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

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.

Author(s):  
Rasnah Appil ◽  
Elly Lilianty Sjattar ◽  
Saldy Yusuf ◽  
Kasmawati Kadir

Objective. To evaluate the effectiveness of family empowerment through educational interventions against HbA1c level and healing progress of diabetic foot ulcers. Method. A quasi-experimental design was employed involving 33 participants from 4 wound care clinics in Makassar, eastern Indonesia. The intervention group consisted of 17 participants and their families; the control group was composed of 16 participants who received nonstructural education. Family empowerment was measured by the Indonesian version of the Family Empowerment Scale instrument. Glycemic control was evaluated with HbA1c levels, and the wound healing process was evaluated on the Diabetic Foot Ulcers Assessment Scale. Result. After 3 months, Family Empowerment Scale scores improved, particularly in the subdomain of family knowledge (16.59 ± 3.92 vs 13.38 ± 1.26; P = .005) and attitude (3.65 ± 0.93 vs 2.75 ± 0.45; P = .002). After 3 months of intervention, HbA1c decreased (from 10.47 ± 2.44% to 8.81 ± 1.83%), compared with the control group ( P = .048). Meanwhile, an independent t test further revealed that the wound healing process tended to be better with the intervention group (4.71 ± 7.74) compared with the control group (17.25 ± 17.06), with P = .010 at the third month. Conclusion. Family-based education intervention creates family empowerment to control HbA1c levels and accelerate wound healing of diabetic foot ulcer.


2020 ◽  
Vol 9 (3) ◽  
pp. 230-239
Author(s):  
Tessy López-Goerne ◽  
Francisco J. Padilla-Godínez ◽  
Luis Pérez-Dávalos ◽  
Paola Ramírez-Olivares ◽  
Daniela Arellano

Background: Diabetic foot ulcers (DFUs) exhibit 80% of prevalence in Mexico. Efficient tissue regeneration therapies are the key factors to avoid amputations. Objective: In this study, the healing properties of a Cu/TiO2-SiO2 nanobiocatalyst applied in DFUs were analyzed. Furthermore, the morphology and crystalline structures were characterized. Methods: The nanobiocatalyst was synthesized by a sol-gel patented method proposed by López et al. The compound was characterized by scanning and transmission electron microscopies and Xray diffraction. The nanoparticles were embedded in a polymeric gel matrix (nanogel), which was utilized as a conservative therapy for chronic non-healing DFU in 8 patients with several comorbidities and chronic complications of diabetes. Wound debridement was performed prior to the nanogel administration. The nanogel was applied over the ulcers on alternate days for different periods of time, depending on the case. Results: Significant improvement in terms of enhanced epithelialization was observed in the wound healing process after a few applications. Infection spread was limited, and tissue regeneration was enhanced, with significant healing of the ulcers observed in each case. Furthermore, the successful outcome allowed to avoid the amputations that were proposed to some of the patients. Conclusion: The study proved the efficiency of the nanobiocatalyst as a safe, conservative therapy for chronic non-healing DFUs. Further investigation must be carried out to fully elucidate the wound-healing mechanisms of the nanoparticles.


