基质金属蛋白酶9对糖尿病足溃疡愈合影响的研究进展

在糖尿病足患者溃疡创面分泌物中,基质金属蛋白酶9 (matrix metalloproteinase-9,MMP-9)过高是预测糖尿病足的发生及足溃疡难愈的主要指标,其可能的机制包括:高水平MMP-9降低VEGF的表达、抑制成纤维细胞的生物学行为影响糖尿病足溃疡愈合;失衡的MMP-9/TIMP-1比值影响糖尿病足溃疡愈合。选择性MMP-9抑制剂(包括小分子抑制剂、高级伤口辅料抑制剂、基于干扰基因水平表达的RNA抑制剂)可以作为促进糖尿病足溃疡愈合的手段,但仍需大样本、多中心随机对照试验以及长期随访进一步验证其疗效及安全性。现查阅近年来涉及MMP-9和糖尿病足溃疡相关的文献,综述MMP-9对糖尿病足溃疡愈合的影响及其机制研究进展。     

Might hyperbaric oxygen therapy (HBOT) reduce renal injury in diabetic people with diabetes mellitus? From preclinical models to human metabolomics

Diabetic kidney disease (DKD) is the leading cause of end-stage renal failure in the western world. Current treatment of diabetic kidney disease relies on nutritional management and drug therapies to achieve metabolic control. Here, we discuss the potential application of hyperbaric oxygen therapy (HBOT) for the treatment of diabetic kidney disease (DKD), a treatment which requires patients to breathe in 100% oxygen at elevated ambient pressures. HBOT has traditionally been used to diabetic foot ulcers (DFU) refractory to conventional medical treatments. Successful clinic responses seen in the DFU provide the underlying therapeutic rationale for testing HBOT in the setting of DKD. Both the DFU and DKD have microvascular endothelial disease as a common underlying pathologic feature. Supporting evidence for HBOT of DKD comes from previous animal studies and from our preliminary prospective clinical trial reported here. We report urinary metabolomic data obtained from patients undergoing HBOT for DFU, before and after exposure to 6 weeks of HBOT. The preliminary data support the concept that HBOT can reduce biomarkers of renal injury, oxidant stress, and mitochondrial dysfunction in patients receiving HBOT for DFU. Further studies are needed to confirm these initial findings and correlate them with simultaneous measures of renal function. HBOT is a safe and effective treatment for DFU and could also be for individuals with DKD.     

Role of Endothelial Progenitor Cells and Inflammatory Cytokines in Healing of Diabetic Foot Ulcers

Background

To evaluate changes in endothelial progenitor cells (EPCs) and cytokines in patients with diabetic foot ulceration (DFU) in association with wound healing.

Methods

We studied healthy subjects, diabetic patients not at risk of DFU, at risk of DFU and with active DFU. We prospectively followed the DFU patients over a 12-week period. We also investigated similar changes in diabetic rabbit and mouse models of wound healing.

Results

All EPC phenotypes except the kinase insert domain receptor (KDR)⁺CD133⁺ were reduced in the at risk and the DFU groups compared to the controls. There were no major EPC differences between the control and not at risk group, and between the at risk and DFU groups. Serum stromal-cell derived factor-1 (SDF-1) and stem cell factor (SCF) were increased in DFU patients. DFU patients who healed their ulcers had lower CD34⁺KDR⁺ count at visits 3 and 4, serum c-reactive protein (CRP) and granulocyte-macrophage colony-stimulating factor (GM-CSF) at visit 1, interleukin-1 (IL-1) at visits 1 and 4. EPCs tended to be higher in both diabetic animal models when compared to their non-diabetic counterparts both before and ten days after wounding.

Conclusions

Uncomplicated diabetes does not affect EPCs. EPCs are reduced in patients at risk or with DFU while complete wound healing is associated with CD34⁺KDR⁺ reduction, suggesting possible increased homing. Low baseline CRP, IL-1α and GM-CSF serum levels were associated with complete wound healing and may potentially serve as prognostic markers of DFU healing. No animal model alone is representative of the human condition, indicating the need for multiple experimental models.     

