Diabetic Wound Research Articles

Metabolomics Revealed the Effects of Momordica charantia L. Saponins on Diabetic Hyperglycemia and Wound Healing in Mice.

Momordica charantia L. saponins (MCS) may promote wound-healing properties but the underlying mechanisms are unclear. This study aimed to examine the effects and mechanisms of MCS on diabetic wounds. The results have shown that higher MCS intake lowered fasting blood glucose levels, serum lipids, and lipopolysaccharides in diabetic mice. MCS-treated diabetic mice exhibited faster wound healing than the diabetic control groups. After three days, the diabetic control groups exhibited a wound area reduction of only 19.3%, while a 39.75% reduction was observed following high-dose MCS treatment. Five potential biomarkers were screened in the metabolomics study. The results revealed that MCS mainly regulated glycerophospholipid metabolism, fructose and mannose metabolism, steroid hormone biosynthesis, pyrimidine metabolism, and the Krebs cycle, thus affecting wound healing. Overall, MCS could not only exert a hypoglycemic effect but also promote diabetic wound healing, making it a potential treatment option for diabetes-related wounds.

Glucose-fueled cationic nanomotors for promoting the healing of infected diabetic wounds

Hyperglycemia-promoted bacterial infection will seriously exacerbate diabetic wounds, and its current clinical treatments are suffering from the adverse effects associated with off-target, bacterial resistance, and glycemic fluctuation. Herein, we present a kind of glucose-fueled cationic nanomotors capable of remarkably enhancing antibacterial efficacy, and thus expediting diabetic wound healing. The nanomotors have positively charged surfaces, and consist of mesoporous bowl-shaped polydopamine nanoparticles grafted with quaternized polymer brushes and coupled with glucose oxidase (GOx) and catalase (CAT). Stemming from the GOx-CAT cascade reaction in diabetic wound microenvironment, they can perform robust chemotactic motion towards both high glucose regions, where bacteria proliferation predominantly occurs, and elevated H2O2 levels, which bacterial metabolism produced. This enables the nanomotors to facilitate targeted migration towards bacteria-rich regions and simultaneous downregulation of glycemic levels, as well as to significantly enhance the electrostatic interaction between antibacterial components and bacteria. Consequently, the nanomotors exhibit amplified contact-killing effects of their attached cationic molecules, leading to an almost 10-fold enhancement in antibacterial efficacy compared to previous counterparts. The in vivo experiments approved that the nanomotors demonstrated the accelerated healing of infected diabetic wounds by S. aureus and biosafety. The results herein provide an insight into the clinical treatment of infected diabetic wounds.

Umbelliferone alleviates impaired wound healing and skin barrier dysfunction in high glucose-exposed dermal fibroblasts and diabetic skins.

Skin wound healing is a complex process involving various cellular and molecular events. However, chronic wounds, particularly in individuals with diabetes, often experience delayed wound healing, potentially leading to diabetic skin complications. In this study, we examined the effects of umbelliferone on skin wound healing using dermal fibroblasts and skin tissues from a type 2 diabetic mouse model. Our results demonstrate that umbelliferone enhances several crucial aspects of wound healing. It increases the synthesis of key extracellular matrix components such as collagen I and fibronectin, as well as proteins involved in cell migration like EVL and Fascin-1. Additionally, umbelliferone boosts the secretion of angiogenesis factors VEGF and HIF-1α, enhances the expression of cell adhesion proteins including E-cadherin, ZO-1, and Occludin, and elevates levels of skin hydration-related proteins like HAS2 and AQP3. Notably, umbelliferone reduces the expression of HYAL, thereby potentially decreasing tissue permeability. As a result, it promotes extracellular matrix deposition, activates cell migration and proliferation, and stimulates pro-angiogenic factors while maintaining skin barrier functions. In summary, these findings underscore the therapeutic potential of umbelliferone in diabetic wound care, suggesting its promise as a treatment for diabetic skin complications. KEY MESSAGES: Umbelliferone suppressed the breakdown of extracellular matrix components in the skin dermis while promoting their synthesis. Umbelliferone augmented the migratory and proliferative capacities of fibroblasts. Umbelliferone activated the release of angiogenic factors in diabetic wounds, leading to accelerated wound healing. Umbelliferone bolstered intercellular adhesion and reinforced the skin barrier by preventing moisture loss and preserving skin hydration.

