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Diabetes mellitus (DM) is a predominant chronic metabolic syndrome, resulting in various complications and high mortality associated with diabetic foot ulcers (DFUs). Approximately 15-30% of diabetic patients suffer from DFUs, which is expected to increase annually. The major challenges in treating DFUs are associated with wound infections, alterat...
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... accumulation of collagen, down regulation in the expression of neuropeptides together with an inammatory response, 45 deciency of brinolysis inhibitor, 46 PDGF modication, 47 decreased amount of epidermal nerves and misbalance between the ECM and MMPs 48 are few other risk factors responsible for impaired diabetic wound healing, as shown in Fig. ...
Citations
... Diabetic foot ulcers (DUs), which are a complication of T2DM, have a high incidence (34% of diabetic patients globally) and present a serious risk to human health [7]. Although current approaches such as debridement, infection control, maintaining a moist wound environment, and decompression are used to treat these ulcers, there are still challenges in achieving optimal efficacy and managing high costs [8,9]. Consequently, patients often experience negative financial consequences. ...
Background
Type 2 diabetes mellitus (T2DM) is closely linked to metabolic syndrome, characterised by insulin resistance, hyperglycaemia, abnormal lipid metabolism, and chronic inflammation. Diabetic ulcers (DUs) comprise consequential complications that arise as a result of T2DM. To investigate, db/db mice were used for the disease model. The findings demonstrated that a scaffold made from a combination of rhubarb charcoal-crosslinked chitosan and silk fibroin, designated as RCS/SF, was able to improve the healing process of diabetic wounds in db/db mice. However, previous studies have primarily concentrated on investigating the impacts of the RSC/SF scaffold on wound healing only, while its influence on the entire body has not been fully elucidated.
Material and methods
The silk fibroin/chitosan sponge scaffold containing rhubarb charcoal was fabricated in the present study using a freeze-drying approach. Subsequently, an incision with a diameter of 8 mm was made on the dorsal skin of the mice, and the RCS/SF scaffold was applied directly to the wound for 14 days. Subsequently, the impact of RCS/SF scaffold therapy on hepatic lipid metabolism was assessed through analysis of serum and liver biochemistry, histopathology, quantitative real-time PCR (qRT-PCR), immunohistochemistry, and Western blotting.
Results
The use of the RCS/SF scaffold led to an enhancement in the conditions associated with serum glucolipid metabolism in db/db mice. An assessment of hepatic histopathology further confirmed this enhancement. Additionally, the qRT-PCR analysis revealed that treatment with RCS/SF scaffold resulted in the downregulation of genes associated with fatty acid synthesis, fatty acid uptake, triglyceride (TG) synthesis, gluconeogenesis, and inflammatory factors. Moreover, the beneficial effect of the RCS/SF scaffold on oxidative stress was shown by assessing antioxidant enzymes and lipid peroxidation. Additionally, the network pharmacology analysis verified that the adenosine monophosphate-activated protein kinase (AMPK) signalling pathway had a vital function in mitigating non-alcoholic fatty liver disease (NAFLD) by utilizing R. officinale. The measurement of AMPK, sterol regulatory element binding protein 1 (SREBP1), fatty acid synthase (FASN), and acetyl CoA carboxylase (ACC) gene and protein expression provided support for this discovery. Furthermore, the molecular docking investigations revealed a robust affinity between the active components of rhubarb and the downstream targets of AMPK (SREBP1 and FASN).
Conclusion
By regulating the AMPK signalling pathway, the RCS/SF scaffold applied topically effectively mitigated hepatic lipid accumulation, decreased inflammation, and attenuated oxidative stress. The present study, therefore, emphasises the crucial role of the topical RCS/SF scaffold in regulating hepatic lipid metabolism, thereby confirming the concept of "external and internal reshaping".
... Interleukin-1β IL- 6 Interleukin-6 IL-8 ...
... A wound with a DFU fails to heal within three months or does not exhibit any symptoms of healing for longer than 6 weeks. Impaired control of glucose levels, peripheral neuropathy, peripheral vascular disease, foot abnormalities, prior foot ulcerations, and smoking all increase the chance of getting a DFU [6]. Pain, drainage, odor, and skin discoloration are some DFU symptoms. ...
... confiding is the process of redistributing pressure away from the ulcer using tools like casts, braces, and shoes. Lower limb amputation, diabetic neuropathy, peripheral vascular disease, and other infections are complications of DFU [6]. ...
