Diabetic Rabbits Research Articles

The effect of aqueous extract of Moringa oleifera seeds on the eyes of diabetic rabbits

The study aimed to induce, diabetes with Alloxan in local. white rabbits, study its effect on eye tissue, and treat it with aqueous extract of Moringa nibbar seeds at a concentration of 200 mg/kg, and observe ,the tissue changes.. After the end of the injection and dosing period after 30 days, the animals were killed and the eye was removed to perform histological techniques on it. 20 white rabbits were taken and divided into three groups: The first group: control group. This group ,was dosed with distilled water, The second group: The group, treated with Alloxan. This group was. injected, with Alloxan intraperitoneally at a dose of 175 mg/kg and, The third group: The group treated, with aqueous extract of moringa seeds at a concentration of 200 mg/kg for 30 days.

Precisely Engineering a ROS‐Regulatable Decellularized Matrix to Rejuvenate Endogenous Repair for Heart Valve Remodeling in Diabetic Cohort

AbstractThe reconstruction of a heart valve through in situ tissue engineering remains a formidable challenge, particularly for patients with diabetes mellitus, because the pathophysiological alterations associated with diabetes substantially impair the cardiovascular system's intrinsic repair capacity. In this study, reactive oxygen species (ROS) regulation are integrated into the fabrication of pro‐endothelialization interfaces to counteract the adverse repair environment. Specifically, a heparin‐mimicking alginate‐derived glycopeptide and the natural ROS scavenger melanin are modified onto the surface of a decellularized extracellular matrix (dECM). This tailored interface significantly enhances endothelial cell (EC) adhesion while reducing platelet adhesion. The incorporation of melanin effectively suppresses ROS elevation in ECs and macrophages under hyperglycemic conditions. Consequently, this intervention promotes EC rejuvenation by enhancing proliferation, migration, and anti‐apoptotic capabilities, while concurrently attenuating the release of inflammatory and pro‐fibrotic factors by macrophages. The dECM is intravascularly implanted in a diabetic rabbit model after being fabricated into a covered stent, demonstrating favorable remodeling characteristics such as enhanced endothelialization and reduced fibrotic deposition. This scaffold design, specifically tailored to the pathological conditions of diabetes, offers a precise biomaterial strategy for in situ heart valve tissue engineering.

Impact of Diabetic Condition on the Remodeling of In Situ Tissue-Engineered Heart Valves.

Most in situ tissue-engineered heart valve (TEHV) evaluation studies are conducted in a healthy physical environment, which cannot accurately reflect the specific characteristics of patients. In this study, we established a diabetic rabbit model and implanted decellularized extracellular matrix (dECM) into the abdominal aorta of rabbits through interventional surgery with a follow-up period of 8 weeks. The results indicated that dECM implants in diabetic rabbits exhibited poorer endothelialization and more severe fibrosis compared to those in healthy animals. Furthermore, mechanistic studies revealed that high glucose induced endothelial cell (EC) apoptosis and impeded their proliferation and migration, accompanied by an increase in reactive oxygen species (ROS) concentration and a decrease in the nitric oxide (NO) level. High glucose also led to elevated ROS levels and an increased expression of inflammatory factors and transforming growth factor β1 (TGF-β1) in macrophages, contributing to fibrosis. These findings suggest that oxidative-stress-mediated mechanisms are likely the primary pathways affecting heart valve repair and regeneration under diabetic conditions. Therefore, future design and evaluation of TEHVs may concern more patient-specific circumstances.

Tibial transverse transport combined with platelet-rich plasma sustained-release microspheres activates the VEGFA/VEGFR2 pathway to promote microcirculatory reconstruction in diabetic foot ulcer

This study proposes to investigate the therapeutic efficacy and mechanism of combining tibial transverse transport (TTT) with platelet-rich plasma (PRP) for diabetic foot ulcer (DFU). The diabetic rabbit model was constructed with Streptozotocin, which was intervened with TTT and PRP. PRP injection combined with TTT significantly promoted vascularisation and enhanced CD31, VEGFA, and VEGFR2 expressions compared to traditional TTT. However, the VEGFR2 inhibitor suppressed these phenomena. In the in vitro injury model, PRP reversed the diminished human umbilical vein endothelial cells (HUVECs) function and vascularisation caused by high-glucose damage. Additionally, PRP reduced inflammation and oxidative stress (approximately 47% ROS level) and enhanced VEGFA and VEGFR2 expression in HUVECs. However, the knockdown of VEGFR2 reversed the effect of PRP. In conclusion, TTT combined with intraosseous flap injection of PRP sustained-release microspheres activated the VEGFA/VEGFR2 pathway to promote microcirculatory reconstruction in DFU. These findings may provide new potential therapeutic strategies for DFU.