In vivo biocompatibility of electrospun chitosan/PEO nanofiber as potential wound dressing material for diabetic burn wound injury of mice

In vivo biocompatibility of electrospun chitosan/PEO nanofiber as potential wound dressing material for diabetic burn wound injury of mice

Multifunctional Hydrogel Microneedle Patches Modulating Oxi-inflamm-aging for Diabetic Wound Healing.

Oxidative stress, chronic inflammation, and immune senescence are important pathologic factors in diabetic wound nonhealing. This study loads taurine (Tau) into cerium dioxide (CeO2) to develop CeO2@Tau nanoparticles with excellent antioxidant, anti-inflammatory, and anti-aging properties. To enhance the drug penetration efficiency in wounds, CeO2@Tau is encapsulated in gelatin methacryloyl (GelMA) hydrogel to prepare CeO2@Tau@Hydrogel@Microneedle (CTH@MN) patch system. Microneedle technology achieves precise and efficient delivery of CeO2@Tau, ensuring their deep penetration into the wound tissue for optimal efficacy. Rigorous in vitro and in vivo tests have confirmed the satisfactory therapeutic effect of CTH@MN patch on diabetic wound healing. Mechanistically, CTH@MN attenuates oxidative damage and inflammatory responses in macrophages by inhibiting the ROS/NF-κB signaling pathway. Meanwhile, CTH@MN activated autophagy-mediated anti-aging activity, creating a favorable immune microenvironment for tissue repair. Notably, in a diabetic mouse wound model, the multifunctional CTH@MN patch significantly promotes wound healing by systematically regulating the oxidation-inflammation-aging (oxi-inflamm-aging) pathological axis. In conclusion, the in-depth exploration of the CTH@MN system in this study provides new strategies and perspectives for treating diabetic non-healing wounds.

Hybrid hydrogel loaded with natural plant extract accelerates diabetic wound healing via ROS scavenging and immunoregulation

Diabetic wound (DW) is often characterised by reactive oxygen species (ROS) accumulation, disordered inflammation, and macrophage polarisation abnormality. Herein, natural plant extract, Kunzea ericoides leaf extract (KELE), was loaded into Gelatin Methacryloyl (GelMA) to fabricate a hybrid hydrogel (referred to as KELE@Gel) as a multi-functional dressing to treat DW. Using the UHPLC-Q-Exactive Orbitrap MS/MS strategy aided by database analysis, multiple compounds with antioxidative and anti-inflammatory properties were identified in KELE. The optimal concentration of GelMA and KELE was determined based on the mechanical properties and biocompatibility evaluation to obtain an ideal hydrogel for wound application. Further in vitro investigations discovered that the KELE@Gel hydrogel possessed a superior cytocompatibility and ROS scavenging capacity on RAW 264.7 cell lines under hydrogen peroxide (H2O2) or lipopolysaccharides (LPS) stimulation. Meanwhile, the hybrid hydrogel inhibited expressions of several cytokines, such as interleukin (IL)-1β, IL-6, and tumour necrosis factor (TNF)-α and manipulated M1/M2 macrophage polarisation in an inflammatory microenvironment. The immunoregulatory mechanism of the hydrogel was investigated through mRNA-sequencing and transcriptomic bioinformatics analysis. Animal experiments also discovered that the KELE@Gel hydrogel significantly promoted DW healing with preferable re-epithelialisation, angiogenesis and collagen deposition by enhanced antioxidative, anti-inflammatory and immunoregulatory activities. Above all, the KELE@Gel hydrogel released bioactive components sustainably, achieving a moderate antioxidative, anti-inflammatory and immunoregulatory capacity alongside the whole course of DW healing. In conclusion, this naturally derived hybrid hydrogel ameliorated undesirable microenvironments in DW and showed great potential to serve as a multi-functional wound dressing in clinical practice.