In today’s culture, obesity and overweight are serious issues that have an impact on how quickly diabetes develops and how it causes complications. For the development of more effective therapies, it is crucial to understand the molecular mechanisms underlying the chronic problems of diabetes. The most prominent effects of diabetes are microvascular abnormalities such as retinopathy, nephropathy, and neuropathy, especially diabetes foot ulcers, as well as macrovascular abnormalities such as heart disease and atherosclerosis. MicroRNAs (miRNAs), which are highly conserved endogenous short non-coding RNA molecules, have been implicated in several physiological functions recently, including the earliest stages of the disease. By binding to particular messenger RNAs (mRNAs), which cause mRNA degradation, translation inhibition, or even gene activation, it primarily regulates posttranscriptional gene expression. These molecules exhibit considerable potential as diagnostic biomarkers for disease and are interesting treatment targets. This review will provide an overview of the latest findings on the key functions that miRNAs role in diabetes and its complications, with an emphasis on the various stages of diabetic wound healing.
... It includes compositional changes and reactive oxygen species (ROS) production, lipid peroxidation, loss of respiratory activity, etc. This ultimately allows biofilm disruption and promotes healing of the DFU (149). ...
Diabetic foot ulcer (DFU) is a major complication of diabetes and is associated with a high risk of lower limb amputation and mortality. During their lifetime, 19%–34% of patients with diabetes can develop DFU. It is estimated that 61% of DFU become infected and 15% of those with DFU require amputation. Furthermore, developing a DFU increases the risk of mortality by 50%–68% at 5 years, higher than some cancers. Current standard management of DFU includes surgical debridement, the use of topical dressings and wound decompression, vascular assessment, and glycemic control. Among these methods, local treatment with dressings builds a protective physical barrier, maintains a moist environment, and drains the exudate from DFU wounds. This review summarizes the development, pathophysiology, and healing mechanisms of DFU. The latest research progress and the main application of dressings in laboratory and clinical stage are also summarized. The dressings discussed in this review include traditional dressings (gauze, oil yarn, traditional Chinese medicine, and others), basic dressings (hydrogel, hydrocolloid, sponge, foam, film agents, and others), bacteriostatic dressings, composite dressings (collagen, nanomaterials, chitosan dressings, and others), bioactive dressings (scaffold dressings with stem cells, decellularized wound matrix, autologous platelet enrichment plasma, and others), and dressings that use modern technology (3D bioprinting, photothermal effects, bioelectric dressings, microneedle dressings, smart bandages, orthopedic prosthetics and regenerative medicine). The dressing management challenges and limitations are also summarized. The purpose of this review is to help readers understand the pathogenesis and healing mechanism of DFU, help physicians select dressings correctly, provide an updated overview of the potential of biomaterials and devices and their application in DFU management, and provide ideas for further exploration and development of dressings. Proper use of dressings can promote DFU healing, reduce the cost of treating DFU, and reduce patient pain.
... Additionally, stem cells can be directed towards the release of cytokines, which enhance immunity, cell recruitment, and regeneration of neurons. Similarly, progenitor stem cells can be employed since they have the potential to differentiate into various cell types such as endothelial cells, keratinocytes, pericytes, and myofibroblasts all of which play an effective role in DFI wound healing [213,214]. Stem cell-based therapy has been approved by the FDA as an effective interventional treatment strategy to treat DFI macerated wounds [213]. Secretome stem cells are derived from undifferentiated human mesenchymal endothelial stem cells; they have been successfully deployed for the treatment of the DFIs. ...
... Similarly, progenitor stem cells can be employed since they have the potential to differentiate into various cell types such as endothelial cells, keratinocytes, pericytes, and myofibroblasts all of which play an effective role in DFI wound healing [213,214]. Stem cell-based therapy has been approved by the FDA as an effective interventional treatment strategy to treat DFI macerated wounds [213]. Secretome stem cells are derived from undifferentiated human mesenchymal endothelial stem cells; they have been successfully deployed for the treatment of the DFIs. ...
... Other approaches are based on the fact that chronic wounds are associated with decreased levels of epidermal growth factor. Hence the application of hormonal growth factors will promote the proliferation and differentiation of fibroblasts, gliocytes, and neo-epidermal cells leading to improved healing rates [213,214]. Other growth factors that modulate signal transduction and replication of epidermal cells were also reported to improve wound healing in DFIs [213,216]. ...
