Diabetic Wound Research Articles

Multi-responsive sodium hyaluronate/tannic acid hydrogels with ROS scavenging ability promote the healing of diabetic wounds

Oxidative stress caused by excessive reactive oxygen species (ROS) accumulation significantly hinders wound healing in patients with diabetes. Scavenging ROS and reducing inflammation are crucial for rapid healing. In this work, a multi-responsive sodium hyaluronate (HA)/tannic acid (TA) hydrogel was developed based on boronate ester bonds. Sodium hyaluronate with 3-aminophenyl boronic acid modification (HA-APBA) was mixed and crosslinked with TA to form HA-APBA/TA hydrogels. These hydrogels are injectable, self-healing, and biocompatible. The HA-APBA/TA hydrogels could release free TA through the collapse of the structure at low pH, high H2O2 concentration, and high glucose concentration, thus possessing good ROS scavenging ability. In full-thickness skin wounds of db/db mice, the HA-APBA/TA hydrogels promoted wound healing, collagen deposition, and significant angiogenesis. Furthermore, they have been shown to effectively reduce the levels of inflammatory factors in wounds and lower the expression of CD86, a pro-inflammatory macrophage surface marker. This resulted in a more effective transition of wound healing from the inflammatory phase to the proliferative phase. This study provides an optional strategy for alleviating oxidative stress and controlling excessive inflammation, thereby promoting diabetic wound healing.

Liraglutide Promotes Diabetic Wound Healing via Myo1c/Dock5.

Non-healing diabetic wounds and ulcer complications, with persistent cell dysfunction and obstructed cellular processes, are leading causes of disability and death in patients with diabetes. Currently, there is a lack of guideline-recommended hypoglycemic drugs in clinical practice, likely due to limited research and unclear mechanisms. In this study, it is demonstrated that liraglutide significantly accelerates wound closure in diabetic mouse models (db/db mice and streptozotocin-induced mice) by improving re-epithelialization, collagen deposition, and extracellular matrix remodeling, and enhancing the proliferation, migration, and adhesion functions of keratinocytes. However, these effects of improved healing by liraglutide are abrogated in dedicator of cytokinesis 5 (Dock5) keratinocyte-specific knockout mice. Mechanistically, liraglutide induces cellular function through stabilization of unconventional myosin 1c (Myo1c). Liraglutide directly binds to Myo1c at arginine 93, enhancing the Myo1c/Dock5 interaction by targeting Dock5 promoter and thus promoting the proliferation, migration, and adhesion of keratinocytes. Therefore, this study provides insights into liraglutide biology and suggests it may be an effective treatment for diabetic patients with wound-healing pathologies.

UV-spectrophotometric and spectroscopic observed Vachellia nilotica and Nigella sativa formulations regularized the histopathological and biochemical parameters during wound contraction.

Diabetes mellitus causes impaired diabetic wounds which is linked to a number of pathological alterations that impede the healing of wounds. In the current research, Swiss albino mice were given alloxan monohydrate to induce diabetes and excision wounds of approximately 6 mm using biopsy punch. The diabetic wounds were treated with various biomaterials including Vachellia nilotica extract (VN), Nigella sativa extract (NS), V. nilotica nanoparticles (VNNPs) and N. sativa nanoparticles (NSNPs). Their effects were determined by evaluating the percent wound contraction, healing time, and histopathological analysis. The serum level of various biochemical parameters that is, pro-inflammatory cytokines, Matrix metalloproteinases (MMPs) and tissue inhibitor matrix metalloproteinases (TIMPs) were also determined. VNNPs group provided the best outcomes, with wound contraction 100% on 12th day. According to histopathological examination, VNNPs group reduced inflammation and encouraged the formation of blood vessels, fibroblasts, and keratinocytes. VNNPs group significantly alleviated the serum level of pro-inflammatory cytokines that are, TNF-α (19.4 ± 1.5 pg/mL), IL-6 (13.8 ± 0.6 pg/mL), and IL-8 (24.8 ± 1.2 pg/mL) as compared with the diabetic mice. The serum level of MMP2 (248.2 ± 7.9 pg/mL), MMP7 (316 ± 5.2 pg/mL), and MMP9 (167.8 ± 12.1 pg/mL) in the same group VNNPs were also observed much less than the diabetic mice. The serum level of TIMPs (176.8 ± 2.9 pg/mL) in the VNNPs group was increased maximally with respect to diabetic mice. It is concluded that nanoparticles and biomaterials possess healing properties and have the ability to repair the chronic/diabetic wound. RESEARCH HIGHLIGHTS: UV-spectrophotometric and Fourier transform infrared spectroscopy observation for functional group analysis and possible linkage between conjugates Optimization of the histopathological and biochemical markers after application of the formulations Microscopic analysis of epithelial tissues for evaluation of healing mechanisms Speedy contraction of wounds as the alleviation of the inflammatory and necrotic factors.