Mechanical Force on Hydrogel Implication on Enhanced Drug Release, Antibacterial, and M2 Macrophage Polarization: New Insights Alleviate Diabetic Wound Healing.

Diabetic foot ulcers/chronic wounds are difficult to treat because of dysfunctional macrophage response and decreased phenotype transition from the M1 to M2 status. This causes severe inflammation, less angiogenesis, microbial infections, and small deformation in wound beds, affecting the healing process. The commercial wound dressing material has limited efficacy, poor mechanical strength, extra pain, and new granulated tissue formed in a mesh of gauze. It is desired to create tough, skin-adhesive, antifouling, sustainable M2 phenotype-enabling, and mechanoresponsive drug-releasing hydrogel. To resolve this, zwitterionic poly(sulfobetaine methacrylate) (SB) incorporated with keratin-exfoliated MoS2 and bee-wax nanoparticles were developed to deliver phenytoin upon application of mechanical forces. Human hair keratin was used for exfoliation of MoS2, and bee-wax nanoparticles loaded with phenytoin were used as cross-linkers of SB hydrogel. The cross-linked SB-MO15-B hydrogel has high mechanical properties, with more tensile strength and strain of 118 kPa and 1485%. Under external mechanical force, hydrogel deformed to release phenytoin of 38% (tensile) and 24% (compressive), which was higher compared to static condition (12%). The penetration of phenytoin into skin tissue was also improved by the mechanical force applied to the hydrogel. SB-MO15-B hydrogel effectively activates the polarization of macrophages toward the M2 phenotype, promotes cell proliferation, and also shows superior antibacterial properties. In vivo results demonstrate that hydrogel rapidly promotes diabetic wound repair through fast antiinflammation and M2 macrophage polarization. Therefore, a robust mechanoresponsive hydrogel would provide a new strategy to deliver the drug and also tune the M2 macrophage polarization for chronic wound healing.

Comparison of the efficacy of tibial transverse transfer and periosteal distraction techniques in the treatment of diabetic foot refractory ulcers.

To investigate the efficacy of comparing tibia transverse transport (TTT) and periosteal distraction in treating diabetic foot ulcers. A retrospective analysis of 19 patients with diabetic foot ulcers treated with both procedures between February 2020 and November 2022, 8 of whom were treated with the tibial transverse transfer technique (transfer group) and 11 with the osteochondral distraction technique (distraction group), was performed to compare and analyze the clinical efficacy of the two methods. All wounds were healed in both groups, and the healing time ranged from 15 to 41days with a mean of 28d. The limb preservation rate was 100%. The operative time, intraoperative bleeding, and pain score in the operative area were significantly less in the distraction group than in the removal group, with statistically significant differences (P < 0.05). Intra-group comparison between the two groups of patients after surgery revealed that the skin temperature, ABI, TcPO2, SWM and VAS of the affected limb were significantly improved compared with those before surgery, and the difference was statistically significant (P < 0.05). The expression levels of VEGF, bFGF, EGF and PDGF were significantly higher than before surgery in both groups, and the difference was statistically significant (P < 0.05). No statistically significant differences were found in skin temperature, ABI, TcPO2, SWM, VAS, VEGF, bFGF, EGF and PDGF between the two groups at the corresponding time points preoperatively and postoperatively (P > 0.05). The Periosteal distraction technique can significantly promote the healing of diabetic foot ulcers. It has the same efficacy as TTT in promoting the healing of diabetic foot ulcer wounds and improving the peripheral circulation of affected limbs. In addition, the periosteal distraction technique has the advantages of small trauma, simple operation, few complications, and convenient nursing care.

