Wound Healing In Rats Research Articles

Acute pilonidal abscess: Prospective nationwide audit in the Netherlands.

The aim of this study was to assess Dutch surgical practice and outcomes for acute pilonidal abscess. Patients with pilonidal sinus disease (PSD) who underwent surgical treatment between 1 March 2020 and 1 March 2021 at 36 participating hospitals were included in a prospective observational cohort study. For the present study, only patients with an acute abscess were included for analysis. Outcomes included symptoms, wound healing, time to resume daily activities and complications. Follow-up was 1 year and included questionnaires on recurrent abscesses, symptomatic chronic PSD, quality of life and patient-reported experience measures. Of 681 included patients, 208 presented with an acute pilonidal abscess. Incision and drainage (I&D) was performed in 205 of these patients (99%). The wound healing rate after I&D was 42.2% at the outpatient clinic, with a median time to closure of 43 days. The complication rate was 4.4%. One-year questionnaires were completed by 158 out of 205 patients (77.1%). Fifteen patients (7.3%) had a recurrent abscess within 1 year. The symptomatic chronic PSD rate was 8.8%. Of all the patients presenting with PSD in this prospective national study cohort, 30% had a pilonidal abscess. Incision and drainage showed a low complication rate but successful wound healing in less than half of the patients. The study showed that 91.2% of patients did not undergo additional surgical treatment for symptomatic chronic PSD within 1 year of follow-up.

Bioactive glass suspension hydrogel promotes wound healing by modulating fibroblasts

The irritation and adhesion of wound healing biomaterials to wet wounds should be addressed for achieving effective wound healing. In this study, a stable multifunctional hydrogels (BGs/HA suspension gels) were prepared using superfine powder of bioactive glasses (BGs), the biocompatible materials hyaluronic acid (HA) and carbomer940, which had good adhesion and low irritation properties for use in moist complex wounds. The average particle size of BGs/HA suspension gels was 13.11 ± 0.29μm, and the BG content was 15.8 ± 0.2% (m m-1). The results of cell proliferation, cell migration, and immunofluorescence staining experiments showed that in the initial stage of wound healing, the ionic extract of BGs formulations promoted the proliferation and migration of L929 cells and induced the secretion ofα-SMA and collagen I. In the final stage of repair, the ionic extract of the BGs formulation regulated the differentiation of fibroblast, which contributed to the reduction of pathological scar formation.In vivoexperiments showed that the wound healing rate of BGs/HA suspension gels group exceeded higher than that of the conventional BGs superfine powder group. Although BGs/HA suspension gels were comparable to its commercially available counterpart (Dermlin paste) in promoting wound healing, it addressed the problem of localized irritation caused by the high pH and low adhesion of BGs products. This study confirmed the specific regulatory effect of BGs/HA suspension gels on L929 cells, which provided a reference for the clinical application of BGs in wound dressing.

Early results of an orthoplastic multidisciplinary approach to diabetic foot ulcer soft tissue reconstruction.

Diabetic foot ulcer (DFU) is a common complication in patients with diabetes. With current treatment, only two-thirds of patients heal, with a median duration of 3-6 months. Hard-to-heal DFUs are a major source of morbidity and mortality. Improving wound healing via soft tissue reconstruction may be the key to improving clinical outcomes. Thus, the Diabetic Limb Salvage (DLS) service in Sengkang General Hospital, Singapore, was established to provide patients with a streamlined, one-stop, comprehensive service dedicated to DFU soft tissue reconstruction. The reconstruction was carried out using secondary closure, skin grafting, local flaps or free flaps, depending on the severity of the wound and patient suitability. This study aims to audit the early outcomes of the DLS service. Patients with DFUs treated by the DLS service were compared with patients with DFUs treated prior to the launch of the DLS service (control). Outcomes including major and minor amputation rates, wound healing rate, mortality and DFU recurrence rates were analysed statistically. A total of 103 patients took part in the study (50 in the DLS service cohort and 50 in the control cohort). There was no significant difference in demographics, comorbidities and wound profiles between the two cohorts. All (100%) patients in the DLS service cohort received soft tissue reconstruction versus only 13% in the control group. The DLS service cohort had a significantly higher healing rate (96% versus 68%, respectively), shorter healing duration (77±30 days versus 111±43 days, respectively), reduced major amputation rate (0% versus 9%, respectively), and reduced recurrence rate (6% versus 25%, respectively) compared with the control cohort within the one-year follow-up. The findings of this study showed that an orthoplastic multidisciplinary approach focused on DFU soft tissue reconstruction improved wound healing rates, shortened healing duration and, as a result, lowered amputation rates and reduced recurrence.

