Wounds In Rats Research Articles

The Effectiveness of Sungkai Leaf (Peronema canescens Jack.) Extract Gel on the Collagen Density of Incision Wounds in Vivo

An incision is an open wound resulting in skin injury and underlying tissues. The wound-healing process involves a proliferative phase that produces collagen. Sungkai leaves (Peronema canescens Jack.) can be used as an alternative therapy for wound healing because it contains flavonoids, tannins, and saponins that stimulate fibroblasts to synthesize collagen. This study aimed to determine the effectiveness of sungkai leaf extract gel in healing incision wounds in vivo based on collagen density scoring. Twenty-five Wistar rats (Rattus norvegicus) were randomly divided into five groups, the negative control group (K1) was given a gelling agent CMC 1%, the positive control group (K2) was given bioplacenton gel 1%, the treatment group (K3, K4, K5) was given a gel sungkai leaf extract concentration of 5, 10, and 15. The treatment is given topically at the incision site of the incision site of 0.1 g once a day for 14 days. The rats were euthanized on the fifteenth day, and the incision area was excised for histopathological preparation. The data obtained were analyzed using Kruskal-Wallis with SPSS 26. The test results showed p=0.010, meaning there is a significant difference (p<0.05) between the entire treatment. Based on these results, the K4 group (Sungkai leaf extract gel concentration of 10%) showed the highest collagen density scoring results compared to other treatments. This study concludes that sungkai leaves effectively heal incision wounds in Wistar rats based on collagen density scoring parameter.

An alginate-Based tube gel delivering 2-deoxy-D-ribose for stimulation of wound healing.

Developing multifunctional wound dressings capable of inducing rapid angiogenesis and with antibacterial activity would be attractive for diabetic and superficial wound healing. Hydrogels delivered from tubes have several desirable features -they are easy to apply, keep the wound moist, reduce the entry of microorganisms and avoid the need for painful dressing removal. Previously we reported that 2 deoxy-D-ribose (2dDR) delivered from a variety of dressings is capable of promoting wound healing by stimulating angiogenesis. Alginate hydrogels are an ideal vehicle to deliver a bioactive agent capable of promoting wound healing. In this study we developed and evaluated a tube hydrogel capable of delivering 2dDR with the aim of achieving a stable, convenient to administer and biologically effective wound treatment. Further, we included the stabilizer 2-phenoxy ethanol which provided antimicrobial activity. We synthesized hydrogels by the Green method, using simple mixing of sodium alginate, propylene glycol, 2-phenoxy ethanol and 2dDR in water. FTIR (Fourier transformation infrared spectroscopy) analysis confirmed an absence of undesirable chemical changes in the gel components, and SEM images of the freeze-dried gels showed porous structures. When 2dDR alginate gel (2dDR-SA hydrogel) was placed in PBS at 37°C, almost 92% of 2dDR was released within 7days. When tested on cultured cells, 2dDR-SA hydrogels did not inhibit metabolic activity or proliferation, achieving up to 90 and 98% of control respectively over 7days. 2dDR-SA hydrogel also showed anti-bacterial activity against E. coli, Pseudomonas aeruginosa, Staphylococcus aureus, and MRSA which was attributable to the stabilizer 2-phenoxy ethanol in the hydrogel. Stimulation of angiogenesis in the chorioallantoic membrane assay by 2dDR-SA hydrogel was found to be significant compared to the blank-SA. Wound healing potential was studied in full-thickness wounds in rats where acceleration of wound healing was seen. H&E staining of the wound tissue showed an enhanced number of blood vessels and re-epithelization, and a reduced number of inflammatory cells in 2dDR-SA treated animals compared to blank-hydrogels while Masson's trichrome staining showed increased collagen deposition. In summary we describe a convenient to apply hydrogel which has promise for use in a range of superficial skin wounds including applications in chronic wound care.

Hydrogel-Containing Biogenic Silver Nanoparticles: Antibacterial Action, Evaluation of Wound Healing, and Bioaccumulation in Wistar Rats.

