The healing effect of nano emulsified Plantago major L extract on oral wounds in a wistar rat model.

INTRODUCTION: Oral lesions are a common clinical symptom arising from various etiologies and disrupt the patient's quality of life. However, no definite treatment is not yet possible, due to the constantly changing environment of the mouth. In recent years, herbal treatments have gained popularity among patients and physicians due to their availability, safety, affordability, and antimicrobial properties. This research aims to investigate the therapeutic effects of a nano-emulsion of Plantago major standardized extract (PMSE) on oral ulcers in a Wistar rat model using histomorphometry and stereological parameters. MATERIALS AND METHODS: The study involved 72 Wistar rats divided randomly into 24 groups of 3 each: groups A1 to A4 received one dose to 4 doses of 5% PMSE nano emulsion, groups B1 to B4 received one dose to 4 doses of 10% PMSE nano emulsion, and groups C1 to C4 received one dose to 4 doses of 20% PMSE nano emulsion, groups D1 to D4 received one dose to 4 doses of nano-emulsion without PMSE, groups E1 to E4 received one dose to 4 doses of PMSE, and group F served as the control group. An incision measuring 2 mm in diameter was made in the animals' hard palate using a biopsy punch. A swab containing the necessary material was used to administer the medication orally to the wound. Histological samples were collected on days 2, 4, 6, and 8 and sent to the pathology laboratory for examination. Data analysis was performed using SPSS 26 and setting statistical significance at p < 0.05. RESULTS: Group A showed a high rate of complete and normal re-epithelialization of the wound at 66.7%, compared to the other groups. Group D had a re-epithelialization rate of 50%, while groups C, E, and F had rates of 7.41% and group B had 7.16%. In terms of inflammation reduction, 23.88% of group A had no inflammation, a higher percentage compared to the other groups. Group B and D had no inflammation in 3.33% of cases, lower than the other groups. The study evaluated frequency of re-epithelialization and inflammation levels in different groups on days 2, 4, 6, and 8 after four doses of the drug with no significant differences found among the groups. CONCLUSION: None of the nano emulsions or PMSE enhanced the healing rate of oral ulcers. However, a 5% PMSE nano emulsion displayed an increase in lesion re-epithelialization.

Dynamic optical coherence tomography for imaging acute wound healing.

The aim of this study was to investigate acute wound healing with dynamic optical coherence tomography (D-OCT). From 22 patients with 23 split skin graft donor sites, vessels at four wound edges, the wound bed, and adjacent and unaffected skin of the contralateral leg were measured by D-OCT at six time points from surgery to 4 weeks of healing. Changes in vessel orientation, density, diameter, morphology and pattern in horizontal, vertical and 3D images were analysed for wound healing and re-epithelialization. At 300 µm depth, there were significant differences of blobs and serpiginous vessels between normal and wounded skin. The wound had significantly more vertically oriented vessels, a higher degree of branching, vessel density and diameter compared with healthy skin. 3D images showed increased angiogenesis from healthy skin towards the wound centre, significantly higher vessel density at the wound than at normal skin and the highest at the interface. During wound healing blobs, coils and serpiginous vessels occurred significantly more frequently in lesional than healthy skin. Vessel density was greatest at the beginning, decreased and then increased by 4 weeks post-surgery. D-OCT helps to evaluate acute wound healing by visualizing and quantifying blood vessel growth in addition to re-epithelialization.

Unveiling the Unexplored Multifactorial Potential of 5-Aminosalicylic Acid in Diabetic Wound Therapy.

Diabetic wounds (DWs) are considered chronic complications observed in patients suffering from type 2 diabetes mellitus (DM). Usually, DWs originate from the interplay of inflammation, oxidation, impaired tissue re-epithelialization, vasculopathy, nephropathy, and neuropathy, all of which are related to insulin resistance and sensitivity. The conventional approaches available for the treatment of DWs are mainly confined to the relief of wound pressure, debridement of the wound, and management of infection. In this paper, we speculate that treatment of DWs with 5-aminosalicylic acid (5-ASA) and subsequent activation of peroxisome proliferator-activated receptor gamma (PPAR-γ) and transforming growth factor beta (TGF-ß) via the AhR pathway might be highly beneficial for DW patients. This estimation is based on several lines of evidence showing that 5-ASA and PPAR-γ activation are involved in the restoration of insulin sensitivity, re-epithelialization, and microcirculation. Additionally, 5-ASA and TGF-ß activate inflammation and the production of pro-inflammatory mediators. Suitable stabilized formulations of 5-ASA with high absorption rates are indispensable for scrutinizing its probable pharmacological benefits since 5-ASA is known to possess lower solubility profiles because of its reduced permeability through skin tissue. In vitro and in vivo studies with stabilized formulations and a control (placebo) are mandatory to determine whether 5-ASA indeed holds promise for the curative treatment of DWs.

