Diabetic Wound Model Research Articles

LNP-RNA-engineered adipose stem cells for accelerated diabetic wound healing

Adipose stem cells (ASCs) have attracted considerable attention as potential therapeutic agents due to their ability to promote tissue regeneration. However, their limited tissue repair capability has posed a challenge in achieving optimal therapeutic outcomes. Herein, we conceive a series of lipid nanoparticles to reprogram ASCs with durable protein secretion capacity for enhanced tissue engineering and regeneration. In vitro studies identify that the isomannide-derived lipid nanoparticles (DIM1T LNP) efficiently deliver RNAs to ASCs. Co-delivery of self-amplifying RNA (saRNA) and E3 mRNA complex (the combination of saRNA and E3 mRNA is named SEC) using DIM1T LNP modulates host immune responses against saRNAs and facilitates the durable production of proteins of interest in ASCs. The DIM1T LNP-SEC engineered ASCs (DS-ASCs) prolong expression of hepatocyte growth factor (HGF) and C-X-C motif chemokine ligand 12 (CXCL12), which show superior wound healing efficacy over their wild-type and DIM1T LNP-mRNA counterparts in the diabetic cutaneous wound model. Overall, this work suggests LNPs as an effective platform to engineer ASCs with enhanced protein generation ability, expediting the development of ASCs-based cell therapies.

Highly Bioactive MXene-M2-Exosome Nanocomposites Promote Angiogenic Diabetic Wound Repair through Reconstructing High Glucose-Derived Immune Inhibition.

The repair of diabetic wounds remains challenging, primarily due to the high-glucose-derived immune inhibition which often leads to the excessive inflammatory response, impaired angiogenesis, and heightened susceptibility to infection. However, the means to reduce the immunosuppression and regulate the conversion of M2 phenotype macrophages under a high-glucose microenvironment using advanced biomaterials for diabetic wounds are not yet fully understood. Herein, we report two-dimensional carbide (MXene)-M2 macrophage exosome (Exo) nanohybrids (FM-Exo) for promoting diabetic wound repair by overcoming the high-glucose-derived immune inhibition. FM-Exo showed the sustained release of M2 macrophage-derived exosomes (M2-Exo) up to 7 days and exhibited broad-spectrum antibacterial activity. In the high-glucose microenvironment, relative to the single Exo, FM-Exo could significantly induce the optimized M2a/M2c polarization ratio of macrophages by activating the PI3K/Akt signaling pathway, promoting the proliferation, migration of fibroblasts, and angiogenic ability of endothelial cells. In the diabetic full-thickness wound model, FM-Exo effectively regulated the polarization status of macrophages and promoted their transition to the M2 phenotype, thereby inhibiting inflammation, promoting angiogenesis through VEGF secretion, and improving proper collagen deposition. As a result, the healing process was accelerated, leading to a better healing outcome with reduced scarring. Therefore, this study introduced a promising approach to address diabetic wounds by developing bioactive nanomaterials to regulate immune inhibition in a high-glucose environment.

Platelet-Derived Growth Factor Nanocapsules with Tunable Controlled Release for Chronic Wound Healing.

Chronic wounds have emerged as an increasingly critical clinical challenge over the past few decades, due to their increasing incidence and socioeconomic burdens. Platelet-derived growth factor (PDGF) plays a pivotal role in regulating processes such as fibroblast migration, proliferation, and vascular formation during the wound healing process. The delivery of PDGF offers great potential for expediting the healing of chronic wounds. However, the clinical effectiveness of PDGF in chronic wound healing is significantly hampered by its inability to maintain a stable concentration at the wound site over an extended period. In this study, a controlled PDGF delivery system based on nanocapsules is proposed. In this system, PDGF is encapsulated within a degradable polymer shell. The release rate of PDGF from these nanocapsules can be precisely adjusted by controlling the ratios of two crosslinkers with different degradation rates within the shells. As demonstrated in a diabetic wound model, improved therapeutic outcomes with PDGF nanocapsules (nPDGF) treatment are observed. This research introduces a novel PDGF delivery platform that holds promise for enhancing the effectiveness of chronic wound healing.

Hesperetin promotes diabetic wound healing by inhibiting ferroptosis through the activation of SIRT3.

