Wounds In Diabetic Rats Research Articles

Immortelle essential oil-based ointment improves wound healing in a diabetic rat model.

The phytochemical analysis of the investigated Immortelle essential oil revealed the presence of monoterpenes and sesquiterpenes as major components that might be efficient as a wound healing potential agent. The present study aimed to develop an ointment based on the Immortelle essential oil and investigate its wound healing effects on excision wounds in diabetic rats. The topical formulated Immortelle ointment was subjected to pharmaco-technical characterization. Thirty-two diabetic rats with the induced excision wound were used to evaluate in vivo wound healing effects of ointment. The animals were randomly divided into four groups untreated or topically treated with either a 1% silver sulfadiazine, the ointment base, or Immortelle ointment. The response to the treatment was assessed by macroscopic, biochemical and histopathological analysis. The ointment, compatible with the skin remained stable for 6 months. Topical application of the Immortelle ointment showed the highest wound contraction with the highest content of hydroxyproline in comparison to the all examined groups. The Immortelle ointment showed significant wound contraction from day 7 to day 21 as compared to other groups. On the day 21, there was an average of 99.32% wound contraction in the Immortelle group, whereas the mean wound contraction in the negative control and ointment base group was 71.36% and 81.26% respectively. The histopathological results validated the potential wound healing effect of Immortelle ointment with evident post-excision scar maturation and increased collagen fibers density. Our findings revealed that the Immortelle ointment approach might serve as a promising and innovative tool for wound healing.

Mussel-inspired collagen-hyaluronic acid composite scaffold with excellent antioxidant properties and sustained release of a growth factor for enhancing diabetic wound healing.

Long-term non-healing diabetic wounds are always a serious challenge and a global healthcare burden that needs to be resolved urgently in the clinic. Prolonged inflammation and impaired angiogenesis are the main direct causes of diabetic wounds. With the development of polymer biomaterials, various wound dressings have been created, but a few of them have been applied to the clinical management of diabetic wounds. Here, we developed a mussel-inspired bioactive scaffold consisting mainly of collagen and hyaluronic acid, which are natural biopolymer materials contained in human tissues. First, we fabricated different polydopamine modified lyophilized collagen hyaluronic acid scaffolds under different concentrations of dopamine alkaline solutions, 0.5, 1, 2 ​mg/mL, so named CHS-PDA-0.5, CHS-PDA-1, CHS-PDA-2. After testing their physical and chemical properties, antioxidant effect, inflammation regulation, as well as drug loading and release capabilities, we obtained a bioactive endothelial growth factor (EGF)-loaded wound dressing, CHS-PDA-2@EGF, which can resist reactive oxygen species (ROS) and promote the regeneration of chronic wounds in diabetic rats by reducing inflammation. In addition, the scaffold showed excellent swelling ability, a certain coagulation effect and reasonable degradation. Therefore, the scaffold has great potential to be used in clinical diabetic wound treatment as a low-cost and easily available wound dressing to accelerate chronic wound healing.

Thioctamer: a novel thioctic acid–glatiramer acetate nanoconjugate expedites wound healing in diabetic rats

The current work aims to design thioctic acid (TA) and glatiramer acetate (GA) nanoconjugate (thioctamer) loaded hydrogel formula as well as evaluation of thioctamer preclinical efficacy in expediting wound healing in a rat model of the diabetic wound. Thioctamer was prepared by conjugation of GA and TA in a 1:1 molar ratio. Particle size, zeta potential, and thermodynamic stability of the prepared thioctamer were assessed. Thioctamer was loaded in hydroxypropyl methylcellulose-based hydrogel and in vitro release study was investigated. The ability of thioctamer to enhance the process of wound healing in diabetic rats was investigated by assessing wound contraction and immunohistochemical assessment of the inflammation markers IL-6 and TNF-α. The results demonstrated that thioctamer showed particle size of 137 ± 21.4 nm, polydispersity index (PDI) of 0.235, and positive zeta potential value of 7.43 ± 4.95 mV. On day 10 of making a skin excision, diabetic rat wounds administered thioctamer preparation showed almost complete healing (95.6 ± 8.6%). Meanwhile, % of wound contraction in animals treated with TA or GA groups exhibited values amounting to 56.5 ± 5.8% and 62.6 ± 7.1%, respectively. Histological investigation showed that the highest healing rate was noted in the thioctamer group animals, as the surface of the wound was nearly fully protected by regenerated epithelium with keratinization, with few inflammatory cells noticed. Thioctamer significantly (p<.05) inhibited IL-6 and TNF-α expression as compared with sections obtained from the negative control, TA, GA, or positive control group animals on day 14. The evidence of the ability of thioctamer to significantly expedite wound healing in the diabetic rats is presented.