Wound infections are feared complications due to their potential to increase healthcare costs and cause mortality since multidrug-resistant bacteria reduce treatment options. This study reports the development of a carbomer hydrogel containing biogenic silver nanoparticles (bioAgNPs) and its effectiveness in wound treatment. This hydrogel showed in vitro bactericidal activity after 2 h, according to the time-kill assay. It also reduced bacterial contamination in rat wounds without impairing their healing since the hydrogel hydrophilic groups provided hydration for the injured skin. The high number of inflammatory cells in the first days of the skin lesion and the greater degree of neovascularization one week after wound onset showed that the healing process occurred normally. Furthermore, the hydrogel-containing bioAgNPs did not cause toxic silver accumulation in the organs and blood of the rats. This study developed a bioAgNP hydrogel for the treatment of wounds; it has a potent antimicrobial action without interfering with cicatrization or causing silver bioaccumulation. This formulation is effective against bacteria that commonly cause wound infections, such as Pseudomonas aeruginosa and Staphylococcus aureus, and for which new antimicrobials are urgently needed, according to the World Health Organization's warning.

3D printing MOF nanozyme hydrogel with dual enzymatic activities and visualized glucose monitoring for diabetic wound healing

Promoting rapid healing of diabetic wounds caused by hyperglycemia, bacterial infection, and chronic inflammation is a global challenge. To address this issue, we design and prepare a novel cerium-based MOF nanozyme hydrogel via 3D printing technology to provide a personalized hydrogel wound dressing. The hydrogel is unique in that cerium-based MOFs are grown into the hydrogel network, simplifying the printing process of MOF hydrogel. The prepared hydrogel exhibits specific catalytic activity to various oxygen free radicals and glucose concentration-dependent color changes due to the interconversion between different valence cerium ions. This feature allows for indirect monitoring of glucose content around the wound. Additionally, the hydrogel presented high antibacterial properties and biocompatibility. In animal experiments, diabetic wounds in rats with a size of 1 cm2 fully healed within 21 days due to the synergistic effect of the anti-inflammatory and hyperglycemia capabilities of the cerium-based MOF nanozyme hydrogel. The results suggest that this novel hydrogel will revolutionize traditional treatment methods in diabetic wounds and provide an efficient, rapid, personalized treatment program.

Pumpkin Seed Oil ‐Loaded Chitosan/Polyvinyl Alcohol Electrospun Nanofiber Scaffold for Dermal and Oral Wound Dressing

AbstractPumpkin seed oil was combined with polyvinyl alcohol (PVA) and chitosan (CS) to develop novel electrospun nanofibers that can serve as wound scaffolds. The main objective of this work is to evaluate the safety, drug release, and performance of these scaffolds for dermal and oral wound healing. The scaffolds were characterized using a field scanning electron microscope (FSEM), and Fourier transform infrared spectroscopy (FTIR). A series of tests were conducted, including the degree of swelling and degradation, in vitro drug release, antibacterial activity, and cytotoxicity in human dermal fibroblasts adult (HDFa). Wound healing activity in an excisional dermal and incisional oral wound's rat model was evaluated after 10 days. Antibacterial tests of the Pumpkin loaded CS/PVA nanofibers showed significant antibacterial activity against S. aureus and E. coli compared to negative controls. In vivo dermal wound healing showed that all treatment groups enhanced wound healing, as demonstrated by the increased wound closure percentages compared to negative control groups on 3, 5, and 10 days. Compared to other treatment groups, pumpkin‐loaded CS/PVA nanofibers significantly enhanced healing on 7 and 10 days, however, healing was delayed afterward. In oral wound healing, the qualitative Hematoxylin and Eosin (H−E) histological examination of the oral wounds treated with pumpkin‐loaded scaffolds showed an enhanced healing rate with healthy architecture compared to the wounds treated with unloaded scaffolds or untreated wounds. These results indicate that Pumpkin loaded nanofibers are promising for both dermal and oral wound healing. They offer a new safe and cheap alternative to the commercial treatments that are used for wound healing. The results also highlight the combination of using natural botanical compounds and emerging nanoscience for biomedical applications, primarily wound healing.