Multifunctional and immunoregulatory microenvironment-responsive hydrogel for whole course management of infected diabetic wounds

Infective diabetic wounds can significantly delay healing and pose severe infection risks. The process of infective diabetic wounds healing (DWH) are not only re-epithelialization and angiogenesis but also anti-bacterial, hair follicles regeneration and nerve growth. In this study, a stable dynamic hydrogel system was formulated by incorporating dynamic borate easter bond and carbon–carbon double bond, which based on tannic acid (TA) − acrylic phenyl boric acid (APBA) and acrylamide (AM). Subsequently, a hydrogel (ATAN-Met) was obtained by modifying the antibacterial ammonium cationic (N+) and loading metformin (Met). This system demonstrated impressive wet adhesion, self-healing, wearable and peelable properties, responding to glucose/reactive oxygen species (ROS) for drug release. In vitro and vivo experiments illustrated that ATAN-Met recruited mesenchymal stem cell (MSC), facilitating interaction between MSC and neural cells, regulating macrophage polarization, and modulating the diabetic wound microenvironment while exhibiting anti-bacterial property, ultimately leading to re-epithelialization and neurovascular-hair follicles regeneration. RNA and metabolomic sequencing indicated that ATAN-Met activate the Hippo pathway, inhibit the TNF pathway, and regulate wound metabolism to improve the diabetic wound microenvironment. These results suggest that the microenvironment-responsive ATAN-Met hydrogel shows considerable potential for the whole course management of infective DWH.

Carbonized Polymer Dot-Tannic Acid Nanoglue: Tissue Reinforcement with Concurrent Fluorescent Tracking, Insulin Delivery, and Reactive Oxygen Species Regulation for Normal and Diabetic Wound Healing.

Nanotizing biosealant components offer a multitude of chemical functionalities for superior adhesion-cohesion, delivering unique properties for comprehensive wound healing that are otherwise impossible to achieve using commercial variants. For the first time, a two-step controlled hydrothermal pyrolysis is reported to nanotize dopamine, phloroglucinol, and glutaraldehyde into carbon dot (CD) to be subsequently converted into carbonized polymer dot (CPD) with gelatin as a co-substrate. Chemical crosslinking of CD with gelatin through Schiff base formation before the second pyrolysis step ensures a complex yet porous polymeric network. The retention of chemical functionalities indigenous to CD substrates and gelatin along with the preservation of CD photoluminescence in CPD for optical tracking is achieved. A unique nanoformulation is created with the CPD through tannic acid (TA) grafting evolving CPD-TA nanoglue demonstrating ≈1.32MPa strength in lap shear tests conducted on porcine skin, surpassing traditional bioadhesives. CPD-TA nanoglue uploaded insulin as chosen cargo disbursal at the wound site for healing normal and in vitro diabetic wound models using HEKa cells with extraordinary biocompatibility. Most importantly, CPD-TA can generate reactive oxygen species (ROS) and scavenge simultaneously under ambient conditions (23W white LED or dark) for on-demand sterilization or aiding wound recovery through ROS scavenging.

Chitosan based extruded nanofibrous bioscaffold for local delivery of mesenchymal stem cells to improve diabetic wound healing