Granular Porous Nanofibrous Microspheres Enhance Cellular Infiltration for Diabetic Wound Healing.

Diabetic foot ulcers (DFUs) are a significant challenge in the clinical care of diabetic patients, often necessitating limb amputation and compromising the quality of life and life expectancy of this cohort. Minimally invasive therapies, such as modular scaffolds, are at the forefront of current DFU treatment, offering an efficient approach for administering therapeutics that accelerate tissue repair and regeneration. In this study, we report a facile method for fabricating granular nanofibrous microspheres (NMs) with predesigned structures and porosities. The proposed technology combines electrospinning and electrospraying to develop a therapeutic option for DFUs. Specifically, porous NMs were constructed using electrospun poly(lactic-co-glycolic acid) (PLGA):gelatin short nanofibers, followed by gelatin cross-linking. These NMs demonstrated enhanced cell adhesion to human dermal fibroblasts (HDF) during an in vitro cytocompatibility assessment. Notably, porous NMs displayed superior performance owing to their interconnected pores compared to nonporous NMs. Cell-laden NMs demonstrated higher Young's modulus values than NMs without loaded cells, suggesting improved material resiliency attributed to the reinforcement of cells and their secreted extracellular matrix. Dynamic injection studies on cell-laden NMs further elucidated their capacity to safeguard loaded cells under pressure. In addition, porous NMs promoted host cell infiltration, neovascularization, and re-epithelialization in a diabetic mouse wound model, signifying their effectiveness in healing diabetic wounds. Taken together, porous NMs hold significant potential as minimally invasive, injectable treatments that effectively promote tissue integration and regeneration.

The influence of maggot debridement therapy on the bacterial flora of hard-to-heal wounds.

Maggot debridement therapy (MDT) is increasingly being used in clinical practice as an alternative treatment for hard-to-heal (chronic) wounds. Among the many benefits of using MDT is its antimicrobial effect. Maggots secrete substances that are known to have antibacterial properties against both Gram-negative and Gram-positive bacteria. Clinically, this results in the effective eradication of pathogenic species and consequently, a faster healing process. The aim of this study was to evaluate the effect MDT has on the bacterial flora of hard-to-heal ulcers. Patients with venous, mixed arteriovenous, decubitus, diabetic and neuropathic wounds were treated with larvae of Lucilia sericata enclosed in bags. Dressings were applied to the wounds for 72 hours. Before and after the therapy, a swab was taken from the wound, and bacterial diversity and bacterial growth scores were assessed. While 16 patients were treated only once, the treatment had to be repeated in four cases until the wounds were fully debrided. Bacteria of the species Pseudomonas aeruginosa, Proteus mirabilis, Staphylococcus aureus and Enterococcus faecalis were the most common strains observed. Of the 20 patients treated, the total number of bacterial strains decreased in eight wounds, but increased in five wounds, while no difference was observed in nine wounds. The average number of bacterial strains in wounds decreased after MDT. A lower incidence of alarm pathogens was also reported. In cases where multiple applications of larvae were administered, greater decreases in bacterial growth scores were observed than in cases with a single application of dressing (37.5% vs 18.1%, respectively). In 18 cases, after disinfection of the wound by larvae, it was reinfected by strains not detected before. Wounds healed completely after MDT in two patients. In this study, MDT changed the bacterial diversity of hard-to-heal wounds. The larvae reduced overall bacterial growth scores and acted on both Gram-positive and Gram-negative bacteria as well as on alarm pathogens. Cleaned wounds appeared to become vulnerable to infection by opportunistic bacteria. The bacterial burden decreased as the number of applications of biological dressings increased.