Hesperetin (HST) is a flavonoid compound naturally occurring in citrus fruits and is widespread in various traditional medicinal herbs such as grapefruit peel, orange peel, and tangerine peel. These plant materials are commonly used in traditional Chinese medicine to prepare herbal remedies. The study aimed to investigate the potential molecular mechanisms through which HST reduces ferroptosis in human umbilical vein endothelial cells (HUVECs) and promotes angiogenesis and wound healing. We employed network pharmacology to predict the downstream targets affected by HST. The expression of markers related to ferroptosis was assessed through Western blot (WB) and polymerase chain reaction. Intracellular levels of ferroptosis-related metabolism were examined using glutathione/oxidized glutathione (GSH/GSSG) and malondialdehyde (MDA) assay kits. Mitochondrial status and iron levels within the cells were investigated through staining with Mitosox, FerroOrange, and JC1 staining. Potential downstream direct targets of HST were identified using molecular docking. Additionally, wound healing and neovascularization within the wound site were analyzed using various methods including HE staining, Masson's staining, immunohistochemistry, and Doppler hemodynamics assessment. HST effectively inhibits the elevated levels of intracellular ferroptosis stimulated by ERASTIN. Furthermore, we observed that HST achieves this inhibition of ferroptosis by activating SIRT3. In a diabetic rat wound model, HST significantly promotes wound healing, reducing levels of tissue ferroptosis, consistent with our in vitro findings. This study demonstrates that HST can inhibit the progression of ferroptosis and protect the physiological function of HUVECs by activating SIRT3. HST holds promise as a natural compound for promoting diabetic wound healing.

Chitosan-based multifunctional oxygenating antibiotic hydrogel dressings for managing chronic infection in diabetic wounds.

Current treatment strategies for infection of chronic wounds often result in compromised healing and necrosis due to antibiotic toxicity, and underlying biomarkers affected by treatments are not fully known. Here, a multifunctional dressing was developed leveraging the unique wound-healing properties of chitosan, a natural polysaccharide known for its numerous benefits in wound care. The dressing consists of an oxygenating perfluorocarbon functionalized methacrylic chitosan (MACF) hydrogel incorporated with antibacterial polyhexamethylene biguanide (PHMB). A non-healing diabetic infected wound model with emerging metabolomics tools was used to explore the anti-infective and wound healing properties of the resultant multifunctional dressing. Direct bacterial bioburden assessment demonstrated superior antibacterial properties of hydrogels over a commercial dressing. However, wound tissue quality analyses confirmed that sustained PHMB for 21 days resulted in tissue necrosis and disturbed healing. Therefore, a follow-up comparative study investigated the best treatment course for antiseptic application ranging from 7 to 21 days, followed by the oxygenating chitosan-based MACF treatment for the remainder of the 21 days. Bacterial counts, tissue assessments, and lipidomics studies showed that 14 days of application of MACF-PHMB dressings followed by 7 days of MACF dressings provides a promising treatment for managing infected non-healing diabetic skin ulcers.

The Modulatory Effect of an Ethanolic Extract of Anredera cordifolia (Ten.) on the Proliferation and Migration of Hyperglycemic Fibroblasts in an In Vitro Diabetic Wound Model.

Diabetes mellitus is associated with chronic wound-healing problems that significantly impact patients' quality of life and substantially increase expenditure on healthcare. Therefore, the identification of compounds that can aid healing is justified. Anredera cordifolia (Ten.) has been used in folk medicine for curative purposes; however, the causal mechanisms underlying its healing effects remain to be elucidated. In this study, the effect of the ethanolic extract of A. cordifolia was evaluated in an in vitro healing model using fibroblasts cultivated under normoglycemic and hyperglycemic environments. The extract was predominantly composed of phytol and exhibited genoprotective activity. Fibroblast migration attenuated the adverse effects of hyperglycemia, favoring cell proliferation. Collagen levels were significantly increased in ruptured fibroblasts under both standard and hyperglycemic environments. The phytogenomic effect of the extract on three genes related to extracellular matrix formation, maintenance, and degradation showed that A. cordifolia increased the expression of genes related to matrix synthesis and maintenance in both normoglycemic and hyperglycemic individuals. Furthermore, it reduced the expression of genes related to matrix degradation. Overall, this is the first study to demonstrate the effectiveness of A. cordifolia in wound healing, elucidating possible causal mechanisms that appear to be based on the genoprotective effect of this plant on the migratory and proliferative phases of the wound healing process; these effects are probably related to phytol, its main constituent.