BackgroundMesenchymal stem cells (MSCs)-based treatment strategy has shown promise in bolstering the healing process of chronic wounds in diabetic patients, who are at risk of amputation and mortality. To overcome the drawbacks of suboptimal cell retention and diminished cell viability at the injury site, a novel nanofibrous biomaterial-based scaffold was developed by using a controlled extrusion of a polymeric solution to deliver the cells (human adipose-derived MSCs (ADMSCs) and placenta-derived MSCs (PLMSCs)) locally to the animal model of diabetic ulcers.MethodsThe physicochemical and biological properties of the nano-bioscaffold were characterized in terms of microscopic images, FTIR spectroscopy, tensile testing, degradation and swelling tests, contact angle measurements, MTT assay, and cell attachment evaluation. To evaluate the therapeutic efficacy, a study using an excisional wound model was conducted on diabetic rats.ResultsThe SEM and AFM images of scaffolds revealed a network of uniform nanofibers with narrow diameters between 100-130 nm and surface roughness less than 5 nm, respectively. ADMSCs and PLMSCs had a typical spindle-shaped or fibroblast-like morphology when attached to the scaffold. Desired characteristics in terms of swelling, hydrophilicity, biodegradation rate, and biocompatibility were achieved with the CS70 formulation. The wound healing process was accelerated according to wound closure rate assay upon treatment with MSCs loaded scaffold resulting in increased re-epithelialization, neovascularization, and less inflammatory reaction. Our findings unequivocally demonstrated that the cell-loaded nano-bioscaffold exhibited more efficacy compared with its acellular counterpart. In summation, our study underscores the potential of this innovative cellular scaffold as a viable solution for enhancing the healing of diabetic ulcers.ConclusionThe utilization of MSCs in a nanofibrous biomaterial framework demonstrates significant promise, providing a novel avenue for advancing wound care and diabetic ulcer management.Graphical

Evaluating the Healing Properties of Quercetin-Enhanced Nanoparticle Ointments in Diabetic Rats

Background: Wound healing problems pose a significant clinical challenge for individuals with diabetes, necessitating innovative treatment strategies. Phenyl Boronic Acid-Quercetin (PBA-Q) nanoparticles offer potential benefits due to their antioxidant, anti-inflammatory, and wound-healing properties. Objective: This study aimed to investigate the morphological events associated with wound healing in diabetic rat models treated with PBA-Q nanoparticles ointment. Methods: Male Albino Wistar rats with streptozotocin-induced diabetes were used. Diabetes was confirmed with blood glucose levels exceeding 250 mg/dL. Excisional wounds of 2 cm diameter were created on the dorsum of each rat. The PBA-Q nanoparticles ointment was applied topically on days 3, 7, 11, and 15 post-wounding. Wound contraction was measured using a Vernier caliper, and tissues were collected for histopathological analysis, immunohistochemistry, and electron microscopy. Statistical analysis was performed using SPSS version 25.0. Results: Compared to controls, diabetic rats treated with PBA-Q nanoparticles showed significantly accelerated wound closure by 42% on day 15, enhanced re-epithelialization, increased collagen deposition by 50%, and reduced inflammatory cell infiltration by 60%. Vascularization was notably improved, with a 70% increase in blood vessel formation by day 15. Conclusion: PBA-Q nanoparticles ointment significantly enhanced wound healing in diabetic rats, demonstrating therapeutic potential for diabetic wound management. Further research is needed to validate these findings in human clinical trials.

M2 macrophage-polarized anti-inflammatory microneedle patch for accelerating biofilm-infected diabetic wound healing via modulating the insulin pathway

Macrophages play a pivotal role in the healing of diabetic ulcers. The sustained elevation of glucose levels damages the insulin signaling pathway in macrophages, leading to dysfunctional macrophages that struggle to transition from pro-inflammatory (M1) to reparative (M2) states. Therefore, modulating macrophage inflammatory responses via the insulin pathway holds promise for diabetic ulcer treatment. Additionally, the presence of biofilm impedes drug penetration, and the resulting immunosuppressive microenvironment exacerbates the persistent infiltration of pro-inflammatory M1 macrophages. Therefore, we designed an array of dissolvable microneedle (denoted as NPF@MN) loaded with self-assembled nanoparticles that could deliver NPF nanoparticles, acid-sensitive NPF-releasing Protocatechualdehyde (PA) with hypoglycemic and insulin-like effects, regulating macrophage polarization to an anti-inflammatory M2 phenotype. Additionally, this study extensively examined the mechanism by which NPF@MN accelerates the healing of diabetic ulcers through the activation of the insulin signaling pathway. Through RNA-seq and GSEA analysis, we identified a reduction in the expression of pathway-related factors such as IR, IRS-1, IRS-2, and SHC. Our work presents an innovative therapeutic approach targeting the insulin pathway in diabetic ulcers and underscores its translational potential for clinical management.