Human adipose-derived stem cell-loaded small intestinal submucosa as a bioactive wound dressing for the treatment of diabetic wounds in rats.

Chronic nonhealing wounds are one of the most common and serious complications of diabetes, which can lead to disability of patients. Adipose-derived stem cells (ADSCs) have emerged as a promising tool for skin wound healing, but the therapeutic potential depends considerably on the cell delivery system. Small intestinal submucosa (SIS) is an extracellular matrix-based membranous scaffold with outstanding repair potential for skin wounds. In this study, we first fabricated a bioactive wound dressing, termed the SIS+ADSCs composite, by using human ADSCs as the seed cell and porcine SIS as the cell delivery vehicle. Then, we systematically investigated, for the first time, the healing potential of this wound dressing in a rat model of type 2 diabetes. In vitro studies revealed that SIS provided a favorable microenvironment for ADSCs and significantly promoted the expression of growth factors critical for chronic wound healing. After implantation in the full-thickness skin wounds of diabetic rats, the SIS+ADSCs composite showed a higher wound healing rate and wound healing quality than those in the PBS, ADSCs, and SIS groups. Along with the ability to modulate the polarization of macrophages in vivo, the SIS+ADSCs composite was potent at promoting wound angiogenesis, reepithelialization, and skin appendage regeneration. Taken together, these results indicate that the SIS+ADSCs composite has good therapeutic potential and high translational value for diabetic wound treatment.

Moringa oleifera Leaf Extract Promotes Healing of Infected Wounds in Diabetic Rats: Evidence of Antimicrobial, Antioxidant and Proliferative Properties.

Moringa oleifera is known to possess wound healing activity. The present study evaluated the healing properties of methanolic extract of M. oleifera leaves in excision wounds infected with methicillin-resistant Staphylococcus aureus (MRSA) or P. aeruginosa in diabetic rats. An in vitro study was also carried out to determine the gene expression of VEGF and TGF-β1. Preliminary phytochemical and GC-MS analyses were carried out to determine different chemical constituents present in the extract. M. oleifera was applied locally as an ointment at two different concentrations. Wound contraction, period of epithelization, antioxidant enzyme activities and histological changes were determined. For the gene expression study, HaCaT cell lines were used. The formulation of M. oleifera extract improved wound contraction and decreased the period of epithelization, which was associated with an increase in antioxidant enzyme activities, epithelization, capillary density and collagen formation in MRSA-infected diabetic rats. However, this effect was reduced in diabetic animals infected with P. aeruginosa. An increase in the expression of VEGF and TGF-β1 was observed in HaCaT cell lines. M. oleifera extract promotes the healing of infected wounds in MRSA-infected diabetic rats but is less effective in the healing of wounds infected with P. aeruginosa in diabetic rats.

Effect on Healing Potential of Biosynthesized Silver Nanoparticles in Streptozotocin induce Diabetic Rat Wound Model

Background: Diabetes mellitus is a complex chronic condition that results in hyperglycemic environment affecting the metabolism of proteins and lipids, promotes inflammation and delays wound healing. Methods: A total of n=30 Wistar rats of either sex were divided into five groups with 6 animals in each. Diabetes mellitus was induced using streptozotocin @ 35 mg/kg body weight and excision wound model was developed in all the animals. Group I and Group II were considered as healthy and diabetic control group respectively. The wounds of Group III, IV and V were treated with topical application of Carica papaya synthesized silver nanoparticles @ 62.5 µg/ml, Carica papaya leafextract @ 31.25 mg/ml and 10% povidone iodine respectively. Result: Present study concluded that the characteristics of silver nanaoparticles synthesized form C. papaya leaf extract make them suitable for the treatment of wound healing in diabetic subjects.

