One of the serious challenges in diabetic patients is the occurrence of complications caused by the disease. One of the most important side effects is wounding in limbs. Due to the multifactorial nature of these wounds, treatments require a multifaceted approach. Therefore, the aim of the present study was whether the human amniotic membrane (HAM) in combination with menstrual blood-derived stem cells (MenSCs) could promote wound healing in diabetic rats. Thirty days after induction of diabetes, the animals were randomly allocated into four equal groups (n=15): the control group, HAM group, MenSC group, and HAM+MenSC group. Sampling was done on days 7, 14, and 21 for histological, molecular, and tensiometrical evaluations. The results showed that the wound healing rate, collagen deposition, volumes of new epidermis and dermis, as well as tensiometrical characteristics were significantly increased in the treatment groups compared to the control group, and these changes were more obvious in the HAM+MenSC ones (P<0.05). Moreover, the expression levels of TGF-β, bFGF, and VEGF genes were considerably increased in treatment groups compared to the control group and were greater in the HAM+MenSC group (P<0.05). This is while expression levels of TNF-α and IL-1β decreased more significantly in the HAM+MenSC group than the other groups (P<0.05). We concluded that the combined use of HAM and MenSCs has a more significant effect on diabetic wound healing.

In the current study, Cnicus benedictus extract was loaded into electrospun gelatin scaffolds for diabetic wound healing applications. Scaffolds were characterized in vitro by mechanical testing, cell culture assays, electron microscopy, cell migration assay, and antibacterial assay. In vivo wound healing study was performed in a rat model of diabetic wound. In vitro studies revealed fibrous architecture of our developed dressings and their anti-inflammatory properties. In addition, Cnicus benedictus extract-loaded wound dressings prevented bacterial penetration. In vivo study showed that wound size reduction, collagen deposition, and epithelial thickness were significantly greater in Cnicus benedictus extract-loaded scaffolds than other groups. Gene expression studies showed that the produced wound dressings significantly upregulated VEGF and IGF genes expression in diabetic wounds.

Chronic inflammation at diabetic wound sites results in the uncontrolled accumulation of pro-inflammatory factors and reactive oxygen species (ROS), which impedes cell proliferation and delays wound healing. To promote the healing of diabetic wounds, chitosan/gelatin hydrogels containing ceria nanoparticles (CNPs) of various sizes were created in the current study. CNPs\' efficacy in removing O 2 • - $$ {\\mathrm{O}}_2^{\\bullet -} $$ , •OH, and H2 O2 was demonstrated, and the scavenging ability of CNPs of varying sizes was compared. The in vitro experiments demonstrated that hydrogels containing CNPs could effectively protect cells from ROS-induced damage and facilitate mouse fibroblast migration. Furthermore, during the treatment of diabetic wounds in vivo, hydrogels containing CNPs exhibited anti-inflammatory activity and could reduce the expression of the pro-inflammatory factors TNF-α (above 30%), IL-6 (above 90%), and IL-1β (above 80%), and effectively promote wound closure (above 80%) by inducing re-epithelialization, collagen deposition, and angiogenesis. In addition, the biological properties and therapeutic effects of hydrogels containing CNPs of various sizes were compared and discussed. The finding revealed that hydrogels with 4 nm CNPs exhibited more significant biological properties and had implications for diabetic wound treatment.

Diabetic wound is one of the serious complications of diabetes, and the wound is persistent and easily recurring, which seriously endangers the health and life of patients. How to effectively promote the healing of diabetic wounds has been a hot spot and difficult area of clinical research. Some previous studies have shown that dihydromyricetin has the effects of regulating blood glucose, controlling the severity, and inhibiting scarring. In the present study, we used polylactic-co-glycolic acid nanoparticles as a carrier to load dihydromyricetin to make drug-loaded nanoparticles and applied them dropwise (200 µL) to diabetic mice wounds by topical application to observe the healing and scar formation of diabetic wounds. We found that the healing rate of the diabetic mice was faster and the scar formation was less obvious. In addition, the elevated blood glucose level and weight loss of the mice in the treatment group were also reduced. Therefore, nanoparticle-mediated dihydromyricetin may be an effective treatment for diabetic wounds.