Hybrid biomaterial hydrogel loading iRGD&PS double modified lipid nanoparticles ameliorates diabetic wound healing through promoting efferocytosis and glycolysis-related macrophage reprogramming

Efferocytosis is a critical process whereby macrophages residing in the wound area play a key role in the efficient clearing and degradation of apoptotic neutrophils. This process is followed by a phenotypic transition toward an anti-inflammatory state, essential for inflammation resolution and tissue repair. The cystine/glutamate antiporter SLC7A11 has recently been identified as an inhibitor of efferocytosis, and its blockade has been found to enhance wound healing. In this study, we demonstrated that tiliroside, a plant-derived glycoside containing flavones, binds directly to SLC7A11 and pyruvate kinase isozyme M2 (PKM2). This was established by molecular docking predictions and activity-based protein profiling (ABPP). Cytological experiments revealed that tiliroside promoted the process of efferocytosis and led to glycolysis-related macrophage reprogramming. To facilitate targeted drug delivery to macrophages at diabetic wound sites, we designed a novel hybrid biomaterial. This hybrid biomaterial, prepared as Gel@Til iRGD&PS@PLGA NPs is manufactured by loading tiliroside (Til)-conjugated iRGD&PS double modified lipid nanoparticles (iRGD&PS@PLGA NPs) into a pH-responsive hydrogel matrix. The administration of Gel@Til iRGD&PS@PLGA NPs in diabetic cutaneous wound models has been shown to significantly promote tissue regeneration through the promotion of efferocytosis and glycolysis-related macrophage reprogramming. Therefore, this study introduces a novel approach to diabetic wound management by leveraging the promotion of efferocytosis.

Injectable natural hydrogel with spatiotemporal self-strengthening, antibacterial and anti-inflammatory properties for treating diabetic wound

Injectable hydrogel dressings provide a promising approach for treating diabetic wounds as they conform to irregular surfaces and foster new tissue development in a moist environment. Nevertheless, post-injection mechanical performance is often mediocre, coupled with inadequate antibacterial protection. Herein, we prepared an injectable hydrogel dressing (CBGT@PDA) consisting of double-network hydrogel (CBGT) and polydopamine nanoparticles (PDA NPs) as a multi-targeted combination therapy system oriented to chronic diabetic wound healing. Efficient enzymatic reactions combined with a slow quaternization procedure regulate the mechanical attributes of injectable hydrogels, offering spatiotemporal self-strengthening and exceptional antibacterial capabilities. The hydrogel system is also equipped with scavenged ROS function, bioadhesion characteristics and remarkable biocompatibility, thus exhibiting high improvement in the healing of the diabetic wound. We believe such injectable hydrogels with spatiotemporal self-strengthening capabilities in both of mechanical and antibacterial properties will provide new insight into the hydrogel-based wound dressing and broaden the application of the bioinspired hydrogels in biomedical fields.

Insulin-Induced Gene 1-Enhance Secretion of BMSC Exosome Enriched in miR-132-3p Promoting Wound Healing in Diabetic Mice.

Chronic diabetic wounds represent a significant clinical challenge because of impaired healing processes, which require innovative therapeutic strategies. This study explores the therapeutic efficacy of insulin-induced gene 1-induced bone marrow mesenchymal stem cell exosomes (Insig1-exos) in promoting wound healing in diabetic mice. We demonstrated that Insig1 enhanced the secretion of bone marrow mesenchymal stem cell-derived exosomes, which are enriched with miR-132-3p. Through a series of in vitro and in vivo experiments, these exosomes significantly promoted the proliferation, migration, and angiogenesis of dermal fibroblasts under high-glucose conditions. They also regulated key wound-healing factors, including matrix metalloproteinase-9, platelet-derived growth factor, vascular endothelial growth factor, transforming growth factor-β1, and platelet endothelial cell adhesion molecule-1, thereby accelerating wound closure in diabetic mice. Histological analysis showed that Insig1-exos were more effective in promoting epithelialization, enhancing collagen deposition, and reducing inflammation. Additionally, inhibition of miR-132-3p notably diminished these therapeutic effects, underscoring its pivotal role in the wound-healing mechanism facilitated by Insig1-exos. This study elucidates the molecular mechanisms through which Insig1-exos promotes diabetic wound healing, highlighting miR-132-3p as a key mediator. These findings provide new strategies and theoretical foundations for treating diabetes-related skin injuries.