Zuyangping formula promotes skin wound healing in diabetic rats.

To evaluate the effects of Zuyangping (, ZYP) formula on wound healing in diabetic rats, as well as the molecular mechanisms involved. The main compounds in ZYP formula were identified by the Liquid chromatography-tandem mass spectrometry. Sprague-Dawley rats, injected with streptozotocin (STZ) to establish diabetes model, then, formed a defective skin trauma in the back, and each group was treated with corresponding drugs once a day. Granulation was taken from each time node for histological analysis. The Western blotting was used to measured protein expression of advanced glycation end products receptor (RAGE) and hypoxia-inducible factor-1α (HIF-1α) axis-related proteins. The relative expression levels of inflammatory cytokines and growth factors were measured by the enzyme-linked immunosorbent assay method. The main ingredients were identified in the ZYP formula. Histological analysis showed that the ZYP formula could inhibit the expression of inflammation, promote angiogenesis and collagen deposition. In addition, the ZYP formula could regulate the expression of RAGE and HIF1-α axis-related proteins, thus promoting the wound healing in diabetic rats. The ZYP formula could accelerate wound healing in diabetic rats.

The oxidized hyaluronic acid hydrogels containing paeoniflorin microspheres regulates the polarization of M1/M2 macrophages to promote wound healing

Controlling excessive inflammation of acute wound is an effective means to shorten the healing time. Therefore, targeted control of the inflammatory response of the wound is a promising therapeutic strategy. In this study, paeoniflorin (Pae) was encapsulated in microspheres and combined with oxidized hyaluronic acid hydrogels to prepare the hydrogel loaded with Pae microspheres (Pae-MPs@OHA) to promote the healing of acute wounds in rats. The results demonstrated that the particle size of the Pae-MPs was 6.84 ± 0.51 μm, and the positive charge was 26.87 ± 1.51 mV. The uniform spherical structure of the Pae-MPs was observed by TEM. The Pae-MPs@OHA can maintain colloidal state in the range of 0.1–3.16 Hz. FTIR suggested that Pae could be effectively wrapped in MPs, and SEM indicated that the Pae-MPs@OHA had a uniform network pore structure. The Pae-MPs@OHA can realize the sustained release of Pae for 96 h. Biocompatibility experiments showed that the Pae-MPs@OHA hydrogels were safe and available. The Pae-MPs@OHA hydrogels can accelerate wound healing in rats. HE and masson staining suggested that the Pae-MPs@OHA could reduce inflammatory cell infiltration, promote re-epithelialization and collagen formation. The Pae-MPs@OHA could decrease the number of M1 and increase the number of M2 in macrophages, thus regulating the release of inflammatory factor TNF-α and IL-1β. The results of molecular docking and western blot results also confirmed that the Pae-MPs@OHA could reduce the expression of NF-κB, pNF-κB, NLRP3, ASC and pro-caspase-1. These findings suggest that the Pae-MPs@OHA has great potential for application in the treatment of inflammatory wound.

Degree of sulfation of freeze-dried calcium alginate sulfate scaffolds dramatically influence healing rate of full-thickness diabetic wounds.

Diabetic foot ulcer (DFU) is a chronic and non-healing wound in all age categories with a high prevalence and mortality in the world. An ideal wound dressing for DFU should possess the ability of adsorbing high contents of exudate and actively promote wound healing. Here, we introduced the calcium alginate sulfate as a new biomaterial appropriate for use in wound dressing to promote the healing of full-thickness ulcers in a diabetic mouse model. In this regard, alginate sulfate (Alg-S) solutions with different degree of substitution (DS) of 0.2, 0.5, and 0.9 were synthesized, freeze-dried, crosslinked by calcium cations, purified by washing and refreeze-dried. Primary analyses including swelling ratio, porosity content and mechanical properties revealed that all Alg-S scaffolds possess necessities for use as a wound dressing. After confirming the cytocompatibility of both alginate and alginate sulfate-based scaffolds by MTT assay, they were used as wound dressing for healing of full-thickness ulcers in diabetic mice. The results of wound healing process confirmed that calcium alginate sulfate scaffolds can heal the wounds faster than both alginate-treated and non-treated wounds. Furthermore, the histological analyses of healed tissues reveled normal regeneration of the skin tissue layers and collagen deposition similar to the healthy tissue.

