Diabetic Wound Research Articles

Advances in rationally engineered cytokines for precision therapy in diabetic wound healing

Advances in rationally engineered cytokines for precision therapy in diabetic wound healing

The histone methyltransferase Mixed-lineage-leukemia-1 drives T cell phenotype via Notch signaling in diabetic tissue repair.

Immune cell-mediated inflammation is important in normal tissue regeneration but can be pathologic in diabetic wounds. Limited literature exists on the role of CD4+ T cells in normal or diabetic wound repair; however, the imbalance of CD4+ Th17/Tregs has been found to promote inflammation in other diabetic tissues. Here, using human tissue and murine transgenic models, we identified that the histone methyltransferase Mixed-lineage-leukemia-1 (MLL1) directly regulates the Th17 transcription factor RORγ via an H3K4me3 mechanism and increases expression of Notch receptors and downstream Notch signaling. Furthermore, we found that Notch receptor signaling regulates CD4+ Th cell differentiation and is critical for normal wound repair, and loss of upstream Notch pathway mediators or receptors in CD4+ T cells resulted in the loss of CD4+ Th cell differentiation in wounds. In diabetes, MLL1 and Notch-receptor signaling was upregulated in wound CD4+ Th cells, driving CD4+ T cells toward the Th17 cell phenotype. Treatment of diabetic wound CD4+ T cells with a small molecule inhibitor of MLL1 (MI-2) yielded a significant reduction in CD4+ Th17 cells and IL-17A. This is the first study to our knowledge to identify the MLL1-mediated mechanisms responsible for regulating the Th17/Treg balance in normal and diabetic wounds and to define the complex role of Notch signaling in CD4+ T cells in wounds, where increased or decreased Notch signaling both result in pathologic wound repair. Therapeutic targeting of MLL1 in diabetic CD4+ Th cells may decrease pathologic inflammation through regulation of CD4+ T cell differentiation.

Dissolvable microneedle-based wound dressing transdermally and continuously delivers anti-inflammatory and pro-angiogenic exosomes for diabetic wound treatment

Due to overactive inflammation and hindered angiogenesis, self-healing of diabetic wounds (DW) remains challenging in the clinic. Platelet-derived exosomes (PLT-Exos), a novel exosome capable of anti-inflammation and pro-angiogenesis, show great potential in DW treatment. However, previous administration of exosomes into skin wounds is topical daub or intradermal injection, which cannot intradermally deliver PLT-Exos into the dermis layer, thus impeding its long-term efficacy in anti-inflammation and pro-angiogenesis. Herein, a dissolvable microneedle-based wound dressing (PLT-Exos@ADMMA-MN) was developed for transdermal and long-term delivery of PLT-Exos. Firstly, a photo-crosslinking methacrylated acellular dermal matrix-based hydrogel (ADMMA-GEL), showing physiochemical tailorability, fast-gelling performance, excellent biocompatibility, and pro-angiogenic capacities, was synthesized as a base material of our dressing. For endowing the dressing with anti-inflammation and pro-angiogenesis, PLT-Exos were encapsulated into ADMMA-GEL with a minimum effective concentration determined by our in-vitro experiments. Then, in-vitro results show that this dressing exhibits excellent properties in anti-inflammation and pro-angiogenesis. Lastly, in-vivo experiments showed that this dressing could continuously and transdermally deliver PLT-Exos into skin wounds to switch local macrophage into M2 phenotype while stimulating neovascularization, thus proving a low-inflammatory and pro-angiogenic microenvironment for DW healing. Collectively, this study provides a novel wound dressing capable of suppressing inflammation and stimulating vascularization for DW treatment.