Integration of texture analysis based on DCE-MRI Ktrans map and metabolomics of early bone marrow microvascular changes in alloxan-induced diabetic rabbits

ObjectiveTo evaluate early bone marrow microvascular changes in alloxan-induced diabetic rabbits using IDEAL-IQ fat quantification, texture analysis based on DCE-MRI Ktrans map, and metabolomics.Materials and methods24 male Japanese rabbits were randomly divided into diabetic (n = 12) and control (n = 12) groups. All rabbits underwent sagittal MRI of the lumbar vertebrae at the 0th,4th, 8th, 12th, and 16th week, respectively. The fat fraction (FF) ratio and quantitative permeability of the lumbar bone marrow was measured. Texture parameters were extracted from DCE-MRI Ktrans map. At 16th week, lumbar vertebrae 5 and 6 were used for histological analysis. Lumbar vertebra 7 was crushed to obtain bone marrow for metabolomics research.ResultsThe FF ratio and Ktrans of the lumbar bone marrow in diabetic group were increased significantly at 16th week (t = 2.226, P = 0.02; Z = -2.721, P < 0.01). Nine texture feature parameters based on DCE-MRI Ktrans map were significantly different between the groups at the 16th week (all P < 0.05). Pathway analysis showed that diabetic bone marrow microvascular changes were mainly related to linoleic acid metabolism. Differential metabolites were correlated with the number of adipocytes, FF ratio, and permeability parameters.ConclusionThe integration of metabolomics with texture analysis based on DCE-MRI Ktrans map may be used to evaluate diabetic bone marrow microvascular changes at an early stage. It remains to be validated in clinical studies whether the integration of metabolomics with texture analysis based on the DCE-MRI Ktrans map can effectively evaluate diabetic bone marrow.

Tibial transverse transport promotes wound healing in diabetic foot ulcers by stimulating endothelial progenitor cell mobilization and homing mediated neovascularization

Background Diabetic foot ulcers (DFUs) are a common and serious complication of diabetes, often leading to amputation and decreased quality of life. Current treatment methods have limited success rates, highlighting the need for new approaches. This study investigates the potential of tibial transverse transport (TTT) to promote wound healing in DFUs. Methods To test this hypothesis, the study used New Zealand White rabbits to establish a diabetic model and simulate foot ulcers, followed by the treatment of unilateral TTT or bilateral TTT. The study employed histological analysis, flow cytometry, ELISA, and qPCR to assess the impact of TTT on tissue repair and endothelial progenitor cell (EPC) mobilization and homing, aiming to understand the underlying biological processes in wound healing. Results TTT significantly enhanced wound healing in diabetic rabbit foot ulcers. Specifically, bilateral TTT led to complete wound healing by day 19, faster than the unilateral TTT group, which healed by day 26, and the sham operation group, which nearly healed by day 37. Histological analysis showed improved tissue architecture, collagen deposition, and neovascularization in TTT-treated groups. Furthermore, TTT treatment resulted in a significant increase in VEGFR2 expression and VEGFR2/Tie-2 positive cells, particularly in the bilateral group. These findings were corroborated by qPCR results, which showed increased expression of VEGFA and CXCL12 by TTT. Conclusions: TTT may be a promising treatment for DFUs, significantly enhancing wound healing by stimulating EPC mobilization and homing mediated angiogenesis. This novel approach could substantially improve treatment outcomes for diabetic patients with chronic foot ulcers.

Abstract P338: Impaired Endothelial-Dependent Vasorelaxation and Myogenic Response in Renal Afferent Arterioles of Diabetic mice: Role of Endothelial NOX1, and New Gene Pathways.