Invivo and ex-vivo evaluation and characterization of wound healing effect of topical calendulaofficinalis and turmeric cream in diabetic rats.

Objective: To evaluate wound healing by topically administration of calendulaofficinalis and tumeric cream to diabetic rats. Study Design: Observational Cross-sectional study Setting: Department of Pharmaceutics, Faculty of Pharmacy, BahaUddin Zakariya University, Multan, Pakistan Period: October 2020-march 2021. Method: Different batches of hydrophilic cream bases (C1-C6) were developed and characterized. The optimized base composition (C6) was loaded with calendula Officinal is extract and turmeric powder as an active ingredient (C7) and evaluated the rate at which wounds heal in diabetic rats. Calendula officinal is and turmeric were combined in a cream, as different stability parameters of the creams were analysed at different temperature. Microbiological action of the cream was also examined. Results: The formulation was homogenous, stable with pH 6.29±0.03, viscosity 381± 6.96 Cps and the microbiological quality met the requirements of European pharmacopeia. The total flavonoid content was less than 1. The formulation showed accelerated wound healing with more than 95% wound contraction after tenth day. Conclusion: The result were favorable and suggested that topical administration of Calendula officinal is and turmeric powder combination would enhance wound healing in diabetic rats with potential for diabetic foot ulcer treatment. Moreover, the designed formulation poses good quality emulsion system stabilizing the active ingredient as well as appropriate release of medicinal agents.

Species differences in glycerol-3-phosphate metabolism reveals trade-offs between metabolic adaptations and cell proliferation

The temperate climate-adapted brown hare (Lepus europaeus) and the cold-adapted mountain hare (Lepus timidus) are closely related and interfertile species. However, their skin fibroblasts display distinct gene expression profiles related to fundamental cellular processes. This indicates important metabolic divergence between the two species. Through targeted metabolomics and metabolite tracing, we identified species-specific variations in glycerol 3-phosphate (G3P) metabolism. G3P is a key metabolite of the G3P shuttle, which transfers reducing equivalents from cytosolic NADH to the mitochondrial electron transport chain (ETC), consequently regulating glycolysis, lipid metabolism, and mitochondrial bioenergetics. Alterations in G3P metabolism have been implicated in multiple human pathologies including cancer and diabetes. We observed that mountain hare mitochondria exhibit elevated G3P shuttle activity, alongside increased membrane potential and decreased mitochondrial temperature. Silencing mitochondrial G3P dehydrogenase (GPD2), which couples the conversion of G3P to the ETC, uncovered its species-specific role in controlling mitochondrial membrane potential and highlighted its involvement in skin fibroblast thermogenesis. Unexpectedly, GPD2 silencing enhanced wound healing and cell proliferation rates in a species-specific manner. Our study underscores the pivotal role of the G3P shuttle in mediating physiological, bioenergetic, and metabolic divergence between these hare species.

Silver functionalized chitosan composite hydrogel with sustained silver release and enhanced antibacterial properties promotes healing of infected wounds

