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。     

Neuroprotective mechanisms of cerium oxide nanoparticles in a mouse hippocampal brain slice model of ischemia

Cerium oxide nanoparticles (nanoceria) are widely used as catalysts in industrial applications because of their potent free radical-scavenging properties. Given that free radicals play a prominent role in the pathology of many neurological diseases, we explored the use of nanoceria as a potential therapeutic agent for stroke. Using a mouse hippocampal brain slice model of cerebral ischemia, we show here that ceria nanoparticles reduce ischemic cell death by approximately 50%. The neuroprotective effects of nanoceria were due to a modest reduction in reactive oxygen species, in general, and ~ 15% reductions in the concentrations of superoxide (O₂^•−) and nitric oxide, specifically. Moreover, treatment with nanoceria markedly decreased (~ 70% reduction) the levels of ischemia-induced 3-nitrotyrosine, a modification to tyrosine residues in proteins induced by the peroxynitrite radical. These findings suggest that scavenging of peroxynitrite may be an important mechanism by which cerium oxide nanoparticles mitigate ischemic brain injury. Peroxynitrite plays a pivotal role in the dissemination of oxidative injury in biological tissues. Therefore, nanoceria may be useful as a therapeutic intervention to reduce oxidative and nitrosative damage after a stroke.     

Various physicochemical and surface properties controlling the bioactivity of cerium oxide nanoparticles

Amidst numerous emerging nanoparticles, cerium oxide nanoparticles (CNPs) possess fascinating pharmacological potential as they can be used as a therapeutic for various oxidative stress-associated chronic diseases such as cancer, inflammation and neurodegeneration due to unique redox cycling between Ce³⁺ and Ce⁴⁺ oxidation states on their surface. Lattice defects generated by the formation of Ce³⁺ ions and compensation by oxygen vacancies on CNPs surface has led to switching between CeO₂ and CeO_2–x during redox reactions making CNPs a lucrative catalytic nanoparticle capable of mimicking key natural antioxidant enzymes such as superoxide dismutase and catalase. Eventually, most of the reactive oxygen species and nitrogen species in biological system are scavenged by CNPs via an auto-regenerative mechanism in which a minimum dose can exhibit catalytic activity for a longer duration. Due to the controversial outcomes on CNPs toxicity, considerable attention has recently been drawn towards establishing relationships between the physicochemical properties of CNPs obtained by different synthesis methods and biological effects ranging from toxicity to therapeutics. Unlike non-redox active nanoparticles, variations in physicochemical properties and the surface properties of CNPs obtained from different synthesis methods can significantly affect their biological activity (inactive, antioxidant, or pro-oxidant). Moreover, these properties can influence the biological identity, cellular interactions, cellular uptake, biodistribution, and therapeutic efficiency. This review aims to highlight the critical role of various physicochemical and the surface properties of CNPs controlling their biological activity based on 165 cited references.     

The Host Defence Peptide LL-37 is Susceptible to Proteolytic Degradation by Wound Fluid Isolated from Foot Ulcers of Diabetic Patients

The pleiotropic effects of host defence peptides (HDPs), including the ability to kill microorganisms, enhance re-epithelialisation and increase angiogenesis, indicates a role for these important peptides as potential therapeutic agents in the treatment of chronic, non-healing wounds. However, the maintenance of peptide integrity, through resistance to degradation by the array of proteinases present at the wound site, is a prerequisite for clinical success. In this study we explored the degradation of exogenous LL-37, one such HDP, by wound fluid from diabetic foot ulcers to determine its susceptibility to proteolytic degradation. Our results suggest that LL-37 is unstable in the diabetic foot ulcer microenvironment. Following overnight treatment with wound fluid, LL-37 was completely degraded. Analysis of cleavage sites suggested potential involvement of both host- and bacterial-derived proteinases. The degradation products were shown to retain some antibacterial activity against Pseudomonas aeruginosa but were inactive against Staphylococcus aureus. In conclusion, our data suggest that stabilising selected peptide bonds within the sequence of LL-37 would represent an avenue for future research prior to clinical studies to address its potential as an exogenously-applied therapeutic in diabetic wounds.     