Diabetes increases the risk of cardiovascular disease and hypertension, in part, by decreasing arterial vasodilation through decreased NO bioavailability and increased superoxide. In the kidney, type 1 diabetes induces a decrease in renal filtration, proteinuria, inflammation, and fibrosis, increasing the incidence of kidney disease. In diabetic rats and rabbits, prone to renal disease, diabetes blunts acetylcholine (Ach)-induced vasorelaxation of afferent arterioles, in part, by enhancing endothelial superoxide. However, it is unclear whether diabetes affects afferent arteriole vasodilation and myogenic response in mice. We hypothesize that diabetes increases endothelial NOX1 mediated superoxide production in mouse afferent arterioles, decreasing Ach-induced vasodilation. We dissected and perfused afferent arterioles from male diabetic Akita mice 12-14 weeks of age and measured the effect Ach (10 -7 -10 -5 M) on luminal diameter after pre-constriction with norepinephrine. Diabetic Akita mice had a largely reduced Ach-induced dilation at all doses of Ach (80±6% average inhibition in dilation, p&lt;0.025, n=6). To study the role of NOX1, we used the inhibitor ML171 (5µM). When added to the endothelial lumen, NOX1 inhibition completely restored Ach-induced dilation of diabetic Akita mice, which was not different from WT controls. In Control C57 mice, ML171 did not change Ach-induced dilation in Aff-Art (n=6). We then examined the myogenic response in diabetic mice by measuring lumen diameter after step increases in perfusion pressure (60-140 mmHg). Afferent arterioles of diabetic Akita mice did not constrict when pressure was increased, even at 140 mmHg, whereas WT mice showed normal myogenic response (delta constriction 60-140 mmHg WT: 2.15±0.41 vs Akita: 0.37±0.32 µm, WT p&lt;0.01 from baseline, Akita n.s from baseline). To understand the mechanisms behind these effects we performed RNAseq in manually micro-dissected afferent arterioles from 12-week-old Akita and WT mice. Bioinformatics analysis showed 530 DEGs (FDR pAdj&lt;0.05, n=6). Most of the DEGs are involved in endothelial cell function/metabolism, smooth muscle cell contractility, activated inflammatory pathways, and free radical/NO production. We conclude that early diabetes has a large effect on renal afferent arteriole reactivity by affecting the expression of hundreds of genes. These effects are likely involved in hypertension and kidney damage progression in type 1 diabetes.

Preventive mechanism of SGLT-2 inhibitor in each organ for diabetic rabbit model

Preventive mechanism of SGLT-2 inhibitor in each organ for diabetic rabbit model

Targeting S100A12 to Improve Angiogenesis and Accelerate Diabetic Wound Healing.

Long-term inflammation and impaired angiogenesis are thought to be the causes of delayed healing or nonhealing of diabetic wounds. S100A12 is an essential pro-inflammatory factor involved in inflammatory reactions and serves as a biomarker for various inflammatory diseases. However, whether high level of S100A12 exists in and affects the healing of diabetic wounds, as well as the underlying molecular mechanisms, remain unclear. In this study, we found that the serum concentration of S100A12 is significantly elevated in patients with type 2 diabetes. Exposure of stratified epidermal cells to high glucose environment led to increased expression and secretion of S100A12, resulting in impaired endothelial function by binding to the advanced glycation endproducts (RAGE) or Toll-like receptor 4 (TLR4) on endothelial cell. The transcription factor Krüpple-like Factor 5 (KLF5) is highly expressed in the epidermis under high glucose conditions, activating the transcriptional activity of the S100A12 and boost its expression. By establishing diabetic wounds model in alloxan-induced diabetic rabbit, we found that local inhibition of S100A12 significantly accelerated diabetic wound healing by promoting angiogenesis. Our results illustrated the novel endothelial-specific injury function of S100A12 in diabetic wounds and suggest that S100A12 is a potential target for the treatment of diabetic wounds.

Physiological Effects of Alloxan on Serum Glucose Levels and Liver Function Test in Male Rabbit