Dracorhodin Perchlorate Regulates the Expression of Inflammatory Cytokines through the TLR4 Pathway and Improves Skin Wound Healing in Diabetic Rats.

Background Dragon's blood is a natural medicine with hemostatic and blood-activating effects and is used to promote wound healing. Dracorhodin perchlorate (DP) is a stable form of dracarhod and is used as a substitute for cochinchinenin. DP promotes the proliferation of rat fibroblasts and promotes wound healing in rats. Methods DP ointment (0.2 mg/mL) was applied to the skin wounds of nondiabetic and diabetic rats, and the skin of the wound was collected. Wound healing rate, H&E staining, Masson staining, TLR4 pathway, related inflammatory factors, nitric oxide synthase, and so forth were detected. Results DP treatment alleviated the prolonged inflammatory cell infiltration time and the increase in the TLR4 pathway and inflammatory factors caused by diabetes. DP also promoted wound healing by increasing eNOS protein expression and NO content in the later stage of wound healing. Conclusion DP promotes wound healing in diabetic rats by regulating the TLR4 pathway and related inflammatory factors. Therefore, adjuvant treatment of DP can be developed for diabetic wound healing.

45S5 Bioglass® works synergistically with siRNA to downregulate the expression of matrix metalloproteinase-9 in diabetic wounds

Diabetic chronic wounds are difficult to heal because of the presence of excessive inflammation and high overexpression of matrix metalloproteinase-9 (MMP-9), which greatly affects the quality of life of patients with diabetes and increases the risk of death. Thus, the regulation of excessive inflammation and inhibition of MMP-9 overexpression are effective strategies to improve diabetic wound healing. The present study is the first to demonstrate that ion products of 45S5 Bioglass® (BG) can work with small interfering RNA of MMP9 (MMP9-siRNA) to reduce MMP-9 expression in tissue-forming cells and enhance the synthesis of extracellular matrix proteins (ECMs). Specifically, the BG ionic products can stimulate macrophages to convert to M2 phenotype, thereby creating a proregenerative inflammation microenvironment to indirectly suppress the expression of MMP-9 in tissue-forming cells. Chitosan nanoparticles encapsulating MMP9-siRNA (MMP9-siNP) can directly lower MMP-9 expression in tissue-forming cells. In addition, BG ionic products can promote the vascularization of endothelial cells and ECM protein synthesis by fibroblasts. Thus, injectable BG/sodium alginate (BG/SA) hydrogels loaded with MMP9-siNP can significantly accelerate the healing process of full-thickness excision wounds of diabetic rats by decreasing MMP-9 expression, improving collagen synthesis, and enhancing angiogenesis in the wounds, thereby demonstrating their great application potential in treating diabetic chronic wounds. Statement of significanceExcessive inflammation and high overexpression of MMP-9 have been considered as factors that severely hinder the healing process of diabetic chronic wounds. Effective strategies are required for the regulation of excessive inflammation and inhibition of MMP-9 overexpression to enhance diabetic wound healing. In the present work, an injectable bioglass/sodium alginate (BG/SA) hydrogel loaded with MMP9-siNP was developed; this hydrogel significantly accelerated the healing process of full-thickness excision wounds of diabetic rats by decreasing MMP-9 expression, improving collagen accumulation, and enhancing angiogenesis in the wounds. Thus, the BG/SA hydrogel loaded with MMP9-siNP has great potential for use in healing of diabetic chronic wounds.