Cold plasma approach fortifies the topical application of thymoquinone intended for wound healing via up-regulating the levels of TGF-ß, VEGF, and α-SMA in rats

Wound healing is a series of coordinated events that involve tissue repair and regeneration. Cold atmospheric plasma approach sheds the light on the mechanism that initiates the inflammatory responses throughout the healing cascade. The present study was planned to assess the effect of thymoquinone treated with cold plasma (TQcp) on the rat wound model compared to thymoquinone (TQ). To assess the wound healing potential of TQcp, a full-thickness wound model was used. The induced wound was smeared, starting just after excision, twice daily with TQcp and TQ for 7 days. Our findings revealed that TQcp improved the skin healing potential by augmenting the skin regeneration indices as evidenced by enhancing the new production of hyaluronic acid and collagen type I. TQcp significantly reduced the skin content of tumor necrosis factor- α and inhibited the hypertrophic scarring by up-regulating the skin content of transforming growth factor-beta. Furthermore, TQcp enhanced the levels of interleukin-10, alpha smooth muscle actin and vascular endothelial growth factor, demonstrating a great potential for wound healing that also reflected in the histopathological and ultra-structural picture of the skin. Finally, our results demonstrated that TQcp revealed a significant potential for wound healing than TQ alone.

Free-flowing, self-crosslinking, carboxymethyl starch and carboxymethyl cellulose microgels, as smart hydrogel dressings for wound repair

Hydrogels are widely recognized and favoured as moist wound dressings due to their beneficial properties. However, their limited capacity to absorb fluids restricts their use in highly exuding wounds. Microgels are small sized hydrogels that have recently gained considerable attention in drug delivery applications due to their superior swelling behaviour and ease of application. In this study, we introduce dehydrated microgel particles (μGeld) that rapidly swell and interconnect, forming an integrated hydrogel when exposed to fluid. These free-flowing microgel particles, derived from the interaction of carboxymethylated forms of starch and cellulose, have been designed to significantly absorb fluid and release silver nanoparticles in order to effectively control infection. Studies using simulated wound models validated the microgels ability to efficiently regulate the wound exudate and create a moist environment. While the biocompatibility and hemocompatibility studies confirmed the safety of the μGel particles, its haemostatic property was established using relevant models. Furthermore, the promising results from a full-thickness wounds in rats have highlighted the enhanced healing potential of the microgel particles. These findings suggest that the dehydrated microgels can evolve as a new class of smart wound dressings.

Shockwave versus ultrasound therapy in the enhancement of Aloe vera in cutaneous wound healing

Objective: To investigate the healing efficacy of topical Aloe vera enhanced by shockwave or ultrasound therapy on wounds in rats and compare both effects. Method: A total of 75 male albino rats were randomly divided into equal groups A, B, C, D and E. Under anaesthesia, a wound (6cm2) was created on the back of each rat. Group A received topical Aloe vera under occlusive dressing followed by shockwave therapy with the following parameters: 600 shocks, four pulses/second and 0.11mJ/mm2. Group B received topical Aloe vera under occlusive dressing followed by therapeutic ultrasound with the following parameters: pulsed mode, 2:8 duty cycle, 1MHz and 0.5 W/cm2. Group C received the same treatment as group A but in a reversed sequence—the shockwave therapy followed by the Aloe vera gel. Group D received the same treatment as group B but in a reversed sequence—therapeutic ultrasound followed by the Aloe vera gel. And control group E only received topical Aloe vera under occlusive dressing. Each group received three sessions per week, for two weeks. Wound extent and shrinkage rates were measured at study initiation and at the end of each week. Results: There were significant wound reductions in groups A and B compared to C and D, respectively, and in group A compared to group B. Conclusion: Shockwaves and ultrasound were found to amplify the effect of the Aloe vera on the wound, and there was improved wound healing in the shockwave group A compared to the ultrasound group B.