Diabetes is a metabolic disorder characterized by elevated blood glucose levels that can lead to various complications. Exploring the physiological alterations in rabbits can provide valuable insights for the development of therapeutic interventions. This research delves into the impact of diabetes on the physiological and biochemical parameters of male rabbits. Objectives: To compare the physiological parameters like body temperature, heart rate, respiration rate, and oxygen saturation) and body weight and biochemical parameters, including blood glucose levels, alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, lactate dehydrogenase (LDH), and total protein levels in diabetic and non-diabetic rabbits. Methods: An experiment on 30 male rabbits divided into diabetic and control groups measured physiological parameters like body temperature, heart rate, respiration rate, and oxygen saturation. Body weight and blood glucose levels were tracked, and blood samples were taken for ALT, AST, creatinine, LDH, cholesterol, triglycerides and total protein levels. Statistical analysis was conducted to compare the physiological and biochemical parameters between the diabetic and control groups. Results: The results showed that induced diabetes in male rabbits affects their physiological and biochemical parameters significantly. Diabetic rabbits had lower body temperature, heart rate, respiration rate, and oxygen saturation compared to the control group. They also had higher body weight and blood glucose levels. Biochemical analysis showed increased ALT, AST, and creatinine levels, and decreased LDH and total protein levels in diabetic rabbits. Conclusions: These results demonstrate the extensive impact of diabetes on rabbit physiology and biochemistry, offering insights for future diabetes research.

Limbal stem cells carried by a four-dimensional -printed chitosan-based scaffold for corneal epithelium injury in diabetic rabbits.

Methods: Herein, we obtained and characterized deltaN p63- and adenosine triphosphate-binding cassette subfamily G member 2-expressing limbal stem cells (LSCs). Chitosan and carboxymethyl chitosan (CTH) were cross-linked to be an in situ thermosensitive hydrogel (ACH), which was printed through four-dimensional (4D) printing to obtain a porous carrier with uniform pore diameter (4D-CTH). Rabbits were injected with alloxan to induce diabetes mellitus (DM). Following this, the LSC-carrying hydrogel was spread on the surface of the cornea of the diabetic rabbits to cure corneal epithelium injury. Results: Compared with the control group (LSCs only), rapid wound healing was observed in rabbits treated with LSC-carrying 4D-CTH. Furthermore, the test group also showed better corneal nerve repair ability. The results indicated the potential of LSC-carrying 4D-CTH in curing corneal epithelium injury. Conclusion: 4D-CTH holds potential as a useful tool for studying regenerative processes occurring during the treatment of various diabetic corneal epithelium pathologies with the use of stem cell-based technologies.

Stimulated Full-Thickness Cutaneous Wound Healing with Bioactive Dressings of Zinc and Cobalt Ion-Doped Bioactive Glass-Coated Eggshell Membranes in a Diabetic Rabbit Model.

Eggshell membrane-based biomedical applications have recently received great attention for their wound-healing properties. However, there are limited studies on diabetic wound healing. In this regard, we devised four types of composite eggshell membrane mats with nanoscale coatings of bioactive glass/Zn/Co-doped bioactive glass (ESM + BAG, ESM + ZnBAG, ESM + CoBAG, and ESM + ZnCoBAG) as wound-dressing materials for chronic nonhealing diabetic wounds. A detailed study of the physicochemical properties of the mats was conducted. In vitro studies demonstrated cytocompatibility and viability of human dermal fibroblasts on all four types of mats. The cells also attached finely on the mats with the help of cellular extensions, as evident from scanning electron microscopy (SEM) and rhodamine-phalloidin and Hoechst 33342 staining of cellular components. Endowed with bioactive properties, these mats influenced all aspects of full-thickness skin wound healing in diabetic animal model studies. All of the mats, especially the ESM + ZnCoBAG mat, showed the earliest wound closure, effective renewal, and restructuring of the extracellular matrix in terms of an accurate and timely accumulation of collagen, elastin, and reticulin fibers. Hydroxyproline and sulfated glycosaminoglycans were significantly (p < 0.01, p < 0.05) higher in ESM-ZnCoBAG-treated wounds in comparison to ESM-BAG-treated wounds, which suggests that these newly developed mats have potential as an affordable diabetic wound care solution in biomedical research.

Effect of pomegranate peel with/without autologous bone marrow on healing of acute cutaneous wounds in alloxan-induced diabetic rabbits.