Nanocomposite conductive r(GO/BSA) hydrogel as an effective dressing for rapid chronic diabetic wound healing

Conductive hydrogels, with their soft, hydrated interface and superior electrical conductivity, represent a groundbreaking solution for diabetic wound healing. However, developing a conductive hydrogel with excellent biocompatibility has proven to be challenging. This study presents the synthesis of a novel conductive hydrogel composed of bovine serum albumin (BSA) protein and graphene oxide (GO) for the treatment of diabetic wounds. The prepared hydrogel is mildly reduced by ascorbic acid to facilitate charge-transfer and enhance its conductivity. Hydrogel is optimized for enhanced mechanical and electrical properties by changing the concentration of GO within the BSA matrix. The nanocomposite hydrogel demonstrates superior antibacterial properties and enhanced biocompatibility compared to the BSA hydrogel. The prepared hydrogel is investigated for wound healing capacity in a rat model, where it demonstrates rapid healing of chronic diabetic wound. The improved therapeutic outcomes are attributed to the hydrogel's ability to facilitate cellular activities through enhanced electrical conductivity by maintaining continuous electrical signal at the wound site. The presented findings suggest that nanocomposite protein-based conductive hydrogel not only hold great potential for advanced diabetic wound care and have potential for future innovation in tissue engineering, regenerative medicine and beyond.

CLEC14A facilitates angiogenesis and alleviates inflammation in diabetic wound healing

BackgroundDelayed wound healing is a serious complication of diabetic wounds, posing a significant challenge to the treatment of patients with diabetes. Diabetic wound healing is a complex dynamic process involving angiogenesis and inflammatory responses. Currently, there are limited targeted therapies to promote diabetic wound healing. This study aimed to reveal the role of CLEC14A in the process of diabetic wound healing, with the hope of identifying new therapeutic targets to accelerate the healing of diabetic wounds. MethodsIn vivo, diabetic mice were generated by combined streptozotocin (STZ) and high-fat diet treatment. The wound healing model was established in wild-type and Clec14a−/− diabetic mice. The degree of wound healing, as well as angiogenesis and inflammation during the healing process, were evaluated through Hematoxylin and Eosin (H&E) staining, immunohistochemical staining, and immunofluorescence staining. In vitro, the angiogenic activities of Human Umbilical Vein Endothelial Cells (HUVECs) were assessed following treatment with high glucose and adenoviruses overexpressing CLEC14A, using scratch assays and tube formation assays. Interleukin-1β (IL-1β) and Tumor Necrosis Factor-α (TNF-α) were utilized to evaluate the levels of inflammation in HUVECs. ResultsCLEC14A expression was suppressed in diabetic wounds. Deletion of the Clec14a inhibited angiogenesis and activated inflammatory responses in vivo. High-glucose treatment led to decreased CLEC14A expression, impaired angiogenic capacity, and elevated inflammatory levels in vitro. However, adenoviral-mediated overexpression of CLEC14A reversed the response induced by high glucose. ConclusionCLEC14A accelerates diabetic wound healing by promoting angiogenesis and reducing wound inflammation.

Exudate Unidirectional Pump to Promote Glucose Catabolism Triggering Fenton-Like Reaction for Chronic Diabetic Wounds Therapy.

The massive accumulation of exudate containing high concentrations of glucose causes wound infection and triggers the release of inflammatory factors, which in turn delays the closure of diabetic wounds. In this study, a Janus membrane is constructed by combining glucose oxidase (GOx) and copper ions (Cu2+) for the treatment of diabetic wounds, which is named as Janus@GOx/Cu2+. It consists of hydrophobic, transitional, and superhydrophilic layers in a three-layer structure with gradient hydrophilicity for self-pumping properties. The Janus@GOx/Cu2+ membrane triggers a series of cascading reactions while pumping out diabetic wound exudates. First, glucose oxidase loaded onto the hydrophilic layer of the Janus@GOx/Cu2+ membrane decomposes glucose into hydrogen peroxide (H2O2) and glucuronic acid, reducing the local glucose level. The generated glucuronic acid neutralizes the local alkaline environment of chronic wounds. Simultaneously, the H2O2 interacts with the Cu2+ contained in the hydrophobic layers of the Janus@GOx/Cu2+ membrane via a Fenton-like reaction, generating hydroxyl radicals with excellent bactericidal properties. Cu2+ promotes angiogenesis and wound healing in diabetic wounds. Under the action of multiple responses, the Janus@GOx/Cu2+ membrane promotes wound healing in diabetic infections.

