we developed a formulation of chloramphenicol microparticles (CPL MPs), which was modified into chitosan hydrogel to increase treatment efficiency in targeting infections and creating an optimal environment to support the healing process. CPL MPs were prepared by a cross-linker stabilized method using whey protein (WPI) biopolymer, and the CPL MPs hydrogel was designed using chitosan biopolymer. Based on the result, CPL-loaded MPs showed desired physical and encapsulation characteristics. In the in vitro study, drug release of CPL MPs in simulated wound fluid represented approximately 99.40 ± 7.01 % of the system after 24 h. The antibacterial activity of CPL-loaded MPs formulation (MIC value 12.5 μg/mL, MBC 25 μg/mL) was effective as MIC concentration increased. Furthermore, the formulation of CPL MPs into hydrogel showed a better dermatokinetic profile compared to hydrogel with pure CPL. Interestingly, the antibacterial activity of the ex vivo infection model showed that Staphylococcus aureus activity decreased by up to 99.98 % after 24 h administration of CPL MPs hydrogel when compared to pure-CPL hydrogel and blank hydrogel. These studies have confirmed that incorporating CPL MPs into hydrogel can provide a promising approach to skin infection treatment.

Engineered reversible adhesive biofoams for accelerated dermal wound healing: Intriguing multi-covalent phenylboronic acid/cis-diol interaction

Development of wound dressings that not only have multiple advantages including good biocompatibility, barrier properties, adhesive properties, but also exhibit anti-bacterial, anti-infection, and promote cell adhesion, accelerated wound healing process, remains challenging in the skin tissue engineering. In this work, a noninvasive adhesive biofoam with interconnectivity structure and antibacterial property was first-time designed through solid surfactant stabilized high internal phase emulsion (HIPE) template, where bacteriostatic Zn-CuO@GO nanosheets dynamic assemble with 4-vinylphenylboronic acid at the oil/water interface as cooperative emulsifier. Taking advantage of the cooperative assembly of the PBA/Zn-CuO@GO, the biofoams display microfibrousity and interconnectivity to facilitate material-cellular interaction as well nutrient exchange, and can effectively inhibit the growth of E. coli and S. aureus. Meanwhile, phenylboronic acid functional groups not only endow biofoam reversible adhesive property though dynamic phenylboronic acid/cis-diol interaction, but also facilitate the rearrangement of Zn-CuO@GO nanosheets in more uniform way at emulsion interface. Taken together, the biofoams can strongly adhere to the wound bed reducing the risk of infection and accelerate earlier tissue regeneration, which exhibit great potential in bioengineering application.

Pullulan-Collagen Hydrogel Wound Dressing Promotes Dermal Remodeling and Wound Healing Compared to Commercially Available Collagen Dressings

PURPOSE: Developing new therapies to promote wound healing and mitigate scarring has the potential to significantly impact patient morbidity, particularly for those who suffer from chronic non-healing wounds and burns. The primary objectives for any therapy that aims to improve wound healing are to provide protection against external factors and to sustain optimal moisture levels within the wound bed. Biologic scaffolds such as hydrogels provide an ideal, physio-mimetic of native ECM that can improve wound healing outcomes after cutaneous injury. While most studies have focused on the benefits of hydrogels in accelerating wound healing, there is minimal data directly comparing the relative efficacies among different hydrogel material compositions. METHODS: In this study we utilized a splinted excisional wound model that recapitulates human-like wound healing in mice, and treated wounds with three different collagen hydrogel dressings. The first dressing was composed of 90% collagen and 10% alginate. The second dressing was composed of 55% collagen and 44% cellulose. Finally, the third dressing was composed of 5% collagen and 95% pullulan. We assessed the feasibility of applying each dressing during standard dressing changes and measured wound areas over time to determine the relative rate of wound closure. We then performed histologic and histopathologic analysis on the explanted scar tissues to assess the effects each hydrogel dressing on collagen architecture, fiber alignment, and cellular response. RESULTS: The days to closure of wounds treated the collagen-pullulan hydrogel (~11.2 days) was significantly shorter than the collagen-cellulose treated (~13.2 days; *p<0.05) and control (~13.8 days; *p<0.01) wounds. Quantitative analysis of collagen architecture demonstrated that collagen-pullulan treated wounds had a lower proportion of mature collagen within the healed scar and significantly more randomly aligned collagen fibers compared to collagen-cellulose treated wounds. Furthermore, we found that collagen-pullulan hydrogel treated wounds displayed significantly shorter fiber length and greater tissue porosity compared to the other wound groups. Finally, histopathologic analysis revealed lower levels of immune cell infiltration and overall tissue response in collagen-pullulan hydrogel treated wounds relative to other groups. CONCLUSION: Our data indicate that the material composition of hydrogel dressings can significantly influence healing time, cellular response, and the resulting architecture of healed scars. Collagen-pullulan hydrogel therapy accelerated wound closure and promoted tissue with less dense, more randomly aligned, and shorter collagen fibers with lower collagen intensity, similar to the natural ‘basket-weave’ architecture of unwounded skin. Further understanding of how specific hydrogel properties affect healing and the resulting tissue architecture of wounds may lead to novel insights and further optimization of the material properties of wound dressings.