Exploring the Molecular Underpinnings of Skin Regeneration and Wound Healing: The Role of Renin Angiotensin.

The aim of this study is to review the role of renin-angiotensin in skin regeneration and wound healing with a focus on molecular mechanisms. Angiotensin receptor type 1 (AT1R) are abundant in the wounded area, and thus, lead to the activation of ERK, STAT1, and STAT3 which can lead to epidermal self-renewal. The expression of Renin Angiotensin System (RAS) components was significantly lower in wounds caused by burning, rather than intact skin, noting that RAS is involved in the re-epithelialization of skin. ERK, STAT and STAT3 are the targets of Ang II, indicating that RAS active components are involved in fibroblast, stem cells and keratinocyte migration. The effect of inhibiting the RAS on wound healing is context-dependent. On one hand, it is suggested that inhibiting RAS during this phase may slow down wound healing speed. On the other hand, studies have shown that RAS inhibition in this phase can lead to α-SMA activation, ultimately accelerating the wound healing process. Most of the investigations indicate that the inhibition of RAS with Angiotensin Receptor Blockers (ARBs) and Angiotensin Converting Enzyme (ACE) plays a significant role in tissue remodeling in the last phase of wound healing. It has been shown that the inhibition of RAS can inhibit scar formation and fibrosis through the downregulation of inflammatory and fibrogenic agents, such as TGF-ß, SMAD2/3, and TAK1, PDGF-BB, and HSP47. To sum up, that local administration of RAS regulators might lead to less scar formation and inflammation in the last phase of wound closure.

Engineered exosomes as a prospective therapy for diabetic foot ulcers.

Diabetic foot ulcer (DFU), characterized by high recurrence rate, amputations and mortality, poses a significant challenge in diabetes management. The complex pathology involves dysregulated glucose homeostasis leading to systemic and local microenvironmental complications, including peripheral neuropathy, micro- and macro-angiopathy, recurrent infection, persistent inflammation and dysregulated re-epithelialization. Novel approaches to accelerate DFU healing are actively pursued, with a focus on utilizing exosomes. Exosomes are natural nanovesicles mediating cellular communication and containing diverse functional molecular cargos, including DNA, mRNA, microRNA (miRNA), lncRNA, proteins, lipids and metabolites. While some exosomes show promise in modulating cellular function and promoting ulcer healing, their efficacy is limited by low yield, impurities, low loading content and inadequate targeting. Engineering exosomes to enhance their curative activity represents a potentially more efficient approach for DFUs. This could facilitate focused repair and regeneration of nerves, blood vessels and soft tissue after ulcer development. This review provides an overview of DFU pathogenesis, strategies for exosome engineering and the targeted therapeutic application of engineered exosomes in addressing critical pathological changes associated with DFUs.

Scar outcomes for conservatively managed children post burn injury: A retrospective study.

Hypertrophic scarring is a significant complication post burn injury, especially for delayed healing after 3 weeks. Burn injuries healing prior to 3 weeks also have the potential to develop hypertrophic scarring, even when prescribed prophylactic conservative scar interventions. A retrospective chart audit reviewed 326 burn patients treated at a paediatric tertiary hospital from 2014 to 2019 who sustained a partial thickness burn, healed >14 days and did not receive skin grafting. A scar was deemed hypertrophic if >1 mm in height. Early hypertrophic scar prevalence was defined as 3-6 months post burn, while persistent hypertrophic scarring was defined as 12-18 months post burn. Median days to wound closure was 18. The prevalence of early and persistent hypertrophic scarring was 56.1% and 16.3%, respectively. Seventeen (5.2%) children underwent medical interventions for scar modulation. Early signs of hypertrophic scarring were seen in just over half the patients presenting to burn therapy and despite scar intervention, persistent hypertrophic scarring was seen in 16.3%. At both time points, just over half of the children presenting healed between 14 and 21 days. Therefore, children healing prior to 21 days have potential to develop hypertrophic scarring.