2021 ◽  
Vol 64 (8) ◽  
pp. 529-536
Author(s):  
Jiyong Ahn

Background: Diabetic foot ulcers (DFUs), a risk factor for infection, remain a difficult clinical complication. Infected DFUs may be associated with lower extremity amputation. To achieve wound healing and avoid amputation, an assortment of dressing materials and negative pressure wound therapy (NPWT) have been used on soft tissue injuries resulting from infected DFUs. A great deal of interest about the use of dressing materials and NPWT in the treatment of DFUs has arisen. However, there have only been a few high-quality studies regarding this topic.Current Concepts: Ideal dressing materials should satisfy certain conditions to alleviate symptoms of DFU infection and enhance the wound healing process. A single dressing material cannot fulfill all of these requirements. Based on clinical trials, different dressing materials must be chosen according to the status of the individual wound environment, including the amount of exudate, degree of pain, severity of the infection, and cost-effectiveness. However, there has been no clear evidence that advanced wound dressing materials are superior to basic dressing materials in wound healing. Recently, NPWT has been used to cover the soft tissue defects of infected DFU with granulation tissue. NPWT may contribute to changing growth factor expression, micro- and macro-deformation, vascular flow, amount of exudate, and the bacterial environment in DFU, despite the unclear mechanism of its role in wound repair.Discussion and Conclusion: Further research to obtain high-quality evidence regarding the benefits of using dressing materials and NPWT is needed. The optimal protocol for DFU and cost-effectiveness should be included in these future studies.


2020 ◽  
Vol 134 (12) ◽  
pp. 1399-1401
Author(s):  
Man K.S. Lee ◽  
Gopalkrishna Sreejit ◽  
Prabhakara R. Nagareddy ◽  
Andrew J. Murphy

Abstract In volume 133 issue 4 of Clinical Science, Liu et al. showed that neutrophils release extracellular traps (NETs) in the setting of diabetes which acts as a stimulus for NLRP3 inflammasome activation in macrophages to promote IL1β-dependent exacerbation of inflammation. They also provide evidence to show that degrading NETs improves the wound healing process. These findings provide an insight into how NETs communicate with other cells in the vicinity (e.g. macrophages) to exacerbate the inflammatory response. Most importantly, they provide novel avenues to improve wound healing process such as diabetic foot ulcers (DFUs) by targeting NETs.


Author(s):  
Ioanna A. Anastasiou ◽  
Ioanna Eleftheriadou ◽  
Anastasios Tentolouris ◽  
Georgia Samakidou ◽  
Nikolaos Papanas ◽  
...  

Diabetic foot ulcers are one of the most dreadful complications of diabetes mellitus and efforts to accelerate diabetic wound healing are of paramount importance to prevent ulcer infections and subsequent lower-limb amputations. There are several treatment approaches for the management of diabetic foot ulcers and honey seems to be a safe and cost-effective therapeutic approach on top of standard of care. The aim of this review was to summarize the therapeutic properties of honey and the data regarding its possible favorable effects on diabetic wound healing. A literature search of articles from 1986 until April 2021 was performed using MEDLINE, EMBASE, and the Cochrane Library to assess for studies examining the therapeutic wound healing properties of honey, it's in vitro effect, and the efficacy and/or mechanism of action of several types of honey used for the treatment of diabetic animal wounds. Honey has antioxidant, anti-inflammatory, and antibacterial properties and in vitro studies of keratinocytes and fibroblasts, as well as studies in diabetic animal models show that treatment with honey is associated with increased re-epithelialization and collagen production, higher wound contraction, and faster wound healing. The use of honey could be a promising approach for the management of diabetic foot ulcers.


2018 ◽  
Vol 2018 ◽  
pp. 1-5 ◽  
Author(s):  
Punyanuch Jindatanmanusan ◽  
Sivat Luanraksa ◽  
Tanit Boonsiri ◽  
Thirayost Nimmanon ◽  
Pasra Arnutti

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.


2019 ◽  
Vol 2 (2) ◽  
pp. 20-28
Author(s):  
Anita Sukarno ◽  
Nur Hidayah ◽  
Musdalifah Musdalifah

