Medical Journal of The Islamic Republic of Iran (MJIRI)

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The effect of electrical currents by different modalities on wound healing has been experimented. In this study a survey of the literature shows different results, and the mechanisms of action have not been elucidated for certain. The aim of this study was to compare the results obtained from low voltage-square wave stimulation of different frequencies. Results show that the healing period for the control group (14.9 ± 0.58 days) was reduced to 11.28 ± 0.52 and 10.37 ± 0.7 days for groups receiving 20 and 80 Hz stimulation respectively. This implies that wound closure as an index of wound healing was significantly increased in animals receiving 80 Hz stimulation. Tensile strength was increased from 2013 ± 192 grams in controls to 2589 ± 235.1 grams in the 80 Hz-receiving study group. We concluded that electrical stimulation can affect the process of healing and a stimulation of 80Hz is more effective than other frequencies.

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 Abstract

 Background & Objectives: Honey has been used as a nutraceutical in many traditional and ancient remedies. Considering well documented benefits of honey to accelerate wound healing, for the first time we aimed to assess intra oral surgical wound healing process with honey.

 Methods: We designed a pilot randomized placebo controlled cross-over clinical trial. Patients who required bilateral Modified Widman Flap (MWF) surgery randomly assigned to receive either 15 cc topical Persian Thymus Vulgaris concentrated honey three times a day or normal saline as placebo with the same amount at the site of the surgery for seven consecutive days. After a 35-day wash-out period the study groups were crossed. The primary efficacy outcome was changes in healing index (Landry index) and the secondary efficacy outcome were changes in gingival and plaque indices (Loe & Sillness, Sillness & Loe indices). It also includes safety issues consisting of any allergic reaction, delayed healing or wound dehiscence.

 Results: Ten patients enrolled with the mean age of 36 (±1.5) ranged between 35-40 yrs. There was a significant improvement in wound healing considering time and treatment effects in both groups, although faster wound healing observed in honey treated patients (P<0.001). In both groups gingival indices were noticed to be improved by the time during the first phase of the study. Both groups displayed aggravated Plaque formation nevertheless it was merely statistically significant in the control group [F (3, 27) =12.88, P value < 0.001]. All wounds healed normally and no adverse events recorded.

 Conclusion: Our study established the safety, efficacy and feasibility of topical honey to promote periodontal surgical wound healing. (IRCT138901192547N2)

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Background: Infection of burn wounds is one of the most important problems in the world. Lactobacillus plantarum is known for burn wound healing because of the immunomodulatory and anti-microbial roles. This study was performed to compare the effects of L. plantarum and imipenem – alone and in combination – on infected burn wound healing.
   Methods: Burn wounds were experimentally induced on 50 rats in three test groups (germ and supernatant of L. plantarum) and two control groups (n=10 each) and were inoculated with Pseudomonas aeruginosa. During a 14-day period, wounds in all groups were daily treated topically. The data were analyzed using one-way analysis of variance followed by Tukey–Kramer and LSD. A p-value of < 0.05 was considered as statistically significant.
   Results: The mean size of the wound on day 14 after the treatment in the probiotic group was significantly lower than the control and the supernatant treated groups (p<0.05).  The percentage of wound healing was significantly higher in the probiotic pellet treated group compared to the imipenem and the supernatant groups (by Anova test: 69.58%, p=0.022). The mean leukocyte count in the probiotic pellet group (12110) and supernatant group (13650) was significantly higher than the imipenem group (7670) (p=0.002 and 0.001, respectively). Wound cultures revealed that the percentage of cases where the pathogens had no growth was significantly different among the comparison groups. In all three test groups, P. aeruginosa was completely eliminated in comparison to the positive control group (p<0.05).
   Conclusion: The results of our study showed that L. plantarum and its by-products promote wound healing and can be used as an alternative to antibiotics to treat ulcer infections caused by resistant bacteria.

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Background: Diabetic foot syndrome (DFS) causes damage to the peripheral arteries in 50% of patients with diabetes mellitus (DM). The purpose of this study was to evaluate the efficacy of endovascular interventions, stenting, and balloon angioplasty for the treatment of patients with purulent and necrotic lesions in DFS.
   Methods: This was a retrospective study. During 2019-2020, stenting and balloon angioplasty were performed in 51 patients (study group) with purulent and necrotic complications of diabetic foot with limb ischemia. There were 32 women (62.7%) and 19 men (37.3%). The age of the patients varied from 45 to 81 years. Endovascular interventions were performed in combination with conservative therapy and topical treatment on 2 to 3 days after the debridement of the purulent lesions. To assess the outcomes of endovascular interventions, we studied the nature of changes in arterial circulation in the lower extremities. The mean blood flow velocity was calculated using the Doppler ultrasonography. The study was performed on the popliteal artery (PA), the posterior tibial artery (PTA), and on the dorsalis pedis artery. In this study, patients were divided into 2 groups: the study group— those who received endovascular intervention— and the control group— those who received only conservative therapy, which included local treatment without surgery.
   Results: The weightbearing function of the foot at discharge from the hospital was preserved in 94.2% (48 patients) of the study group and in 73.4% (22 patients) of the control group. During the next 6 months, repeated small foot surgeries were required in 7.3% (3 patients) of patients from the study group and in 20% (4 patients) of patients from the control group. Six months after discharge, the weightbearing function of the foot was preserved in all the patients from the study group available for follow-up and in 85% of the patients from the control group.
   Conclusion: The results of the study demonstrate the positive corrective effects of endovascular interventions, stenting, and balloon angioplasty on the clinical course of ischemic and neuroischemic forms of DFS.