An Advanced Hydrogel Dressing System with Progressive Delivery and Layer-to-Layer Response for Diabetic Wound Healing

Wound healing in diabetic patients presents a significant challenge due to delayed inflammatory responses, which obstruct subsequent healing stages. In response, we have developed a progressive, layer-by-layer responsive hydrogel, specifically designed to meet the dynamic requirements of diabetic wounds throughout different healing phases. This hydrogel initiates with a glucose-responsive layer formed by boronate ester bonds between 4-arm-poly (ethylene glycol) succinimidyl glutarate (4arm-PEG-SG) and 3-aminophenylboronic acid. This configuration ensures precise control over the physicochemical properties, facilitating accurate drug release during the healing process. Furthermore, we have incorporated an active pharmaceutical ingredient ionic liquid (API) composed of diclofenac and L-carnitine. This combination effectively tackles the solubility and stability issues commonly associated with anti-inflammatory drugs. To further refine drug release, we integrated matrix metalloproteinase-9 (MMP-9)-sensitive gelatin microcapsules, ensuring a controlled release and preventing the abrupt, uneven drug distribution often seen in other systems. Our hydrogel's rheological properties closely resemble human skin, offering a more harmonious approach to diabetic wound healing. Overall, this progressive layer-by-layer responsive wound management system, which is a safe, efficient, and intelligent approach, holds significant potential for the clinical treatment of diabetic wounds. Statement of SignificanceThe two main problems of diabetic wounds are the long-term infiltration of inflammation and the delayed repair process. In this experiment, a glucose-responsive hierarchical drug delivery system was designed to intelligently adjust gel properties to meet the needs of inflammation and repair stage of wound healing, accelerate the transformation of inflammation and repair stage, and accelerate the process of repair stage. In addition, in order to achieve accurate drug release in anti-inflammatory layer hydrogels and avoid sudden drug release due to poor solubility of anti-inflammatory small molecule drugs, we constructed a ionic liquid of active pharmaceutical ingredients (API-ILs) using diclofenac and L-carnitine as raw materials. It was wrapped in MMP-9 enzyme active gelatin microcapsule to construct a double-reaction anti-inflammatory layer gel to achieve accurate drug release. These findings highlight the potential of our system in treating diabetic wounds, providing a significant advance in wound treatment.

Inflammatory regulation of squid cartilage gelatin with different molecular weights for treatment of chronic wounds in diabetes

Squid, as a very important economic marine species, accounts for 5 % of the total catch of fish and cephalopods. The waste from the processing process of squid can be used for collagen extraction, which has great application value in the field of biomedical materials. Here, we obtained squid cartilage gelatin (SCG) with different molecular weights by adjusti.ng the reaction conditions and used for the treatment of chronic wounds in diabetes. SCG extracted at low temperatures and short heating times demonstrated a more intact structure, higher molecular weight, and superior gel stability. Based on cell study and transcriptome analysis, SCG with high molecular weight significantly promoted cell adhesion, because it provided more contact sites for cells, whereas small molecules of SCG could directly reduce inflammation. Animal studies have demonstrated that SCG significantly promotes diabetic wound healing as evidenced by reducing inflammation, inducing vascular regeneration, promoting tissue growth, re-epithelialization, collagen deposition and remodeling. This study elucidated the immunoregulatory mechanisms of SCG with different molecular weights, and validated its potential application in chronic wound healing in diabetes.