糖尿病患者足部溃疡感染的病原菌分布及药敏性分析

目的:研究糖尿病患者足部溃疡感染的病原菌分布及药敏性。方法:选取2016年2月至2017年2月我院收治的糖尿病足患者102例作为研究对象,采用全自动细菌鉴定仪和Kirby-Baure(K-B)法分别检测所有患者足部溃疡分泌物中病原菌分布和药敏性。结果:96例成功分离出菌株的糖尿病患者足部溃疡分泌物中共分离出107株菌株,其中革兰阴性菌61株(57.01%)、革兰阳性菌43株(40.19%)和真菌3株(2.80%),占总菌株百分比前三位的病原菌分别为金黄色葡萄球菌22株(20.56%)、奇异变形杆菌14株(13.08%)和肺炎克雷伯菌10株(9.35%);前三位革兰阴性菌(奇异变形杆菌、肺炎克雷伯菌和大肠埃希菌)对亚胺培南、美罗培南、头孢哌酮及阿米卡星的敏感性较高(高于90.00%);金黄色葡萄球菌和表皮葡萄球菌对万古霉素、利奈唑胺及利福平敏感性较高(高于95.00%);粪肠球菌对红霉素、氨苄西林、万古霉素及利奈唑胺敏感性较高(高于90.00%)。结论:糖尿病患者足部溃疡感染的病原菌以金黄色葡萄球菌和奇异变形杆菌为主,耐药情况严峻,临床诊疗过程中应根据药敏结果规范使用抗菌药物。     

Evaluation of anticancer effects of cerium oxide nanoparticles on mouse fibrosarcoma cell line

Cerium oxide nanoparticles are associated with anticancer effects. While protecting normal cells, these nanoparticles exert their anticancer effects via oxidative stress and apoptosis in the cancer cells. In this study, the anticancer properties of nanoceria on fibrosarcoma cell line are evaluated. Cerium oxide nanoparticles were synthesized by the coprecipitation method and their anticancer effects on mouse fibrosarcoma tumor cells (WEHI164) were investigated. Viability assay was evaluated by MTT, and the DC-FDA assay performed for the detection of reactive oxygen species. For apoptosis assay, the annexin V/PI test was done as well as measuring the mRNA and protein expression levels of Bax and Bcl2 by real-time PCR and western blot method, respectively. Characterization of nanoceria reveals that synthesized nanoceria has cubic floruit structure with a size of about 30 nm. Toxicity assessment results show that nanoceria increases ROS levels and induced apoptosis in a dose-dependent manner in cancer cells (WEHI164), whereas low levels of toxicity were observed in normal cells (L929), even at the concentrations above 250 µg/ml in MTT assay. Real-time PCR and western blot assays showed that nanoceria could significantly increase the Bax expression in cancer cells. The results showed that nanoceria could act as a potential therapeutic agent for the treatment of fibrosarcoma.     

Natural antioxidants attenuate mycolactone toxicity to RAW 264.7 macrophages

Mycobacterium ulcerans produces a macrolide exotoxin, mycolactone which suppresses immune cells activity, is toxic to most cells and the key virulence factor in the pathogenesis of Buruli ulcer disease. Mycolactone is reported to mediate the production of reactive oxygen species in keratinocytes; cells that play critical role in wound healing. Increased levels of reactive oxygen species have been shown to disrupt the well-ordered process of wound repair; hence, the function of wound-healing cells such as macrophages, keratinocytes, and fibroblast could be impaired in the presence of the reactive oxygen species mediator, mycolactone. To ensure regeneration of tissues in chronic ulcers, with proper and timely healing of the wounds, natural antioxidants that can combat the effects of induced reactive oxygen species in wound-healing cells ought to be investigated. Reactive oxygen species activity was determined in mycolactone-treated RAW 264.7 macrophages and the scavenging ability of the antioxidants (ascorbic acid, gallic acid, and green tea kombucha) against mycolactone-induced reactive oxygen species (superoxide anions) was assessed using fluorescein probe (DCF-DA) and nitroblue tetrazolium dye. Cytotoxicity of the antioxidants, mycolactone, and the protective effect of the antioxidants on the cells upon treatment with mycolactone were determined using the Alamar blue assay. The expression levels of endogenous antioxidant enzyme genes (superoxide dismutase, catalase, and glutathione peroxidase) in response to mycolactone-mediated reactive oxygen species were determined using RT-qPCR. Mycolactone induced the production of reactive oxygen species in RAW 264.7 macrophages, and the resulting superoxide anions were scavenged by some of the antioxidants. The selected endogenous antioxidant enzyme genes in the macrophages were upregulated in the presence of the antioxidants and mycolactone. The exogenously supplied ascorbic acid and green tea kombucha offered moderate protection to the macrophages against the toxicity of mycolactone. We conclude that the results provide insights into alternate and adjunct therapeutic approaches in Buruli ulcer treatment, which could significantly attenuate the toxicity of the pathogenic factor; mycolactone.     