Appendage-resident epithelial cells expedite wound healing response in adult zebrafish.

Adult zebrafish are able to heal large-sized cutaneous wounds in hours with little to no scarring. This rapid re-epithelialization is crucial for preventing infection and jumpstarting the subsequent regeneration of damaged tissues. Despite significant progress in understanding this process, it remains unclear how vast numbers of epithelial cells are orchestrated on an organismic scale to ensure the timely closure of millimeter-sized wounds. Here, we report an unexpected role of adult zebrafish appendages (fins) in accelerating the re-epithelialization process. Through whole-body monitoring of single-cell dynamics in live animals, we found that fin-resident epithelial cells (FECs) are highly mobile and migrate to cover wounds in nearby body regions. Upon injury, FECs readily undergo organ-level mobilization, allowing for coverage of body surfaces of up to 4.78 mm2 in less than 8 h. Intriguingly, long-term fate-tracking experiments revealed that the migratory FECs are not short-lived at the wound site; instead, the cells can persist on the body surface for more than a year. Our experiments on "fin-less" and "fin-gaining" individuals demonstrated that the fin structures are not only capable of promoting rapid re-epithelialization but are also necessary for the process. We further found that fin-enriched extracellular matrix laminins promote the active migration of FECs by facilitating lamellipodia formation. These findings lead us to conclude that appendage structures in regenerative vertebrates, such as fins, may possess a previously unrecognized function beyond serving as locomotor organs. The appendages may also act as a massive reservoir of healing cells, which speed up wound closure and tissue repair.

Electric fields reverse the differentiation of keratinocyte monolayer by down-regulating E-cadherin through PI3K/AKT/Snail pathway.

Re-epithelialization is an important step in skin wound healing, referring to the migration, proliferation, and differentiation of keratinocytes around the wound. During this process, the edges of the wound begin to form new epithelial cells, which migrate from the periphery of the wound towards the center, gradually covering the entire wound area. These newly formed epithelial cells proliferate and differentiate, ultimately forming a protective layer over the exposed dermal surface. Wound endogenous electric fields (EFs) are known as the dominant factor to facilitate the epidermal migration to wound center. However, the precise mechanisms by which EFs promote epidermal migration remains elusive. Here, we found that in a model of cultured keratinocyte monolayer in vitro, EFs application reversed the differentiation of cells, as indicated by the reduction of the early differentiation markers K1 and K10. Genetic manipulation confirmed that EFs reversed keratinocyte differentiation through down-regulating the E-cadherin-mediated adhesion. By RNA-sequencing analysis, we screened out Snail as the transcription suppressor of E-cadherin. Snail knockdown abolished the down-regulation of E-cadherin and the reversal of differentiation induced by EFs. KEGG analysis identified PI3K/AKT signaling for Snail induction under EFs. Inhibition of PI3K by LY294002 diminished the EFs-induced AKT activation and Snail augmentation, largely restoring the level of E-cadherin reduced by EFs. Finally, in model of full-thickness skin wounds in pigs, we found that weakening of the wound endogenous EFs by the direction-reversed exogenous EFs resulted in an up-regulation of E-cadherin and earlier differentiation in newly formed epidermis in vivo. Our research suggests that electric fields (EFs) decrease E-cadherin expression by suppressing the PI3K/AKT/Snail pathway, thereby reversing the differentiation of keratinocytes. This discovery provides us with new insights into the role of electric fields in wound healing. EFs intervene in intracellular signaling pathways, inhibiting the expression of E-cadherin, which results in a lower differentiation state of keratinocytes. In this state, keratinocytes exhibit increased migratory capacity, facilitating the migration of epidermal cells and wound reepithelialization.

Sirtuin-6 knockout causes exacerbated stalled healing of diabetic ulcers in mice.

