Mechanisms of diabetic foot ulceration: A review

Journal of Diabetes, Journal Year: 2023, Volume and Issue: 15(4), P. 299 - 312

Published: March 9, 2023

Diabetic foot ulcers (DFUs) are associated with complex pathogenic factors and considered a serious complication of diabetes. The potential mechanisms underlying DFUs have been increasingly investigated. Previous studies focused on the three aspects diabetic peripheral vascular disease, neuropathy, wound infections. With advances in technology, researchers gradually conducting using immune cells, endothelial keratinocytes, fibroblasts, as they involved healing. It has reported that upregulation or downregulation molecular signaling pathways is essential for healing DFUs. recent increase awareness epigenetics, its regulatory role become much sought-after trend treatment This review focuses four pathogenesis DFUs: physiological pathological mechanisms, cellular pathway epigenetics. Given challenge DFUs, we hopeful our will provide new ideas peers.糖尿病足溃疡(DFUs)与复杂的病理因素有关，被认为是糖尿病的严重并发症。目前，潜在的DFUs机制已经越来越受到研究关注。以往的研究主要集中在糖尿病周围血管疾病、神经病变和创伤感染三个方面。随着技术的进步，研究人员逐渐开始使用免疫细胞、内皮细胞、角质细胞和成纤维细胞进行研究，因为它们参与了创伤愈合过程。报道称，分子信号通路的上调或下调对DFUs的愈合至关重要。随着对表观遗传学认识的增强，它在创伤愈合中的调控作用成为治疗DFUs的热门趋势。本综述关注DFUs发病机制涉及的四个方面:生理和病理机制、细胞机制、分子信号通路机制和表观遗传学。鉴于DFUs治疗的挑战，我们希望本综述能为同行提供新思路。.

Language: Английский

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Enhancing angiogenesis: Innovative drug delivery systems to facilitate diabetic wound healing

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 170, P. 116035 - 116035

Published: Dec. 19, 2023

Diabetic wounds (DW) constitute a substantial burden on global healthcare owing to their widespread occurrence as complication of diabetes. Angiogenesis, crucial process, plays pivotal role in tissue recovery by supplying essential oxygen and nutrients the injury site. Unfortunately, diabetes mellitus, various factors disrupt angiogenesis, hindering wound healing. While biomaterials designed enhance angiogenesis hold promise for treatment DWs, there is an urgent need more in-depth investigations fully unlock potential clinical management. In this review, we explore intricate mechanisms that are DW recovery. We introduce rational design angiogenesis-enhancing drug delivery systems (DDS) provide comprehensive summary discussion diverse facilitating Lastly, address emerging challenges prospects DDS healing, aiming offer understanding critical issue solutions.

Language: Английский

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Zinc oxide loaded chitosan-elastin-sodium alginate nanocomposite gel using freeze gelation for enhanced adipose stem cell proliferation and antibacterial properties

International Journal of Biological Macromolecules, Journal Year: 2023, Volume and Issue: 233, P. 123519 - 123519

Published: Feb. 8, 2023

Language: Английский

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Endoscopic Nasal Delivery of Engineered Endothelial Progenitor Cell-Derived Exosomes Improves Angiogenesis and Neurological Deficits in Rats with Intracerebral Hemorrhage

Materials Today Bio, Journal Year: 2025, Volume and Issue: 32, P. 101652 - 101652

Published: March 12, 2025

Intracerebral hemorrhage (ICH) remains a life-threatening condition due to its high mortality and limited treatment options. This study explores novel therapeutic strategy using engineered exosomes derived from endothelial progenitor cells (EPC-EXOs) improve ICH outcomes. EPC-EXOs were modified with CD47-enriched red blood cell membrane via co-extrusion enhance their anti-phagocytic properties, thereby reducing degradation by activated microglia after ICH. A minimally invasive endoscopic-guided delivery system was developed facilitate the targeted intranasal administration of these (m-Oe-EXOs), allowing direct entry into brain tissue. We confirmed m-Oe-EXOs' retention effective distribution in brain. Functional analysis demonstrated that significantly promoted proliferation, migration, angiogenesis microvascular (BMECs), proteomic identifying HSP90 as key protein activating Akt pathway BMECs. In vivo, m-Oe-EXOs efficacy improving blood-brain barrier integrity, hematoma volume, enhancing neurological recovery rats. Collectively, our findings highlight potential invasive, an innovative approach for treatment, providing new insights targeted, exosomes-based regenerative therapies.