Temperature-responsive self-contraction nanofiber/hydrogel composite dressing facilitates the healing of diabetic-infected wounds

Bacterial infections and long-term inflammation cause serious secondary damage to chronic diabetic wounds and hinder the wound healing processes. Currently, multifunctional hydrogels have shown promising effects in chronic wound repair. However, traditional hydrogels only keep the wound moist and protect it from bacterial infection, and cannot provide mechanical force to contract the wound edges to achieve facilitated wound closure. Here, an asymmetric composite dressing was created by combining biaxially oriented nanofibers and hydrogel, inspired by the double-layer structure of the traditional Chinese medicinal plaster patch, for managing chronic wounds. Specifically, electrospun Poly-(lactic acid-co-trimethylene carbonate) (PLATMC) nanofibers and methacrylate gelatin (GelMa) hydrogel loaded with Epinecidin-1@chitosan (Epi-1@CS) nanoparticles are assembled as the temperature-responsive self-contracting nanofiber/hydrogel (TSNH) composite dressing. The substrate layer of PLATMC nanofibers combines topological morphology with material properties to drive wound closure through temperature-triggered contraction force. The functional layer of GelMa hydrogel is loaded with Epi-1@CS nanoparticles that combine satisfactory cytocompatibility, and antioxidant, anti-inflammatory, and antibacterial properties. Strikingly, in vivo, the TSNH dressing could regulate the diabetic wound microenvironment, thereby promoting collagen deposition, facilitating angiogenesis, and reducing the inflammatory response, which promotes the rapid healing of chronic wounds. This study highlights the potential of synergizing mechanical and biochemical signals in enhancing chronic wound treatment. Overall, this TSNH composite dressing is provided as a reliable approach to solving the long-standing problem of chronically infected wound healing.

Interplay Between FoxM1 and Dab2 Promotes Endothelial Cell Responses in Diabetic Wound Healing.

Diabetes mellitus can cause impaired and delayed wound healing, leading to lower extremity amputations; however, the mechanisms underlying the regulation of vascular endothelial growth factor (VEGF)-dependent angiogenesis remain uncertain and could reveal new therapeutic targets. In our study, the molecular underpinnings of endothelial dysfunction in diabetes were investigated, focusing on the roles of Disabled-2 (Dab2) and Forkhead Box M1 (FoxM1) in VEGF receptor 2 (VEGFR2) signaling and endothelial cell (EC) function. Bulk RNA-sequencing analysis identified significant downregulation of Dab2 in high concentrations glucose treated primary mouse skin ECs, simulating hyperglycemic conditions in diabetes mellitus. In diabetic mice with a genetic EC deficiency of Dab2 angiogenesis was reduced in vivo and in vitro when compared with wild-type mice. Restoration of Dab2 expression by injected mRNA-containing lipid nanoparticles rescued impaired angiogenesis and wound healing in diabetic mice. At the same time, FoxM1 was downregulated in skin ECs subjected to high glucose conditions as determined by RNA-sequencing analysis. FoxM1 was found to bind to the Dab2 promoter, regulating its expression and influencing VEGFR2 signaling. The FoxM1 inhibitor FDI-6 reduced Dab2 expression and phosphorylation of VEGFR2. These findings indicate that restoring Dab2 expression through targeted therapies can enhance angiogenesis and wound repair in diabetes. To explore this therapeutic potential, we tested LyP-1-conjugated lipid nanoparticles (LNPs) containing Dab2 or control mRNAs to target ECs and found the former significantly improved wound healing and angiogenesis in diabetic mice. This study provides evidence of the crucial roles of Dab2 and FoxM1 in diabetic endothelial dysfunction and establishes targeted delivery as a promising treatment for diabetic vascular complications.

Development and In vivo Evaluation of Nanogel Drug Delivery System for Promoting Wound Healing in Diabetic Induced Rats

Recently, researchers have looked at the use of nanotechnology as a drug-delivery system for topical and transdermal applications. The transport of medications and active ingredients to the skin via formulations, including nanoparticles, is a subject of substantial contemporary interest. The present work is proposed to prepare the atorvastatin nanogels to promote wound healing in a diabetic animalmodel.Atorvastatin nanogels were prepared by precipitation polymerization technique using hydroxy propyl methacrylate as polymer. The drug and polymer were selected in ratios of 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7 and 1:8. Additionally, the produced nanogel was evaluated in vivo and examined for its particle size, trapping effectiveness, and drug release in vitro. The particle size of the prepared various formulations (F1-F8) showed a size range of 68 to 80nm, and entrapment efficiency was seen to be in the range of 58.36-86.75%. The cumulative percentage of drug release was reported to be 61.96 to 73.76 percent over a period of 12hours during the in vitro drug release investigation, which was conducted using phosphate buffer at pH 7.4.The drug release followeda non-fiction mechanism of release kinetics. On the other hand, in vivo comparative study showed a complete wound healing effect for nanogels on the 11th day, whereas for conventional gel on the 15th day.This study indicates that nanogels formulation heals the diabetic wound completely at a faster rate, and also the drug atorvastatin also can be used for diabetic wound healing.