Histological Evaluation of Skin Wound Healing After Using the Human Adipose Tissue-derived Stem Cells in Male Diabetic Rats

Background and Objectives The use of stem cells for skin wound healing is still facing serious challenges. This study aims to determine the effectiveness of human adipose tissue-derived stem cells (ADSCs) spray in histologically improving skin wounds in male diabetic rats. Subjects and Methods In this experimental study, mesenchymal stem cells were isolated from adipose tissue and cultured and characterized by evaluating the expression of specific CD markers. Microbial contamination in samples was assessed before treatment. Then, 18 male Wistar rats were divided into control and treatment groups. Diabetes was induced by a single injection of streptozotocin. Then, wounds with a diameter of 0.8 cm were created in the back of the rats. The ADSCs were sprayed on the wound area in the treatment group. Wound healing was assessed on days 7, 14, and 21 after treatment using visual observation and histopathological examination. The data were analyzed using ANOVA. Results Wound closure was accelerated on days 7, 14 and 21 in the treatment group compared to the control group. Histological examination showed that the skin thickness, angiogenesis, and epithelialization were higher in the treatment group on days 7, 14, and 21 compared to the control group. Conclusion The spray of ADSCs on the wound area can accelerate the healing process and can be used for skin wound repair.

A Comparative Study of Dichloromethane and Ethyl Acetate Root Extracts of <i>Celosia trigyna</i>: Phytochemical and Wound Healing Effect Analyses

Background: <i>Celosia</i> species have been validated to possess antimicrobial, anti-inflammatory, and antioxidant potential. This study was thus designed to comparatively determine the effect of dichloromethane and ethyl acetate root extracts of <i>Celosia trigyna</i> on Wistar rat wounds created by 8 mm biopsy punches.Methods: Phytochemical screening was performed on dichloromethane and ethyl acetate root extracts of <i>C. trigyna</i>. For animal studies, 25 adult female Wistar rats were randomly divided into five groups (group A-E; n=5). Group A served as the negative control, group B as a positive control, group C received dichloromethane extract (once/day), group D ethyl acetate extract (once/day), and group E was the vehicle control. All extracts and medication were administered topically. Wound area, wound contraction, period of epithelialization, macroscopic analysis, and histological examination were studied.Results: Phytochemical screening showed that saponins and terpenoids were particularly high in dichloromethane extracts while ethyl acetate extracts were highly rich in terpenoids. The results of wound areas, wound contraction, periods of epithelialization, and macroscopic and histological analyses showed that dichloromethane extract, ethyl acetate extract, and penicillin-treated groups showed better remediation respectively in order of efficacy compared to the negative and vehicle control groups. The histological examination revealed an evidence of tissue regeneration and collagen deposition in the extract-treated groups compared to the positive, negative, and vehicle control groups.Conclusion: In conclusion, both extracts of <i>C. trigyna</i> have a better healing potential compared to penicillin treatment with dichloromethane extract having a better wound healing potential than the ethyl acetate extract.

The hemostatic effect and wound healing of novel collagen-containing polyester dressing

Collagen plays an important role in hemostasis and tissue repair processes. Traditional passive wound dressings like gauze, bandage, and cotton wool could hardly fit the open wounds and exerted no active effect on wound healing. Even worse, they would adhere to the skin tissue, causing dehydration and second injury upon replacement. Polyester is commonly used in the medical field and is a safe and inexpensive polymer. Due to the hydrophobic surface, polyester does not adhere to tissue; however, polyester does not have the hemostatic properties. We designed a material composed of collagen and polyester, encapsulated hydrolyzed collagen in polyester particles, and made collagen-polyester non-woven fabric by melt blowing method, The collagen content was 1% and the collagen-polyester dressing exhibited a hydrophobic nature, preventing moisture from sticking to its surface. The purpose of this study was to compare the hemostatic effect of collagen-polyester nonwovens with conventional polyester pads, and to observe the adhesion of the pads to the wound. The wound healing and shrinkage rates of collagen-polyester dressings and conventional pads were compared in a rat wound healing test. The hemostatic test showed that the polyester pads containing 1% collagen significantly shortened the bleeding time compared with the traditional polyester pads, and retained the hydrophobicity and non-adhesion properties. The collagen-polyester dressing had better angiogenesis and granulation degree than the control group on the 14th day, and reduced the wound shrinkage rate. Collagen polyester dressings have excellent hemostasis, regeneration, shrinkage reduction and non-adhering for wounds. Overall, the novel collagen-containing polyester dressing is ideal choice for wound dressings.

