scholarly journals Topically Applied Connective Tissue Growth Factor/CCN2 Improves Diabetic Preclinical Cutaneous Wound Healing: Potential Role for CTGF in Human Diabetic Foot Ulcer Healing

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
F. R. Henshaw ◽  
P. Boughton ◽  
L. Lo ◽  
S. V. McLennan ◽  
S. M. Twigg
Keyword(s):  
Wound Healing ◽  
Granulation Tissue ◽  
Ulcer Healing ◽  
Diabetic Foot ◽  
Healing Rate ◽  
Foot Ulcer ◽  
Foot Ulcers ◽  
Diabetic Foot Ulcers ◽  
Wound Fluid ◽  
Diabetic Wounds

Aims/Hypothesis. Topical application of CTGF/CCN2 to rodent diabetic and control wounds was examined. In parallel research, correlation of CTGF wound fluid levels with healing rate in human diabetic foot ulcers was undertaken.Methods. Full thickness cutaneous wounds in diabetic and nondiabetic control rats were treated topically with 1 μg rhCTGF or vehicle alone, on 2 consecutive days. Wound healing rate was observed on day 14 and wound sites were examined for breaking strength and granulation tissue. In the human study across 32 subjects, serial CTGF regulation was analyzed longitudinally in postdebridement diabetic wound fluid.Results. CTGF treated diabetic wounds had an accelerated closure rate compared with vehicle treated diabetic wounds. Healed skin withstood more strain before breaking in CTGF treated rat wounds. Granulation tissue from CTGF treatment in diabetic wounds showed collagen IV accumulation compared with nondiabetic animals. Woundα-smooth muscle actin was increased in CTGF treated diabetic wounds compared with untreated diabetic wounds, as was macrophage infiltration. Endogenous wound fluid CTGF protein rate of increase in human diabetic foot ulcers correlated positively with foot ulcer healing rate (r=0.406;P<0.001).Conclusions/Interpretation. These data collectively increasingly substantiate a functional role for CTGF in human diabetic foot ulcers.

scholarly journals Wound Fluid Matrix Metalloproteinase-9 as a Potential Predictive Marker for the Poor Healing Outcome in Diabetic Foot Ulcers

2018 ◽  
Vol 2018 ◽  
pp. 1-5 ◽  
Author(s):  
Punyanuch Jindatanmanusan ◽  
Sivat Luanraksa ◽  
Tanit Boonsiri ◽  
Thirayost Nimmanon ◽  
Pasra Arnutti
Keyword(s):  
Wound Healing ◽  
G Protein ◽  
Diabetic Foot ◽  
Healing Process ◽  
Foot Ulcers ◽  
Diabetic Foot Ulcers ◽  
Wound Fluid ◽  
The Poor ◽  
Wound Size

Background and Objective. Evidence for the roles of matrix metalloproteinases-9 (MMP-9) in the healing process of diabetic foot ulcers has remained unclear. We therefore aimed to demonstrate the relationship of MMP-9 with the wound healing process and determine its potential usefulness in predicting the wound healing outcome. Methods. Twenty-two patients with diabetic foot ulcer were recruited. The wound size was determined, and the wound fluid was collected for the measurement of MMP-9 levels using an ELISA during the 12-week follow-up period regularly. The patients were categorized as good healers and poor healers when the wound area reduction was ≥ 50% and < 50% at week 4 when compared to the initial wound size at week 0. Results. Median wound fluid MMP-9 levels in the poor healer group were shown to be significantly higher than those in the good healer group (1.03 pg/µg protein vs. 0.06 pg/µg protein, p = 0.001), and the levels fluctuated throughout the 12-week follow-up period. In contrast to the poor healer group, the MMP-9 levels were demonstrated to be constantly low throughout the follow-up period in the good healer group. ROC analysis showed that the MMP-9 level of 0.38 pg/µg protein was able to predict the wound healing outcome with the sensitivity of 81.8%, the specificity of 64.6%, and the area under the curve of 0.901 (CI 0.78-1.03, p = 0.001). Conclusion. These findings suggested that determination of wound fluid MMP-9 levels might become a promising biomarker predicting wound healing outcomes and a novel potential therapeutic target for diabetic foot ulcers.