Diabetes is a chronic disease that is considered one of the most stubborn global health problems that continues to defy the efforts of scientists and physicians. The prevalence of diabetes in the global population continues to grow to alarming levels year after year, causing an increase in the incidence of diabetes complications and health care costs all over the world. One major complication of diabetes is the high susceptibility to infections especially in the lower limbs due to the immunocompromised state of diabetic patients, which is considered a definitive factor in all cases. Diabetic foot infections continue to be one of the most common infections in diabetic patients that are associated with a high risk of serious complications such as bone infection, limb amputations, and life-threatening systemic infections. In this review, we discussed the circumstances associated with the high risk of infection in diabetic patients as well as some of the most commonly isolated pathogens from diabetic foot infections and the related virulence behavior. In addition, we shed light on the different treatment strategies that aim at eradicating the infection.
... 25 Liposomes loaded with the hydrophobic drugs in the double layer of phospholipid and the hydrophilic drug encapsulated within the aqueous core served as a potent antimicrobial drug delivery agent for diabetic foot infections. 26 The use of bioactive glass in osteomyelitis potentiates cellular proliferation and improved angiogenesis by effectively bonding to the living tissue creating a stable interface while being coated with the nanocrystalline hydroxyapatite. The material S53P4 which is similar to bioglass initially releases sodium from the surface causing an alkaline surrounding and later releases calcium, silicon, and phosphorous imparting elevated osmotic pressure and inhibiting the bacterial adhesion and colonization to the surface. ...
Diabetes is a fast-growing chronic metabolic disorder that is widely associated with foot ulcers. The major challenge among these ulcers is wound infections, altered inflammatory responses, and a lack of angiogenesis that can complicate limb amputation. The foot, because of its architecture, becomes the part most prone to complications and the infection rate is higher mainly between the toes due to the humid nature. Therefore, the infection rate is significantly higher. Wound healing in diabetes is a dynamic process usually delayed due to poor immune function. Diabetes-related pedal neuropathy and perfusion disturbances can lead to a loss of sensation in the foot. This neuropathy can further be a risk factor for ulcer development due to repetitive mechanical stress that later might get infected by the invasion of microorganisms extending to the bone and causing an infection called pedal osteomyelitis. This review details the pathophysiology, the biomaterials aiding in the infection cure and regeneration of bone along with their limitations, as well as their future prospects.
... More over focal points on foot, wound infections, and excessive exudates limit the regenerative potential of the wound tissue as it increases the inflammatory phase of wound and impair the macrophage phenotypic conversion in to the regenerative macrophage type M2. Lack of factors necessary for the normal healing process, like regenerative cytokines, matrix metalloproteases (MMPs) lead to impaired collagen accumulation and downregulation of neuropeptide expression and thus, reduced proliferation and migration of fibroblasts and keratinocytes to the wound site are common in the development of DFU [46]. The decreased renal function, poor nutrition and smoking or drinking habits are some of the additional contributing factors for the development of chronic DFU [3,22]. ...
... Currently, nanomaterial-based treatments are emerging using nanoemulsions, nanoliposomes, nanofibers etc. Moreover, nanomaterial based antibacterial hyperthermia therapy and gene therapy are also under development for DFU [36,46]. ...
... Wound regeneration property: An ideal material should stimulate angiogenesis and neuronal regeneration by inducing growth factor release from the fibroblasts and by stimulating homing of stem cells in the wound site which leads to regeneration of endothelial cells and other wound cells. Wound Regeneration Property (F10) [2,34,46] Secondly, widely used dressing materials of DFU were chosen for the graph theoretic analysis of its performance evaluation and ranking. Hydrogel dressings (M4) 5 Hydrocolloid dressings (M5) 6 Honey dressing (M6) 7 ...
Diabetic foot ulcer is a chronic health issue leading to lower leg amputations in approximately 15% of patients with diabetics. There are many factors directly or indirectly involved in the physiology of wound healing but being a multisystem disorder, wound healing in diabetic patients retard or worsen with heavy exudates and severe microbial infections. Wound management is of prime importance and is an emerging area to incorporate wound regenerative materials in natural or synthetic dressing materials along with proper microbial control. The article aim to identify suitable dressing materials which exhibit inherent wound healing properties at the same time flexible to be used as drug carriers for slow, consistent and effective delivery of ‘functional drugs’ to the wound environment. The authors selected nine materials from the popular and well accepted dressings of patient choice, analyzed them using graph theoretic approach and ranked them on the basis of graph index values obtained. A critical review has also been done on the basis of their ranking, providing insights to the advantages, disadvantage and potential of top 5 ranked candidate materials. Alginate, Honey, Medifoam, Saline, and Hydrogel dressings were the top five candidate materials ranked respectively, even then, the authors suggests that ‘modified hydrogels’ can have the potential to be used as a future candidate in DFU treatment as it is the only material (among the top ranked ones) which can effectively used as regenerative drug carrier, while providing all other wound healing properties in relative proportions. The proposed framework can be modified and applied in the selection and ranking of materials for any kind of applications both in industry and medical fields by identifying factors influencing the final outcome of study and by listing the characteristics of the materials selected.