Effect of aqueous extract from root and leaf of Sphenocentrum jollyanum pierre on wounds of diabetic rats: Influence on wound tissue cytokines, vascular endothelial growth factor and microbes

Ethnopharmacological relevanceSphenocentrum jollyanum is a flowering plant of the Menispermaceae family with bright yellow roots and wedged-shaped leaves. The plant is reputed to possess exceptional wound healing properties and used in folkloric medicine to dress chronic wounds. Aim of the studyWound repair in a hyperglycemic state is known to be impaired and delayed making treatment a difficult challenge. This study sought how the aqueous extracts of root and leaf of Sphenocentrum jollyanum facilitated wound healing by modulating pro-inflammatory cytokines, vascular endothelial growth factor and microbial colonization on excision wound created in diabetic rats. MethodsDiabetes (blood glucose >250 mg/dl) was induced by feeding normal rats with high fat diet for 14 days after which intraperitoneal injection of low dose streptozotocin (35 mg/kg b.w.) was administered. Wounds were subsequently created and treatments administered afterwards for 14 days. ResultsAdministration of Sphenocentrum jollyanum root and leaf extracts both orally and topically (100 and 200 mg/kg b.w) significantly (p < 0.05) reduced secretion of pro-inflammatory cytokines (TNF-α, IL-6), number of microbial colonies (CFU/ml × 102), activity of myeloperoxidase and significantly increased growth factor secretion on wounds of the diabetic rats. Histological evaluations of wound tissues of treated diabetic rats revealed matured tissue granulation, presence of new blood vessels, collagen and fibroblast with fewer inflammatory cells. ConclusionThe use of Sphenocentrum jollyanum effectively enhanced wound healing which may be related to constituents identified by GC-MS analysis and can thus, be suggested as a therapeutic agent for diabetic wound management.

The Healing Capability of Clove Flower Extract (CFE) in Streptozotocin-Induced (STZ-Induced) Diabetic Rat Wounds Infected with Multidrug Resistant Bacteria.

Treatment of diabetic foot ulcer (DFU) is of great challenge as it is shown to be infected by multidrug resistant bacteria (MDR bacteria). Sixty four bacterial isolates were isolated from DFU cases; antibiotic susceptibility tests were carried out for all of them. One bacterial isolate (number 11) was shown to resist the action of 8 out of 12 antibiotics used and was identified by both a Vitek-2 system and 16S rRNA fingerprints as belonging to Proteus mirabilis, and was designated Proteus mirabilis LC587231 (P. mirabilis). Clove flower extract (CFE) inhibited distinctively the P. mirabilis bacterium obtained. GC-MS spectroscopy showed that this CFE contained nine bioactive compounds. The effect of CFE on wound healing of Type 1 diabetic albino rats (Rattus norvegicus) was studied. The results indicated that topical application of CFE hydrogel improved wound size, wound index, mRNA expression of the wound healing markers (Coli1, MMP9, Fibronectin, PCNA, and TGFβ), growth factor signaling pathways (PPAR-α, PGC1-α, GLP-1, GLPr-1, EGF-β, EGF-βr, VEGF-β, and FGF-β), inflammatory cytokine expression (IL8, TNFα, NFKβ, IL1β, and MCP1), as well as anti-inflammatory cytokines (IL4 & IL10), pro-apoptotic markers (FAS, FAS-L, BAX, BAX/BCL-2, Caspase-3, P53, P38), as well as an antiapoptotic one (BCL2). Furthermore, it improved the wound oxidative state and reduced the wound microbial load, as the cefepime therapy improved the wound healing parameters. Based on the previous notions, it could be concluded that CFE represents a valid antibiotics alternative for DFU therapy since it improves diabetic wound healing and exerts antibacterial activity either in vitro or in vivo.