Healing of bum wounds is commonly associated with many complications. Every year various new repair materials are developed and experimentally used for treating burn wounds. Humans with diabetes mellitus usually suffer from chronic wound healing. Vascular, neuropathic, immune function, and biochemical abnormalities each contribute to the altered tissue repair. One underlying factor that accompanies all diabetic ulcerations is poor vascular flow, a circumstance that impedes proper wound healing. Numerous studies have highlighted the importance of adequate vascular sufficiency and vessel proliferation in tissue repair and the lack thereof in diabetic wound healing. Other studies have looked at whether disarrayed capillary remodeling and maturation of vessels might play a role in impaired diabetic wound healing. This investigation has been planned to report the influence of treatment with a mixture of both the powder of pomegranate peel (PP) accompanied with an autologous bone marrow (BM) on the cure of burn injuries in experimentally induced diabetic rabbits. Alloxan monohydrate has been applied to create diabetes in 50 rabbits. Then in each rabbit, two deep second-degree burn wounds were experimentally created. The animals were then divided randomly into 5 treatment sections: non-treatment controls (C1), treated with an available commercial powder for wound (C2), treatment with powder of PP, treatment with alone BM, and the final group treated with PP powder with bone marrow (PPBM). The speed of wound closure and the histopathological changes during healing were measured. The levels of the biomarkers of rabbit platelet-derived growth factor AA (PDGF-AA) and rabbit protease-activated receptor 1 (PAR-1) were measured on days 0, 4, 8, and 12. Wound healing was markedly more rapid in all the treatment groups versus the control non-treated group. Interestingly, a rapid wound cure was significantly observed in the PPBM group versus the other treatment ones. The histological assessment clarified a significant elevation in the fibroblast and collagen scores in the PPBM group versus the other sections. In addition, there were significant increases in the serum levels of the biomarkers PDGF-AA and PAR-1 among groups. Dependent on the results of current research, it can be concluded that both PP powder with BM PPBM significantly accelerate the healing process of burn wounds in experimentally induced diabetic rabbits.

Rutin encapsulated decellularized earthworm granulation hydrogel promotes angiogenesis in wound healing of diabetic rabbit model by inhibiting TRAF1/NF-κB pathway

Diabetic micro-vasculopathy is induced by accumulation of Reactive Oxygen Species (ROS) which results in delayed wound healing under hyperglycemic conditions. The classical practice of treating diabetic wound includes surgical debridement, hyperbaric oxygen therapy and use of antibiotics to control infection. The therapeutic interventions based on these classical practices have been found ineffective in management of diabetic wound healing and diabetic vasculopathy. Henceforth, engineered biomaterials with anti-oxidant activity have become research hotspots for their high biological activity, due to sustained release of active principles and weak immunogenicity. Based on these postulates, current study was conducted to evaluate diabetic wound healing potential of Rutin encapsulated decellularized earthworm granulation tissue (RdECM) with special reference on angiogenesis. The angiogenetic activity of RdECM was evaluated on cell line under hyperglycemic conditions and we found significant decline in ROS induced Deoxyribonucleic acid (DNA) damage and inhibition of Nuclear factor kappa B (NF-Kβ) pathway with subsequent aggregation of cells in tubular structure. Application of RdECM on diabetic wound resulted in accelerated wound healing, reduction in ROS induced DNA damage and down regulation of TNF receptor associated factor 1 (TRAF1). These changes results in inhibition of TRAF1-mediated NF-κB signal activation and subsequently angiogenesis in hyperglycemic conditions of diabetic wound. These findings support therapeutic utility of RdECM as angiogenetic agent and its potential use against diabetic wound healing.

Extracellular Matrix-Mimetic Intrinsic Versatile Coating Derived from Marine Adhesive Protein Promotes Diabetic Wound Healing through Regulating the Microenvironment.

The management of diabetic wound healing remains a severe clinical challenge due to the complicated wound microenvironments, including abnormal immune regulation, excessive reactive oxygen species (ROS), and repeated bacterial infections. Herein, we report an extracellular matrix (ECM)-mimetic coating derived from scallop byssal protein (Sbp9Δ), which can be assembled in situ within 30 min under the trigger of Ca2+ driven by strong coordination interaction. The biocompatible Sbp9Δ coating and genetically programmable LL37-fused coating exhibit outstanding antioxidant, antibacterial, and immune regulatory properties in vitro. Proof-of-concept applications demonstrate that the coating can reliably promote wound healing in animal models, including diabetic mice and rabbits, ex vivo human skins, and Staphylococcus aureus-infected diabetic mice. In-depth mechanism investigation indicates that improved wound microenvironments accelerated wound repair, including alleviated bacterial infection, lessened inflammation, appearance of abundant M2-type macrophages, removal of ROS, promoted angiogenesis, and re-epithelialization. Collectively, our investigation provides an in situ, convenient, and effective approach for diabetic wound repair.