Localized Surface Plasmon Resonance-Enhanced Photocatalytic Antibacterial of In Situ Sprayed 0D/2D Heterojunction Composite Hydrogel for Treating Diabetic Wound.

Chronic diabetic wounds pose significant challenges due to uncontrolled bacterial infections, prolonged inflammation, and impaired angiogenesis. The rapid advancement of photo-responsive antibacterial therapy shows promise in addressing these complex issues, particularly utilizing 2D heterojunction materials, which offer unique properties. Herein, an in situ sprayed Bi/BiOCl 0D/2D heterojunction composite fibrin gel with the characteristics of rapid formation and effective near-infrared activation is designed for the treatment of non-healing diabetes-infected wounds. The sprayed composite gel can provide protective shielding for skin tissues and promote endothelial cell proliferation, vascularization, and angiogenesis. The Bi/BiOCl 0D/2D heterojunction, with its localized surface plasmon resonance (LSPR), can overcome the wide bandgap limitation of BiOCl, enhancing the generation of local heat and reactive oxygen species under near-infrared irradiation. This facilitates bacterial elimination and reduced inflammation, supporting the accelerated healing of diabetes-infected wounds. This study underscores the potential of LSPR-enhanced heterojunctions as advanced wound therapies for chronic diabetic wounds.

Prevalence and Molecular Characterization of Carbapenem and Colistin-Resistance Genes in Clinical Strains of Pseudomonas aeruginosa Isolated from Diabetic Patients

Abstract Introduction Pseudomonas aeruginosa is one of the important opportunistic nosocomial pathogens that are increasingly becoming resistant to many drugs including the drugs of last resort, carbapenems, and colistin. Methods The study involved the examination of clinical isolates of P. aeruginosa recovered from diabetic patients for the presence of acquired genes implied in carbapenem and colistin resistance. Results A total of 100 clinical isolates from diabetic patients' wound and sputum were investigated for their susceptibility to imipenem and colistin followed by phenotypic assay and resistance gene screening. The study revealed 27 sputum isolates being resistant to imipenem further confirmed by a modified Hodge test and 28 wound isolates were resistant to colistin. The resistant isolates of wound and sputum were found to possess blaOXA-48 , blaVIM , mcr-1, and mcr-5 genes. The strains had a coexistence of carbapenem- and colistin-resistant genes. Conclusion Considering the fact that infection by such resistant isolates in diabetics could be frightening, clinical laboratories must employ rapid diagnostic methods to detect resistance which can aid in the treatment decision-making.

Promotes M1-polarization and diabetic wound healing using Prussian blue nanozymes

Long-term inflammation and impaired angiogenesis are the main reasons for the difficulty of diabetic wound healing. What to do to effectively promote vascular endothelial cell response and immune cell reprogramming is the key to diabetic skin healing. However, contemporary therapies cannot simultaneously coordinate the promotion of vascular endothelial cells and macrophage polarization, which leads to an increased rate of disability in patients with chronic diabetes. Therefore, we developed a method of repair composed of self-assembling Prussian blue nanoenzymes, which achieved synergistic support for the immune microenvironment, and also contributed to macrophage polarization in the tissue regeneration cycle, and enhanced vascular endothelial cell activity. The template hydrothermal synthesis PB-Zr nanoplatform was prepared and locally applied to wounds to accelerate wound healing through the synergistic effect of reactive oxygen species (ROS). PB-Zr significantly normalized the wound microenvironment, thereby inhibiting ROS production and inflammatory response, which may be because it inhibited the M1 polarization of macrophages in a rat model of wound. PB-Zr treatment significantly promoted the activity of vascular endothelial cells, which better promoted the growth and regeneration of other tissues in the body. The results confirmed the disease microenvironment of PB-Zr-mediated wound therapy and indicated its application in other inflammation-related diseases.