BACKGROUND: Diabetic ulcers (DUs) are characterized by chronic inflammation and delayed re-epithelialization, with a high incidence and weighty economic burden. The primary therapeutic strategies for refractory wounds include surgery, non-invasive wound therapy, and drugs, while the optimum regimen remains controversial. Sirtuin-6 (SIRT6) is a histone deacetylase and a key epigenetic factor that exerts anti-inflammatory and pro-proliferatory effects in wound healing. However, the exact function of SIRT6 in DUs remains unclear. METHODS: We generated tamoxifen-inducible SIRT6 knockout mice by crossing SIRT6flox/flox homozygous mice with UBC-creERT2+ transgenic mice. Systemic SIRT6 null mice, under either normal or diabetic conditions, were utilized to assess the effects of SIRT6 in DUs treatment. Gene and protein expressions of SIRT6 and inflammatory cytokines were measured by Western blotting and RT-qPCR. Histopathological examination confirmed the altered re-epithelialization (PCNA), inflammation (NF-κB p50 and F4/80), and angiogenesis (CD31) markers during DUs restoration. RESULTS: Knockout of SIRT6 inhibited the healing ability of DUs, presenting attenuated re-epithelialization (PCNA), exacerbated inflammation responses (NF-κB p50, F4/80, Il-1ß, Tnf-α, Il-6, Il-10, and Il-4), and hyperplasia vascular (CD31) compared with control mice. CONCLUSIONS: SIRT6 could boost impaired wound healing through improving epidermal proliferation, inflammation, and angiogenesis. Our study highlighted the therapeutic potential of the SIRT6 agonist for DUs treatment.

Performance of multiple therapeutic approaches for palatal wound healing after soft tissue graft removal - an overview of systematic reviews.

OBJECTIVE: To overview the literature to answer the following question: "What is the performance of different therapies on wound healing and postoperative discomfort after palatal ASTG removal?" METHODS: SRs that evaluated the wound healing (WH), postoperative pain, bleeding, and analgesic consumption of patients submitted to de-epithelialized/free gingival grafts (FGG) or subepithelial connective tissue grafts (SCTG) removed from the palate were included. The searches were conducted on six white and two gray databases up to December 2023. Methodological quality was evaluated through AMSTAR 2. The synthesis of results was described as a narrative analysis. RESULTS: Ten SRs (involving 25 randomized clinical trials) related to low-level laser therapy (LLLT) (3), platelet-rich fibrin (PRF) (4), cyanoacrylate tissue adhesives (CTA) (2), and ozone therapy (OT) (1) were included in this overview. All techniques demonstrated improvements in WH. LLT, PRF, and CTA reduced pain and analgesic consumption. PRF and CTA reduced bleeding. Regarding methodological quality, the SRs were classified as critically low (2), low (5), moderate (2), or high quality (1). CONCLUSIONS: In SRs related to LLLT, PRF, CTA, and OT, the use of different therapies after palatal ASTG removal improved WH and postoperative discomfort. Due to the studies' low methodological quality and high heterogeneity, data should be interpreted with caution. CLINICAL RELEVANCE: The present overview compiles the evidence of SRs related to different therapies for WH and patients' postoperative experience and reveals that different treatments can significantly improve the clinical outcomes of patients who require ASTG removal for periodontal or peri-implant surgeries. REGISTRATION: PROSPERO registration number: CRD42022301257.

Barriers and co-designed strategies for the implementation of negative pressure wound therapy in acute pediatric burn care in Australia: A mixed method study.

PURPOSE: Pediatric burn injuries are a global clinical issue causing significant morbidity. Early adjunctive negative pressure wound therapy improves re-epithelialization rates in children with burns, yet adoption in acute burn care is inconsistent. This investigation aimed to determine barriers to the implementation of adjunctive negative pressure wound therapy for the acute management of pediatric burns and co-design targeted implementation strategies. METHODS: A sequential mixed methods design was used explore barriers to adjunctive negative pressure wound therapy implementation in acute pediatric burn care. An online questionnaire was disseminated to healthcare professionals within four major Australian pediatric hospitals, each with a dedicated burns service. Barriers were coded according to the Consolidated Framework for Implementation Research (CFIR). Semi-structured interviews with senior clinicians tailored implementation strategies to local contexts. A stakeholder consensus meeting consolidated implementation strategies and local processes. RESULTS: Sixty-three healthcare professionals participated in the questionnaire, and semi-structured interviews involved nine senior burn clinicians. We identified eight implementation barriers across all five CFIR domains then co-designed targeted strategies to address identified barriers. Barriers included lack of available resources, limited access to knowledge and information, individual stage of change, patient needs and resources, limited knowledge and beliefs about the intervention, lack of external policies, intervention complexity, and poor implementation planning. CONCLUSION: Multiple contextual factors affect negative pressure wound therapy uptake in acute pediatric burn settings. Results will inform a multi-state stepped-wedge cluster randomized controlled trial. Additional resources, education, training, updated policies, and guidelines are required for successful implementation. It is anticipated that adjunctive negative pressure wound therapy, in conjunction with tailored implementation strategies, will enhance adoption and sustainability. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry: ACTRN12622000166774. Registered 1 February 2022.