Bacterial infections during wound healing often cause inflammation, which delays the healing process. Therefore, innovative wound dressings are urgently needed to inhibit bacterial infections and promote healing. This study proposes an Ag-functionalized chitosan hydrogel dressing, formed via a Schiff-base reaction between alkynyl Ag substituted chitosan (Ag-CS) and octafunctionalized polyhedral oligomeric silsesquioxane with benzaldehyde-terminated polyethylene glycol (POSS-PEG-CHO), to address the issue of bacterial infection in wounds. The hydrogel demonstrated excellent injectability and self-healing properties. AgNPs and alkynyl Ag, produced by the reducing effect of chitosan and the reversible reaction of alkynyl Ag, delay the release of Ag+. Furthermore, the hydrogel exhibits a broad-spectrum antibacterial effect and effectively inhibits bacterial biofilm formation. The release of Ag+ lasts for 7 days, ensuring sustainable antibacterial properties. In a mouse infected wound model, the composite hydrogel significantly accelerated wound healing. By the eighth day, the wound healing rate reached 99 %, whereas the control group achieved only 91 %. Histological and immunofluorescence staining results indicated that hydrogel-treated wounds had faster re-epithelialization, collagen deposition, and angiogenesis, with reduced inflammation. In conclusion, the Ag-functionalized chitosan hydrogel, with sustained Ag release and enhanced antibacterial properties, shows great potential as a wound dressing for promoting the healing of infected wounds.

The Correlation between BRAFV600E Expression and Integrin β3 in Melanoma Cells

This study investigated the relationship between ITGB3 and BRAFV600E expression in melanoma. It specifically focused on how the overexpression of BRAFV600E and Integrin $\beta $3 impacts wound healing and the TGF-β pathway. The findings provide valuable insights into melanoma progression and highlight potential therapeutic targets. Homozygous BRAFV600E-carrying A375 and heterozygous BRAFV600E-carrying M14 melanoma cell lines were utilized. ITGB3 mRNA levels were measured in both A375 and M14 cells, while Integrin β3 protein levels were analyzed in BRAFV600E-overexpressing A375 cells. The impact of increased BRAFV600E and Integrin β3 on cell migration was assessed using an in vitro wound healing assay. Additionally, the influence of BRAFV600E and Integrin β3 overexpression on the TGF-β pathway was evaluated through luciferase reporter assays and real-time PCR. ITGB3 levels were significantly higher in A375 cells compared to M14 cells. Overexpression of BRAFV600E in A375 cells resulted in a marked increase in Integrin β3 levels. Cells overexpressing both BRAFV600E and Integrin β3 demonstrated enhanced wound healing rates and elevated TGF-β activity. These findings suggest a strong correlation between BRAFV600E expression and Integrin β3 levels in melanoma cells. This study uncovers a significant relationship between BRAFV600E expression and Integrin β3 levels in melanoma cells. The overexpression of both BRAFV600E and Integrin β3 enhances wound healing and promotes TGF-β signalling. These findings suggest that Integrin β3 may contribute to melanoma progression and poor prognosis by influencing cell migration and the TGF-β pathway. Targeting integrins, the TGF-β pathway, and BRAFV600E present potential therapeutic strategies for melanoma treatment.

Preoperative malnutrition in elderly gastric cancer patients and adverse postoperative outcomes of radical gastrectomy

Malnutrition is not only a prevalent condition among the elderly but also a common comorbidity in elderly people with gastric cancer (GC). Malnutrition is closely linked to high rates of postoperative complications and poor wound healing in elderly GC patients, which may lead to a higher incidence and mortality rate of GC. Malnutrition decreases the physical function of elderly GC patients after surgery, severely affecting their postoperative life quality and hindering subsequent treatments. This retrospective study was conducted by Zhao et al , focusing on the clinical baseline data, postoperative complications, and hospitalization times of elderly GC patients who underwent curative gastrectomy. Additionally, the underlying causes of poor outcomes for patients were discussed. This study may provide a solid basis for the clinical treatment of elderly GC patients in the future. Therefore, malnutrition can serve as a negative prognostic factor for curative surgery in GC patients. Addressing malnutrition and its adverse effects can benefit elderly GC patients from surgical treatment.

Fabrication of curcumin-incorporated human amniotic membrane extracellular matrix-derived scaffold to enhance full-thickness wound healing in diabetic rats.