scholarly journals Observational study of the effects of silver-based dressing materials in 50 cases of diabetic foot ulcers

2019 ◽  
Vol 6 (2) ◽  
pp. 508
Author(s):  
Rushabh Maisuria ◽  
Jawansing Manza ◽  
Devendra Chaudhari ◽  
Divyang Dave
Keyword(s):  
Wound Healing ◽  
Observational Study ◽  
Granulation Tissue ◽  
Diabetic Foot ◽  
Healing Rate ◽  
Foot Ulcer ◽  
Purulent Discharge ◽  
Diabetic Patients ◽  
Wide Range ◽  
Dressing Materials

Background: Diabetic foot remains the most common chronic medical problem being the most common cause of the hospital visit and/or admission, amongst the diabetic patients. Topical antimicrobial dressings, including those that contain silver are used to prevent or manage infection in a wide range of wounds.Methods: This is the prospective, observational study which included 50 cases of diabetic foot ulcer patients and effects of silver-based dressing materials will be evaluated.Results: After application of silver based dressing materials for two weeks, wound was evaluated on the basis of discharge from the wound, healing rate, appearance of the granulation tissue and culture and sensitivity report which showed that out of 50 cases studied, 3 cases (6%) had purulent discharge from the wound, absent granulation tissue, culture report showed presence of micro-organism and thus poor healing rate while other 47 cases (94%) had minimal/serous discharge, presence of healthy granulation tissue, no organism on culture report and thus good healing rate.Conclusions: Silver based dressing materials are effective in terms of promoting wound healing and more patient compliance.

scholarly journals Combined Transplantation of Mesenchymal Stem Cells and Endothelial Colony-Forming Cells Accelerates Refractory Diabetic Foot Ulcer Healing

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Liling Zhao ◽  
Zi Guo ◽  
Ke Chen ◽  
Wenjun Yang ◽  
Xinxing Wan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Diabetic Foot ◽  
Healing Rate ◽  
Foot Ulcer ◽  
Diabetic Foot Ulcer ◽  
Foot Ulcers ◽  
Diabetic Foot Ulcers ◽  
Cell Injection ◽  
Endothelial Colony Forming Cells

Background. This study is aimed at investigating the effect of combined transplantation of umbilical cord mesenchymal stem cells (UCMSCs) and umbilical cord blood-derived endothelial colony-forming cells (ECFCs) on diabetic foot ulcer healing and at providing a novel therapy for chronic diabetic foot ulcer. Methods. We reported the treatment of refractory diabetic foot ulcers in twelve patients. Among them, five patients had two or more wounds; thus, one wound in the same patient was treated with cell injection, and other wounds were regarded as self-controls. The remaining seven patients had only one wound; therefore, the difference between the area of wound before and after treatment was estimated. The UCMSCs and ECFCs were injected into the wound along with topically applied hyaluronic acid (HA). Results. In this report, we compared the healing rate of multiple separate wounds in the same foot of the same patient: one treated with cell injection combined with topically applied HA-based hydrogel and was later covered by the hydrocolloid dressings, while the self-control wounds were only treated with conventional therapy and covered by the hydrocolloid dressings. The wound underwent cell injection showed accelerated healing in comparison to control wound within the first week after treatment. In other diabetic patients with only one refractory wound, the healing rate after cell transplantation was significantly faster than that before injection. Two large wounds healed without needing skin grafts after combination therapy of cell injection and HA. After four weeks of combination treatment, wound closure was reached in six patients, and the wounds of the other six patients were significantly reduced in size. Conclusions. Our study suggests that the combination of UCMSCs, ECFCs, and HA can safely synergize the accelerated healing of refractory diabetic foot ulcers.

scholarly journals Integrative Analysis of miRNA Expression Profiling of Diabetic Foot Ulcers Wound Treated With Zizhu Ointment