Copaiba oil minimizes inflammation and promotes parenchyma re-epithelization in acute allergic asthma model induced by ovalbumin in BALB/c mice.

Introduction: Asthma is a condition of airflow limitation, common throughout the world, with high mortality rates, especially as it still faces some obstacles in its management. As it constitutes a public health challenge, this study aimed to investigate the effect of copaiba oil (e.g., Copaifera langsdorffii), as a treatment resource, at doses of 50 and 100 mg/kg on certain mediators of acute lung inflammation (IL-33, GATA3, FOXP3, STAT3, and TBET) and early mechanisms of lung remodeling (degradation of elastic fiber tissues, collagen deposition, and goblet cell hyperplasia). Methods: Using an ovalbumin-induced acute allergic asthma model in BALB/c mice, we analyzed the inflammatory mediators through immunohistochemistry and the mechanisms of lung remodeling through histopathology, employing orcein, Masson's trichrome, and periodic acid-Schiff staining. Results: Copaiba oil treatment (CO) reduced IL-33 and increased FOXP3 by stimulating the FOXP3/GATA3 and FOXP3/STAT3 pathways. Additionally, it upregulated TBET, suggesting an additional role in controlling GATA3 activity. In the respiratory epithelium, CO decreased the fragmentation of elastic fibers while increasing the deposition of collagen fibers, favoring epithelial restructuring. Simultaneously, CO reduced goblet cell hyperplasia. Discussion: Although additional research is warranted, the demonstrated anti-inflammatory and re-epithelializing action makes CO a viable option in exploring new treatments for acute allergic asthma.

Single-cell profiling and functional screening reveal crucial roles for lncRNAs in the epidermal re-epithelialization of human acute wounds.

Objectives: Re-epithelialization is an important physiological process for repairing skin barrier function during wound healing. It is primarily mediated by coordinated migration, proliferation, and differentiation of keratinocytes. Long noncoding RNAs (lncRNAs) are essential components of the noncoding genome and participate in various biological processes; however, their expression profiles and function in re-epithelialization during wound healing have not been established. Methods: We investigated the distribution of lncRNAs during wound re-epithelialization by comparing the genomic profiles of uninjured skin and acute wound (AW) from healthy donors. We performed functional screening of differentially expressed lncRNAs to identify the important lncRNAs for re-epithelialization. Results: The expression of multiple lncRNAs is changed during human wound re-epithelialization process. We identified VIM-AS1, SMAD5-AS1, and LINC02581 as critical regulators involved in keratinocyte migration, proliferation, and differentiation, respectively. Conclusion: LncRNAs play crucial regulatory roles in wound re-epithelialization. We established lncRNA expression profile in human acute wounds compared with intact skin, offering valuable insights into the physiological mechanisms underlying wound healing and potential therapeutic targets.

Multi-functional bandage - bioactive glass/metal oxides/alginate composites based regenerative membrane facilitating re-epithelialization in diabetic wounds with sustained drug delivery and anti-bactericidal efficacy.

Chronic wounds, especially diabetic, foot and pressure ulcers are a major health problem affecting >10 % of the world's populace. Calcium phosphate materials, particularly, bioactive glasses (BG), used as a potential material for hard and soft tissue repair. This study combines nanostructured 45S5 BG with titania (TiO2) and alumina (Al2O3) into a composite via simple sol-gel method. Prepared composites with alginate (Alg) formed a bioactive nanocomposite hydrogel membrane via freezing method. X-ray diffraction revealed formation of two phases such as Na1.8Ca1.1Si6O14 and ß-Na2Ca4(PO4)2SiO4 in the silica network. Fourier transformed InfraRed spectroscopy confirmed the network formation and cross-linking between composite and alginate. <2 % hemolysis, optimal in vitro degradation and porosity was systematically evaluated up to 7 days, resulting in increasing membrane bioactivity. Significant cytocompatibility, cell migration and proliferation and a 3-4-fold increase in Collagen (Col) and Vascular Endothelial Growth Factor (VEGF) expression were obtained. Sustained delivery of 80 % Dox in 24 h and effective growth reduction of S. aureus and destruction of biofilm development against E. coli and S. aureus within 24 h. Anatomical fin regeneration, rapid re-epithelialization and wound closure were achieved within 14 days in both zebrafish and in streptozotocin (STZ) induced rat in vivo animal models with optimal blood glucose levels. Hence, the fabricated bioactive membrane can act as effective wound dressing material, for diabetic chronic infectious wounds.