Background: Diabetic foot ulcers were common diabetes complication that progressively growth globally. The effectivity of Manuka honey in wound healing process was huge published currently. Modern dressing and Manuka honey may not affordable and cost effective since these dressings were not produced originally in Indonesia. In addition, the published study of Indonesian honey is still lack. Therefore, we conducted this study to investigate the effectivity of Indonesian honey in diabetic foot ulcers healing process. Method: This study design was observational case study. This study was conducted among type 2 diabetes with diabetic foot ulcers in Griya Afiat Homecare and ETN Center in Makassar City, Indonesia from March to June 2014. The Bates Wound Assessment Tool (BWAT) were used to collect the score of diabetic foot ulcer healing process regarding wound size, depth, edges, undermining, necrotic tissue type, necrotic amount, granulation, epithelization, exudate type and amount, surrounding skin color, edema and induration. Descriptive, Independent t-test, Analysis of Variance (ANOVA) and Wilcoxon signed rank test were conducted appropriately. Results: In total, 10 type 2 diabetes patients with diabetic foot ulcers were participated. The factors associated with wound healing process were diabetes treatment (t= 2.44, p= 0.041) and primary dressing (t= -2.76, p= 0.025). The effect of honey primary dressing was in reducing wound size (p= 0.043), improving necrotic tissue type (p= 0.041), reducing necrotic tissue amount (p= 0.042), increasing granulation (p= 0.038) and epithelization (p= 0.042). In the counterpart, the effect of modern dressing was in improving necrotic tissue type (p= 0.046) and increasing granulation (p= 0.042). Conclusion: Indonesian honey is beneficial on diabetic foot ulcers healing process. Recommendation: Therefore, findings suggest that honey should be considered as the alternative, cost effective and beneficial wound dressing on the diabetic foot ulcers.


2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Hadeel A. Al-Rawaf ◽  
Sami A. Gabr ◽  
Ahmad H. Alghadir

Background. Circulating micro-RNAs are differentially expressed in various tissues and could be considered as potential regulatory biomarkers for T2DM and related complications, such as chronic wounds. Aim. In the current study, we investigated whether ginger extract enriched with [6]-gingerol-fractions either alone or in combination with vitamin D accelerates diabetic wound healing and explores underlying molecular changes in the expression of miRNA and their predicted role in diabetic wound healing. Methods. Diabetic wounded mice were treated with [6]-gingerol-fractions (GF) (25 mg/kg of body weight) either alone or in combination with vitamin D (100 ng/kg per day) for two weeks. Circulating miRNA profile, fibrogenesis markers, hydroxyproline (HPX), fibronectin (FN), and collagen deposition, diabetic control variables, FBS, HbA1c, C-peptide, and insulin, and wound closure rate and histomorphometric analyses were, respectively, measured at days 3, 6, 9, and 15 by RT–PCR and immunoassay analysis. Results. Treatment of diabetic wounds with GF and vitamin D showed significant improvement in wound healing as measured by higher expression levels of HPX, FN, collagen, accelerated wound closure, complete epithelialization, and scar formation in short periods (11-13 days, (P<0.01). On a molecular level, three circulating miRNAs, miR-155, miR-146a, and miR-15a, were identified in diabetic and nondiabetic skin wounds by PCR analysis. Lower expression in miR-155 levels and higher expression of miR-146a and miR-15a levels were observed in diabetic skin wounds following treatment with gingerols fractions and vitamin D for 15 days. The data showed that miRNAs, miR-146a, miR-155, and miR-15a, correlated positively with the expression levels of HPX, FN, and collagen and negatively with FBS, HbA1c, C-peptide, and insulin in diabetic wounds following treatment with GF and /or vitamin D, respectively. Conclusion. Treatment with gingerols fractions (GF) and vitamin D for two weeks significantly improves delayed diabetic wound healing. The data showed that vitamin D and gingerol activate vascularization, fibrin deposition (HPX, FN, and collagen), and myofibroblasts in such manner to synthesize new tissues and help in the scar formation. Accordingly, three miRNAs, miR-155, miR-146a, and miR-15, as molecular targets, were identified and significantly evaluated in wound healing process. It showed significant association with fibrin deposition, vascularization, and reepithelialization process following treatment with GF and vitamin D. It proposed having anti-inflammatory action and promoting new tissue formation via vascularization process during the wound healing. Therefore, it is very interesting to consider miRNAs as molecular targets for evaluating the efficiency of nondrug therapy in the regulation of wound healing process.


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