Quantitative assessment of early kidney injury using high frame rate contrast-enhanced ultrasonography in a rabbit model of diabetic nephropathy.

To explore benefits of high-frame-rate contrast-enhanced ultrasonography (H-CEUS) for early kidney injury in arabbit model of diabetic nephropathy (DN). Diabetic rabbits were induced with alloxan administration and split into2 groups with or without urinary microalbuminuria after a fatty and sugary diet: diabetic rabbits with nephropathy (Group A)and diabetic rabbits without nephropathy (Group B). The control group (Group C) comprised healthy rabbits. Renal H-CEUSand conventional CEUS (C-CEUS) imaging were conducted. Serum creatinine (SCR), blood urea nitrogen (BUN) and urinarymicroalbuminuria were measured. SCR and BUN levels were barely changed in Groups B and C (p>0.05), whereasGroup A exhibited a rise (p<0.05). Perfusion parameters of the two CEUS modalities showed reduced peak intensity (PI) andascending slope (AS) and elevated area under the curve (AUC) and time to peak (TTP) in Group A versus Group B (p<0.05)and Group B versus Group C (p<0.05). The arrival time (AT) and descending slope (DS) exhibited little difference among thethree groups. H-CEUS had a stronger correlation of perfusion parameters with SCR and BUN than C-CEUS. H-CEUS outperforms C-CEUS in diagnosing early renal damage in DN. H-CEUS perfusion parameters demonstrate temporalsuperiority over routine laboratory indices.

Evaluation of Interleukin-1β, Interleukin-6 and Interleukin-10 Profiles in Serum and Surgically Created Wound Exudates of Alloxan-Induced Diabetic Rabbits

The knowledge of immune-modulatory actions of interleukins could be of immense value in the management of diabetic wounds. This study evaluated the interleukin profiles of diabetic wounded rabbits. Sixteen New Zealand White rabbits of mean weight 2.5 ± 0.7 kg used for this study were divided into four groups; A, B, C and D, of four rabbits each; A (non-diabetic and non-wounded) as control, B (diabetic and non-wounded, C (wounded and non-diabetic) and D (wounded and diabetic). Three (3) cm2 skin wounds were created in a standard aseptic procedure while diabetes was induced by administration of alloxan monohydrate. Serum and wound exudate were harvested on days 0, 3, 7, 14, 21 and 28 for Interleukin-1β, Interleukine-6 and Interleukine-10 assays. The increases in the serum concentration of Interleukin-1β and Interleukine-6 in the C rabbit group between days 3 and 7 (Interleukin-1β) and between days 3 and 28 (Interleukine-6) were relatively higher than the corresponding day 0 and control values. The decrease in the serum concentration of IL-10 (ng /mL) in B rabbit group from days 7 (36.96 ± 8.7) to 14 (128.12 ± 12.05) were significantly lower (P˂0.05) than the corresponding values in groups A and C rabbits. The values of Interleukine-10 in wound exudate of C rabbit group from days 7 (160.57 ± 23.76 ng /mL) to 21 (177.30 ± 8.60 ng /mL) were significantly higher (P&lt;0.05) than the corresponding group D values. The evidence shows that, the values of Interleukin-1β and Interleukine-6 are up regulated in the inflammatory phase of wound healing in normoglycaemic and diabetic rabbits while the values of Interleukine-10 is down regulated during wound healing in diabetic rabbits. Therefore, the knowledge of interleukin markers shall be of significant roles in proffering solution for management of normoglycaemic and diabetic wounds.

Microgels-Encapsulated Magnesium/Emodin-based metal organic framework nanorods for diabetic bone regeneration