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.

Mechanical Stimulation of Anti-Inflammatory and Antioxidant Hydrogels for Rapid Re-Epithelialization.

The epithelium, an essential barrier to protect organisms against infection, exists in many organs. However, rapid re-epithelialization to restore tissue integrity and function in an adverse environment is challenging. In this work, a long-term anti-inflammatory and antioxidant hydrogel with mechanical stimulation for rapid re-epithelialization, mainly composed of the small molecule thioctic acid, biocompatible glycine, and γ-Fe2O3 nanoparticles is reported. Glycine-modified supramolecular thioctic acid is stable and possesses outstanding mechanical properties. The incorporating γ-Fe2O3 providing the potential contrast function for magnetic resonance imaging observation, can propel hydrogel reconfiguration to enhance the mechanical properties of the hydrogel underwater due to water-initiated release of Fe3+. In vitro experiments show that the hydrogels effectively reduced intracellular reactive oxygen species, guided macrophages toward M2 polarization, and alleviated inflammation. The effect of rapid re-epithelialization is ultimately demonstrated in a long urethral injury model in vivo, and the mechanical stimulation of hydrogels achieves effective functional replacement and ultimately accurate remodeling of the epithelium. Notably, the proposed strategy provides an advanced alternative treatment for patients in need of large-area epithelial reconstruction.

Termografía infrarroja como método de diagnóstico en quemaduras: una revisión exploratoria de la literatura / Infrared thermography as a method of diagnosis in burns: an exploratory review of the literature

Objetivos: Revisar el uso y eficacia de la termografía infrarroja como instrumento diagnóstico y de medida de las quemaduras. Metodología: Se realizan 2 búsquedas, una general y otra específica, utilizando estrategia de búsqueda mediante un lenguaje controlado con términos MESH. Para seleccionar los artículos se filtra por título, resumen y palabras clave, además de aplicarse los criterios de inclusión y exclusión. Resultados: Durante la búsqueda general, se encontraron 165 artículos en PubMed, de los cuales 7 han sido seleccionados y 6 han sido incluidos. Mientras que con la búsqueda específica se obtienen 28 artículos, de los cuales se seleccionan 7 que no aparecían en la búsqueda general y se incluyen finalmente 6 de ellos. Conclusiones: La termografía infrarroja es un instrumento con mucho potencial y que ha mostrado buenos resultados, pero en ocasiones mucha variabilidad e inconsistencia, por lo que es necesaria la estandarización de una serie de medidas que nos permitan contrarrestar las dificultades a las que se expone y minimizar los sesgos, hecho que podrá mejorar más los resultados. Además, es necesaria una mayor investigación aplicando las variables térmicas encontradas para identificar el grado de influencia e importancia que tienen y comparar las diferentes modalidades de termografía infrarroja, estática y dinámica.(AU)

Objectives: To review the use and efficacy of infrared thermography as a diagnostic instrument and measurement of burns. Methodology: Two searches were carried out, one general and the other specific, using a controlled language search strategy with MESH terms. To select the articles we filtered them by title, abstract and key words, besides applying the inclusion and exclusion criteria. Results: During the general search, 165 articles were found in PubMed, of which 7 were selected and 6 were included. The specific search yielded 28 articles, of which 7 were selected that did not appear in the general search and 6 were finally included. Conclusions: Infrared thermography is an instrument with great potential that has shown good results but much variability and inconsistency at times, so it is necessary to standardize a series of measures that allow us to counteract the difficulties to which it is exposed and minimize biases, a fact that could further improve the results. In addition, further research is needed by applying the thermal variables found to identify the degree of influence and importance that they have and by comparing the different infrared thermography modalities, static and dynamic.(AU)

New Medical Herbalism Formulations as a Targeted Therapeutic Strategies Used in Southern Tunisia to Promote Neo-Epithelium, Angiogenesis, and Collagen Biosynthesis and to Impede Scar Formation Post-Third-Degree Burned Skin.