Effects of Hypericum scabrum L. essential oil on wound healing in streptozotocin-induced diabetic rats

Background The purpose of this study was to see if the essential oil of Hypericum scabrum L. (H. scabrum L.) has a protective and therapeutic effect on the wound in streptozotocin-induced diabetic rats. Methods In the study, 63 Sprague-Dawley male rats weighing 250–300 g were divided into nine groups, each with seven rats (major groups: control group, diabetes group, and treatment group). For diabetes and treatment groups, streptozotocin (STZ) was given in a single dose of 60 mg/kg/i.p. In 7 days, the animals with diabetes (blood glucose level > 250 mg/dL) will be assigned to wound groups. All of the rats had circular full-thickness incisions in their dorsal skin caused by a 5 mm punch biopsy tool. The rats were slaughtered, blood was obtained, and their forwound tissues were dissected on the 3rd, 10th, and 14th post-wounding days. The levels of malondialdehyde (MDA) and glutathione (GSH), as well as the activities of glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) in plasma and wound tissues, were all measured. Results While GSH level, GPx, SOD, and CAT activities were decreased in the plasma and wound tissues, MDA level increased in the diabetic group as compared to the control group. When compared to the diabetes group, GSH level, GPx, SOD, and CAT activities were increased in the H. scabrum L. essential oil treatments, but MDA levels were decreased. In comparison to the other groups, the wounds in the H. scabrum L. essential oil diabetic groups healed better and faster. H. scabrum L. essential oil can help to reduce lipid peroxidation, oxidative stress, and the associated complications that come with it, as well as play a beneficial role in the treatment of diabetic wounds. Conclusion Since no information was found in the literature search, future work would focus on new research examining H. scabrum L. essential oil applications to come up with new findings in determining the mechanisms of action of H. scabrum L. essential oil in diabetic wounds and preventing wound healing complications in diabetic rats.

AGEs-induced MMP-9 activation mediated by Notch1 signaling is involved in impaired wound healing in diabetic rats

AimsTo elucidate the relationship between advanced glycation end products (AGEs), Notch1 signaling, nuclear factor-kappa B (NF-κB), and matrix metalloproteinase-9 (MMP-9) in diabetic wound healing in vitro and in vivo. MethodsWe incubated primary keratinocytes with AGEs alone or AGEs along with γ-secretase inhibitor DAPT, and established diabetic rat wound model by intraperitoneal streptozotocin treatment. The Notch1 signaling components and MMP-9 expression were detected by qPCR, western blotting and gelatin zymography. ResultsThe exposure of primary keratinocytes to AGEs led to a significant increase in Notch intracellular domain (NICD), Delta-like 4 (Dll4), and Hes1; however, Notch1 expression was inhibited by the RAGE siRNA. Furthermore, MMP-9 activation was up-regulated, secondary to AGEs treatment. In contrast, increased MMP-9 expression by AGEs-stimulation was eliminated after treatment with DAPT. NF-κB activation participated in the Notch1-modulated MMP-9 expression. Notably, in the diabetic animal model, inhibition of the Notch signaling pathway with DAPT attenuated NICD and MMP-9 overexpression, improved collagen accumulation, and ultimately accelerated diabetic wound healing. ConclusionsThese findings identified that activation of the Notch1/NF-κB/MMP-9 pathway, in part, mediates the repressive effects of AGEs on diabetic wound healing and that targeting this pathway may be a potential strategy to improve impaired diabetic wound healing.

Paracrine effects of adipose-derived stem cells in cutaneous wound healing in streptozotocin-induced diabetic rats.