EVALUATION OF THERAPEUTIC EFFICACY OF ALOE VERA GEL FOR EXCISIONAL WOUND HEALING MECHANISM USING ANIMAL MODEL

Wound-healing diseases are considered significant clinical issues in patients, which become more complicated in association with obesity, diabetes mellitus, and high blood pressure conditions. Various therapeutic options were available for the wound-repairing process. The current study project evaluated the healing properties of Aloe Vera gel on epidermal wounds in rats. Experimental animals (adult rats) were divided into groups A, B, and C with equal distribution. These groups represent treatment, without treatment, and control, respectively. A pair of wounds measuring 2cm x 2cm each was created hygienically on the back of each rat lateral to the spinal cord. The wounds were treated with homogenized Aloe Vera gel, while the injuries in the second group were treated with normal saline. Blood samples were collected on days 21 for hematology analysis with a standard method. Animals in group ‘A’ had significantly faster healing with shorter days of skin fall-off than the control and untreated group. Further biochemical changes in the packed cell volume, mean corpuscular volume, lymphocyte and neutrophil counts also showed significant results compared to the control group. The study concluded that Aloe Vera effectively treated epidermal wounds in adult rat models. An improvement occurred in the hematological profile of the experimental animals. These findings will go a long way in expanding the horizon of the clinical application of this plant in solving wound-healing problems in humans and other animal species.

Facile synthesis of zinc acetate/niacin MOFs for use in wound healing

Niacin (NA) and zinc (Zn) were used to fabricate metal organic frameworks (Zn-NA MOFs), based on coordination chemistry via a simple, rapid technique conducted at room temperature. The identity of the prepared MOFs was confirmed by Fourier-transform infrared, x-ray diffraction, scanning electron microscopy, and transmission electron microscopy, which showed cubic shaped, crystalline, microporous MOFs with an average size of 150 nm. Release of the active ingredients from the MOFs was proved to be pH dependent in a slightly alkaline medium (pH 8.5) with a sustained release rate of its two ingredients, NA and Zn, which have wound healing activity. Zn-NA MOFs proved to be biocompatible in the tested concentrations range (5–100 mg ml−1), with no cytotoxic effect on WI-38 cell line. Zn-NA MOFs at 10 and 50 mg ml−1 concentrations and their components, NA and Zn, exerted antibacterial effects against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. Wound healing effect of the Zn-NA MOFs (50 mg ml−1) was evaluated on full excisional rat wounds. Significant reduction of the wound area was observed after 9 d of treatment using the Zn-NA MOFs compared to the other treatment groups. Additionally, wounds were fully healed after 10 d of treatment with the Zn-NA MOFs with histological and immunohistochemical evidence of re-epithelization, collagen formation, and angiogenesis. Similar histological evidence was also observed in wounds treated with niacin only; however, with no significant wound closure rates. Nevertheless, the formation of new blood vessels, as confirmed by the vascular endothelial growth factor protein expression, was highest in the niacin group. Zn-NA MOFs synthesized using a facile, low-cost method are potentially capable of healing wounds rapidly and effectively.

Combined Use of Photobiomodulation and Curcumin-Loaded Iron Oxide Nanoparticles Significantly Improved Wound Healing in Diabetic Rats Compared to Either Treatment Alone.