Photothermal and Photocatalytic Glycol Chitosan and Polydopamine-Grafted Oxygen Vacancy Bismuth Oxyiodide (BiO1-x I) Nanoparticles for the Diagnosis and Targeted Therapy of Diabetic Wounds.

Treatment of diabetic wounds is a significant clinical challenge due to the massive infections caused by bacteria. In this study, multifunctional glycol chitosan and polydopamine-coated BiO1-x I (GPBO) nanoparticles (NPs) with near-infrared (NIR) photothermal and photocatalytic abilities are prepared. When infection occurs, the local microenvironment becomes acidic, and the pH-switchable GPBO can target the bacteria of the wound site. The NIR-assisted GPBO treatment exhibits anti-bacterial effects with fast response, high efficiency, and long duration to Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. GPBO achieves excellent photothermal imaging and CT imaging of the mouse subcutaneous abscess model. With the assistance of NIR irradiation, the GPBO promotes the healing of the diabetic wound model with the effects of anti-bacteria, anti-inflammation, the M2 polarization promotion of macrophages, and angiogenesis. This is the first-time report of nano-sized BiO1-x I. The synthesis and selected application for the imaging and targeted therapy of diabetic wounds are presented. This study offers an example of the NP-assisted precise diagnosis and therapy of bacterial infection diseases.

One-step fabrication of an injectable antibacterial collagen hydrogel with in situ synthesized silver nanoparticles for accelerated diabetic wound healing

Developing antibacterial collagen-based wound dressings that target multidrug-resistant bacteria holds promise for healing diabetic wounds prone to infection, yet traditional approaches pose persistent challenges of cytotoxicity and uneconomical steps. To address these issues, we develop a biocompatible, eco-friendly, one-step cross-linking and reduction strategy, fabricating injectable antibacterial collagen hydrogels containing in situ-generated silver nanoparticles for diabetic wound care. By exposing the collagen-silver ion (Ag+) mixture to visible light, collagen-silver nanoparticle (Col I/AgNPs) hydrogels were one step created, eliminating the need for additional cross-linkers and toxic reducing agents. The synergistic interaction between collagen and silver ions was the first time investigated, revealing a pivotal redox reaction with a dual role that simultaneously initiated collagen cross-linking and reduced Ag+ to AgNPs. The resulting biocompatible Col I/AgNPs hydrogel was found to have multifunctional properties, exhibiting excellent injectability, enhanced biological activity, and outstanding broad-spectrum antimicrobial ability. Furthermore, animal experiments utilizing a diabetic full-thickness wound model demonstrated their excellent in vivo healing efficacies, capable of establishing efficient antibacterial barriers and serving as bioactive regenerative scaffolds. Our study proposes an innovative one-step approach to create injectable antibacterial collagen-silver nanoparticle hydrogels, highlighting their potential as advanced dressings for diabetic wound treatment and other biomedical applications.

A novel bola-molecular self-assembling hydrogel for enhancing diabetic wound healing

HypothesisChronic wounds, particularly those caused by diabetes, pose a significant challenge for clinical treatment due to their prolonged healing process and associated complications, which can lead to increased morbidity. A biocompatible hydrogel with strong antibacterial properties and the ability to promote angiogenesis can be directly absorbed in the wound site for healing. ExperimentsA series of self-healing, antibacterial bolaamphiphilic supramolecular self-assembling hydrogels (HLQMes/Cu) were developed based on metal–ligand coordination between various concentrations of Cu2+ solution and the head group of l-histidine methyl ester in HLQMes. This is the first report on the application of bola-molecular supramolecular hydrogels for the treatment of chronic wounds. FindingsThe bola-molecular hydrogels reduced the toxicity of copper ions by coordination, and the HLQMes/Cu hydrogel, with 1.3 mg/mL Cu2+ (HLQMes/Cu1.3), demonstrated good biocompatibility and antibacterial properties and effectively enhanced wound healing in a diabetic wound model with full-thickness injuries. Immunohistochemical analysis revealed that the HLQMes/Cu1.3 hydrogel enhanced epithelial formation and collagen deposition in wounds. Immunofluorescence studies confirmed that the HLQMes/Cu1.3 hydrogel attenuated the expression of proinflammatory factor (IL-6) and promoted angiogenesis by upregulating α-SMA and CD31. These findings demonstrate the potential of this bolaamphiphilic supramolecular self-assembling hydrogel as a promising candidate for diabetic wound treatment.