2021 ◽  
Author(s):  
Xiaoming Hu ◽  
Renyan Huang ◽  
Wenhui Li ◽  
Xiao Yang ◽  
Weijing Fan ◽  
...  
Keyword(s):  
Wound Healing ◽  
Chinese Medicine ◽  
Diabetic Foot ◽  
Expression Profiling ◽  
Foot Ulcer ◽  
Diabetic Foot Ulcer ◽  
Foot Ulcers ◽  
Diabetic Foot Ulcers ◽  
Differentially Expressed Mirnas ◽  
Mirna Expression Profiling

Abstract Background: A major complication of diabetes is diabetic foot ulcers. Millions of patients suffer from the physiological and psychosocial effects of diabetic foot ulcers. However, the current treatment is not effective, and the patients’ prognosis has not been significantly improved.Results: Traditional Chinese medicine-Zizhu ointment exhibited its own characteristics and advantages in treating diabetic foot ulcer by promoting wound healing. The mechanism of Zizhu ointment promoting diabetic foot ulcer wound healing was explored by detecting its miRNA expression profiling. Eighty-three differentially expressed miRNAs were identified, 30 of which were upregulated and 53 were downregulated in diabetic cutaneous wounds treated with Zizhu ointment. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of the differentially expressed miRNAs showed that they were involved in several pathways that could regulate the proliferation, differentiation, apoptosis, migration, and secretion of tissue repair cells, and were linked to inflammatory cells, the extracellular matrix, growth factors, and other relevant factors related to wound healing. Furthermore, miRNA-Target regulatory network and protein-protein interaction network were constructed. Twenty hub genes of networks were obtained.Conclusions: Our preliminary study provides a new alternative drug treatment for diabetic foot ulcers by traditional Chinese medicine, and will assist in better understanding its therapeutic targets.

scholarly journals Nutrition Supplementation and Education May Increase the Healing Rate in Diabetic Patients with Foot Ulcers (P19-005-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Raedeh Basiri ◽  
Maria Spicer ◽  
Bahram Arjmandi
Keyword(s):  
Wound Healing ◽  
Treatment Group ◽  
Diabetic Foot ◽  
Healing Rate ◽  
High Protein ◽  
Foot Ulcers ◽  
Control Group ◽  
Diabetic Patients ◽  
Diabetic Foot Ulcers ◽  
Wound Healing Rate

Abstract Objectives This study examined the effects of high protein dietary supplementation and nutrition education on the healing of diabetic foot ulcers. Methods Twenty-nine adults with diabetic foot ulcers were recruited from the Tallahassee Memorial Hospital Wound Care Clinic. Participants were randomly assigned to treatment (n = 15) or control (n = 14) group. The treatment group received two carbohydrate controlled high protein shakes to consume daily, and was educated regarding adequate intake of low-fat protein sources, fruits, vegetables, complex carbohydrates and minimizing simple carbohydrates. The control group did not receive any intervention. Daily supplementation provided a total of 500 kilocalories, 28 grams of high-quality protein, and approximately 50% of micronutrient requirements. Anthropometric measurements (weight, height, BMI) and wound planimetry were examined at baseline and every four weeks until the wound healed or up to 12 weeks. Results There was no significant difference between the groups at baseline for BMI (mean = 33.8 ± 7 kg/m2), age (mean = 53.34 ± 11.14 years), duration of diabetes (mean = 13 years), duration of wounds (mean 10.8 months) or wound area (mean = 450 mm2). Wound healing rate (decrease in the area of the wound/week) for the treatment group was three times faster than the control group (151.1 mm2/week vs. 45.2 mm2/week respectively). Conclusions Improved nutritional intake using nutritional supplementation and patient education has a strong positive effect on the wound healing rate of diabetic foot ulcers. Faster wound healing improves quality of life and functionality of patients with diabetic foot ulcers. Funding Sources Dissertation award.