Introduction: Here, we assess the therapeutic effects of photobiomodulation (PBM) and curcumin (CUR)-loaded superparamagnetic iron oxide nanoparticles (SPIONs), alone or together, on the maturation step of a type 1 diabetes (DM1) rat wound model. Methods: Full-thickness wounds were inflicted in 36 rats with diabetes mellitus (DM) induced by the administration of streptozotocin (STZ). The rats were randomly allocated to four groups. Group one was untreated (control); group two received CUR; group 3 received PBM (890 nm, 80 Hz, 0.2 J/cm2); group 4 received a combination of PBM plus CUR. On days 0, 4, 7, and 15, we measured microbial flora, wound closure fraction, tensile strength, and stereological analysis. Results: All treatment groups showed a substantial escalation in the wound closure rate, a substantial reduction in the count of methicillin-resistant Staphylococcus aureus (MRSA), a substantial improvement in wound strength, a substantially improvement in stereological parameters compared to the control group, however, the PBM+CUR group was superior to the other treatment groups (all, P≤0.05). Conclusion: All treatment groups showed significantly improved wound healing in the DM1 rat model. However, the PBM+CUR group was superior to the other treatment groups and the control group in terms of wound strength and stereological parameters.

Hydrophilic ZnO/C nanocomposites with superior adsorption, photocatalytic, and photo-enhanced antibacterial properties for synergistic water purification

Owing to the numerous potential applications of ZnO nanomaterials, the development of ZnO-based nanocomposites has become of great scientific interest in various fields. In this paper, we are reporting the fabrication of a series of ZnO/C nanocomposites through a simple “one-pot” calcination method under three different temperatures, 500 ℃, 600 ℃, and 700 ℃, with samples labeled as ZnO/C-500, -600, and -700, respectively. All samples exhibited adsorption capabilities and photon-activated catalytic and antibacterial properties, with the ZnO/C-700 sample showing superior performance among the three. The carbonaceous material in ZnO/C is key to expanding the optical absorption range and improving the charge separation efficiency of ZnO. The remarkable adsorption property of the ZnO/C-700 sample was demonstrated using Congo red dye, and is credited to its good hydrophilicity. It was also found to exhibit the most notable photocatalysis effect due to its high charge transfer efficiency. The hydrophilic ZnO/C-700 sample was also examined for antibacterial effects both in vitro (against Escherichia coli and Staphylococcus aureus) and in vivo (against MSRA-infected rat wound model), and it was observed to exhibit synergistic killing performance under visible-light irradiation. A possible cleaning mechanism is proposed on the basis of our experimental results. Overall, this work presents a facile way of synthesizing ZnO/C nanocomposites with outstanding adsorption, photocatalysis, and antibacterial properties for the efficient treatment of organic and bacterial contaminants in wastewater.

Mikania micrantha extract enhances cutaneous wound healing activity through the activation of FAK/Akt/mTOR cell signaling pathway

Mikania micrantha (MM) has been traditionally used for various health benefits, including mental health, anti-inflammatory, wound dressing, and healing of sores. However, the molecular mechanisms and dose required for the wound healing activity of MM have yet to be reported. Therefore, a study was conducted to evaluate the wound healing potential of a cold methanolic extract of MM through in vitro and in vivo studies. Human dermal fibroblast adult (HDFa) cells were treated with 0 (control), 75 ng/ml, 125 ng/ml, 250 ng/ml, and 500 ng/ml of MMmethanolic extract (MME) for 24 h. MME at 75 ng/ml has significantly (p˂0.05) promoted HDFa cell proliferation and migration. Further, MME has also been shown to enhance the invasiveness of human umbilical vascular endothelial cells (HUVECs), indicating the neovasculature for wound healing. The tube formation assay demonstrated a significant (p<0.05) increase in the angiogenic effect of the MME starting at a concentration of 75 ng/ml as compared to the control. Treatment of excision wounds in Wistar rats with 5% and 10% MME ointment significantly enhanced wound contraction compared to control animals. Incision wounds in rats treated with 5% and 10% MME showed a significant (p<0.01) increase in tensile strength compared to control. HDFa cells, and granulation tissue collected on day 14 post-wounding, revealed the modulation of the FAK/Akt/mTOR cell signaling pathway during the enhancement of wound healing. The results of gel zymography showed increased activity of MMP-2 and MMP-9 in the HDFa cells after treatment with the extract. It is concluded that MMEcan potentially accelerate cutaneous wound healing.