Diabetic bone defect repair is one of the major challenges in clinic, because the pathological microenvironments such as hyperglycemia, oxidative stress, and inflammation exist in the bone defect area of diabetes mellitus. Although the current tissue-engineered bone has achieved favorable bone regeneration and functional reconstruction, it is still unsatisfactory for diabetic bone defect repair only by correcting a single pathological factor. In this study, we develop a multifunctional nano-releasing system of GelMA/HAMA microgels-encapsulated Mg2+/Emodin (MgEm) nanorods based on MOF design principle (denoted as MEGH) for reversing the diabetic pathological microenvironment. For the slow-release system of MEGH microgels, Emodin exert the hypoglycemic, antioxidant, and anti-inflammatory function, while Mg2+ ions could promote angiogenesis for bone regeneration. Subsequently, we combine decalcified bone matrix with the bone regenerative units based on BMSCs-loaded MEGH microgels (BMSCs@MEGH-D) for the construction of tissue-engineered bone. Finally, the pre-constructed BMSCs@MEGH-D scaffolds successfully promote the vascularized bone regeneration in diabetic rabbit skull models due to the effective correction of diabetic pathological microenvironment. The underlying mechanism indicates a synergetic efficacy of regulate glucose, inflammation, oxygen-related bioprocesses, as well as osteogenesis-related pathways. Our findings provide a promising treatment for reversing the diabetic pathological microenvironment to accelerate bone defect repair.

Use of Therapeutic RNAs to Accelerate Wound Healing in Diabetic Rabbit Wounds.

Introduction: Diabetes mellitus (DM) affects over 422 million people globally. Patients with DM are subject to a myriad of complications, of which diabetic foot ulcers (DFUs) are the most common with ∼25% chance of developing these wounds throughout their lifetime. Innovation: Currently there are no therapeutic RNAs approved for use in DFUs. Use of dressings containing novel layer-by-layer (LbL)-formulated therapeutic RNAs that inhibit PHD2 and miR-210 can significantly improve diabetic wound healing. These dressings provide sustained release of therapeutic RNAs to the wounds locally without systemic side effects. Clinical Problem Addressed: Diabetic foot wounds are difficult to heal and often result in significant patient morbidity and mortality. Materials and Methods: We used the diabetic neuroischemic rabbit model of impaired wound healing. Diabetes was induced in the rabbits with alloxan, and neuroischemia was induced by ligating the central neurovascular bundle of each ear. Four 6-mm full-thickness wounds were created on each ear. A LbL technique was used to conformally coat the wound dressings with chemically modified RNAs, including an antisense oligonucleotide (antimiR) targeting microRNA-210 (miR-210), an short synthetic hairpin RNA (sshRNA) targeting PHD2, or both. Results: Wound healing was improved by the antimiR-210 but not the PHD2-sshRNA. Specific knockdown of miR-210 in tissue as measured by RT-qPCR was ∼8 Ct greater than nonspecific controls, and this apparent level of knockdown (>99%) suggests that delivery to the tissue is highly efficient at the administered dose. Discussion: Healing of ischemic/neuropathic wounds in diabetic rabbits was accelerated upon inhibition of miR-210 by LbL delivery to the wound bed. miR-210 inhibition was achieved using a chemically modified antisense RNA.

Modulation of immune cum inflammatory pathway by earthworm granulation tissue extract in wound healing of diabetic rabbit model

Regeneration is a rare occurrence in the animal kingdom, but the earthworm stands out as a remarkable example of this phenomenon. Recent research has highlighted the promising wound healing properties of extracts derived from earthworms. Therefore, we propose that earthworm granulation tissue extract (EGTE) may facilitate wound healing by regulating immune responses in a rabbit diabetic wound model. Electron microscopy reveals that 70 % EGTE possesses noteworthy porosity with spherical to irregularly oval configuration. Gas chromatography–mass spectrometry (GC–MS) Characterization of EGTE revealed higher levels of ergosta-5,7,22-trien-3-ol, (3. beta.,22E). In-Vitro studies revealed significant anti-oxidant, anti-inflammatory and anti-bacterial properties in dose dependent manner. Likewise, cytotoxicity assessments reveal that 70 % EGTE exhibits minimal harm to cells while displaying substantial antioxidant and anti-inflammatory activities. For In-Vivo studies excision wounds were created on the dorsal regions of the experimental animals and were divided as Group I (50 % EGTE), Group II (70 % EGTE), Group III (vehicle) and Group IV (distilled water). Over a 21-day observation period 70 % EGTE facilitated the early healing of wounds in the experimental animals, evident through prompt wound closure, granulation tissue formation, increased DNA content, enhanced tensile strength of the wound area and enhanced the expression/synthesis of wound healing markers/proteins. From these results it can be postulated that EGTE accelerates wound healing by immune modulation, dampening of inflammatory pathway and enhanced expression of growth markers. Henceforth making it promising candidate for therapeutic use in diabetic wound healing.