Baicalin derivative dynamically cross-linked natural polysaccharide hydrogel for diabetic wound healing

Diabetes is a chronic disease affects nearly 10% of the global population, the prolonged metabolic abnormalities and the complex microenvironment in diabetic wounds often leading to impaired healing. To address the typical characteristics of diabetic wounds, such as hyperglycemia, low pH, excessive reactive oxygen species (ROS) production, and chronic inflammation, this study designed a baicalin derivative dynamically cross-linked natural polysaccharide hydrogel (CFPB) and explored its potential to promote diabetic wound healing. The framework of CFPB utilized chitosan and modified with dextran to introduce aldehyde groups via mild grafting, and crosslinked with the modified active substance baicalin to effectively extend the drug delivery time. A series of characterizations demonstrated that CFPB hydrogel possesses excellent mechanical properties, self-healing ability, and responsive release capability. Subsequently, multi-level biological experiments validated the promoting effect of CFPB hydrogel on diabetic wound healing in vitro and in vivo. This study not only offers a potential candidate for the local therapy of diabetic wounds, but also provides new insights for the development of advanced wound dressings.

Accelerated healing of intractable biofilm-infected diabetic wounds by trypsin-loaded quaternized chitosan hydrogels that disrupt extracellular polymeric substances and eradicate bacteria

Complex and stubborn bacterial biofilm infections significantly hinder diabetic wound healing and threaten public health. Therefore, a dressing material that effectively clears biofilms and promotes wound healing is urgently required. Herein, we introduce a novel strategy for simultaneously dispersing extracellular polymeric substances and eradicating drug-resistant bacteria. We prepared an ultrabroad-spectrum and injectable quaternized chitosan (QCS) hydrogel loaded with trypsin, which degrades biofilm extracellular proteins. Increased temperature initiated QCS gelation to form the hydrogel, enabling the sustained release of trypsin and effective adherence of the hydrogel to irregularly shaped wounds. To reproduce clinical scenarios, biofilms formed by a mixture of Staphylococcus aureus (S. aureus), Methicillin-resistant S. aureus, and Pseudomonas aeruginosa were administered to the wounds of rats with streptozotocin-induced diabetes. Under these severe infection conditions, the hydrogel efficiently suppressed inflammation, promoted angiogenesis, and enhanced collagen deposition, resulting in accelerated healing of diabetic wounds. Notably, the hydrogel demonstrates excellent biocompatibility without cytotoxicity. In summary, we present a trypsin-loaded QCS hydrogel with tremendous clinical applications potential for the treatment of chronic infected wounds.

Genetically Encoded Incorporation of IFN-α into Collagen-like Protein–Hyaluronic Acid Hydrogels for Diabetic Chronic Wound Healing

Genetically Encoded Incorporation of IFN-α into Collagen-like Protein–Hyaluronic Acid Hydrogels for Diabetic Chronic Wound Healing

On-demand Opto-Laser activatable nanoSilver ThermoGel for treatment of full-thickness diabetic wound in a mouse model

Patients suffering from diabetes mellitus are prone to develop diabetic wounds that are non-treatable with conventional therapies. Hence, there is an urgent need of hour to develop the therapy that will overcome the lacunas of conventional therapies. This investigation reports the Quality by Design-guided one-pot green synthesis of unique Opto-Laser activatable nanoSilver ThermoGel (OL→nSil-ThermoGel) for hyperthermia-assisted treatment of full-thickness diabetic wounds in mice models. The characterization findings confirmed the formation of spherical-shaped nanometric Opto-Laser activatable nanoSilver (30.75 ± 2.7 nm; ∆T: 37 ± 0.2 °C → 66.2 ± 0.1 °C; at 1.8 W/cm2 NIR laser density). The findings indicated acceptable in vitro cytocompatibility and significant keratinocyte migration (95.04 ± 0.07 %) activity of OL→nSil towards HaCaT cells. The rheological data of OL→nSil hybridized in situ thermoresponsive gel (OL→nSil-ThermoGel) showed the gelling temperature at 32 ± 2 °C. In vivo studies on full-thickness diabetic wounds in a Mouse model showed OL→nSil-ThermoGel accelerated wound closure (94.42 ± 1.03 %) and increased collagen synthesis, angiogenesis, and decreased inflammatory markers. Similarly, immunohistochemistry study showed significant angiogenesis and faster phenotypic switching of fibroblasts to myofibroblasts in OL→nSil-ThermoGel treated diabetic wounds. Histological evaluation revealed a marked rise in keratinocyte migration, organized collagen deposition, and early regeneration of the epithelial layer compared to the diabetic wound control. In conclusion, the OL→nSil-ThermoGel modulates the cytokines, re-epithelialization, protein expression, and growth factors, thereby improving the repair and regeneration of diabetic wounds in mice.