糖尿病足溃疡的危险因素探讨及亲水性纤维含银敷料促进患者伤口愈合的临床对照研究

摘要 目的：探讨糖尿病足溃疡（DFU）的危险因素,并研究亲水性纤维含银敷料促进患者伤口愈合的应用价值。方法：选取2017年8月-2020年12月期间我院收治的糖尿病患者230例。230例糖尿病患者中发生DFU的79例,纳为DFU组,剩余151例未发生DFU,纳为无DFU组。DFU组的患者采用随机数字表法分为治疗1组39例和治疗2组40例,治疗1组给予传统纱布敷料,治疗2组给予亲水性纤维含银敷料。采用多因素Logistic回归分析DFU发生的危险因素。观察治疗1组、治疗2组的临床疗效和临床指标。结果：DFU组、无DFU组在性别、年龄、户籍地、糖尿病病程、并发下肢血管病变、并发周围神经病变、足底有胼胝、血红蛋白（Hb）、C反应蛋白（CRP）、白蛋白（ALB）、总胆固醇（TC）、纤维蛋白原（FIB）、红细胞沉降率（ESR）、高密度脂蛋白（HDL）、 胱抑C（CysC）、 低密度脂蛋白（LDL）、脂蛋白a[Lp(a)]、糖化血红蛋白（HbAlc）方面对比差异有统计学意义（P<0.05）。男性、糖尿病病程、并发下肢血管病变、并发周围神经病变、足底有胼胝、ALB、ESR、CysC、CRP、Lp(a)、HbAlc均是DFU发生的危险因素（P<0.05）。治疗2组的临床总有效率明显高于治疗1组（P<0.05）。治疗2组的创面愈合时间、出现明显肉芽时间、住院时间短于治疗1组,住院费用高于治疗1组（P<0.05）。结论：DFU的发生受到多种因素影响,包括男性、糖尿病病程、并发下肢血管病变等,因此临床应加强对这些因素的预防和控制。此外,亲水性纤维含银敷料可促进DFU患者创面愈合,疗效显著。     

Assessment of Mineral Pathophysiology in Patients with Diabetic Foot Ulcer

Biological Trace Element Research - Chronic non-healing diabetic foot ulcers (DFU) with a recurrence rate of over 50% in 3&nbsp;years account for more than 1,08000 non-traumatic lower extremity...     

Polyherbal formulation exerts wound healing,anti-inflammatory,angiogenic and antimicrobial properties: Potential role in the treatment of diabetic foot ulcers

Diabetic foot ulcer (DFU) is a common and devastating complication in diabetic patients and is associated with an elevated risk of amputation and mortality. DFU remains a major therapeutic challenge due to poor understanding of its underlying pathogenesis. This complication is characterized by impaired wound healing; however, mechanisms causing this impairment are complicated and involve interactions between many different cell types and infections. In addition to other conventional DFU treatments, herbal foot baths are also common, although little is known about their mechanisms of action, and they contain a wide variety of herbal ingredients. In this study, we aimed to examine the effects of three polyherbal formulations consisting of medicinal plants used in traditional Thai herbal foot baths on wound healing, anti-inflammation, angiogenesis, and extracellular matrix modulation using high-concentration glucose-treated human keratinocytes, in addition to antibacterial evaluation. Our results showed that formulation 3 (F3) possessed the greatest potential to restore the impairment of keratinocytes caused by high glucose concentrations. We found that F3 could inhibit the growth of Staphylococcus aureus, accelerate wound healing, and upregulate the expression of TIMP-1, VEGF, and TGF-β, and downregulate the expression of TNF-α, IL-6, and MMP-9. Collectively, these data support the potential of F3 for therapeutic development in the treatment of DFU.     

MHR、sCD14-ST、ApoM与糖尿病足溃疡预后的关系及对预后的预测价值

摘要 目的：探讨单核细胞数/高密度脂蛋白胆固醇比值（MHR）、可溶性白细胞分化抗原14亚型（sCD14-ST）、载脂蛋白M（ApoM）与糖尿病足溃疡（DFU）患者预后的关系及对预后的预测价值。方法：选取2018年1月-2020年12月本院收治的100例DFU患者资料进行回顾性分析,记录其性别、年龄、病程、体重指数（BMI）等一般临床资料以及空腹血糖、MHR、sCD14-ST、ApoM等实验室指标,并对纳入的100例患者进行6个月的随访,获得患者DFU愈合、截肢及死亡例数。采用单因素分析以及二元Logistics回归分析MHR、sCD14-ST、ApoM与DFU患者预后的关系,并采用ROC曲线检测MHR、sCD14-ST、ApoM水平及三项指标联合检测对不良预后的预测价值。结果：预后不良患者DFU病程、Wagner分级、MHR、sCD14-ST、ApoM水平均与预后良好患者有统计学差异（P＜0.05）。随着MHR、sCD14-ST水平的升高,不良结局发生率呈上升趋势（P＜0.05）;随着ApoM水平升高,不良结局发生率呈下降趋势（P＜0.05）。二元Logistic回归分析结果显示,DFU病程、MHR、sCD14-ST为DFU患者不良结局发生的独立危险因素（P＜0.05）,而ApoM为保护因素（P＜0.05）。ROC曲线分析显示,MHR、sCD14-ST、ApoM以及三项指标联合检测对DFU患者不良结局发生的预测线下面积（AUC）分别为0.731、0.729、0.763和0.864,其中联合检测的预测效能最高,其预测敏感度为68.57%、特异度为89.23%。结论：MHR、sCD14-ST、ApoM均与DFU患者的预后存在相关性,三项指标联合检测具有一定的预后预测价值。     