Metformin as a Modulator of Autophagy and Hypoxia Responses in the Enhancement of Wound Healing in Diabetic Rats.

The molecular mechanisms underlying delayed wound repair in diabetes involve dysregulation of key cellular processes, including autophagy and hypoxia response pathways. Herein, we investigated the role of topical metformin, an established anti-diabetic drug with potential autophagy-inducing properties, in improving wound healing outcomes under hypoxic conditions. Full-thickness skin wounds were created in streptozotocin-induced diabetic rats, and tissue samples were collected at regular intervals for molecular and histological analysis. The expression levels of autophagy markers LC3B and Beclin-1 were evaluated via immunohistochemistry and qRT-PCR, while the amount of AMP-activated protein kinase (AMPK) and hypoxia-inducible factor-1α (HIF-1α) were determined via ELISA. Our results demonstrated that metformin administration resulted in the upregulation of LC3B and Beclin-1 in the wound bed, suggesting induction of autophagy in response to the treatment. Mechanistically, metformin treatment also led to the increased amount of AMPK, a critical regulator of cellular energy homeostasis, and a subsequent reduction in HIF-1α amount under hypoxic conditions. In conclusion, our findings demonstrate that metformin promotes wound healing in diabetes mellitus by enhancing autophagy through AMPK activation and modulating HIF-1α amount in a hypoxic microenvironment. This study offers a new therapeutic approach by shedding light on the potential benefits of metformin as adjunctive therapy in diabetic wound management.

Multifunctional hydrogel combined with electrical stimulation therapy for promoting diabetic wound healing

Multifunctional hydrogel combined with electrical stimulation therapy for promoting diabetic wound healing

Diabetic wound healing potentials of phenylethanoid glycosides from Clerodendrum glandulosum Lindl.: Connecting the dots by integrating network pharmacology, molecular docking, and molecular dynamics simulation

The diabetic wound is one of the severe complications of diabetes mellitus, accounting for 20 % of limb amputations in diabetic patients. This creates a need to search for newer natural compounds to target the different molecular pathways of diabetic wounds to accelerate the repair. The phenylethanoid glycosides (PhGs) isolated from Clerodendrum glandulosum (CG) have been shown to exhibit antioxidant, antimicrobial, and anti-inflammatory properties but have never been explored for diabetic wound healing. Thus, this study focuses on exploring the diabetic wound-repairing properties of PhGs through in-silico approaches. The PhGs present in CG were identified through extensive literature searching, which were further subjected to database searching in BindingDB, TargetNet, PharmMapper, Super-PRED, and Swiss Target Prediction to find the potential targets, which included PRKCA, PRKCG, PRKCZ, TDP1, and Pol. Subsequently, these targets were used to determine the disease IDs related to diabetic wounds from databases such as DisGeNET, Gene Expression Omnibus, GeneCards, and OMIM. A network was established using Cytoscape to study the relationship among the PhGs, the protein targets, and their associated disease IDs. The top twenty molecular pathways associated with the target proteins were determined using the ShinyGO database. Genetic enrichment analysis showed that the Sphingolipid signalling pathway included the maximum number of genes and had the lowest false discovery rate value, which concluded that this pathway is the potential target of the PhGs. PRKCA and PRKCZ were found to be the only two genes involved in this pathway, and thus, molecular docking was used to evaluate the binding affinity of the PhGs with the proteins. Docking scores were between -13.2859 and -5.10928, suggesting a strong molecular interaction between the PhGs and their targets. Thus, it is concluded that PhGs present in CG can be the potential compounds to treat diabetic wounds; however, further in-vitro and in-vivo investigations are necessary.

Near Infrared-Triggered Nitric Oxide-Release Nanovesicles with Mild-Photothermal Antibacterial and Immunomodulation for Healing MRSA-Infected Diabetic Wounds.