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.     

Vitamin B2 functionalized iron oxide nanozymes for mouth ulcer healing

Mouth ulcer is associated with inflammation and high risk of bacterial infection, which aggravates the patient's condition.Currently, there is no effective treatment for mouth ulcer. Herein, we report that vitamin-modified iron oxide nanoparticles improve the healing of mouth ulcer through anti-inflammation and antibacterial activities. We discovered that vitamin B_2(VB_2)modified iron oxide nanoparticles performed enhanced peroxidase-like, catalase-like, and superoxide dismutase(SOD)-like activities, acting as typical iron oxide nanozymes(IONzymes) with triad activities. In particular, VB_2 modification significantly improved the SOD-like activity, thus providing a reactive oxygen species(ROS)-scavenging ability. Cellular antioxidant experiments showed that vitamin B_2 modified IONzymes(VB_2-IONzymes) protect human oral keratinocytes(HOK) and BALB/3 T3 cells from hydrogen peroxide(H_2O_2), and these cells have high biocompatibility to eukaryotic cells. In addition, VB_2-IONzymes exerted an antibacterial activity against Streptococcus mutans, Staphylococcus aureus, and Escherichia coli. Importantly, VB2-IONzymes accelerated the recovery of mouth ulcer and reduced the local secretion of inflammatory factors in mouse ulcer model via ROS scavenging and antibacterial activity. Taken together, our work demonstrates that vitamin B_2 modification endows iron oxide nanoparticles with enhanced enzyme-like activities and VB_2-IONzymes may be a promising reagent in the treatment of mouth ulcer because of their intrinsic anti-inflammation and antibacterial capabilities.     

Cerium Oxide Nanoparticles Protect Endothelial Cells from Apoptosis Induced by Oxidative Stress

Oxidative stress is well documented to cause injury to endothelial cells (ECs), which in turn trigger cardiovascular diseases. Previous studies revealed that cerium oxide nanoparticles (nanoceria) had antioxidant property, but the protective effect of nanoceria on ROS injury to ECs and cardiovascular diseases has not been reported. In the current study, we investigated the protective effect and underlying mechanisms of nanoceria on oxidative injury to ECs. The cell viability, lactate dehydrogenase release, cellular uptake, intracellular localization and reactive oxygen species (ROS) levels, endocytosis mechanism, cell apoptosis, and mitochondrial membrane potential were performed. The results indicated that nanoceria had no cytotoxicity on ECs but had the ability to prevent injury by H₂O₂. Nanoceria could be uptaken into ECs through caveolae- and clathrin-mediated endocytosis and distributed throughout the cytoplasma. The internalized nanoceria effectively attenuated ROS overproduction induced by H₂O₂. Apoptosis was also alleviated greatly by nanoceria pretreatment. These results may be helpful for more rational application of nanoceria in biomedical fields in the future.     

Gelatin/nanoceria nanocomposite fibers as antioxidant scaffolds for neuronal regeneration

BackgroundThe design of efficient nerve conduits able to sustain the axonal outgrowth and its guidance towards appropriate targets is of paramount importance in nerve tissue engineering.MethodsIn this work, we propose the preparation of highly aligned nanocomposite fibers of gelatin/cerium oxide nanoparticles (nanoceria), prepared by electrospinning. Nanoceria are powerful self-regenerative antioxidant nanomaterials, that behave as strong reactive oxygen species scavengers, and among various beneficial effects, they have been proven to inhibit the cell senescence and to promote the neurite sprouting.ResultsAfter a detailed characterization of the developed substrates, they have been tested on neuron-like SH-SY5Y cells, demonstrating strong antioxidant properties and beneficial multi-cue effects in terms of neurite development and alignment.ConclusionsObtained findings suggest efficiency of the proposed substrates in providing combined topographical stimuli and antioxidant effects to cultured cells.General significanceProposed nanocomposite scaffolds represent a promising approach for nerve tissue engineering and regenerative medicine.     