The aim of the study is to assess the suitability of the herbal formulation for topical application as a skin burn dressing on the in vivo wound-closure of third-degree wound injuries. Rat wound models were used to prove the in vivo skin burn-healing process. Body weight gain, food and water intake, and behavior were investigated daily during treatment period. Cutaneous biopsies of the burned wound surfaces were monitored at days 4, 13, and 28. Formulation markedly (P < .05) increased wound repair rate and collagen production compared to untreated burnt skin. Macroscopic and histological analysis of the wound of formula (F)-treated group showed significant skin contraction rate and rapid wound healing without scar through regeneration of epidermis that were approved in formula mixed with honey (F-hY)- and Drs-treated wound compared with thymol, and the untreated wound tissues that were not covered by denuded epithelial. Furthermore, the wound healing efficacy of F-hY, F, and Drs cream was proved by decreased the amount of malondialdehyde compared to untreated rats. In conclusion, F and F-hY was found to promote cutaneous wound repair. In all case, the formula alone or mixed with honeybees was even better than thymol in the repair of cutaneous wound.

Bioactive self-healing umbilical cord blood exosomes hydrogel for promoting chronic diabetic wound healing.

The deleterious effects of diabetes mellitus on wound healing have become a major public health concern worldwide. Given the complex microenvironment of diabetic wounds and the high prevalence of diabetes, the design and development of novel wound dressing materials with versatile capabilities is urgent. Extracellular vesicles (EVs) derived from human umbilical cord blood have demonstrated the potential to counter inflammation and accelerate wound healing. Herein, we explored the efficacy of incorporating human umbilical cord blood-derived exosomes (UCB-Exos) into an ABA-type amphiphilic hydrogel, which possesses the attributes of exosome (Exo) encapsulation, temperature-triggered reversible sol-gel conversion, and Exo-regulated release, for enhancing the stability and retention of Exos. We sought to examine the feasibility of this strategy in augmenting the therapeutic efficacy of UCB-Exos for the healing of diabetes-related wounds. The injectable hydrogel was conveniently applied directly onto the wound surface and the enclosed Exo significantly facilitated the healing process, resulting in faster wound closure, enhanced collagen deposition, accelerated re-epithelialization, and enhanced neo-vascularization within two weeks compared with the hydrogel-only treatment group. In summary, some hydrogels hold great promise for promoting wound healing in diabetics and represent a novel therapeutic option for diabetes-related ulcers.

Automated Electrical Stimulation Therapy Accelerates Re-Epithelialization in a Three-Dimensional In Vitro Human Skin Wound Model.

Objective: Electrical Stimulation Therapy (EST) shows promise for the purpose of accelerating wound healing, but the right electrical stimulation parameters and its mode of action remain unclear. We aim to evaluate the effect of a new EST clinical device on epidermal repair using an in vitro human skin wound model. Approach: We scaled up a well-established 3D De-Epidermized Dermis-Human Skin Equivalent (DED-HSE) wound model to fit a clinically used device that delivers preprogrammed microcurrent EST. The impact of EST on re-epithelialization of 4-mm circular epidermal wounds was assessed after 4 and 7 days of treatment, using metabolic activity assay, immunohistochemistry (IHC) staining, and RNA in situ hybridization. Results: EST was successfully applied to the wounded in vitro skin model. Large DED-HSEs retained good cell viability for up to 7 days of EST treatment. Excisional wounds subjected to EST for 4 days consistently exhibited faster closure (mean 65.8%, n = 9) compared to untreated wounds (mean 49.7%, n = 9) (p < 0.05). Wounds exposed to EST exhibited significantly longer epithelial tongues (re-epithelialization mean 50.3%, n = 9) than untreated wounds (mean 26.2%, n = 9) (p < 0.001), suggesting faster keratinocyte migration and proliferation. Increased MMP1 transcription (p < 0.05) in ES-treated periwound suggests a mechanism for enhanced keratinocyte migration. IHC staining showed advanced epidermal proliferation (p63) and differentiation (K10) in EST-exposed wounds (n = 15), as well as stronger attachment of the newly formed epidermis into the dermis compared to untreated controls (n = 15) (p < 0.001). Innovation: We present a novel approach to assess an EST clinical device designed to stimulate wound healing. Using a scaled-up 3D human skin wound model, we could demonstrate the positive effect of EST on epithelial cell responses and shed light on possible mechanism. Conclusion: Our study provides experimental evidence that microcurrent therapy accelerates wound closure and improves the quantity and quality of re-epithelialization.