The multifactorial nature of diabetic wounds necessitates a mixed approach for successful treatment. Compensation of degenerated wound tissue extracellular matrix (ECM) and application of anti-inflammatory and antioxidant agents have been shown to be promising. Here, an attempt was made to fabricate a biocompatible wound dressing from curcumin-incorporated human amniotic membrane (HAM) ECM-derived scaffold to accelerate diabetic wound healing in rats. Therefore, after inducing diabetes, an excisional ischemic wound was created on rat skin, then treatments were administered for a period of 21days. The main groups were the diabetic animals that received an engraftment of HAM scaffold (HAMS group) and the curcumin-incorporated HAMS (HAMS/β/C group). Evaluation at post-wounding days 7, 14, and 21 indicated that the parameters related to regeneration, including wound closure, volume of new epidermis and dermis, proliferating cells, fibroblasts, blood vessels, collagen deposition, and tensile strength, as well as transcripts of Vegf, bFgf, and Tgf-β genes of the healed wound in both HAMS and HAMS/β/C groups were considerably greater than those of the diabetic group. Conversely, the presence of inflammatory cells, i.e., neutrophils and macrophages, and the transcripts of Tnf-α and Il-1β showed a dramatic decrease in the treated groups relative to the diabetic group. Finally, compared to the HAMS group, considerable differences were found with the HAMS/β/C group in almost all evaluated parameters. Overall, these results suggest that using the complementary or synergistic effects of curcumin and HAMS could be a promising approach to improve diabetic wound healing.

Exploration of the Topical Nanoemulgel Bearing with Ferulic Acid and Essential Oil for Diabetic Wound Healing

Aim: To investigate the anti-inflammatory, antioxidant, and diabetic wound healing properties of the novel topical formulation [Ferulic acid-loaded nanoemulgel (DLMGO-G)]. Methods: Ferulic acid nanoemulsion developed with lemongrass oil is investigated in diabetic wound healing. Further nanoemulsion is incorporated into 1% carbopol® 934 to obtain the DLMGO-G. Nanoemulsion was characterized for particle size, and polydispersity index (PDI) was obtained by Malvern Zetasizer (Zetasizer Nano ZS, Malvern, AL, USA), and morphology by TEM (JEM 1400, JOEL, Akishima, Japan). Furthermore, in vitro cell line and in vivo studies were carried out. Results: The developed nanoemulsion showed a globule size of 28.04 ± 0.23 nm and PDI of 0.07 ± 0.01. The morphology of nanoformulations by TEM confirmed the spherical and uniform nature. Further, the nanoformulation in in vitro cell line experiments revealed that the IC50 value was increased by 1.52 times compared to the drug solution. The treatment groups have shown that fibroblast morphologies were spindle-shaped, suggesting that nanoformulation was compatible with the cells and developed normally on nanoformulation. It also reduced ROS with improved internalization more than the control group. The in vitro wound healing model also revealed that nanoformulation had better wound healing activity. In the in vivo diabetic wound studies on male SD rats, the levels of inflammatory markers such as TNF-α, IL-6, IL-22, and IL-1β declined significantly when treated with DLMGO-G. IL-10 levels significantly increased compared to the diseased group, and MMP-9 levels were remarkably decreased compared to the diseased group. Furthermore, histopathological studies showed the regeneration and granulation of tissues. Conclusions: Thus, these findings indicate that FA-loaded nanoemulgel greatly accelerates the healing of wounds in diabetic rats.

DIEP flap with implant placement has a favorable complication profile compared to implant-only or flap-only reconstruction.

Hybrid deep inferior epigastric perforator (DIEP) flap and simultaneous silicone implant breast reconstruction procedures ("DIEP+I") have many conceptual advantages compared to either reconstruction method alone, but the outcomes of DIEP+I reconstruction have not yet been well studied. Therefore, the purpose of this study was to compare the outcomes of DIEP+I with implant-only and DIEP-only reconstruction. A retrospective review was conducted of patients undergoing DIEP+I, implant-only, and DIEP-only breast reconstruction from 2019-2023 at a single institution. Demographics and complication rates were compared between groups. A total of 145 patients were included in the DIEP+I (N = 26), implant-only (N = 59), and DIEP-only (N = 60) groups. The DIEP+I group had a lower overall complication rate than implant-only reconstruction (18.4% vs 41.1%, P = 0.014), which was primarily due to the lower incidence of infections in the DIEP+I group (2.6% vs 22.2%, P = 0.006). Accordingly, DIEP+I reconstruction decreased the odds of infection by 90% (OR = 0.095, P = 0.024) compared to implant-only reconstruction. The DIEP+I group had similar rates of wound healing and implant-related complications compared to the implant-only and DIEP-only groups, and no patients in the DIEP+I group experienced flap loss. DIEP+I breast reconstruction had a lower rate of infectious complications than implant-only reconstruction, and no higher rate of flap compromise or wound healing complications. This technique could be considered as a means of minimizing infection risk in patients with other risk factors who are seeking implant-based reconstruction, and of enhancing breast projection in patients who are seeking DIEP flap reconstruction.