Bacterial infection-induced excessive inflammation is a major obstacle in diabetic wound healing. Nitric oxide (NO) exhibits significant antibacterial activity but is extremely deficient in diabetes. Hence, a near-infrared (NIR)-triggered NO release system is constructed through codelivery of polyarginine (PArg) and gold nanorods (Au) in an NIR-activatable methylene blue (MB)polypeptide-assembled nanovesicle (Au/PEL-PBA-MB/PArg). Upon NIR irradiation, the quenched MB in the nanovesicles is photoactivated to generate more reactive oxygen species (ROS) to oxidize PArg and release NO in an on-demand controlled manner. With the specific bacterial capture of phenylboronic acid (PBA), NO elevated membrane permeability and boosted bacterial vulnerability in the photothermal therapy (PTT) of the Au nanorods, which is displayed by superior mild PTT antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) at temperatures<49.7°C in vitro. Moreover, in vivo, the antibacterial nanovesicles greatly suppressed the burst of MRSA-induced excessive inflammation, NO relayed immunomodulated macrophage polarization from M1 to M2, and the excessive inflammatory phase is successfully transferred to the repair phase. In cooperation with angiogenesis by NO, tissue regeneration is accelerated in MRSA-infected diabetic wounds. Therefore, nanoplatform has considerable potential for accelerating the healing of infected diabetic wounds.

TWEAK increases angiogenesis to promote diabetic skin wound healing by regulating Fn14/EGFR signaling.

Tumor necrosis factor-like weak inducer of apoptosis (TWEAK), a member of tumor necrosis factor superfamily, can bind to fibroblast growth factor-inducible 14 (Fn14) receptor and stimulate angiogenesis. The interaction between epidermal growth factor receptor (EGFR) and endothelial growth factor (EGF) leads to EGFR signal transduction and promotes angiogenesis. The objective of this study was to explore whether TWEAK participated in the diabetic skin wound healing by regulating Fn14/EGFR signaling. Human umbilical vein endothelial cells (HUVECs) were treated with 35 mmol/L d-glucose and classified into the Control Group, High Glucose (HG) Group and HG + TWEAK Group. Then, the TWEAK expression and the proliferation, migration and tubule formation of HUVECs were detected, respectively. Invivo experiment, the diabetic model was established by injecting streptozotocin (STZ, 50 mg/kg) into male BALB/c mice. On the back of successfully modeled diabetic mice, a full-thickness skin wound of 6 mm diameter was formed. Then, the mice were randomly assigned into three groups: Blank Group, Phosphate Buffer Saline (PBS) Group, and TWEAK Group. Subsequently, expression levels of TWEAK, Fn14, EGFR and vascular endothelial growth factor (VEGF)-A were measured, and the CD31 expression in the wounded skin tissue of mice was checked by immunohistochemistry staining. The expression level of TWEAK in HUVECs of HG Group decreased significantly, as well as the viability, migration, and tubule formation of cells. After over-expression of TWEAK, the cell viability, migration, and tubule formation abilities of HUVECs recovered remarkably. Invivo, the wound healing rate of diabetic mice was raised, the neovascularization was increased, and the CD31 expression in the wounded tissue was obviously upregulated after injection with recombinant TWEAK antibody. TWEAK stimulates angiogenesis and accelerates the wound healing of diabetic skin by regulating Fn14/EGFR signaling.

In vitro and in vivo evaluation of the diabetic wound healing properties of Saffron (Crocus Sativus L.) petals