Comparison of the effect of stem cell therapy and percutaneous transluminal angioplasty on diabetic foot disease in patients with critical limb ischemia

Background aimsThe aim of our study was to compare the effect of autologous stem cell therapy (SCT) and percutaneous transluminal angioplasty (PTA) on diabetic foot disease (DFD) in patients with critical limb ischemia (CLI).MethodsThirty-one patients with DFD and CLI treated by autologous stem cells and 30 patients treated by PTA were included in the study; 23 patients with the same inclusion criteria who could not undergo PTA or SCT formed the control group. Amputation-free survival, transcutaneous oxygen pressure (TcPO₂) and wound healing were assessed over 12 months.ResultsAmputation-free survival after 6 and 12 months was significantly greater in the SCT and PTA groups compared with controls (P = 0.001 and P = 0.0029, respectively) without significant differences between the active treatment groups. Increase in TcPO₂ did not differ between SCT and PTA groups until 12 months (both Ps < 0.05 compared with baseline), whereas TcPO₂ in the control group did not change over the follow-up period. More healed ulcers were observed up to 12 months in the SCT group compared with the PTA and control groups (84 versus 57.7 versus 44.4 %; P = 0.042).ConclusionsOur study showed comparable effects of SCT and PTA on CLI, a major amputation rate that was superior to conservative therapy in patients with diabetic foot and an observable effect of SCT on wound healing. Our results support SCT as a potential promising treatment in patients with CLI and diabetic foot.     

Neurotensin-loaded collagen dressings reduce inflammation and improve wound healing in diabetic mice

Impaired wound healing is an important clinical problem in diabetes mellitus and results in failure to completely heal diabetic foot ulcers (DFUs), which may lead to lower extremity amputations. In the present study, collagen based dressings were prepared to be applied as support for the delivery of neurotensin (NT), a neuropeptide that acts as an inflammatory modulator in wound healing. The performance of NT alone and NT–loaded collagen matrices to treat wounds in streptozotocin (STZ) diabetic induced mice was evaluated. Results showed that the prepared dressings were not-cytotoxic up to 72 h after contact with macrophages (Raw 264.7) and human keratinocyte (HaCaT) cell lines. Moreover, those cells were shown to adhere to the collagen matrices without noticeable change in their morphology. NT–loaded collagen dressings induced faster healing (17% wound area reduction) in the early phases of wound healing in diabetic wounded mice. In addition, they also significantly reduced inflammatory cytokine expression namely, TNF-α (p < 0.01) and IL-1β (p < 0.01) and decreased the inflammatory infiltrate at day 3 post-wounding (inflammatory phase). After complete healing, metalloproteinase 9 (MMP-9) is reduced in diabetic skin (p < 0.05) which significantly increased fibroblast migration and collagen (collagen type I, alpha 2 (COL1A2) and collagen type III, alpha 1 (COL3A1)) expression and deposition. These results suggest that collagen-based dressings can be an effective support for NT release into diabetic wound enhancing the healing process. Nevertheless, a more prominent scar is observed in diabetic wounds treated with collagen when compared to the treatment with NT alone.     

自体富血小板凝胶联合冷沉淀制剂对糖尿病足溃疡患者创面愈合、血管生成因子及生活质量的影响

目的:探讨自体富血小板凝胶联合冷沉淀制剂对糖尿病足溃疡患者创面愈合、血管生成因子及生活质量的影响。方法:选取西宁市第一人民医院于2016年8月～2018年8月间收治的糖尿病足溃疡患者54例,依据数表法将患者随机分为对照组(n=27)和观察组(n=27)。对照组采用常规基础治疗,观察组在对照组基础上序贯使用自体富血小板凝胶联合冷沉淀制剂治疗。比较两组疗效、溃疡愈合时间、住院时间,比较两组患者治疗前及治疗20d后的肉芽组织中碱性成纤维细胞生长因子(bFGF)和血管内皮细胞生长因子(VEGF)表达水平以及糖尿病患者生存质量特异性量表评分。结果:观察组总有效率高于对照组(P0.05)。观察组溃疡愈合时间和住院时间均明显短于对照组,差异有统计学意义(P0.05)。治疗20d后,两组患者肉芽组织bFGF、VEGF表达水平均明显升高(P0.05),且观察组肉芽组织bFGF、VEGF表达水平均明显高于对照组(P0.05)。治疗20d后,两组患者生理功能、社会关系、心理或精神以及治疗影响四个维度评分均明显下降(P0.05),且观察组低于对照组(P0.05)。结论:自体富血小板凝胶联合冷沉淀制剂治疗糖尿病足溃疡疗效确切,可提高患者生活质量,可促进肉芽组织中血管生成和创面愈合。     