The purpose of this study was to explore the paracrine effects of adipose-derived stem cells (ASCs) on cutaneous wound healing in diabetic rats. The ASCs were isolated and identified by immunofluorescent staining. The ASCs-conditioned medium (ASCs-CM) was harvested. Cell counting kit (CCK)-8 assay, scratch experiments, western blot and quantitative polymerase chain reaction (qPCR) were performed to observe the effects of ASCs-CM on fibroblasts. A full-thickness skin wound diabetic rat model was prepared, using 34 male, Sprague Dawley rats. ASCs-CM or negative-control medium (N-CM) was injected around the wound surface. The existing wound area was measured on days 4, 8, 12 and 16 after the postoperative day, and the wound tissues were collected for immunohistochemical staining and qPCR quantitative study. In this experiment, the isolated cells were characterised as ASCs. The results of CCK-8 assay, cell scratch test, western blot and qPCR showed ASCs-CM could significantly promote the proliferation, migration and differentiation of fibroblasts. Simultaneously, the healing rate of full-thickness skin wounds in diabetic rats was significantly higher in the ASCs-CM group than the N-CM group on days 4, 8, 12 and 16. Immunohistochemical staining and qPCR results showed that the expression of vascular endothelial growth factor (VEGF, days 4 and 8), α-smooth muscle actin (SMA) (days 4 and 16), transforming growth factor (TGF)-β1 (days 4, 8 and 12) were higher in the ASCs-CM group than that of the N-CM group (p<0.05). This experiment demonstrated that ASCs-CM may accelerate wound healing in diabetic rats by promoting the secretion of TGF-β1, VEGF and the proliferation, migration and differentiation of fibroblasts.

Topical Polydeoxyribonucleotide Loaded in Hydrogel Formulation for Wound Healing in Diabetic Rats

Patients with diabetes mellitus experience delayed wound healing because of the uncontrolled glucose level leads to impaired cell proliferative function, poor circulation, decreased production and repair of new blood vessels. Polydeoxyribonucleotide (PDRN) is used in wound healing as a substance that stimulates tissue repair. A hydrogel is a reticular substance generally used as a dressing formulation to accelerate wound healing, and also used as a bio-applicable scaffold or vehicle. The aim of study is to investigate the effects of PDRN loaded in hydrogel on wound healing, in combination and separately, in an animal diabetic wound model.&#x0D; Methods: We studied the effects of PDRN in diabetes-related healing defect using an incisional skin-wound model produced on the back of male diabetic rats. A total of 36 wounds, were classified into 3 groups: a control group, a hydrogel-only group, a PDRN loaded in hydrogel combined-treatment group. All rats were assessed for changes in wound size and photographed on scheduled dates. The skin specimen sample of diabetic rat wound model were observed on 3, 7, 14 and 21 days after skin injury to measure tissue remodeling through histological evaluation of fibroblasts proliferation, and collagen production, also the number of blood vessels was measured in all specimens.&#x0D; Results: Differences in the decrease and change in wound size in the PDRN loaded in hydrogel group were more significant than those in the control and hydrogel single-treatment groups. Analysis of the fibroblasts proliferation, collagen production and number of blood vessels through histological examination showed a pattern of increase over time that occurred in PDRN loaded in hydrogel combined-treatment group.&#x0D; Conclusion: This experiment demonstrated improved wound healing using a PDRN loaded in hydrogel combined treatment compared to either two groups, resulting in a decrease in diabetic wound size and a shortening of the healing period

Acceleration of wound healing by quercetin in diabetic rats requires mitigation of oxidative stress and stimulation of the proliferative phase

ABSTRACT Increased oxidative stress in diabetic wound areas impairs wound healing. Quercetin exhibits significant antioxidant properties. We investigated the effects of topical quercetin on antioxidant status in diabetic wound areas and its effect on wound healing in rats. A 2 cm2 cutaneous wound was produced on the back of streptozotocin induced diabetic and normal rats. Rats were divided into three groups of 20: normal healthy control group, diabetic group and quercetin treated diabetic group. The control and diabetic groups were treated topically with ointment base once daily for 21 days. The quercetin treated diabetic rats were treated similarly with ointment containing quercetin. The quercetin treated diabetic group exhibited increased levels of catalase, glutathione peroxidase, superoxide dismutase and total thiols compared to the diabetic group. Nitrite levels in the diabetic group were decreased significantly on day 3 compared to the healthy control group. Malondialdehyde levels were decreased in the quercetin treated diabetic group compared to the diabetic group. The expression of proliferating cell nuclear antigen) (PCNA) was greater in the quercetin treated diabetic group on day 7 compared to healthy control and diabetic groups. Formation of granulation tissue and the quality of healed tissue was improved in the quercetin treated diabetic group compared to the diabetic group. Quercetin improves antioxidant status in wounds of diabetic rats and stimulates the proliferation phase, which accelerates wound healing.