Language: Английский

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Bioinspired nanovesicles released from injectable hydrogels facilitate diabetic wound healing by regulating macrophage polarization and endothelial cell dysfunction

Journal of Nanobiotechnology, Journal Year: 2023, Volume and Issue: 21(1)

Published: Oct. 3, 2023

Abstract Wound healing is one of the major global health concerns in diabetic patients. Overactivation proinflammatory M1 macrophages could lead to delayed wound diabetes. 4-octyl itaconate (4OI), a derivative metabolite itaconate, has aroused growing interest recently on account its excellent anti-inflammatory properties. Cell membrane coating widely regarded as novel biomimetic strategy deliver drugs and inherit properties derived from source cells for biomedical applications. Herein, we fused induced pluripotent stem cell-derived endothelial cell (iEC) together with type macrophage construct hybrid (iEC-M) camouflaged 4OI nanovesicles (4OI@iEC-M). Furthermore, bioinspired 4OI@iEC-M are incorporated into injectable, multifunctional gelatin methacryloyl hydrogels repair regeneration. In our study, achieve dual-targeted both cells, thereby promoting polarization protecting cells. With synergistically immunoregulative effects, nanovesicles-loaded facilitate neovascularization exhibit superior Taken together, this study might provide healing, reducing limb amputation mortality

Language: Английский

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The Effects of Mesenchymal Stem Cells-Derived Exosomes on Metabolic Reprogramming in Scar Formation and Wound Healing

International Journal of Nanomedicine, Journal Year: 2024, Volume and Issue: Volume 19, P. 9871 - 9887

Published: Sept. 1, 2024

Pathological scarring results from aberrant cutaneous wound healing due to the overactivation of biological behaviors human skin fibroblasts, characterized by local inordinate inflammation, excessive extracellular matrix and collagen deposition. Yet, its underlying pathogenesis opinions vary, which could be caused increased mechanical tension, enhanced continuous gene mutation, as well cellular metabolic disorder, etc. Metabolic reprogramming is process pattern cells undergoes a systematic adjustment transformation adapt changes external environment meet needs their growth differentiation. Therefore, abnormality in within wounds scars attaches great importance scar formation. Mesenchymal stem cells-derived exosomes (MSC-Exo) are vesicles that play an important role tissue repair, cancer treatment immune regulation. However, there not work detail relevant studies. Herein, we gave comprehensive summary existing research on three main metabolisms, including glycometabolism, lipid metabolism amino acid metabolism, MSC-Exo regulating formation for further reference.

Language: Английский

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Advances and perspective on animal models and hydrogel biomaterials for diabetic wound healing.

PubMed, Journal Year: 2022, Volume and Issue: 3(3), P. 188 - 200

Published: Jan. 1, 2022

Diabetic wounds are a common complication in diabetes patients. Due to peripheral nerve damage and vascular dysfunction, diabetic prone progress local ulcers, wound gangrene even require amputation, bringing huge psychological economic burdens However, the current treatment methods for mainly include accessories, negative pressure drainage, skin grafting surgery; there is still no ideal promote healing at present. Appropriate animal models can simulate physiological mechanism of wounds, providing basis translational research treating healing. Although that fully mimic pathophysiological mechanisms humans, it vital explore simulation used basic preclinical studies wounds. In addition, hydrogel materials regarded as promising because their good antimicrobial activity, biocompatibility, biodegradation appropriate mechanical properties. Herein, we review discuss different investigate pathological We further future application biomaterials