Synthesis and characterization of silver nanoparticles decorated polydopamine coated hexagonal boron nitride and its effect on wound healing

BackgroundWound healing is an essential physiological process involving many cell types and their products acting in a marvellous harmony to repair damaged tissues. During the healing process, cellular proliferation and extracellular matrix remodelling stages could be interrupted by undesired factors including microorganisms and altered metabolic activities. In such a case, the process requires some external stimulants to accelerate or remediate the healing stages.MethodsIn this study, we report a multifunctional wound healing stimulating agent. In this context, hexagonal boron nitride (hBN) nanoparticles, silver nanoparticles (AgNPs) and polydopamine(pdopa) were used through mussel-inspired chemistry of dopamine to obtain pdopa coated hBN (hBN@pdopa) and AgNPs decorated hBN@pdopa (hBN@pdopa-AgNPs). These two nanostructures were investigated to observe stages of healing.ResultsAgNPs were chosen for inflammation reduction and hBN for induced cell proliferation and migration. In in vitro experiments, firstly, high cellular uptake capacity and biocompatibility of hBN@pdopa and hBN@pdopa-AgNPs were evaluated. They were also tested for their reaction against increased concentration of reactive oxygen species (ROS) in injured cells. Finally, their effect on cellular migration, intracellular tube formation and F-actin organization were monitored by light and confocal microscopy, respectively.ConclusionThe results clearly indicate that the hBN@pdopa-AgNPs significantly decrease ROS production, promote wound closure, and reorganize tube formation in cells.     

Protective potential of cerium oxide nanoparticles in diabetes mellitus

BackgroundDiabetes mellitus (DM) is a non-communicable metabolic disease which is closely related to excessive oxidative stress after constant exposure to high plasma glucose. Although the current antidiabetic medications are effective in lowering blood glucose, these medications do not prevent or reverse the disease progression. Thus, there is a crucial need to explore new therapeutic interventions that could address this shortcoming. As cerium oxide nanoparticles (CONPs) possess antioxidant property, this agent may be used as a treatment option for the management of DM.PurposeThis review aims to provide a critical evaluation of the pharmacological and antidiabetic effects of CONPs in cell and animal models. The roles of CONPs in attenuating DM complications are also presented in this report.MethodsWe conducted a literature search in the PubMed database using the keywords “cerium oxide”, “cerous oxide”, “ceria”, “nanoceria”, and “diabetes” from inception to December 2020. The inclusion criteria were primary source articles that investigated the role of CONPs in DM and diabetic complications.ResultsWe identified 47 articles from the initial search. After the thorough screening, only 31 articles were included in this study. We found that CONPs can attenuate parameters that are related to DM and diabetic complications in various animals and cell culture models.ConclusionCONPs could potentially be used in the treatment of those with DM and complications caused by the disease.     

Polymicrobial nature of chronic diabetic foot ulcer biofilm infections determined using bacterial tag encoded FLX amplicon pyrosequencing (bTEFAP)

Background

Diabetic extremity ulcers are associated with chronic infections. Such ulcer infections are too often followed by amputation because there is little or no understanding of the ecology of such infections or how to control or eliminate this type of chronic infection. A primary impediment to the healing of chronic wounds is biofilm phenotype infections. Diabetic foot ulcers are the most common, disabling, and costly complications of diabetes. Here we seek to derive a better understanding of the polymicrobial nature of chronic diabetic extremity ulcer infections.

Methods and Findings

Using a new bacterial tag encoded FLX amplicon pyrosequencing (bTEFAP) approach we have evaluated the bacterial diversity of 40 chronic diabetic foot ulcers from different patients. The most prevalent bacterial genus associated with diabetic chronic wounds was Corynebacterium spp. Findings also show that obligate anaerobes including Bacteroides, Peptoniphilus, Fingoldia, Anaerococcus, and Peptostreptococcus spp. are ubiquitous in diabetic ulcers, comprising a significant portion of the wound biofilm communities. Other major components of the bacterial communities included commonly cultured genera such as Streptococcus, Serratia, Staphylococcus and Enterococcus spp.