林下密集蕨类层生态学研究进展

林下密集蕨类层在森林尤其是受干扰森林中广泛存在,对森林更新具有强烈的过滤效应,能够改变林下层的多样性,影响群落的结构、功能和动态,林下密集蕨类层的生态学研究,对揭示森林群落物种分布格局和群落构建机制具有重要意义.结合国内外最新研究,论述了林下密集蕨类层的特征,从机制上解释了林下密集蕨类层形成的主要原因;分类阐述了林下密...     

Microbubble detection following hyperbaric chamber dives using dual-frequency ultrasound

Venous gas emboli (VGE) can be readily detected in the bloodstream using existing ultrasound methods. No method currently exists to detect decompression-induced microbubbles in tissue. We hypothesized that dual-frequency ultrasound (DFU) could detect these microbubbles. With DFU, microbubbles are driven with two frequencies: a lower "pump" (set to the resonant frequency of the desired bubble size) and a higher "image" frequency. A bubble of the resonant size emits the sum and difference of the two transmitted frequencies. For this study we used a pump frequency of 2.25 MHz and an image frequency of 5.0 MHz, which detects bubbles of roughly 1-10 μm in diameter in a water tank. Four anesthetized swine were pressurized at 4.5 ATA for 2 h and decompressed over 5 min, inducing moderate to very severe VGE scores. Four sites on the thigh of each swine were monitored with DFU before and after the dives. A single mock dive was also performed. The number of sites returning signals consistent with microbubbles increased dramatically after the chamber dive (P < 0.01), but did not change with the mock dive. The increase in DFU signal after the chamber dive was sustained and present at multiple sites in multiple swine. This research shows for the first time that decompression-induced tissue microbubbles can be detected using DFU and that DFU could be used to monitor decompression-induced microbubbles at multiple sites on the body. Additionally, DFU could be used to track the time course of microbubble formation and growth during decompression stress.     

Comparative Genomic,MicroRNA, and Tissue Analyses Reveal Subtle Differences between Non-Diabetic and Diabetic Foot Skin

Diabetes Mellitus (DM) is a chronic, severe disease rapidly increasing in incidence and prevalence and is associated with numerous complications. Patients with DM are at high risk of developing diabetic foot ulcers (DFU) that often lead to lower limb amputations, long term disability, and a shortened lifespan. Despite this, the effects of DM on human foot skin biology are largely unknown. Thus, the focus of this study was to determine whether DM changes foot skin biology predisposing it for healing impairment and development of DFU. Foot skin samples were collected from 20 patients receiving corrective foot surgery and, using a combination of multiple molecular and cellular approaches, we performed comparative analyses of non-ulcerated non-neuropathic diabetic foot skin (DFS) and healthy non-diabetic foot skin (NFS). MicroRNA (miR) profiling of laser captured epidermis and primary dermal fibroblasts from both DFS and NFS samples identified 5 miRs de-regulated in the epidermis of DFS though none reached statistical significance. MiR-31-5p and miR-31-3p were most profoundly induced. Although none were significantly regulated in diabetic fibroblasts, miR-29c-3p showed a trend of up-regulation, which was confirmed by qPCR in a prospective set of 20 skin samples. Gene expression profiling of full thickness biopsies identified 36 de-regulated genes in DFS (>2 fold-change, unadjusted p-value ≤ 0.05). Of this group, three out of seven tested genes were confirmed by qPCR: SERPINB3 was up-regulated whereas OR2A4 and LGR5 were down-regulated in DFS. However no morphological differences in histology, collagen deposition, and number of blood vessels or lymphocytes were found. No difference in proliferative capacity was observed by quantification of Ki67 positive cells in epidermis. These findings suggest DM causes only subtle changes to foot skin. Since morphology, mRNA and miR levels were not affected in a major way, additional factors, such as neuropathy, vascular complications, or duration of DM, may further compromise tissue’s healing ability leading to development of DFUs.     