Potential Use of Tailored Citicoline Chitosan-Coated Liposomes for Effective Wound Healing in Diabetic Rat Model.

PurposeThis study aimed to formulate citicoline-loaded chitosan-coated liposomes (CT-CS-LPs) for topical administration and evaluated for wound healing in a diabetic animal model.MethodsCT-LPs were formulated via a thin-film hydration approach and coated with chitosan (CS). Box-Behnken statistical design investigated the effects of lipid amount, chitosan concentration, and cholesterol amount on vesicle diameter, surface charge, and entrapment efficiency. The potential of the optimized CT-CS-LPs gel for wound healing was further evaluated in streptozocin-induced diabetic rats. The different healing stages were evaluated by several techniques, including general and special staining techniques, in addition to antibody immunohistochemistry.ResultsThe optimized CT-CS-LPs obtained had a mean size of 211.6 nm, a 50.7% entrapment efficiency, and a positive surface charge of 32.1 mV. In addition, the optimized CT-CS-LPs exhibited in vitro sustained release behavior. The in vivo experiments revealed that treatment with the optimized CT-CS-LPs boosts the healing process of the skin wound in diabetic rats by reducing inflammation, accelerating re-epithelization, angiogenesis, fibroblast proliferation, and connective tissue remodeling, leading to rapid wound closure.ConclusionChitosan-coated liposomes containing citicoline have emerged as a potential approach for promoting the healing process in diabetic rats. However, the therapeutic effectiveness of the suggested approach in diabetic patients needs to be investigated.

Herbal Oils for Treatment of Chronic and Diabetic Wounds: A Systematic Review.

In the present scenario, diabetes is a growing health challenge, and its occurrence is growing across the globe. Diabetes, with its complications like diabetic wounds, vasculopathy, neuropathy, wound infections, and oxidative stress, is a serious cause of mortality worldwide. Among the various complications, treatment of diabetic foot and ulcers is one of the major concerns in patients who are suffering from diabetes. The causative factors for this condition include increased oxidative stress, high blood glucose levels, vascular insufficiency, and microbial infections, and many a time, if left untreated, it may even lead to amputations of the lower extremities. The present therapy for the treatment of diabetic wounds mainly involves the use of synthetic moieties and other biotechnology-derived biomolecules, including growth factors. Few plant products are also useful in the treatment of wounds. Essential oils derived from various herbs are reported to possess significant wound healing potential and promote blood clotting, help to fight infections, and accelerate the wound healing process. Hence, the present review is a systematic analysis of all the available data on the use of the natural oils with their biological source, active phytochemical constituents present, and the probable mechanism of action for the treatment of chronic and diabetic wounds in suitable animal models. A methodical collection of data was performed, and information was searched up to April 2020 in entirety. Key phrases used for the data search include the pathophysiology of wounds, diabetic foot wound and its complications, natural oils for chronic and diabetic wound treatment. This review summarizes the natural oils which are reported in the literature to be beneficial in the treatment of chronic wounds, while some oils have been specifically also studied against wounds in diabetic rats. Essential oils are said to interact with the body pharmacologically, physiologically and psychologically and help in rapid wound healing. However, the majority of the literature studies have demonstrated wound healing activity only in animal models (preclinical data), and further clinical studies are necessary. This review provides a platform for further studies on the effective utilization of natural oils in the treatment of chronic and diabetic wounds, especially if oils are to receive credibility in the management of chronic wounds.