Evaluation of wound temperature monitoring at various anatomical sites in the management of patients with diabetic foot undergoing microcirculation reconstruction

ObjectiveThis study aims to assess the significance of monitoring temperature change trends at various wound sites in the healing process of diabetic foot ulcers after microcirculation reconstruction surgery.MethodsA retrospective analysis was conducted on individuals with diabetic foot ulcers who had been admitted to the Department of Orthopedics at the Second Hospital of Shanxi Medical University between July 2020 and February 2022. Temperature changes were regularly monitored at the center of the wound and the distal tibia of the ipsilateral lower leg to assess microcirculatory blood perfusion. Wound, ischemia, and foot infection (WIFi) grading was performed at admission and the final follow-up was to determine the value of temperature monitoring at various sites. Additionally, the formation of collateral microarterial vessels was monitored to determine their consistency with the observed trends in temperature differences. Follow-up assessments included the recurrence of ulcers, development of ulcers at different locations, re-amputation of the toe or limb, and diabetes-related mortality.ResultsA total of 29 patients were included in the follow-up, with an average age of 57.14 ± 14.75 years and a follow-up period of 9.79 ± 4.13 months. Following microcirculation reconstruction surgery, as the microvascular network formed, the temperature difference between the center of the wound and the distal tibia on the same side gradually decreased, with no statistical difference observed at 4 weeks postoperatively. At both admission and the final follow-up, there was a significant reduction in the wound (W) and ischemia (I) grades within the WIFi classification. The temperature at the wound center showed progressive improvement as collateral microarterial vessels developed. During the follow-up period, there were 2 cases of ulcer recurrence, 1 case of an ulcer appearing at a different location, no cases of re-amputation of the toe or limb, and 2 diabetes-related fatalities.ConclusionSkin temperature monitoring offers a direct and reliable indication of microcirculatory blood perfusion. Its simplicity and cost-effectiveness make it a valuable tool for widespread use in evaluating wound healing following microcirculation reconstruction surgery.

The wound healing of deep partial-thickness burn in Bama miniature pigs is accelerated by a higher dose of hUCMSCs

BackgroundDeep partial-thickness burns have a significant impact on both the physical and mental health of patients. Our previous study demonstrated human Umbilical Cord Mesenchymal stem cells (hUCMSCs) could enhance the healing of severe burns in small animal burn models, such as rats. Furthermore, our team has developed a deep partial-thickness burn model in Bama miniature pigs, which can be utilized for assessing drug efficacy in preclinical trials for wound healing. Therefore, this study further determine the optimal dosage of hUCMSCs in future clinical practice by comparing the efficacy of low-to-high doses of hUCMSCs on deep partial-thickness burn wounds in Bama miniature pigs.Materials and methodsThe male Bama miniature pigs (N = 8, weight: 23–28 kg and length: 71–75 cm) were used to establish deep partial-thickness burn models, which used a continuous pressure of 1 kg and contact times of 35 s by the invented electronic burn instrument at 100℃ to prepare 10 round burn wounds with diameter of 5 cm according to our previous report. And then, 0 × 10^7, 1 × 10^7, 2 × 10^7, 5 × 10^7 and 1 × 10^8 doses of hUCMSCs were respectively injected into burn wounds of their corresponding groups. After treatment for 7, 14 and 21 days, the burned wound tissues were obtained for histological evaluation, including HE staining for histopathological changes, immunohistochemistry for neutrophil (MPO+) infiltration and microvessel (CD31+) quantity, as well as Masson staining for collagen deposition. The levels of inflammatory factors TNF-α, IL-1β, IL-10 and angiogenesis factors angiopoietin-2 (Ang-2), vascular endothelial growth factor (VEGF), as well as collagen type-I/type-III of the wound tissues were quantified by ELISA.ResultsAll of doses hUCMSCs can significantly increase wound healing rate and shorten healing time of the deep partial-thickness burn pigs in a dose-dependent manner. Furthermore, all of doses hUCMSCs can significantly promote epithelialization and decreased inflammatory reaction of wound, including infiltration of inflammatory cells and levels inflammatory factors. Meanwhile, the amounts of microvessel were increased in all of doses hUCMSCs group than those in the burn group. Furthermore, the collagen structure was disordered and partially necrotized, and ratios of collagen type-I and type-III were significantly decreased in burn group (4:1 in normal skin tissue), and those of all hUCMSCs groups were significantly improved in a dose-dependent manner. In a word, 1 × 10^8 dose of hUCMSCs could regenerate the deep partial-thickness burn wounds most efficaciously compared to other dosages groups and the burn group.ConclusionThis regenerative cell therapy study using hUCMSCs demonstrates the best efficacy toward a high dose, that is dose of 1 × 10^8 of hUCMSCs was used as a reference therapeutic dose for treating 20 cm2 deep partial-thickness burns wound in future clinical practice.Graphical abstract