BACKGROUND: Diabetes mellitus (DM) impairs wound healing. The aim was to determine whether DM influences mitochondrial respiration in wounded skin (WS) and non-wounded skin (NWS), in a pre-clinical wound healing model of streptozotocin (STZ)-induced diabetes.
METHODS: Six weeks after diabetes induction, two wounds were created in the back of C57BL/J6 mice. Using high-resolution respirometry (HRR), oxygen flux was measured, in WS and NWS, using two substrate-uncoupler-inhibitor titration protocols, at baseline (day 0), day 3 and 10 post-wounding, in STZ-DM and non-diabetic (NDM) mice. Flux control ratios for the oxidative phosphorylation (OXPHOS) capacity were calculated.
RESULTS: A significant increase in mitochondrial respiration was observed in STZ-DM skin compared to control skin at baseline. The OXPHOS capacity was decreased in WS under diabetes at day 3 post-wounding (inflammation phase). However, at day 10 post-wounding (remodeling phase), the OXPHOS capacity was higher in WS from STZ-DM compared to NDM mice, and compared to NWS from STZ-DM mice. A significant relative contribution of pyruvate, malate and glutamate (PMG) oxidation to the OXPHOS capacity was observed in WS compared to NWS from STZ-DM mice, at day 10, while the relative contribution of fatty acid oxidation to the OXPHOS capacity was higher in NWS. The OXPHOS capacity is altered in WS from STZ-DM compared to NDM mice across the healing process, and so is the substrate contribution in WS and NWS from STZ-DM mice, at each time point.
CONCLUSIONS: HRR may be a sensitive tool to evaluate the underlying mechanisms of tissue repair during wound healing.

Diabetic foot ulcer is one of the most serious chronic complications of diabetes mellitus. It may lead to amputation of the lower extremities for diabetics. Our study was to evaluate the effect of electrospun poly (L-lactide-co-caprolactone) and formulated porcine fibrinogen (PLCL/Fg) wound dressing on animal wound model. A blend ratio of PLCL/Fg scaffold was 4 (PLCL):1 (Fg). The scanning electron microscopy findings showed that the fibers\' diameter was 122.5 ± 80.3 nm, and the tensile strength was 9.2 ± 0.2 MPa. In-vivo study of the hog normal model demonstrated that PLCL/Fg dressing had better biocompatibility, degradability, and ability to restore the skin\'s normal structure. We evaluated the wound healing processes in the rat diabetic model by macroscopic observation and histological observation at 1, 2, and 3 post-operation weeks. In our study, the PLCL/Fg group performed better 3 weeks after surgery, in terms of macroscopic healing and scarring. After surgery, the PLCL/Fg group showed better fibroblast accumulation, tissue granulation, and collagen expression than the control group. Topical treatment with PLCL/Fg dressing effectively enhanced wound healing in both normal and hyperglycemic conditions, suggesting that it may possess wound-healing potential.

Diabetic foot ulcers are a common complication that occurs in approximately 15 percent of patients with diabetes mellitus. Over 60% of diabetic foot ulcers are caused by underlying neuropathy. Former studies on diabetic animals with foot wounds found that vibration platforms significantly accelerate wound healing by catalyzing epithelization, promoting angiogenesis, and enhancing muscle bulk. This result suggests that there is evidence that vibrations may accelerate diabetic neuropathic ulcer healing in human patients. However, to the best of our knowledge, the effect of vibration on the enhancements of diabetic foot ulcer healing in human patients is rarely investigated. Hence, in this work, we conducted an experimental study with human subjects to investigate whether vibration therapy, as a complement to the standard wound treatment, can accelerate the wound healing rate of diabetic neuropathic foot ulcers. In this prospective experimental study, 80 participants diagnosed with Wagner grades I−III diabetic neuropathic foot ulcers were randomly distributed to experimental (n = 40) and control groups (n = 40). Patients in the intervention group received standard wound treatment and vibration wound therapy (VWT), whereas patients in the control group retrieved only standard wound treatment. The results (p = 0.024, α = 0.05) show notable differences in the median healing rate between the intervention group (25 days, 95% CI: 20.3−29.7) and control group (33 days, 95% CI: 25.6−40.4), with the effect-size r, Cohen’s d, Glass’s Δ, and Hedges’ g, respectively, being 0.810, 2.764, 2.311, and 2.772. Moreover, the nitric oxide (NO) level, wound closure area, and wound healing score after intervention significantly differed between the two groups (p < 0.05), putting the intervention group on a higher level than the control group. Furthermore, positive associations were found between the NO level and wound healing closure rates. These findings suggested that VWT enhances diabetic neuropathic foot ulcer healing in terms of healing rate, wound closure area, healing score, and elevated NO level. Considering that no clinically adverse effects were found in the patients induced with vibration intervention, VWT can be regarded as a complementary therapy to the existing ones to accelerate the healing of DFUs.