Human amniotic membrane hydrogel loaded with exosomes derived from human placental mesenchymal stem cells accelerate diabetic wound healing

Diabetic wound is one of the most common and costly complication in diabetic patients. Hence, numerous studies have been carried out to discover a suitable approach to enhance the process of wound healing. Biological hydrogels are commonly utilized for wound healing due to their suitable properties among different materials available. Herein we investigated whether human amniotic membrane hydrogel (hAMH) loaded with human placental mesenchymal stem cells (PlaMSCs)-derived exosomes could promote healing in diabetic rats. Sixty diabetic rats were randomly assigned into the control group, hAMH group, exosome group, and hAMH+Exosome group. According to the phases of wound healing, sampling was done on days 7, 14, and 21 for further assessments. Our findings showed a significant increase in wound contraction rate, new epidermal length, fibroblast and blood vessel count, collagen density, and the levels of antioxidative factors (GSH, SOD, and CAT) in the treatment groups compared to the control group, with more pronounced effects observed in the hAMH+Exosome group. Furthermore, the levels of bFGF and VEGF gene expression significantly increased in each treatment group when compared to the control group, with the highest levels observed in the hAMH+Exosome group. This occurred as the hAMH+Exosome group showed a greater decrease in neutrophil count, the expression of TNF-α and IL-1β genes, and the levels of an oxidative factor (MDA) compared to the other groups. In summary, the combination of hAMH and PlaMSCs-derived exosomes was determined to have a more significant effect on healing diabetic wounds.

Tea polyphenol nano-crosslinked dynamical hyaluronic acid-based hydrogel for diabetic wound healing

Diabetic wound healing remains a significant clinical challenge for the complex wound microenvironment characterized by oxidative stress, inflammation, and bacterial infection. To address these challenges, we present a novel hydrogel incorporates tea polyphenol-stabilized silver nanoparticles (TP@Ag NPs) into a dynamic hyaluronic acid-phenylboronic acid network crosslinked via borate ester bonds. This design leverages the inherent biocompatibility and biodegradability of hyaluronic acid alongside the antioxidant, anti-inflammatory, and antibacterial properties of tea polyphenols and silver nanoparticles. The HP-TP@Ag hydrogel exhibited glucose-responsive degradation and TP@Ag NPs release, enabling targeted delivery within the diabetic wound microenvironment. In vitro assays demonstrated the hydrogel's potent antioxidant activity, effectively scavenging ROS and protecting both HaCaT and RAW264.7 cells from oxidative stress. Furthermore, the HP-TP@Ag hydrogel significantly suppressed the production of pro-inflammatory cytokines and exhibited robust antibacterial activity against both E. coli and S. aureus. In vivo studies using a diabetic mouse model revealed accelerated wound closure, reduced inflammation, enhanced collagen deposition, and promoted angiogenesis and tissue remodeling in HP-TP@Ag hydrogel-treated wounds. These findings highlight the promise of HP-TP@Ag hydrogel as an advanced wound dressing for effective diabetic wound management, offering a synergistic approach to overcome the multifaceted challenges associated with this complex condition.

Topical Anti-ulcerogenic Effect of the Beta-adrenergic Blockers on Diabetic Foot Ulcers: Recent Advances and Future Prospectives.

Patients with diabetes suffer from major complications like Diabetic Retinopathy, Diabetic Coronary Artery Disease, and Diabetic Foot ulcers (DFUs). Diabetes complications are a group of ailments whose recovery time is especially delayed, irrespective of the underlying reason. The longer duration of wound healing enhances the probability of problems like sepsis and amputation. The delayed healing makes it more critical for research focus. By understanding the molecular pathogenesis of diabetic wounds, it is quite easy to target the molecules involved in the healing of wounds. Recent research on beta-adrenergic blocking drugs has revealed that these classes of drugs possess therapeutic potential in the healing of DFUs. However, because the order of events in defective healing is adequately defined, it is possible to recognize moieties that are currently in the market that are recognized to aim at one or several identified molecular processes. The aim of this study was to explore some molecules with different therapeutic categories that have demonstrated favorable effects in improving diabetic wound healing, also called the repurposing of drugs. Various databases like PubMed/Medline, Google Scholar and Web of Science (WoS) of all English language articles were searched, and relevant information was collected regarding the role of beta-adrenergic blockers in diabetic wounds or diabetic foot ulcers (DFUs) using the relevant keywords for the literature review. The potential beta-blocking agents and their mechanism of action in diabetic foot ulcers were studied, and it was found that these drugs have a profound effect on diabetic foot ulcer healing as per reported literatures. There is a need to move forward from preclinical studies to clinical studies to analyze clinical findings to determine the effectiveness and safety of some beta-antagonists in diabetic foot ulcer treatment.