Multifunctional antibiotic hydrogel doped with antioxidative lycopene-based liposome for accelerative diabetic wound healing

In the daily management of infected diabetic wound, antibiotics resistance derived from broad-spectrum antimicrobe is still inevitable. Together with the complicated inflammatory environment induced by hyperglycemia and bacteria colonization, it’s urgent to develop a novel bioactive ingredient integrating both anti-oxidative and modulation on inflammatory environment to be combined with disinfection. In regard of this, lycopene (LYC), an abundant, natural and unsaturated alkene carotenoid extracted from tomatoes was intercalated into the Dipalmitoyl-phosphatidylcholine (DPPC) liposomes loading with tobramycin (TOB), and further formulated with HAMA hydrogel (LT NPs@Gel) to prepare a novel multifunctional antibiotic wound dressing. The in vitro study showed that the intercalation of LYC and the loaded TOB brought LT NPs antioxidative and antibacterial properties, thus effectively inhibit the proliferation of bacteria and relieve endoplasmic reticulum (ER) stress to promote cell migration and angiogenesis. In an infected diabetic wound model on rat, the local administration of LT NPs@Gel significantly promoted wound healing within 14 days. Owing to the synchronized management on the inflammation environment and bacteria colonization, the massive oxidative stress in the wound were significantly alleviated, followed by the distinctive promotion of angiogenesis, re-epithelization, and collagen deposition. We believe that this functional hybrid HAMA hydrogel formulated with novel LYC-intercalated antibiotic liposome can achieve the multi-dimensional management of infected diabetic wounds.

Enhancement of bactericidal effects of bacteriophage and gentamicin combination regimen against Staphylococcus aureus and Pseudomonas aeruginosa strains in a mice diabetic wound model.

Diabetic patients are more susceptible to developing wound infections resulting in poor and delayed wound healing. Bacteriophages, the viruses that target-specific bacteria, can be used as an alternative to antibiotics to eliminate drug-resistant bacterial infections. Pseudomonas aeruginosa (P. aeruginosa) and Staphylococcus aureus (S. aureus) are among the most frequently identified pathogens in diabetic foot ulcers (DFUs). The aim of this study was assessment of bacteriophage and gentamicin combination effects on bacterial isolates from DFU infections. Specific bacteriophages were collected from sewage and animal feces samples and the phages were enriched using S. aureus and P. aeruginosa cultures. The lytic potential of phage isolates was assessed by the clarity of plaques. We isolated and characterized four lytic phages: Stp2, Psp1, Stp1, and Psp2. The phage cocktail was optimized and investigated in vitro. We also assessed the effects of topical bacteriophage cocktail gel on animal models of DFU. Results revealed that the phage cocktail significantly reduced the mortality rate in diabetic infected mice. We determined that treatment with bacteriophage cocktail effectively decreased bacterial colony counts and improved wound healing in S. aureus and P. aeruginosa infections, especially when administrated concomitantly with gentamicin. The application of complementary therapy using a phage cocktail and gentamicin, could offer an attractive approach for the treatment of wound diabetic bacterial infections.

Multifunctional photothermally responsive hydrogel as an effective whole-process management platform to accelerate chronic diabetic wound healing

The management of chronic diabetic wounds is a complex issue that requires wound repair, regulation of inflammatory levels, and intervention to prevent bacterial infection. To address this issue, we developed a multifunctional photothermally responsive hydrogel (PAG-CuS) as an effective platform for managing the entire wound-healing process, including promoting wound healing, providing anti-inflammatory therapy, and performing photothermal sterilization. Constructed through copolymerization of acrylic acid (AA), methacrylic anhydride-modified gelatin (GelMA), and lipoic acid sodium (LAS) coated copper sulfide nanoparticles (CuS@LAS), PAG-CuS possessed a porous three-dimensional structure that promoted cell adhesion and had a substantial water-holding capacity. Additionally, the internal CuS@LAS not only conferred photothermal antibacterial properties to the hydrogel but also served as physical cross-linking agents, thus enhancing its mechanical strength. Under the NIR-induced photothermal effect, the porous hydrogel liberates CuS@LAS, and later CuS@LAS expels LAS via micelle deassembly to eliminate intracellular ROS. This results in the down-regulation of MMP-9 expression, promoting ECM production and facilitating wound healing. Meanwhile, the release of Cu2+ from PAG-CuS could enhance CD31 expression in endothelial cells, promoting microvessel formation, which is crucial for wound healing. In the diabetic wound model of GK rats, the PAG-CuS hydrogel reduced ROS levels, increased microvessel count, improved epithelialization, and enhanced wound healing. Therefore, this versatile photothermal hydrogel has the potential to be applied in sterilization, scavenging free radicals, and promoting angiogenesis, making it an effective and comprehensive solution to manage the challenges of diabetic wounds. Statement of significanceAssessment of functional recovery and timely adjustment of treatment strategy is critical in the management of chronic diabetic wounds. In this work, we prepared PAG-CuS composite hydrogels by integrating in situ reduction, chemical crosslinking, and nanoenhancement techniques. The near-infrared light-induced photothermal effect of PAG-CuS gel rapidly kills bacteria at the lesion site, and the generated heat simultaneously promotes the multilevel release of LAS from the gel, which could regulate the levels of ROS and MMP-9 to promote extracellular matrix formation. In addition, the Cu2+ released from the gel can promote the formation of blood vessels to improve blood oxygenation. Therefore, this project proposes a synergistic solution to realize the whole process of management to accelerate chronic diabetic wound healing.