Preparation of pro-angiogenic, antibacterial and EGCG-modified ZnO quantum dots for treating bacterial infected wound of diabetic rats

The complex wound environment and abnormalities in self-metabolism of diabetic skin defects lead to impaired angiogenesis, which can easily lead to bacterial infection and increased inflammation. Therefore, there is an urgent need for multifunctional composites with antimicrobial and pro-angiogenic properties to improve the current therapeutic outcomes of diabetic wounds. In this study, we described an EGCG-modified zinc oxide quantum dots (ZnO QDs) hydrogel (ZnO-EGCG@H) for the treatment of delayed diabetic wounds. In vitro antimicrobial assays showed that ZnO-EGCG@H effectively cleared 95.6% of MRSA and 97% of AmprE. coli with good bactericidal activity. Western blotting assay analysis showed that ZnO-EGCG@H downregulated trauma inflammatory factors (TNF-α, IL-6) by 46.9% and 57%, respectively, while upregulating 1.7-fold VEGF and 2-fold EGF, accelerating wound healing by reducing inflammatory response and promoting proliferation of vascular endothelial cells and skin epidermal cells. After 15 days of ZnO-EGCG@H treatment, the rate of skin lesion closure in rats was 96.3%, which was much better than that of 65.4% in the control group. Safety experiments showed that ZnO-EGCG@H was reassuringly biocompatible and harmless to vital organs. The obtained results suggested that ZnO-EGCG@H had the potential to be a safe and effective treatment method with a promising future as a diabetic wound treatment material.

B1 siRNA Increases de novo DNA Methylation of B1 Elements and Promotes Wound Healing in Diabetic Rats.

Alu (B1 in rodents) hypomethylation, commonly found in diabetes mellitus patients, increases DNA damage and, consequently, delays the healing process. Alu siRNA increases Alu methylation, reduces DNA damage, and promotes cell proliferation. Aim: To explore whether B1 siRNA treatment restores B1 hypomethylation, resulting in a reduction in DNA damage and acceleration of the healing process in diabetic rat wounds. Methods: We generated splinted-excisional wounds in a streptozotocin (STZ)-induced type I diabetic rat model and treated the wounds with B1 siRNA/Ca-P nanoparticles to generate de novo DNA methylation in B1 intersperse elements. After treatment, we investigated B1 methylation levels, wound closure rate, wound histopathological structure, and DNA damage markers in diabetic wounds compared to nondiabetic wounds. Results: We reported that STZ-induced diabetic rat wounds exhibited B1 hypomethylation, wound repair defects, anatomical feature defects, and greater DNA damage compared to normal rats. We also determined that B1 siRNA treatment by Ca-P nanoparticle delivery restored a decrease in B1 methylation levels, remedied delayed wound healing, and improved the histological appearance of the wounds by reducing DNA damage. Conclusion: B1 hypomethylation is inducible in an STZ-induced type I diabetes rat model. Restoration of B1 hypomethylation using B1 siRNA leads to increased genome stability and improved wound repair in diabetes. Thus, B1 siRNA intervention may be a promising strategy for reprogramming DNA methylation to treat or prevent DNA damage-related diseases.

Allotransplantation of ascorbic acid-treated fibroblasts improves healing of excisional cutaneous wound in diabetic rats

The purpose of this study was to evaluate the effects of ascorbic acid (AA)-treated fibroblasts transplantation on excisional diabetic wound healing. An excisional wound was created between the shoulders of streptozotocin-induced diabetic rats. On day three, 1 ml of PBS, ‎1 × 106 ‎intact homologous fibroblasts, and ‎1 × 106 ‎ fibroblasts treated with 50 μM AA were injected subcutaneously around the wound edges in control, treatment-1 and treatment-2 groups, respectively. In the sham group, the wound was left intact. Wound area was measured by planimetry. On day 15, samples were harvested for histopathological examination and hydroxyproline content. Wound area in treatment-1 and − 2 groups was ‎significantly decreased compared to other groups, on days 11 and 15. The hydroxyproline content was significantly lower in the control group compared to the other groups. Histopathology revealed significant increases in the number of neovessels, macrophages, lymphocytes and fibroblasts in the treatment-2 group compared to the other groups. Trichrome staining showed the highest level of collagen deposition and orientation in the treatment-2 group. In conclusion, allotransplantation of ‎50 μM ‎ AA-treated fibroblasts ‎could result in progressive healing and improved reparative indices of excisional dermal wound in diabetic rats.