胫骨横向骨搬移术联合封闭引流技术治疗糖尿病足溃疡的临床比较研究

摘要 目的：观察胫骨横向骨搬移术联合封闭引流技术（VSD）治疗糖尿病足溃疡（DFU）的治疗效果。方法：选取2018年4月~2020年7月我院收治的65例DFU患者。根据治疗方式的不同将患者分为A组（32例,VSD治疗）和B组（33例,胫骨横向骨搬移术联合VSD治疗）。对比两组围术期指标、患足皮温、视觉模拟评分法（VAS）评分、踝肱指数（ABI）和血清相关指标变化,记录两组并发症发生率。结果：两组术后1个月,患足皮温、ABI升高,VAS评分下降,且B组的变化幅度明显大于A组（P<0.05）。两组完全负重时间、下地行走时间组间对比无差异（P>0.05）。B组的溃疡愈合时间、去除外固定架时间明显短于A组（P<0.05）。两组术后1个月血管内皮生长因子（VEGF）水平升高,白细胞计数（WBC）、C反应蛋白（CRP）水平下降,且B组的变化幅度明显大于A组（P<0.05）。两组并发症发生率组间对比无统计学差异（P>0.05）。结论：胫骨横向骨搬移术联合VSD治疗DFU,可促进创面愈合,效果显著。     

Reliability and Validity of the Perfusion,Extent, Depth,Infection and Sensation (PEDIS) Classification System and Score in Patients with Diabetic Foot Ulcer

Aims

To validate the perfusion, extent, depth, infection and sensation (PEDIS) classification system and to make the clinical practice easier, we created a score system and compared this system with two previously published common score systems.

Methods

A retrospective cohort study was conducted on patients with diabetic foot ulcer (DFU) attending our hospital (n=364) from May 2007 to September 2013. Participants’ characteristics and all variables composing the PEDIS classification system were assessed.

Results

During a median follow-up of 25 months (range 6-82), ulcers healed in 217 of the 364 patients (59.6%), remained unhealed in 37 patients (10.2%), and were resolved by amputation in 62 patients (17.0%); 48 patients (13.2%) died. When measured using the PEDIS classification system, the outcome of DFU deteriorated with increasing severity of each subcategory. Additionally, longer ulcer history, worse perfusion of lower limb, a larger extent of the ulcer, a deeper wound, more severe infection, and loss of protective sensation were independent predictors of adverse outcome. More importantly, the new PEDIS score system showed good diagnostic accuracy, especially when compared with the SINBAD and Wagner score systems.

Conclusions

The PEDIS classification system, which encompasses relevant variables that contribute to the outcome of DFU and has excellent capacity for predicting the ulcer outcome, demonstrated acceptable accuracy. The PEDIS classification system might be useful in clinical practice and research both for the anticipation of health care costs and for comparing patient subgroups.     

Topical hyperbaric oxygen and low energy laser therapy for chronic diabetic foot ulcers resistant to conventional treatment

Chronic foot ulcers are common in long-standing diabetes, may herald severe complications and are often resistant to therapy. To evaluate the effects of adjunctive topical hyperbaric oxygen treatment (THBO) and low energy laser (LEL) irradiation on ulcer healing, a 100 consecutive patients with chronic diabetic foot ulcers (DFU) refractory to 4.5 +/- 1.2 months of comprehensive treatment, were enrolled in a prospective open study. While conventional treatment was continued as necessary, THBO was administered by pumping 100 percent oxygen into a disposable sealed polythylene hyperbaric chamber (150 min x 2 to 3/wk at up to 1.04 atm). Helium-neon LEL irradiation was given concurrently using a Unilaser Scan Unit at 4 J/cm2 for 20 min. Some patients continued THBO at home or their treatment was confined to THBO at home. Patients were monitored every two weeks revealing 81 percent cure after 25 +/- 13 treatments over 3.2 +/- 1.7 months. On follow-up (median 18 months), only 3/81 (4 percent) had reulceration, which responded to THBO/LEL retreatment. Nonresponders had significantly lower ankle brachial indices (ABI) than patients whose ulcers were healed (0.55 vs. 0.78, p < 0.01) and ultimately required amputation. Patient compliance was full and no adverse events occurred. In conclusion, although the study was open and uncontrolled, an 81 percent healing of DFU in patients who previously did not respond to a comprehensive treatment program, constitutes an intriguing preliminary result. Thus, THBO/LEL therapy may be a safe, simple, and inexpensive early adjunctive treatment for patients with chronic diabetic foot ulcers. Our findings should prompt its evaluation by large randomized controlled trials.     