Tailor-made curdlan based nanofibrous dressings enable diabetic wound healing

The development and application of novel polysaccharides that can improve diabetic wound healing is crucial. Dressings containing curdlan have the potential to promote healing in diabetic wounds, but the underlying mechanism remain unclear. In addition, the functional modifications that could further enhance the activity of curdlan in promoting diabetic wound healing have not been explored. Herein, we investigated the capabilities of curdlan (CU) and its four derivatives i.e., sulfated curdlan (SC), amino-curdlan (AC) carboxymethyl curdlan (CMC) and CMC/ZnO nanocomposites for diabetic wound healing. Pristine CU and its derivatives were blended with polyvinyl alcohol (PVA) to fabricate electrospun nanofiber dressings (ENDs) with uniform appearances. The PVA/CU, PVA/CMC and PVA/CMC-ZnO ENDs were more compatible with keratinocytes, fibroblasts, and macrophages than that of PVA/AC ENDs. Notably, PVA/CMC ENDs and PVA/CMC-ZnO ENDs exhibited superior wound healing efficiencies than other ENDs. Among various dressings, PVA/CU, PVA/SC, PVA/CMC ENDs effectively reduced M1 macrophages and facilitated M2 phenotype at early stage of diabetic wound healing. Collectively, the PVA/CMC ENDs demonstrated greater therapeutic potential against diabetic wounds compared to other modified scaffolds via regulating macrophage polarization.

In silico Profiling and Pharmacokinetic Modelling of Olivetol: Evaluating its Potential as a Therapeutic Agent for Diabetic Wound Healing.

Diabetic wound healing poses a significant challenge due to the intricate disruptions in cellular and molecular processes induced by hyperglycaemia, leading to delayed or impaired tissue repair. Computational techniques offer a promising avenue for unravelling the complexities of diabetic wound healing by elucidating the molecular mechanisms involved. This study utilized in silico molecular docking and dynamics simulations to explore the potential therapeutic effectiveness of olivetol, a phenolic compound, in the context of diabetic wound healing. Furthermore, computational methodologies, encompassing pkCSM, Swiss ADME, OSIRIS® property explorer, PASS online web resource, and MOLINSPIRATION® software, were employed to forecast the pharmacokinetic properties, biological actions, and in vitro analyses, such as MTT and scratch assays, to evaluate the therapeutic effectiveness of olivetol in wound healing. Our findings have revealed olivetol to be a promising candidate for targeting multiple pathways implicated in diabetic wound healing. Its ability to modulate inflammation, oxidative stress, extracellular matrix remodeling, angiogenesis, and cell signaling suggests a multifaceted approach to promoting effective wound repair. Moreover, olivetol has been found to demonstrate strong binding affinity with key MRSA target proteins, indicating its potential as an antimicrobial agent against MRSA infections in diabetic wounds. The in vitro MTT assay demonstrated cell viability with an IC50 value of 40.80 μM, highlighting its cytotoxicity potential. Additionally, the scratch assay confirmed promising wound healing activity, showcasing its effectiveness in promoting cell migration and closure. Olivetol emerges as a promising candidate for targeted interventions in non-healing diabetic wounds, particularly due to its ability to address prolonged inflammation, a common obstacle in diabetic wound healing.