scholarly journals Targeting MMP-9 in Diabetic Foot Ulcers

2019 ◽  
Vol 12 (2) ◽  
pp. 79 ◽  
Author(s):  
Jeffrey I. Jones ◽  
Trung T. Nguyen ◽  
Zhihong Peng ◽  
Mayland Chang
Keyword(s):  
Wound Healing ◽  
Diabetic Foot ◽  
Healing Process ◽  
Foot Ulcers ◽  
Wound Healing Process ◽  
Diabetic Foot Ulcers ◽  
Novel Approach ◽  
Medical Need ◽  
Diabetic Wound Healing ◽  
Diabetic Wounds

Diabetic foot ulcers (DFUs) are significant complications of diabetes and an unmet medical need. Matrix metalloproteinases (MMPs) play important roles in the pathology of wounds and in the wound healing process. However, because of the challenge in distinguishing active MMPs from the two catalytically inactive forms of MMPs and the clinical failure of broad-spectrum MMP inhibitors in cancer, MMPs have not been a target for treatment of DFUs until recently. This review covers the discovery of active MMP-9 as the biochemical culprit in the recalcitrance of diabetic wounds to healing and targeting this proteinase as a novel approach for the treatment of DFUs. Active MMP-8 and MMP-9 were observed in mouse and human diabetic wounds using a batimastat affinity resin and proteomics. MMP-9 was shown to play a detrimental role in diabetic wound healing, whereas MMP-8 was beneficial. A new class of selective MMP-9 inhibitors shows clinical promise for the treatment of DFUs.

scholarly journals Genetic parameters of wound healing in patients with neuropatic diabetic foot ulcers

2017 ◽  
Vol 20 (5) ◽  
pp. 344-349
Author(s):  
Ekaterina L. Zaitseva ◽  
Alla Y. Tokmakova ◽  
Iya A. Voronkova ◽  
Vasily M. Petrov ◽  
Anatoly N. Tiulpakov ◽  
...  
Keyword(s):  
Wound Healing ◽  
Granulation Tissue ◽  
Diabetic Foot ◽  
Local Treatment ◽  
Foot Ulcers ◽  
Diabetic Foot Ulcers ◽  
Inflammatory Infiltration ◽  
Tissue Samples ◽  
Clinical Pictures ◽  
Collagen Genes

Background. Tissue repair processes are impaired in diabetic foot ulcers (DFUs). Previous research has shown that glycaemic control, cytokines and growth factors play an important role in wound healing. Emerging evidence also suggests that genes play a role via their regulation of cell proliferation, collagen synthesis and granulation tissue formation. Aim. To evaluate collagen genes expression in different stages of wound healing in patients with DFUs. Materials and methods. Prospective study included four patients with neuropathic DFUs after surgical debridement. Tissue samples were taken for morphological and genetic tests on days 0, 10 and 15 of local treatment to evaluate expression of collagen genes (i.e. COL1A1, COL1A2, COL3A1) and to perform morphological tests. Results. The present study confirmed that the size of wounds decreased by 8.8 7% after 10 days of local treatment and by 18.3 8% after 15 days of local treatment. According to histological examination of wound biopsies at day 10, all patients showed a tendency for lower levels of inflammatory infiltrate, increased number of fibroblast-like cells, presence of maturing granulation tissue and emergence of connective tissue fibres. After 15 days, we detected inflammatory infiltration in the wounds, despite the formation of mature granulation tissue. According to results of genetic analysis on day 10 of local wound treatment, we found a tendency for increased expression of collagen genes relative to the baseline: COL1A1 increased by 3.2 1.3 times, COL1A2 by 2.0 1.0 times and COL3A1 by 1.25 1.1 times. On day 15 of local treatment, in contrast, we found a tendency for decreased expression of COL1A1, COL1A2 and COL3A1 relative to the baseline (1.7 0.6, 2.5 2 and 20.0 3 times, respectively). Conclusions. The expression of collagen genes (COL1A1, COL1A2, COL3A1) is more pronounced in proliferation phase and is subsequently reduced towards the end. These data were confirmed by morphological study and clinical pictures.