Attenuation of dermal wounds through topical application of ointment containing phenol enriched fraction of Caesalpinia mimosoides Lam.

Caesalpinia mimosoides Lam. is one of the important medicinal plants used by the traditional healers of Uttara Kannada district, Karnataka (India) for treating wounds. In our previous study ethanol extract of the plant was evaluated for its wound healing activity. In continuation, the present study was aimed to evaluate the phenol enriched fraction (PEF) of ethanol extract for wound healing activity along with its antioxidant, anti-inflammatory and antimicrobial properties. The potent wound healing activity of PEF was evidenced by observation of increased rate of cell migration in L929, 3T3L1 and L6 cells (92.59 ± 1.53%, 98.42 ± 0.82% and 96.63 ± 0.61% respectively) at 7.81 μg/ml doses in assays carried out in vitro. Significantly enhanced rate of wound contraction (97.92 ± 0.41%), tensile strength (973.67 ± 4.43 g/mm2), hydroxyproline (31.31 ± 0.64 mg/g) and hexosamine (8.30 ± 0.47 mg/g) contents were observed on 15th post wounding day in 5% PEF treated animals. The enzymatic and non-enzymatic cellular antioxidants (superoxide dismutase, catalase and reduced glutathione) were upregulated (15.89 ± 0.17 U/mg, 48.30 ± 4.60 U/mg and 4.04 ± 0.12 μg/g respectively) with the administration of 5% PEF. The significant antimicrobial, antioxidant and anti-inflammatory activities support the positive correlation of PEF with its enhanced wound healing activity. PEF contains expressive amounts of total phenolic and total flavonoid contents (578.28 ± 2.30 mg GAE/g and 270.76 ± 2.52 mg QE/g). Of the various chemicals displayed in RP-UFLC-DAD analysis of PEF, gallic acid (68.08 μg/mg) and ethyl gallate (255.91 μg/mg) were predominant. The results indicate that PEF has great potential for the topical management of open wounds.

Micronized dermal grafts (Rigenera™) and split-thickness skin grafts alone or in combination for deep dermal burn wounds

IntroductionFull-thickness skin damage due to deep dermal burn (DDB) and deep burn (DB) often requires skin grafting. Adverse effects of these grafts include unsightly scars and scar contracture, leading to functional limitations and cosmetic appearance issues. Micronized dermal grafts have been reported to improve not only wound healing, but also the cosmetic appearance of scars, which is consistent with the treatment goals of DDB. Our study presents observations on the effectiveness of treating DDB and DB using a micronized dermal graft alone or in combination with a split-thickness skin graft (STSG). Patients and methodsThis is a retrospective case series of six patients with DDB or DB; three were treated either with micronized dermal graft alone (16 to 21 days after injury) and three were treated in combination with meshed STSG at a ratio of 1:3 (7 to 22 days after injury). Autologous micrografts for grafting were obtained using Rigenera™ technology. Clinical observations of the wounds until complete epithelization was done, noting incidence of hypertrophic scars and viscoelasticity based on the Vancouver Scar Scale (VSS). Histopathological examination including hematoxylin and eosin stain, Elastica van Gieson stain, immunohistochemistry, and transmission electron microscopy was performed on the specimens of one patient with a large burn area treated half by STSG alone and half by STSG with a micronized dermal graft. ResultsComplete epithelization was observed 34.5 ± 6.7 days after sustaining injury and 18.2 ± 7.6 days from the micronized dermal graft treatment across all six patients. The mean total VSS score was 2.5 ± 1.9 at 7.5 ± 5.3 months after the procedure. No differences were noted between the micronized dermal graft alone and combination with STSG groups. For the patient treated with STSG or combination of STSG with micronized dermal graft, the combinatorial treated skin area showed a less obvious mesh pattern. Tissue imaging revealed mature fibroblasts with ordered collagen fibers, anchoring fibrils, and no abnormalities in the basal lamina for the combinatorial treatment. ConclusionMicronized dermal grafts show promise as an effective treatment for burn wounds with or without STSG.

Selenium-Stimulated Exosomes Enhance Wound Healing by Modulating Inflammation and Angiogenesis

Mesenchymal stem cell (MSC)-derived exosomes have emerged as an attractive cell-free tool in tissue engineering and regenerative medicine. The current study aimed to examine the anti-inflammatory, pro-angiogenic, and wound-repair effects of both exosomes and selenium-stimulated exosomes, and check whether the latter had superior wound healing capacity over others. The cellular and molecular network of exosomes, as a paracrine signal, was extensively studied by performing miRNA arrays to explore the key mediators of exosomes in wound healing. Selenium is known to play a critical role in enhancing the proliferation, multi-potency, and anti-inflammatory effects of MSCs. Selenium-stimulated exosomes showed significant effects in inhibiting inflammation and improving pro-angiogenesis in human umbilical vein endothelial cells. Cell growth and the migration of human dermal fibroblasts and wound regeneration were more enhanced in the selenium-stimulated exosome group than in the selenium and exosome groups, thereby further promoting the wound healing in vivo. Taken together, selenium was found to augment the therapeutic effects of adipose MSC-derived exosomes in tissue regeneration. We concluded that selenium may be considered a vital agent for wound healing in stem cell-based cell-free therapies.