Effect of photobiomodulation at 830 nm on gene expression correlated with JAK/STAT signalling in wounded and diabetic wounded fibroblasts in vitro.

Treatment of chronic diabetic wounds is an ongoing socio-economic challenge. Dysregulated signalling pathways characterise cells from chronic diabetic wounds. Photobiomodulation (PBM) stimulates healing by eliciting photochemical effects that affect gene regulation. JAK/STAT signalling is a primary signal transduction pathway involved in wound healing. This in vitro study aimed to determine if PBM at 830 nm and a fluence of 5 J/cm2 regulates genes related to JAK/STAT signalling in wounded and diabetic wounded fibroblast cells. A continuous wave diode laser (12.53 mW/cm2 ) was used to irradiate cells. Forty-eight hours post-PBM, RT-qPCR was used to analyse 84 genes related to JAK/STAT signalling. Five genes were upregulated and four downregulated in wounded cell models, while six genes were downregulated in diabetic wounded models. The results show drastic gene expression differences between wounded and diabetic wounded cell models in response to PBM using 830 nm.

A Facilely Prepared Adhesive Dressing Derived from Non-Ionic Hydrogel for Accelerated Diabetic Wound Healing

Hydrogels are an important category of polymeric materials with physicochemical features such as moisturizability and biocompatibility that are ideal for developing dressings for diabetic wounds. However, conventional non-ionic hydrogel materials generally exhibit poor mechanical properties and poor adhesion, which compromise their ability to self-sustain in mechanically dynamic wound microenvironments. In this research, we developed a hybrid hydrogel as a highly biocompatible adhesive wound dressing that met the mechanical requirements of the skin to promote chronic wound healing in diabetic mouse models. A 7.5% (w/v) hydrogel corresponded to a Young’s modulus of 6.3 kPa. In vitro cell-based and subcutaneous implantation experiments in mice demonstrated the excellent biocompatibility and optimal biodegradability of hydrogel dressings. In a diabetic mouse splint wound model for evaluating wound healing in vivo, the hydrogel dressing showed robust adhesion to the wound and efficiently accommodated mechanical deformations around the wound, resulting in significantly improved healing rates of chronic diabetic wounds. Thus, our work illustrates a newly alternative strategy for the simple and efficacious treatment of chronic wounds in the context of diabetes care.

Multifunctional Regeneration Silicon-Loaded Chitosan Hydrogels for MRSA-Infected Diabetic Wound Healing.

Repeated microbial infection, excess reactive oxygen species (ROS) accumulation, cell dysfunction, and impaired angiogenesis under hyperglycemia severely inhibit diabetic wound healing. Therefore, developing multifunctional wound dressings accommodating the complex microenvironment of diabetic wounds is of great significance. Here, a multifunctional hydrogel (Regesi-CS) is prepared by loading regeneration silicon (Regesi) in the non-crosslinked chitosan (CS) solution, followed by freeze-drying and hydration. As expected, the blank non-crosslinked CS hydrogel (1%) shows great antibacterial activity against Escherichia coli, Staphylococcus aureus, and methicillin-resistant S. aureus (MRSA), improves fibroblast migration, and scavenges intracellular ROS. Interestingly, after loading 1% Regesi, the Regesi-CS (1%-1%) hydrogel shows greater antibacterial activity, significantly promotes fibroblasts proliferation and migration, scavenges much more ROS, and substantially protects fibroblasts under oxidative stress, yet Regesi alone has no or even negative effects. In the MRSA-infected diabetic wound model, Regesi-CS (1%-1%) hydrogel effectively promotes wound healing by eliminating bacterial infection, enhancing granulation tissue formation, promoting collagen deposition, and improving angiogenesis. In conclusion, Regesi-CS hydrogel may be a potential wound dressing for the effective treatment and management of chronic diabetic wounds.