In Vivo Evaluation of Chitosan-Titanium Dioxide Nanopowder as Wound Dressing Material.

Films used for wound healing have many advantages, but should be flexible, robust, adherable and prevent maceration. Both Chitosan (CS) and Titanium dioxide nanopowder (TiO2 NP) have good properties to accelerate wound healing and can be used in preparing films. CS and TiO2 NP are combined to formulate films for wound healing. The physical, thermal, chemical, and mechanical characteristics of these films are to be assessed. The antibacterial activity of the films and their performance on wounded rats will be explored. Films made of CS and TiO2 NP were characterized by FTIR, TGA, DSC, XRD, and SEM. The films' mechanical characteristics and antimicrobial activity were tested. Films with acceptable mechanical properties were evaluated on rats. Generally, CS-TiO2 films had higher weight and thickness but lowered flexibility compared to films prepared using CS only. The chosen film showed excellent folding endurance with weight and thickness of around 21.98 mg and 0.16 mm. The surface pH for CS-TiO2 films was acidic, and for the selected film, it was 5.18. CS-TiO2 film was active against all studied bacteria and significantly higher than CS films. The antimicrobial activity of Gram-negative bacteria (P. aeruginosa and E. coli) was higher than that of Gram-positive bacteria (S. aureus). Finally, adding TiO2 NP to the films accelerated the healing process of the created wounds in a murine model, compared to control and CS-treated groups. Films of TiO2 NP and CS have suitable properties to be used in wound healing and can be further used in the future to load drugs.

Preparation of Ultra-Small Copper Nanoparticles-Loaded Self-Healing Hydrogels with Antibacterial, Inflammation-Suppressing and Angiogenesis-Enhancing Properties for Promoting Diabetic Wound Healing.

Bacterial invasion, protracted inflammation, and angiogenesis inhibition are hallmarks of chronic diabetic wounds, bringing about patient morbidity and rising healthcare costs. For such wounds, there are currently few efficient therapies available. We reported the development of carboxymethyl chitosan (CMCS)-based self-healing hydrogel loaded with ultra-small copper nanoparticles (Cunps) for local treatment of diabetic wound healing. The structure of Cunps was identified by XRD, TEM, XPS and other methods, and the characterization of the synthesized Cunps-loaded self-healing carboxymethyl chitosan (CMCS)-protocatechualdehyde (PCA) hydrogel (Cunps@CMCS-PCA hydrogel) was further investigated. The therapeutic effect of Cunps@CMCS-PCA hydrogel in diabetic wound healing was explored in vitro and in vivo. The findings showed that a kind of ultra-small size copper nanoparticles with excellent biocompatibility was prepared. CMCS was chemically conjugated to PCA to form self-healing hydrogels via the formation of an amide bond followed by the loading of ultra-small copper nanoparticles. The obtained Cunps@CMCS-PCA hydrogel showed a typical three-dimensional interlinked network structure with self-healing ability and porosity. It exhibited good biocompatibility in diabetic wounds. Furthermore, Cunps@CMCS-PCA hydrogel group significantly prevented bacterial growth in the skin wound of diabetic rats as compared to model group and CMCS-PCA hydrogel-treated group. After 3 days, no visible bacterial proliferation was observed. It also increased angiogenesis through Cunps mediated activation of ATP7A to prevent induction of autophagy. Furthermore, Cunps@CMCS-PCA hydrogel mainly depended on PCA-induced inhibition on inflammation of macrophage via JAK2/STAT3 signaling pathway. As a result, compared with delayed wound healing process with lower wound healing rate valued at 68.6% within 7 days in the model group, Cunps@CMCS-PCA significantly accelerated wound healing recovery and increased wound healing rate to 86.5%, suggesting that Cunps@CMCS-PCA hydrogel effectively accelerated wound healing. Cunps@CMCS-PCA hydrogel offered a new therapeutic approach for quickening diabetic wound healing.