1,25-Dihydroxyvitamin D3 Induces LL-37 and HBD-2 Production in Keratinocytes from Diabetic Foot Ulcers Promoting Wound Healing: An In Vitro Model

Diabetic foot ulcers (DFU) are one of the most common diabetes-related cause of hospitalization and often lead to severe infections and poor healing. It has been recently reported that patients with DFU have lower levels of antimicrobial peptides (AMPs) at the lesion area, which contributes with the impairment of wound healing. The aim of this study was to determine whether 1,25-dihydroxyvitamin D₃ (1,25 (OH)₂ D₃) and L-isoleucine induced HBD-2 and LL-37 in primary cultures from DFU. We developed primary cell cultures from skin biopsies from 15 patients with DFU and 15 from healthy donors. Cultures were treated with 1,25 (OH)₂D₃ or L-isoleucine for 18 h. Keratinocytes phenotype was identified by western blot and flow cytometry. Real time qPCR for DEFB4, CAMP and VDR gene expression was performed as well as an ELISA to measure HBD-2 and LL-37 in supernatant. Antimicrobial activity, in vitro, wound healing and proliferation assays were performed with conditioned supernatant. The results show that primary culture from DFU treated with 1,25(OH)₂D₃, increased DEFB4 and CAMP gene expression and increased the production of HBD-2 and LL-37 in the culture supernatant. These supernatants had antimicrobial activity over E. coli and induced remarkable keratinocyte migration. In conclusion the 1,25(OH)₂D₃ restored the production of AMPs in primary cell from DFU which were capable to improve the in vitro wound healing assays, suggesting their potential therapeutic use on the treatment of DFU.     

Metformin Induces Cell Cycle Arrest,Reduced Proliferation,Wound Healing Impairment In Vivo and Is Associated to Clinical Outcomes in Diabetic Foot Ulcer Patients

BackgroundSeveral epidemiological studies in diabetic patients have demonstrated a protective effect of metformin to the development of several types of cancer. The underlying mechanisms of such phenomenon is related to the effect of metformin on cell proliferation among which, mTOR, AMPK and other targets have been identified. However, little is known about the role that metformin treatment have on other cell types such as keratinocytes and whether exposure to metformin of these cells might have serious repercussions in wound healing delay and in the development of complications in diabetic patients with foot ulcers or in their exacerbation.ResultsMetformin treatment significantly reduces cell proliferation; colony formation and alterations of the cell cycle are observed also in the metformin treated cells, particularly in the S phase. There is a significant increase in the area of the wound of the metformin treated animals at different time points (P<0.05). There is also a significant increase in the size and wound area of the patients with diabetic foot ulcers at the time of hospitalization. A protective effect of metformin was observed for amputation, probably associated with the anti inflammatory effects reported of metformin.ConclusionsMetformin treatment reduces cell proliferation and reduces wound healing in an animal model and affects clinical outcomes in diabetic foot ulcer patients. Chronic use of this drug should be further investigated to provide evidence of their security in association with DFU.     

The FDA and designing clinical trials for chronic cutaneous ulcers

Treatment of chronic wounds can present a challenge, with many patients remaining refractory to available advanced therapies. As such, there is a strong need for the development of new products. Unfortunately, despite this demand, few new wound-related drugs have been approved over the past decade. This is in part due to unsuccessful clinical trials and subsequent lack of Food and Drug Administration (FDA) approval. In this article, we discuss the FDA approval process, how it relates to chronic wound trials, common issues that arise, and how best to manage them. Additionally, problems encountered specific to diabetic foot ulcers (DFU) and venous leg ulcers (VLU) are addressed. Careful construction of a clinical trial is necessary in order to achieve the best possible efficacy outcomes and thereby, gain FDA approval. How to design an optimal trial is outlined.     