HMOX1-overexpressing mesenchymal stem cell-derived exosomes facilitate diabetic wound healing by promoting angiogenesis and fibroblast function

Many scholars have suggested that exosomes (Exos) can carry active molecules to induce angiogenesis and thus accelerate diabetic wound healing. Heme oxygenase-1 (HO-1) encoded by the gene HMOX1 promotes wound healing in DM by enhancing angiogenesis. Nevertheless, whether HMOX1 regulates wound healing in DM through mesenchymal stem cell-derived exosomes (MSC-Exos) remains to be further explored. The primary isolated- and cultured-cells expressed MSC-specific marker proteins, and had low immunogenicity and multi-differentiation potential, which means that MSCs were successfully isolated in this study. Notably, HO-1 protein expression was significantly higher in Exo-HMOX1 than in Exos, indicating that HMOX1 could be delivered to Exos as an MSCs-secreted protein. After verifying the -Exo structure, fibroblasts, keratinocytes, and human umbilical vein endothelial cells (HUVECs) were incubated with Exo-HMOX1 or Exo, and the findings displayed that Exo-HMOX1 introduction promoted the proliferation and migration of fibroblasts, keratinocytes and the angiogenic ability of HUVECs in vitro study. After establishing diabetic wound model mice, PBS, Exo, and Exo-HMOX1 were subcutaneously injected into multiple sites on the 1st, 3rd, 7th, and 14th day, DM injected with Exo-HMOX1 showed faster wound healing, re-epithelialization, collagen deposition, and angiogenesis than those in PBS and Exo groups in vitro study. In summary, Exo-HMOX1 could enhance the activity of fibroblasts, keratinocytes, and HUVEC, and accelerate wound healing by promoting angiogenesis in DM.

Mechanisms of resveratrol against diabetic wound by network pharmacology and experimental validation

Background Resveratrol (RSV) that possesses anti-oxidative, anti-inflammatory, and pro-angiogenic effects is an effective drug for diabetic wound (DW), while its pharmacological mechanism remains to be elucidated. In this study, we apply network pharmacology and experimental validation approach to reveal the potential mechanism of RSV against DW. Methods We obtained potential targets for RSV and DW from the publicly available database. Using interaction networks and conducting GO and KEGG pathway enrichment analyses, we constructed target-pathway networks to explore the relationship between RSV and DW. To validate the pharmacological mechanism of RSV, we induced the DW model. Results Ninety overlapped targets between RSV and DW were obtained, and the hub genes of the PPI network included TNF, IL-6, CASP3, MAPK3, VEGFA, IL-1β, AKT1, and JUN. Based on target-pathway networks, the AGE-RAGE signalling pathway was involved in the RSV treatment of DW. Furthermore, in vivo experiments revealed that RSV significantly promoted wound healing in diabetic mice and attenuated the expression of pro-inflammatory cytokines in wound tissue. Meanwhile, RSV could inhibit the AGE-RAGE signalling pathway and thus reduce the activation of NF-κB. Conclusion This study initially revealed the biological mechanism of RSV for treating DW through multi-target and multi-pathway. AGE-RAGE, FoxO, MAPK, PI3K-AKT and other signalling pathways may be the main pathways of RSV in treating DW. RSV reduces the inflammatory response by inhibiting the AGE-RAGE signalling pathway, which in turn promotes DW healing.

A Berberine-Loaded Bletilla striata Polysaccharide Hydrogel as a New Medical Dressing for Diabetic Wound Healing.