scholarly journals PENATALAKSANAAN ULKUS KAKI DIABETES SECARA TERPADU

2013 ◽  
Vol 3 (2) ◽  
Author(s):  
Yuanita A. Langi
Keyword(s):  
Wound Healing ◽  
Growth Factors ◽  
Peripheral Arterial Disease ◽  
Diabetic Foot ◽  
Foot Ulcer ◽  
Diabetic Foot Ulcer ◽  
Arterial Disease ◽  
Foot Ulcers ◽  
Diabetic Foot Ulcers ◽  
Peripheral Arterial

Abstract: A diabetic foot ulcer is a common and fearful chronic complication of diabetes mellitus often resulting in amputation, and even death. A diabetic foot ulcer can be prevented by early screening and education in high risk individuals, and the management of underlying conditions such as neuropathy, peripheral arterial disease, and deformity. The prevalence of diabetic foot ulcer patients is 4-10% of the general population, with a higher prevalence in elderly people. Around 14-24 % of diabetic foot ulcer patients need amputations with a recurrence rate of 50% after three years. The main pathogenesis of diabetic foot ulcer is neuropathy and peripheral arterial disease (PAD). PAD contributes to diabetic foot ulcers in 50% of cases; however, it rarely stands alone. Other factors such as smoking, hypertension, and hyperlipidemia may contribute, too. In addition, PAD reduces the access of oxygen and antibiotics to the ulcers. Management of diabetic foot ulcers includes treatment of ischemia by promoting tissue perfusion, debridement for removing necrotic tissues, wound treatment for creating moist wound healing, off-loading the affected foot, surgery intervention, management of the co-morbidities and infections, and prevention of wound recurrences. Other adjuvant modalities include hyperbaric oxygen treatment, GCSF, growth factors, and bioengineered tissues. Key words: diabetic ulcer, debridement, off loading.   Abstrak: Ulkus kaki diabetes (UKD) merupakan salah satu komplikasi kronik diabetes melitus yang sering dijumpai dan ditakuti oleh karena pengelolaannya sering mengecewakan dan berakhir dengan amputasi, bahkan kematian. UKD dapat dicegah dengan melakukan skrining dini serta edukasi pada kelompok berisiko tinggi, dan penanganan penyebab dasar seperti neuropati, penyakit artei perifer dan deformitas. Prevalensi pasien UKD berkisar 4-10% dari populasi umumnya, dengan prevalensi yang lebih tinggi pada manula. Sekitar 14-24% pasien UKD memerlukan amputasi dengan rekurensi 50 % setelah tiga tahun. Patogenesis utama UKD yaitu neuropati dan penyakit arteri perifer (PAP). PAP berkontribusi 50% pada pasien UKD, tetapi hal ini jarang dijumpai tunggal. Terdapat faktor-faktor lain yang turut berperan seperti merokok, hipertensi dan hiperlipidemia. Selain itu PAP menurunkan akses oksigen dan antibiotik ke dalam ulkus. Penatalaksanaan UKD meliputi penanganan iskemia dengan meningkatkan perfusi jaringan, debridemen untuk mengeluarkan jaringan nekrotik, perawatan luka untuk menghasilkan moist wound healing, off-loading kaki yang terkena, intervensi bedah, pananganan komorbiditas dan infeksi, serta pencegahan rekurensi luka. Terapi ajuvan meliputi terapi oksigen hiperbarik, pemberian granulocyte colony stimulating factors (GCSF), growth factors dan bioengineerd tissues. Kata kunci: ulkus diabetes, debridemen, off loading.

scholarly journals Healing of Diabetic Foot Ulcers in Patients Treated at the Copenhagen Wound Healing Center in 1999/2000 and in 2011/2012