Nanoscale copper oxide (CuO NPs) with diameters in the 80–150 nm range has been biosynthesized using lipopeptide biosurfactant derived from Bacillus vallismortis and characterized by XRD and FE-SEM. The CuO NPs could be introduced as nanocarrier systems for combination therapy and a potential candidate for antibacterial, antioxidant, anticancer, and anti-diabetic activity. The antibacterial activity of CuO NPs was studied by incorporating the nanoparticles with fluorescent antibiotic Ciprofloxacin HCL (CIP) to form CIP@CuO NPs and tracked inside HEK-293 cell lines. The MIC values of CIP@CuO NPs against 1 × 106 CFU ml−1 Pseudomonas aeruginosa was determined to be 76 µg ml−1and 69 µg ml−1 against 1 × 106 CFU ml−1 Staphylococcus aureus. The CuO NPs were conjugated with the anticancer drug Doxorubicin (DOX) to form DOX@CuONPs, improving delivery toward cancer (HeLa) cells. The intracellular uptake of the drug-loaded CuO NPs was confirmed from confocal micrographs. Finally, the in vitro anti-diabetic activity of lipopeptide-coated CuO NPs was confirmed by the inhibitory activity of α-amylase. In contrast, the in vivo anti-diabetic efficacy of CuO NPs was validated by a significant reduction in blood glucose and glutathione levels. The CuO NPs positively affected the histopathological changes of the pancreas in induced diabetic mice. Cytotoxicity testing with Zebrafish demonstrated abnormal organ development with varying viability and hatching rates at 72 and 96 hpf, with an LC50 of 45 µg/l. Aside from the various potential medicinal characteristics, the study provided valuable information on cytotoxic impact, which can be used in future investigations of their eco-toxicological impacts.
Diabetic wounds are a significant complication of diabetes that is characterized by delayed wound healing and a high risk of amputation. Pro‐inflammatory macrophages (M1) and Matrix Metallo protease‐9 (MMP‐9) overexpression play pivotal roles in the extended inflammatory phase observed in diabetic wounds. This study developed a multifunctional lipid nanoemulsion containing quercetin and rosemary oil (Q‐RLNE) that can efficiently convert M1 macrophages to M2, inhibit MMP‐9, and prevent microbial infection, accelerating diabetic wound healing. In‐vitro studies demonstrated that Q‐RLNEs showed excellent biocompatibility and cellular uptake. Additionally, Q‐RLNEs demonstrated effective ROS scavenging, macrophage polarization, MMP‐9 inhibition, and excellent anti‐microbial properties against Staphylococcus aureus (S. aureus). In‐vivo results demonstrated that Q‐RLNE can accelerate and achieve complete wound healing in diabetic‐induced rats by reducing inflammation and promoting angiogenesis with proper collagen deposition and dermal projection regeneration. This study also highlighted the application of the Segment Anything Model (SAM) for precise wound region segmentation. SAM combines attention‐fusion and hybrid fusion strategies for accurate segmentation, enabling comprehensive analysis of wound attributes over time and guiding treatment decisions. The SAM analysis results also align with Q‐RLNE in‐vitro and in‐vivo. The findings of this study suggest that Q‐RLNE is a promising new therapeutic agent for accelerating diabetic wound healing.
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Diabetic foot ulcers (DFU) are a common and often debilitating complication of diabetes that can result in lower limb amputations if left untreated. Hydrogel dressings are three‐dimensional networks of hydrophilic polymers that can absorb and retain large amounts of water, and have been shown to possess excellent biocompatibility, low toxicity, and excellent fluid handling properties. In addition, hydrogels create a moist wound environment that promotes wound healing by supporting cell proliferation, migration, and angiogenesis. Hydrogels, therefore, have emerged as promising wound dressings for promoting DFU healing. In this review, we attempt to chart the landscape of the emerging field of hydrogel as wound dressing for DFU treatment. We will explicitly review the assorted preparation methods for DFU hydrogels as well as a detailed discussion of various types of hydrogels deployed for DFU study. We also crystallize key findings, identify remaining challenges, and present an outlook on the future development of this enticing field.