Language: Английский

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KLF5 enhances CXCL12 transcription in adipose-derived stem cells to promote endothelial progenitor cells neovascularization and accelerate diabetic wound healing

Cellular & Molecular Biology Letters, Journal Year: 2025, Volume and Issue: 30(1)

Published: March 4, 2025

Adipose-derived stem cells (ADSCs) have been shown to accelerate diabetic wound healing by promoting neovascularization, though the underlying mechanisms are not fully understood. This study aims explore whether ADSCs influence endothelial progenitor (EPCs) function enhance healing. Human adipose-derived (hADSCs) were isolated from patient adipose tissue and cultured under normal high glucose (HG) conditions. RNA sequencing analyzed gene expression, while immunofluorescence validated findings in tissues. Mouse C57BL/6 mice evaluated vitro for their effects on EPCs HG using EdU, Transwell, tube formation assays. A mouse model was used assess therapeutic via digital imaging, histology, immunofluorescence. Kruppel-like factor 5 (KLF5), identified JASPAR database, confirmed immunohistochemistry KLF5 C-X-C motif chemokine 12 (CXCL12) expression levels measured enzyme-linked immunosorbent assay (ELISA), western blot, quantitative reverse transcription polymerase chain reaction (RT-qPCR), relationship through dual-luciferase We constructed a neovascularization-related signature (NRS) comprising 75 genes basis of differentially expressed (DEGs) linked neovascularization. GO KEGG analyses revealed that NRS is primarily involved vasculature development receptor-ligand activity. Seven hub (CD34, CXCL12, FGF7, FGF18, FGF1, TEK, KIT) validated. In model, CXCL12 knockdown reduced ability lower patients with ulcers tissues compared tissues, treatment significantly increased wounds. Dual-luciferase reporter assays as an upstream CXCL12. Additionally, knocking down impaired vitro, addition exogenous recombinant protein restored proliferation, migration, vasculogenic capacity environment after silencing ADSCs. Our underscore pivotal role enhancing within ADSCs, thereby facilitating EPC-mediated neovascularization improving emerges promising target accelerating repair

Language: Английский

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2‐Hydroxyl hispolon reverses high glucose‐induced endothelial progenitor cell dysfunction through the PI3K/Akt/eNOS and AMPK/HO‐1 pathways

British Journal of Pharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: March 4, 2025

In diabetes (DM), elevated blood sugar levels contribute to the overproduction of reactive oxygen species (ROS), leading endothelial progenitor cell (EPC) dysfunction. This study aimed determine potential 2-hydroxy hispolon (2HH), a derivative hispolon, reverse high glucose-induced EPC Under in vitro high-glucose (HG) conditions, we investigated effects 2HH on three types angiogenic cells: outgrowth cells (OECs), circulating (CACs) and (ECs). vivo, high-fat diet streptozotocin-induced diabetic mice with hindlimb ischaemia were used evaluate angiogenesis CAC mobilisation. Treatment significantly improved proliferation, migration, tube formation, NO synthesis ROS reduction EPCs (OECs CACs) under HG conditions by activating AMP-activated protein kinase (AMPK)/haem oxygenase-1 (HO-1) phosphoinositide 3-kinase (PI3K)/Akt/endothelial NOS (eNOS) signalling pathways but failed restore EC vivo model, administration DM enhanced flow recovery ischaemic hindlimbs, limb salvageability, increased number CACs capillary density muscle. Furthermore, activated AMPK/HO-1 PI3K/Akt/eNOS muscles. treatment effectively reduced oxidative stress synthesis, thereby preventing HG-induced dysfunction, primarily through pathways. These findings offer promising therapeutic avenue for attenuating susceptibility critical patients DM.

Language: Английский

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A dual-action strategy: Wound microenvironment responsive hydrogel and exosome-mediated glucose regulation enhance inside-out diabetic wound repair

Journal of Controlled Release, Journal Year: 2025, Volume and Issue: unknown, P. 113716 - 113716

Published: April 1, 2025

Language: Английский

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