Diabetic wounds significantly affect the life quality of patients and may cause amputation and mortality if poorly managed. Recently, a wide range of cell-based methods has emerged as novel therapeutic methods in treating diabetic wounds. Adipose-derived stem cells (ASCs) are considered to have the potential for widespread clinical application of diabetic wounds treatment in the future. This review summarized the mechanisms of ASCs to promote diabetic wound healing, including the promotion of immunomodulation, neovascularization, and fibro synthesis. We also review the current progress and limitations of clinical studies using ASCs to intervene in diabetic wound healing. New methods of ASC delivery have been raised in recent years to provide a standardized and convenient use of ASCs.

A hydrocellular functional material as a wound dressing is developed and it is found to be superior in its efficacy as compared to some of the comparator controls in diabetic wound healing studies. A study on wound contraction and Histopathological analysis is done in rats. The efficacy of the dressing is comparable to the established wound dressings like Carboxymethyl cellulose alginate dressings and autolytic enzyme based hydrogel. It is found to be superior to Polyhexamethylene biguanide dressing used as reference controls in this study.The reason for good wound healing performance of the dressing can be attributed to a combined property of effective exudates management and broad spectrum antimicrobial effect. The concept of functional hydro cellular material has shown good results due to the excellent balance of exudates pickup and drying it out. This ensures moist wound healing conditions on the wound. Because of its porous nature it allows good air flow and gaseous exchange in the structure.The cationic sites created on the surface of the dressing ensure a good antimicrobial action on the exudates in the dressing. It reduces the infection load on the wound. The nonleaching property of the dressing also helps in preventing the generation of more resistant and mutant strains of the microbes.The developed dressing can be used as a relatively durable long lasting dressing for wound management in diabetic wounds. The need of repetitive wound dressing changes can be brought down with this concept of dressing. It is not only cost effective in terms of its material cost but also is a cost effective solution when entire wound management cost is considered. Such novel wound dressing material can change the quality of life of diabetic wound patients especially in developing world, where access to functional advanced wound care dressings is limited.

Healing of skin wound is a multi-factorial and complex process. Proper treatment of diabetic wounds is still a major clinical challenge. Although diabetes mellitus can occur in ruminants, healing of wounds in diabetic ruminants has not yet been investigated. The aim of this study was to evaluate healing of ovine excisional diabetic wound model. Eight 4-month-old Iranian Makoui wethers were equally divided to diabetic and nondiabetic groups. Alloxan monohydrate (60 mg kg(-1), IV) was used for diabetes induction. In each wether, an excisional wound was created on the dorsum of the animal. Photographs were taken in distinct times for planimetric evaluation. Wound samples were taken on day 21 post-wounding for histopathologic evaluations of epidermal thickness, number of fibroblasts and number of new blood vessels. The planimetric study showed slightly delay in wound closure of diabetic animals, however, it was not significantly different from nondiabetic wounds (p ≥ 0.05). Furthermore, epidermal thickness, number of fibroblasts and number of blood vessels were significantly lower in diabetic group (p < 0.05). We concluded that healing of excisional diabetic wounds in sheep may be compromised, as seen in other species. However, contraction rate of these wounds may not be delayed due to metabolic features of ruminants and these animals might go under surgeries without any serious concern. However, healing quality of these wounds may be lower than normal wounds.