Conclusions

In this article, we highlight the patterns of population diversity observed in the samples and introduce preliminary evidence to support the concept of functional equivalent pathogroups (FEP). Here we introduce FEP as consortia of genotypically distinct bacteria that symbiotically produce a pathogenic community. According to this hypothesis, individual members of these communities when they occur alone may not cause disease but when they coaggregate or consort together into a FEP the synergistic effect provides the functional equivalence of well-known pathogens, such as Staphylococcus aureus, giving the biofilm community the factors necessary to maintain chronic biofilm infections. Further work is definitely warranted and needed in order to prove whether the FEPs concept is a viable hypothesis. The findings here also suggest that traditional culturing methods may be extremely biased as a diagnostic tool as they select for easily cultured organisms such as Staphylococcus aureus and against difficult to culture bacteria such as anaerobes. While PCR methods also have bias, further work is now needed in comparing traditional culture results to high-resolution molecular diagnostic methods such as bTEFAP.     

Clinical challenges of chronic wounds: searching for an optimal animal model to recapitulate their complexity

The efficient healing of a skin wound is something that most of us take for granted but is essential for surviving day-to-day knocks and cuts, and is absolutely relied on clinically whenever a patient receives surgical intervention. However, the management of a chronic wound – defined as a barrier defect that has not healed in 3 months – has become a major therapeutic challenge throughout the Western world, and it is a problem that will only escalate with the increasing incidence of conditions that impede wound healing, such as diabetes, obesity and vascular disorders. Despite being clinically and molecularly heterogeneous, all chronic wounds are generally assigned to one of three major clinical categories: leg ulcers, diabetic foot ulcers or pressure ulcers. Although we have gleaned much knowledge about the fundamental cellular and molecular mechanisms that underpin healthy, acute wound healing from various animal models, we have learned much less about chronic wound repair pathology from these models. This might largely be because the animal models being used in this field of research have failed to recapitulate the clinical features of chronic wounds. In this Clinical Puzzle article, we discuss the clinical complexity of chronic wounds and describe the best currently available models for investigating chronic wound pathology. We also assess how such models could be optimised to become more useful tools for uncovering pathological mechanisms and potential therapeutic treatments.KEY WORDS: Animal models, Chronic wounds, Diabetic foot ulcer, Ischemia, Pressure ulcer, Venous leg ulcer     

The effect of the boron-based gel on the treatment of diabetic foot ulcers: A prospective,randomized controlled trial

BackgroundChronic ulcers represent impaired healing capacity with high mortality in the elderly or patients with systemic disorders such as diabetes. Boron is an effective agent in wound healing by promoting cell migration and proliferation and reducing inflammation in the wound area. This study aimed to evaluate the therapeutic effect of a sodium pentaborate-based topical formulation compared to control on the treatment of diabetic foot ulcers.MethodsA prospective, double-blind, randomized controlled trial was conducted to apply randomly the topical sodium pentaborate 3% gel or topical conventional remedy (control) by patients diagnosed with diabetic foot ulcers. The 171 eligible participants aged 18–75 years received the allocated medicines twice a day for a month with an allocation ratio of 3:1. Twenty-five days and two months after the end of the trial, participants were reinvestigated for their ulcer condition and any recurrence. Wagner’s classification of diabetic foot ulcers was applied to this purpose (0−5).Results161 participants (57 females, 104 males; mean age: 59.37) completed this study. After the intervention, most participants in the intervention group had a lower ulcer grade than the control group (adjusted mean difference (95% CI): − 0.91 (−1.1 to −0.73); p < 0.001). Moreover, most participants in the intervention group (n = 109 (90.8%)) were treated at a higher rate than the control group (n = 5 (12.2%)) after intervention (adjusted odds ratio (95% CI): 0.008 (0.002–0.029); p < 0.001). There was no case of recurrence in the intervention group while its rate was (n = 2 (40%)) in the control group (p < 0.001).ConclusionThe present study suggests that topical sodium pentaborate gel may help treat and decrease the grade of diabetic foot ulcers and prevent the recurrence of diabetic foot ulcers.