Two Novel Membranes Based on Collagen and Polyphenols for Enhanced Wound Healing.

Two novel membranes based on collagen and two polyphenols, taxifolin pentaglutarate (TfG5) and a conjugate of taxifolin with glyoxylic acid (DfTf), were prepared. Fourier transform infrared spectroscopy examination confirmed the preservation of the triple helical structure of collagen. A scanning electron microscopy study showed that both materials had a porous structure. The incorporation of DfTf into the freeze-dried collagen matrix increased the aggregation of collagen fibers to a higher extent than the incorporation of TfG5, resulting in a more compact structure of the material containing DfTf. It was found that NIH/3T3 mouse fibroblasts were attached to, and relatively evenly spread out on, the surface of both newly obtained membranes. In addition, it was shown that the membranes enhanced skin wound healing in rats with a chemical burn induced by acetic acid. The treatment with the materials led to a faster reepithelization and granulation tissue formation compared with the use of other agents (collagen without polyphenols and buffer saline). It was also found that, in the wound tissue, the level of thiobarbituric acid reactive substances (TBARS) was significantly higher and the level of low-molecular-weight SH-containing compounds (RSH) was significantly lower than those in healthy skin, indicating a rise in oxidative stress at the site of injury. The treatment with collagen membranes containing polyphenols significantly decreased the TBARS level and increased the RSH level, suggesting the antioxidant/anti-inflammatory effect of the materials. The membrane containing TfG5 was more effective than other ones (the collagen membrane containing DfTf and collagen without polyphenols). On the whole, the data obtained indicate that collagen materials containing DfTf and TfG5 have potential as powerful therapeutic agents for the treatment of burn wounds.

Diabetic rats skin wounds treated with heterologous fibrin sealant followed by photobiomodulation therapy.

Diabetes mellitus is characterized by elevated blood glucose levels causing sometimes impairment of the body's ability to repair itself. Promising treatments for tissue repair have included photobiomodulation therapy and heterologous fibrin biopolymer (HFB). This study aimed to evaluate the impact of photobiomodulation therapy by LED, both as a standalone treatment and in conjunction with heterologous fibrin biopolymer in treatment of skin lesions of diabetic rats. Diabetes was induced using alloxan. Full-thickness skin wounds were induced on the backs of 56 Wistar rats, which were randomly allocated into four groups: control group, heterologous fibrin biopolymer group, photobiomodulation therapy by LED group, and photobiomodulation therapy by LED combined with heterologous fibrin biopolymer group. The treatments spanned two experimental periods, lasting 7 and 14 days. Notably, the HFB group exhibited results similar to those of the LED group concerning wound regression, while demonstrating superior resistance to healing. Interestingly, the LED + HFB group showed greater skin damage at 7 days, but an improved repair process at 14 days compared to the control group. The findings indicate that combining photobiomodulation by LED with HFB did not enhance wound healing in diabetic rats beyond the effects of each treatment alone. Both treatments were effective individually, with HFB showing particular strength in promoting collagen maturation and improving tissue biomechanical properties.This study contributes tothe ongoing body of research on skin repair with this innovative HFB. Future clinical trials will be essential to validate this proposition.