Quaternary ammonium grafted chitosan hydrogel with enhanced antibacterial performance as tannin acid and deferoxamine carrier to promote diabetic wound healing

The delay of diabetic wound healing puts a huge burden on the society. The key factors hindering wound healing include bacterial infection, unresolved inflammation and poorly generated blood vessels. In this paper, glycidyl trimethyl ammonium chloride (GTA) was grafted to chitosan (CS) to obtain quaternary ammonium grafted chitosan (QCS) with enhanced antibacterial performance, and then cross-linked by dialdehyde terminated poly(ethylene oxide) (PEO DA) to construct QCS/PEO DA hydrogel with tissue adhesion, biodegradation and self-healing properties. The QCS/PEO DA hydrogel is loaded with tannin acid (TA) and deferoxamine (DFO) to enhance antioxidant property and angiogenesis. At the same time, the TA and DFO loaded TA@DFO/hydrogel preserved the biocompatibility and biodegradability of chitosan. Moreover, the multifunctional hydrogel behaved excellent hemostatic properties in mice model and significantly promoted the healing efficacy of diabetic wounds. Overall, the TA@DFO/hydrogel is promising anti-infection dressing material for diabetic wound healing.

Hypoxic microenvironment promotes diabetic wound healing by polarizing macrophages to the M2 phenotype in vivo.

In diabetic wounds, M2 polarization of macrophages regulates the transition from an inflammatory phase to a proliferative phase. Prior investigations have demonstrated the potential of deferoxamine (DFO) in creating a localized hypoxic microenvironment, which could stimulate angiogenesis by promoting vascular endothelial growth factor (VEGF) secretion in diabetic wound healing. Nevertheless, there is still no clear information on whether this chemically induced hypoxic microenvironment modulates macrophage polarization to promote diabetic wound healing. The 18 diabetic mice were randomly divided into three groups: a control group (n = 6), a 100µM DFO group (n = 6), and a 200µM DFO group (n = 6). Subsequently, a full-thickness wound with a diameter of 1.00cm was created on the dorsal region of the diabetic mice. Observe wound closure regularly during treatment. At the end of the observation, tissue specimens were collected for a series of experiments and analyses, including hematoxylin and eosin (H&E), Masson, immunofluorescent, and immunohistochemical staining. The role and mechanism of DFO in regulating macrophage polarization were studied using RAW264.7 cells. In comparison to the control group, the administration of DFO notably facilitates wound healing in diabetic mice. In diabetic wounds, DFO increases blood supply by upregulating VEGF, which promotes angiogenesis. Additionally, The expression of HSP70 and CD206 were also upregulated by DFO in both vivo and in vitro, while iNOS expression was downregulated. Additionally, knk437 inhibited the expression of HSP70 in RAW264.7 cells, resulting in a reduction of M2 polarization and an increase in M1 polarization. The induction of a hypoxic microenvironment by DFO has been found to exert a substantial influence on the process of diabetic wound healing. DFO treatment enhances the capacity of diabetic wounds to stimulate angiogenesis and modulate macrophage polarization that may be associated with HSP70 expression, thereby expediting the transition of these wounds from an inflammatory to a proliferative state.