Wound healing is a complex process orchestrated by interactions between a variety of cell types, including keratinocytes, fibroblasts, endothelial cells, inflammatory cells, and bioactive factors such as extracellular matrix (ECM) components, growth factors, and cytokines. Chronic wounds exhibit delayed proliferative phase initiation, reduced angiogenesis, impaired ECM synthesis, and persistent inflammatory response. Chronic wounds are one of the main challenges to the healthcare system worldwide, with a high cost for medical services. Hence, investigation of new approaches to accelerate wound healing is essential. Phytomedicines are considered as potential agents for improving the wound healing by accelerating epithelization, collagen synthesis, and angiogenesis. These natural compounds have various advantages including availability, ease of application, and high effectiveness in wound managment. This study aimed to investigate the biological effects of saffron or Crocus sativus L. (C. sativus) petal extract on cell survival, migration, and angiogenesis using MTT, scratch and in vitro tube formation assays. Moreover, the expression of collagen type I alpha 1 (COL1A1) and vascular endothelial growth factor (VEGF) were evaluated in human dermal fibroblasts (HDF)s and human umbilical vein endothelial cells (HUVEC)s, respectively. The effect of the C. sativus extract on the skin of diabetic mice was also monitored. The results showed that C. sativus petal extract promoted the viability and migration of HDFs and HUVECs. Moreover, C. sativus petal extract enhanced the formation of tube-like structures by HUVECs cultured on the Matrigel basement membrane matrix, indicating its potential to stimulate angiogenesis. Gene expression studies have shown the the C. sativus extract increases wound healing by upregulation of COL1A1 and VEGF, which are crucial factors involved in collagen deposition, epithelialization, and angiogenesis. Histological analysis revealed that C. sativus petal extract enhanced vascularity and increased the number of fibroblasts and collagen synthesis, ultimately accelerating wound closure compared to wounds treated with eucerin and commercial ointment in diabetic mice. Therefore, C. sativus petal extract has potential as a herbal treatment to improve the healing of diabetic wounds.

Glucose/ROS/pH Triple Editing “Domino Hydrogel” Accelerates Diabetic Wound Healing via Hypoglycemic, Antioxidant, Antibacterial, and Macrophage Polarization

Glucose/ROS/pH Triple Editing “Domino Hydrogel” Accelerates Diabetic Wound Healing via Hypoglycemic, Antioxidant, Antibacterial, and Macrophage Polarization

Diphasic CeO2 Nanocrystal/Bioactive Glass Nanosphere-Based Composite Hydrogel for Diabetic Wound Healing by Reactive Oxygen Species Scavenging and Inflammation Regulation.

Background: Antioxidant therapy aimed at reducing excessive local oxidative stress is one of the most important strategies for promoting diabetic wound repair. The reversible transformation of Ce3+/Ce4+ in ceria (CeO2) can reduce excessive local oxidative stress. However, inducing angiogenesis, local anti-inflammatory effects, and other positive effects are challenging. Therefore, ideal dressings for chronic diabetic wound management must concurrently reduce excessive oxidative stress, promote angiogenesis, and have anti-inflammatory effects. Methods: In this study, Ce-doped borosilicate bioactive glasses (BGs) were prepared using the sol-gel method, and CeO2 nanocrystals (CeO2-NCs) were precipitated on the glass surface by heat treatment to obtain BG-xCe composite glass nanospheres. Subsequently, nanospheres were modified by amino group and combined with dopamine and acrylamide to obtain BG-xCe/polydopamine/polyacrylamide (PDA/PAM) composite hydrogel. Then, the morphology and properties of composite hydrogels were detected, and the properties to treat the diabetic wounds were also evaluated. Results: The results demonstrated that the BG-10Ce/PDA/PAM composite hydrogel possessed excellent tensile and adhesive properties. Invitro, the migration and angiogenesis of human umbilical vein endothelial cells (HUVECs) and fibroblasts (L929) were enhanced by reducing reactive oxygen species (ROS) levels in the conditioned medium. Animal experiments have shown that CeO2-NCs in hydrogels effectively scavenge ROS in diabetic wounds, and Sr dissolved from the glassy phase can modulate macrophage polarization to the M2 phenotype. Conclusions: The synergistic effect of both amorphous materials and nanocrystals provides the BG-10Ce/PDA/PAM composite hydrogel with great potential for diabetic wound healing.

Histone modifications and their roles in macrophage-mediated inflammation: a new target for diabetic wound healing.