Unidades de pie diabético en España: conociendo la realidad mediante el uso de un cuestionario

ObjectiveTo ascertain the number of diabetic foot units (DFUs) in Spain, the specialists working in them, and the population covered by them.Material and methodsThe Spanish Group on the Diabetic Foot (SGDF) prepared and agreed a questionnaire based on the recommendations of the 2011 International Consensus on the Diabetic Foot (ICDF). From October to December 2012, the questionnaire was sent to members of three scientific societies formed by professionals involved in the care of patients with diabetes mellitus. Population coverage of the responding centers and DFUs was estimated using the 2012 population census.ResultsSeventy five questionnaires were received, 64 of them from general hospitals, which accounted for 13% of the general hospitals of the National Health System. It was calculated that they provided coverage to 43% of the population. Thirty four centers answered that they had a DFU. Specialized diabetic foot care was only provided to 25% of the population. The number of different professionals working at diabetic foot units was 6.3 ± 2.7. Classification of DFUs based on their complexity was as follows: 5 basic units (14.7%), 20 intermediate units (58.8%), and 9 excellence units (26.5%).ConclusionsThe number of DFUs reported in this study in Spain is low, and allow for foot care of only one out of every four patients with diabetes. Spanish health system needs to improve diabetic foot care by creating new DFUs and improving the existing ones.     

Cyclooxygenase‐2 over‐expression inhibits liver apoptosis induced by hyperglycemia

Increased expression of COX‐2 has been linked to inflammation and carcinogenesis. Constitutive expression of COX‐2 protects hepatocytes from several pro‐apoptotic stimuli. Increased hepatic apoptosis has been observed in experimental models of diabetes. Our present aim was to analyze the role of COX‐2 as a regulator of apoptosis in diabetic mouse liver. Mice of C57BL/6 strain wild type (Wt) and transgenic in COX‐2 (hCOX‐2 Tg) were separated into Control (vehicle) and SID (streptozotocin induced diabetes, 200 mg/kg body weight, i.p.). Seven days post‐injection, Wt diabetic animals showed a decrease in PI3K activity and P‐Akt levels, an increase of P‐JNK, P‐p38, pro‐apoptotic Bad and Bax, release of cytochrome c and activities of caspases‐3 and ‐9, leading to an increased apoptotic index. This situation was improved in diabetic COX‐2 Tg. In addition, SID COX‐2 Tg showed increased expression of anti‐apoptotic Mcl‐1 and XIAP. Pro‐apoptotic state in the liver of diabetic animals was improved by over‐expression of COX‐2. We also analyzed the roles of high glucose‐induced apoptosis and hCOX‐2 in vitro. Non‐transfected and hCOX‐2‐transfected cells were cultured at 5 and 25 mM of glucose by 72 h. At 25 mM there was an increase in apoptosis in non‐transfected cells versus those exposed to 5 mM. This increase was partly prevented in transfected cells at 25 mM. Moreover, the protective effect observed in hCOX‐2‐transfected cells was suppressed by addition of DFU (COX‐2 selective inhibitor), and mimicked by addition of PGE₂ in non‐transfected cells. Taken together, these results demonstrate that hyperglycemia‐induced hepatic apoptosis is protected by hCOX‐2 expression. J. Cell. Biochem. 114: 669–680, 2013. © 2012 Wiley Periodicals, Inc.     

Inhibition of exosomal miR‐24‐3p in diabetes restores angiogenesis and facilitates wound repair via targeting PIK3R3

Diabetic foot ulcer (DFU) is one of the common ailments of elderly people suffering from diabetes. Exosomes containing various active regulators have been found to play a significant role in apoptosis, cell proliferation and other biological processes. However, the effect and the underlying mechanism of action of diabetes patients derived from circulating exosomes (Dia‐Exos) on DFU remain unclear. Herein, we aim to explore the potential regulatory role of Dia‐Exos. First, we attempted to demonstrate the harmful effect of Dia‐Exos both in vivo and in vitro. miRNA‐24‐3p (miR‐24‐3p) was found enriched with Dia‐Exos. Hence, inhibition of this miRNA could partially reverse the negative effect of Dia‐Exos, thus, in ture, accelerates wound repair. Luciferase assay further verified the binding of miR‐24‐3p to the 3′‐UTR of phosphatidylinositol 3‐kinase regulatory subunit gamma (PIK3R3) mRNA and the PIK3R3 expression enhanced human umbilical vein endothelial cells functionality in vitro. Hence, the findings of this study reveal the regulatory role of Dia‐Exos in the process of wound healing and provide experimental evidence for the therapeutic effects of knocking down miR‐24‐3p in DFU treatment.