Association Between Wound Healing and the Japanese Below-the-Knee Chronic Total Occlusion Score in Patients With Chronic Limb-Threatening Ischemia After Endovascular Therapy.

In the current study, we hypothesized that the Japanese below-the-knee chronic total occlusion score could be used to stratify the lesion difficulty of endovascular therapy for below-the-knee chronic total occlusion through angiographic evaluation. We thus aimed to evaluate the prognostic impact of the Japanese below-the-knee chronic total occlusion score in patients with chronic limb-threatening ischemia after successful endovascular therapy for below-the-knee chronic total occlusion. This was a retrospective, single-center observational study. We enrolled 139 consecutive patients with chronic limb-threatening ischemia (149 limbs), who underwent successful endovascular therapy for chronic total occlusion between February 2008 and December 2017. The Japanese below-the-knee chronic total occlusion score was assessed based on the definition of the target arterial path. The evaluation items were the rate of amputation-free survival and wound healing at 1 year, and the association between wound healing at 1 year and the Japanese below-the-knee chronic total occlusion score. The rates of amputation-free survival and wound healing at 1 year were 88.0 and 56.4%, respectively. Multivariate Cox proportional hazard analysis identified direct flow to the wound (hazard ratio: 2.34, 95% confidence interval: 1.28-4.66; p<0.01); Wound, Ischemia, and foot Infection stages 1-3 (hazard ratio: 2.81, 95% confidence interval: 1.63-5.18; p<0.01); and a Japanese below-the-knee chronic total occlusion score ≤1 (hazard ratio: 1.70, 95% confidence interval: 1.02-2.98; p=0.04) to be predictors of wound healing. A Japanese below-the-knee chronic total occlusion score ≤1, direct flow to the wound, and Wound, Ischemia, and foot Infection stages 1-3 were found to be associated with wound healing after successful endovascular therapy for below-the-knee chronic total occlusion in patients with chronic limb-threatening ischemia. This study was conducted to evaluate the prognostic impact of the Japanese below-the-knee chronic total occlusion (J-BTK CTO) score in patients with chronic limb-threatening ischemia (CLTI) after successful endovascular treatment (EVT). The results showed that the J-BTK CTO score not only evaluates the difficulty of EVT but also can predict limb prognosis. Using the J-BTK CTO score, it seems possible to predict the limb prognosis and make it useful in clinical practice.

The Investigation of the Effect of Boron on Intestinal Incision Wound Healing in Rats

In this study 250-300 g 38 adult male Wistar Albino rats were used, randomly divided into six groups as four groups that received boron (n=7/group) and two control groups (n=5/group). Etibor-48 (Borax pentahydrate) was diluted in saline and administered by gavage. The Boron 1 group received 10 mg/kg boron for three days and the Boron 2 group received 10 mg/kg for seven days, Boron 3 group received 30 mg/kg for three days, and the Boron 4 group, received 30 mg/kg for seven days before the start of the study. On day 0, colon incisional wound was performed for all rats under general anesthesia and sutured. Control groups took no drugs and were euthanized on the third and seventh postoperative days. Blood sampling were done via cardiac punction at necropsy to measure Interleukin-1, IL-6, TNF-α, MPO, MDA, NO, GSH, and AOA. The sutured bowel incision line was evaluated histopathologically. Inflammatory cell measurement results in Boron 1, 2, 3, and 4 groups, and Control 3- and 7-day groups were 2.93±0.41, 3.93±0.41, 3.61±0.55, 3.93±0.41, 1.26±0.41, and 1.43±0.51, respectively. There were statistical difference between the groups (P˂0.05). AOA measurement results in the Boron 1, 2, 3, and 4 groups, and Control 3- and 7-day groups were 7.38±0.64, 8.27±0.57, 9.07±1.16, 9.06±0.86, 10.00±1.47, and 9.86±0.54 mmol/L, respectively. There were statistical difference between the Boron 1 and the Control 3- and 7-day groups (P˂0.05). It is concluded that Borax pentahydrate solution 30 mg/kg had a positive effect on intestinal incisional wound healing, contrary to the literature.