Accelerated Wound Healing in Diabetic Rat by miRNA-185-5p and Its Anti-Inflammatory Activity.

Addressing both inflammation and epithelialization during the treatment of diabetic foot ulcers is an important step, but current treatment options are limited. MiRNA has important prospects in the treatment of diabetic foot refractory wound ulcers. Previous studies have reported that miR-185-5p reduces hepatic glycogen production and fasting blood glucose levels. We herein hypothesized that miR-185-5p might play an important role in the field of diabetic foot wounds. MiR-185-5p in skin tissue samples from patients with diabetic ulcers and diabetic rats were measured using quantitative real-time PCR (qRT-PCR). The streptozotocin-induced diabetes rat model (male Sprague-Dawley rats) for diabetic wound healing was conducted. The therapeutic potential was observed by subcutaneous injection of miR-185-5p mimic into diabetic rat wounds. The anti-inflammation roles of miR-185-5p on human dermal fibroblast cells were analyzed. We found that miR-185-5p is significantly downregulated in diabetic skin (people with DFU and diabetic rats) compared to controls. Further, in vitro upregulation of miR-185-5p decreased the inflammatory factors (IL-6, TNF-α) and intercellular adhesion molecule 1 (ICAM-1) of human skin fibroblasts under advanced glycation end products (AGEs). Meanwhile, the increase of miR-185-5p promoted cell migration. Our results also confirmed that the topical increase of miR-185-5p decreases diabetic wound p-nuclear factor-κB (p-NF-κB), ICAM-1, IL-6, TNF-α, and CD68 expression in diabetic wounds. MiR-185-5p overexpression boosted re-epithelization and expedited wound closure of diabetic rats. MiR-185-5p accelerated wound healing of diabetic rats, reepithelization, and inhibited the inflammation of diabetic wounds in the healing process, a potentially new and valid treatment for refractory diabetic foot ulcers.

UJI EFEKTIVITAS SALEP EKSTRAK ETANOL DAUN SIRIH CINA (Peperomia pellucida) TERHADAP PENYEMBUHAN LUKA EKSISI PADA TIKUS PUTIH (Rattus norvegicus)

ABSTRAK Wahyuni. Test the effectiveness of Chinese betel leaf ethanol extract ointment on excision wound healing in white rats (Supervised by: apt.Rika Puspita Sari, S.farm.,M.Si ) Wounds are physical injuries that can cause tears and damage to skin tissue. One type of the wound is an excision wound. An excision of wound caused by the cutting of tissue by a sharp object. The main goal in wound management is to achieve rapid healing with optimal fuction and good result. That can be achieved by preventing infection and trauma by providing an environtment that optimizes wound healing. One of the plants that have the potential to heal wounds is the Chinese betel plant that have the potential to heal wounds is the Chinese betel plant the purpose of the research to determine the effectiveness of giving Chinese betel leaf extract on excision wound healing in white rats(rattus norvegicus). The research was conducted in the laboratory of health the husada deli tua. The method of the research conducted out experimentally, the sample was extracted by the maceration method. And then the extract was formulated into ointment availability with concentrations of 2%,4%, and 8% furthermore, on evaluation of the availability of the ointment was carried out, by organoleptic test, homogeneity test, pH test and spreadability test. The result of the research for each group gave the best treatment experienced a decrease in the diameter of the cut wound was the positive control group (povidone iodine) and 8% concentration. Conclusions: the ethanol extract of chial betel leaf has the effectiveness of healing excision wounds at a concentration of 8% Keywords: Chinese betel leaf extract, excision wound