A one-stop integrated natural antimicrobial microneedles with anti-inflammatory, pro-angiogenic and long-term moisturizing properties to accelerate diabetic wound healing

Diabetic ulcers present a formidable obstacle in diabetes management, typically leading to high mortality and amputation rates. To overcome traditional monotherapy drawbacks, We developed a novel microneedle strategy for combined antimicrobial action: ingeniously integrating quercetin with Platelet-derived Growth Factor-BB(PDGF-BB) and Sucrose Octasulfate(SOS) into the microneedle system(QPS MN). This method allows to penetrate through biofilms, administering quercetin nanocrystals and PDGF-BB deep into the tissue to combat microbial infection, mitigate inflammation, and promote angiogenesis. The accompanying backing material contains SOS, which absorbs wound exudate and forms a dressing that provides a moist environment for wound healing In an in vitro wound-scratch assay demonstrated that co-cultivating Human Umbilical Vein Endothelial Cells(HUVEC) with QPS MN for 48 h (90.3 ± 2.51 %) significantly enhanced cell migration compared to the control group (20.2 ± 1.41 %). Moreover, treatment of streptozotocin-induced diabetic wounds in rats with QPS MN for 14 days resulted in a wound healing rate of 96.56 ± 3.44 %, far surpassing the healing rate of only 40.34 ± 7.26 % observed in the untreated control group. Furthermore, the QPS MN treated wounds exhibited a notable increase in skin appendages and neovascularisation, indicating promising potential for achieving complete wound healing. These results suggest that QPS MN may offer substantial therapeutic benefits for addressing diabetic wounds.

Suppression the glucose-induced ferroptosis in endothelial cells by 4OI-loading exosomes hydrogel for the treatment of diabetic foot ulcer

The prevalence of diabetic foot ulcer in individuals with diabetes is approximately 15%, and it is frequently accompanied by vascular dysfunction and infection. The management challenges make it the primary cause for amputation; however, the underlying mechanisms remain poorly understood, thereby impeding the advancement of novel wound dressings and medication. Herein, single-cell sequencing analysis revealed that ferroptosis induced by high glucose levels in vascular endothelial cells (VECs) represents a significant molecular pathological feature in diabetic foot ulcer (DFU) tissue. Furthermore, 4-Octyl itaconate (4OI) exhibited a pronounced protective effect against VECs injury induced by high glucose (HG), and its underlying molecular mechanisms involve the mitigation of HG-induced reactive oxygen species (ROS) injury and ferroptosis in VECs through the regulation Keap1/Nrf2/GPX4. For enhanced application, incubation at 37℃ was used to load 4OI into exosomes, which were subsequently encapsulated within an Alg-DA/GelMA-based hydrogel matrix. Remarkably, the utilization of 4OI-Exo-Gel not only expedited wound healing but also significantly improved the overall quality of healing in DFU. In conclusion, these findings not only demonstrate, for the first time, the remarkable ability of 4OI to enhance diabetic wound healing by mitigating VECs ferroptosis induced by HG, but also provide evidence for the potential clinical translation of a 4OI-loaded exosomes hydrogel in diabetic wound therapy.

Effects of continuous negative pressure suction combined with autologous platelet-rich gel on the levels of CRP, IL-6, wound healing and length of stay in clients with diabetic foot

ObjectiveContinuous passive pressure suction and APG gel therapy effect diabetic foot IL-6, CRP, wound healing, and hospitalization. MethodsClinicopathological data from 102 diabetic foot ulcer patients treated at our institution between March 2018 and May 2022 was examined. Tables generated 51 joint and controlling teams randomly. The observation team received passive pressure suction and APG gel whereas the controlled team received conventional treatment. Teams monitored therapy outcomes, adverse responses, wound healing, hospital stay, and costs. Both teams compared blood uric acid, cystatin C, homocysteine, and serum IL-6, IL-10, and CRP before and after medication. ResultsThe joint team had higher hospitalization costs, shorter stays, and faster wound healing than the controlled team. Diaparity was significant (P < 0.05). The united team worked 100 %, unlike the controlling team. This difference was significant (P < 0.05). Both teams showed significant decreases in CRP, IL-6, and IL-10 levels after therapy (P < 0.05). After therapy, both the combined and controlled teams had substantial differences in blood CRP, IL-6, and IL-10 levels (P < 0.05). Both teams had significantly decreased uric acid, cystatin C, and homocysteine after treatment. The combined team showed significantly decreased uric acid, cystatin C, homocysteine levels following therapy compared to the control team (P < 0.05). ConclusionThe joint team experienced considerably fewer adverse events (3.92 % vs. 17.65 %) than the controls team (P < 0.05). Permanent passive pressure suction and APG gel therapy lower inflammatory response, blood uric acid, cystatin C, and homocysteine, speeding wound healing, reducing side effects.