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Marie Louise Buhl Sørensen ◽  
Rasmus Bo Jansen ◽  
Therese Wilbek Fabricius ◽  
Bo Jørgensen ◽  
Ole Lander Svendsen
Keyword(s):  
Wound Healing ◽  
Median Time ◽  
Diabetic Foot ◽  
Foot Ulcer ◽  
Diabetic Foot Ulcer ◽  
Healing Time ◽  
Foot Ulcers ◽  
Time Range ◽  
Diabetic Foot Ulcers ◽  
One Year

Aim. To describe differences in healing time of diabetic foot ulcers for patients treated at the Copenhagen Wound Healing Center, Bispebjerg Hospital, between the years 1999/2000 and 2011/2012. The Center is highly specialized and receives diabetes patients with hard-to-heal foot ulcers. A further aim is to attempt to find predictors of healing time of diabetic foot ulcers. Methods. A retrospective descriptive study of records from patients with diabetic foot ulcer treated at the Copenhagen Wound Healing Center in 1999, 2000, 2011, or 2012. Follow-up data was collected until the 3rd of August 2018. Results. Median time (range) to healing was 6 (61.3) months in 1999/2000 and 6.6 (67.8) in 2011/2012 (p=0.2). About 33% of ulcers were healed, 17% were minor or major amputated, and 1.5% were dead within one year in 1999/2000, whereas 30% of ulcers were healed (p=0.6), 14% were amputated (p=0.2), and 12.8% were dead within one year in 2011/2012 (p<0.001). The single factor found significantly associated with longer ulcer duration was infection. Related to shorter ulcer duration were toe localization of the ulcer and good glycemic control. Conclusion. The median time to healing of a diabetic foot ulcer was long, around 6 months and with a high recurrence rate in 1999/2000 as well as in 2011/2012. Some factors were found to be significantly related to healing time, and intervention addressing these may improve the time to heal, although such interpretations must be taken with precaution from the present study and should be proven in randomized prospective intervention trials.

scholarly journals DIABETIC FOOT ULCERS;

2019 ◽  
Vol 26 (02) ◽  
Author(s):  
SOHAIL Farooq ◽  
Shaukat Javed ◽  
Nazish Jahan
Keyword(s):  
Granulation Tissue ◽  
Diabetic Foot ◽  
Controlled Trial ◽  
Foot Ulcer ◽  
Diabetic Foot Ulcer ◽  
Foot Ulcers ◽  
Diabetic Foot Ulcers ◽  
Wound Size ◽  
Group A ◽  
Group B

Introduction: Traditionally, moist dressings are being in used routinely by surgeons for management of diabetic foot ulcers. Recently, there is an encouraging trend of using VAC dressings in such patients. This study aimed to compare the outcome of VAC with moist dressing for management of diabetic foot ulcer. Study Design: Prospective randomized controlled trial. Setting: Department of Surgery, Al-Bukyriah General Hospital, Al-Bukayriah, Alqaseem KSA. Period: June 2012 to 07 December 2016. Methods and Material: 200 patients with diabetic foot ulcers. The patients were divided in two equal groups containing 100 patients each. In group A, 100 patients received VAC dressing treatment while in group B, 100 patients received wet dressings. Wound size, % reduction in wound size, appearance of granulation tissue and fate of wound were main outcome measured which were noted at start of study and at the end of study (4th week of therapy). Results: In group A, there were 73 (73%) men and 27 (27%) women with a mean age of 54.98+7.68 years and in group B, there were there were 75 (75%) men and 25 (25%) women with a mean age of 55.23+6.98 years. Size of wound before treatment in group A was 14.23± 6.78 cm2 which reduced to 5.11±1.91 cm2 at 4th wee and in group B it was 14.41±5.93 cm2 in the start which reduced to 11.29±3.63 cm2 at 4th week (p<0.05). Mean %reduction in wound size in group A was 63.22±9.19 and 22.92±7.18 in group B (p<0.05). In group A, 43 (43%) wounds healed spontaneously with shrinkage and group B only 2(2%) healed spontaneously (p<0.05). Conclusions: VAC therapy is superior to moist dressing in terms of achieving early granulation tissue, reduction in wound size and spontaneous wound shrinkage.

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