The healing process of a diabetic wound (DW) is often impeded by a series of interrelated factors, including severe infection, persistent inflammation, and excessive oxidative stress. Therefore, it is particularly crucial to develop a medical dressing that can address these issues simultaneously. To this end, different ratios of Bletilla striata polysaccharide (BSP) and berberine (BER) were physically blended with Carbomer 940 (CBM940) to develop a composite hydrogel as a medical dressing. The BSP/BER hydrogel was characterized using SEM, FTIR, rheological testing and other techniques. The anti-inflammatory, antioxidant, and antibacterial properties of the hydrogel were evaluated using cell and bacterial models in vitro. A DW model of ICR mice was established to evaluate the effect of the hydrogel on DW healing in vivo. The hydrogel exhibited excellent biocompatibility and remarkable antibacterial, anti-inflammatory, and antioxidant properties. In addition, animal experiments showed that the BSP/BER hydrogel significantly accelerated wound healing in DW mice. Among the different formulations, the LBSP/BER hydrogel (2% BSP, mBER:mBSP = 1:40) demonstrated the most remarkable efficacy. In conclusion, the BSP/BER hydrogel developed exhibited immense properties and great potential as a medical dressing for the repair of DW, addressing a crucial need in clinical practice.

A highly stretchable, adhesive, and antibacterial hydrogel with chitosan and tobramycin as dynamic cross-linkers for treating the infected diabetic wound

Diabetic wounds pose a significant challenge due to their susceptibility to bacterial infection in a high-glucose environment, which impedes the wound healing process. To address this issue, there is a pressing need to develop suitable hydrogels that can promote the regeneration of diabetic wounds in clinical practice. In this study, we designed and fabricated a highly stretchable, adhesive, transparent, and antibacterial hydrogel through a one-pot radical polymerization of N-[Tris (hydroxymethyl) methyl] acrylamide (THMA) and acrylic acid (AA), and with chitosan and the antibiotic tobramycin as the dynamic physical crosslinkers. The copolymer contains a large number of carboxyl and hydroxyl groups, which can form an interpenetrating network structure with chitosan and tobramycin through multiple dynamic non-covalent bonds. This hydrogel exhibited over 1600 % elongation through an energy dissipation mechanism and strong adhesion to various surfaces without any chemical reaction. In vivo, studies conducted on a staphylococcus aureus-infected full-thickness diabetic skin wound model demonstrated that the hydrogel loaded with tobramycin as one of the crosslinkers had a long-lasting antibacterial activity and effectively accelerated wound healing. Therefore, the antibiotic-loaded adhesive hydrogel we proposed holds great promise as a treatment for bacteria-infected diabetic wounds.

Nociceptive and Transcriptomic Responses in a Swine Diabetic Wound Model Treated With a Topical Angiotensin 1 Receptor Antagonist.

Painful, treatment-resistant wounds are prevalent among diabetic patients and significantly affect health-related quality of life (HRQOL). Topical treatments may help alleviate pain without risk of dependence or side effects. However, there is a lack of topical wound compounds targeting pain-specific receptors. One possible target is proinflammatory angiotensin 1 receptor (AT1R), which is upregulated in diabetic skin and has been implicated in nociception. We investigated the effects of topical valsartan, an AT1R antagonist, on pain (nociceptive thresholds) and gene expression changes (transcriptomics) in a swine model of diabetic wounds. Eight wounds were surgically induced in diabetic, hyperglycemic Yucatan miniature swine ( n = 4). Topical AT1R antagonist was applied to wounds on one side and vehicle on the other side. Nocifensive testing was conducted at baseline and then weekly, beginning 7 days after wound induction. Mechanical and thermal stimuli were applied to the wound margins until a nocifensive reaction was elicited or a predetermined cutoff was reached. After 7 weeks of testing, tissue from the dorsal horn, dorsal root ganglion, and wounds were sequenced and analyzed with DESeq2. Unbiased pathway analyses using Metascape were conducted on differentially expressed genes. There was no significant difference in mechanical tolerance threshold between AT1R antagonist-treated and vehicle-treated wounds ( p = .106). Thermal tolerance was significantly higher in AT1R antagonist-treated wounds compared to vehicle-treated ( p = .015). Analysis of differentially expressed genes revealed enriched pathways of interest: interleukin-18 signaling in dorsal horn laminae IV-V and sensory perception of mechanical stimulus in wound tissue. In this study, wounds modeling diabetic ulcers were created in hyperglycemic swine and treated with a topical AT1R antagonist. AT1R-antagonist-treated wounds had a higher tolerance threshold than vehicle-treated wounds for thermal hyperalgesia, but not mechanical allodynia. Pathway analyses of differentially expressed genes revealed several pathways of interest for future pain research. Although further studies are needed to confirm the findings, this study can improve nursing care by providing information about a potential future treatment that may be used to decrease pain and improve HRQOL in patients with diabetic wounds.