Impaired wound healing is one of the main clinical complications of type 2 diabetes (T2D) and a major cause of lower limb amputation. Diabetic wounds exhibit a sustained inflammatory state, and reducing inflammation is crucial to diabetic wounds management. Macrophages are key regulators in wound healing, and their dysfunction would cause exacerbated inflammation and poor healing in diabetic wounds. Gene regulation caused by histone modifications can affect macrophage phenotype and function during diabetic wound healing. Recent studies have revealed that targeting histone-modifying enzymes in a local, macrophage-specific manner can reduce inflammatory responses and improve diabetic wound healing. This article will review the significance of macrophage phenotype and function in wound healing, as well as illustrate how histone modifications affect macrophage polarization in diabetic wounds. Targeting macrophage phenotype with histone-modifying enzymes may provide novel therapeutic strategies for the treatment of diabetic wound healing.

A potential therapeutic strategy of an innovative probiotic formulation toward topical treatment of diabetic ulcer: an in vivo study

BackgroundThe probiotic potential of Lacticacid bacteria has been studied in various medical complications, from gastrointestinal diseases to antibiotic resistance infections recently. Moreover, diabetic ulcer (DU) is known as one of the most significant global healthcare concerns, which comprehensively impacts the quality of life for these patients. Given that the conventional treatments of DUs have failed to prevent later complications completely, developing alternative therapies seems to be crucial.MethodsWe designed the stable oleogel-based formulation of viable probiotic cells, including Lactobacillus rhamnosus (L. rhamnosus), Lactobacillus casei (L. casei), Lactobacillus fermentum (L. fermentum), and Lactobacillus acidophilus (L. acidophilus) individually to investigate their effect on wound healing process as an in vivo study. The wound repair process was closely monitored regarding morphology, biochemical, and histopathological changes over two weeks and compared it with the effects of topical tetracycline as an antibiotic approach. Furthermore, the antibiofilm activity of probiotic bacteria was assessed against some common pathogens.ResultsThe findings indicated that all tested lactobacillus groups (excluded L. casei) included in the oleogel-based formulation revealed a high potential for repairing damaged skin due to the considerably more levels of hydroxyproline content of tissue samples along with the higher numerical density of mature fibroblasts cell and volume density of hair follicles, collagen fibrils, and neovascularization in comparison with antibiotic and control groups. L. acidophilus and L. rhamnosus showed the best potential of wound healing among all lactobacillus species, groups treated by tetracycline and control groups. Besides, L. rhamnosus showed a significant biofilm inhibition activity against tested pathogens.ConclusionsThis experiment demonstrated that the designed formulations containing probiotics, particularly L. acidophilus and L. rhamnosus, play a central role in manipulating diabetic wound healing. It could be suggested as an encouraging nominee for diabetic wound-healing alternative approaches, though further studies in detailed clinical trials are needed.

Electrospun Cerium Oxide Nanoparticle/Aloe Vera Extract-Loaded Nanofibrous Poly(Ethylene Oxide)/Polyurethane Mats As Diabetic Wound Dressings.

Currently the prevalence of diabetic wounds brings a huge encumbrance onto patients, causing high disability and mortality rates and a major medical challenge for society. Therefore, in this study, we are targeting to fabricate aloe vera extract infused biocompatible nanofibrous patches to facilitate the process of diabetic wound healing. Additionally, clindamycin has been adsorbed onto the surface of in-house synthesized ceria nanoparticles and again used separately to design a nanofibrous web, as nanoceria can act as a good drug delivery vehicle and exhibit both antimicrobial and antidiabetic properties. Various physicochemical characteristics such as morphology, porosity, and chemical composition of the produced nanofibrous webs were investigated. Bacterial growth inhibition and antibiofilm studies of the nanofibrous materials confirm its antibacterial and antibiofilm efficacy against Gram-positive and Gram-negative bacteria. An in vitro drug release study confirmed that the nanofibrous mat show a sustained drug release pattern (90% of drug in 96 h). The nanofibrous web containing drug loaded nanoceria not only showed superior in vitro performance but also promoted greater wound contraction (95 ± 2%) in diabetes-induced mice in just 7 days. Consequently, it efficaciously lowers the serum glucose level, inflammatory cytokines, oxidative stress, and hepatotoxicity markers as endorsed by various ex vivo tests. Conclusively, this in-house-fabricated biocompatible nanofibrous patch can act as a potential medicated suppository that can be used for treating diabetic wounds in the proximate future.