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    Background: The burn wound is one of the health problems in the world that affects physical and mental health. Today, adipose-derived mesenchymal stem cells (ADSCs) have received medical attention for their accessibility and the ability to reproduce and repair. The present study was designed to investigate the effect of ADSCs on burn wound healing.
   Methods: The present experimental study was performed on 36 male Wistar rats divided into 1 control group and 3 experimental groups. The second-degree burns with a radius of 10 mm were induced after anesthesia. ADSCs and Dulbecco's Modified Eagle Medium (DMEM) were injected into the dermis around the burn area in the ADSCs and DMEM groups, respectively. Silver sulfadiazine (SSD) ointment was applied topically once daily as the SSD group. The control group did not receive any treatment. The rats were evaluated for 21 days. Wound healing rate, histopathological parameters, and the number of fibroblasts were evaluated by the immunofluorescence technique and vascular endothelial growth factor and transforming growth factor β (TGF-β) gene expression by reverse transcription-polymerase chain reaction. The results were entered into SPSS software (SPSS Inc) and analyzed with 1-way analysis of variance and repeated measures analysis.
   Results: The number of fibroblasts, the number of vessels, TGF-β, and VEGF gene expression in the burn area were significantly higher in the ADSCs group than in the SSD, DMEM, and control groups. The results also showed that the amount of inflammation was significantly lower in the ADSCs group compared with the control group (p<0.001). Moreover, the percentage of wound recovery was significantly higher in the ADSCs group compared with other groups (p<0.001).
   Conclusion: ADSCs accelerate and improve burn wound healing by affecting fibroblasts, keratinocytes, and inflammatory cells as well as increasing the expression of the TGF-β and VEGF genes, and thus increase in angiogenesis.

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Background: The quality of the wound healing at the donor site significantly determines the overall condition of the burn patient, the extent of wound fluid and protein losses, the severity of any systemic in-flammatory reaction, and the intensity of the pain syndrome. It is known that the stromal vas-cular fraction (SVF)  has a beneficial effect on the healing of wound defects. This study is aimed at assessing the safety and effectiveness of the application of the SVF of autologous adipose tis-sue to stimulate wound healing of the donor site in patients with burns.
   Methods: This placebo-controlled clinical study included 38 patients with third-degree thermal skin burns. The patients underwent liposuction, enzymatic isolation of the SVF, and intradermal injection of the preparation into the wounds in the donor site, followed by tewametry, cutome-try, thermography and biopsy after 12 days. Quantitative indicators were compared using the Mann-Whitney test for unrelated groups and the Wilcoxon test for related groups. Spearman's rank correlation coefficient (RS) was used to assess the correlation
   Results: Epithelization of the wounds in all patients was seen over an average area of 88 (84;92) %, there being no significant differences between the actual and the control wound sites for this parameter. Transdermal water loss in the test wound sites was 2 times lower than in the control sites (P = 0.001). The wound donor sites regained their temperature distribution faster than the control sites (P = 0.042). Histological preparations of the skin of the wound sites revealed that their epidermal layer was 19% thicker compared to the controls (P = 0.043). It should be noted that five adverse events related to manipulations in the postoperative period were registered.
   Conclusions: Transplantation of SVF autologous adipose tissue into the wound area in most clinical cases proceeded without complications. The area of epithelialization of wound areas af-ter the introduction of SVF did not change, although a significant decrease in transdermal water loss was observed in the wound areas with an improvement in their thermoregulation and an increase in the thickness of the epidermis.
 

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Background: Gene therapy holds immense potential in the field of wound healing. However, we still do not recognize this procedure well enough to give oversight effectively to improve healing processes. A wide range of information has been achieved from the database for gene expression profiling by clinical trials, So we performed this study to gain a better understanding of the mechanisms behind wound healing and how it could be utilized to develop new therapies and treatments.
   Methods: In this study, we have been focusing on wound-healing genes, conducting a thorough review to explore the various genes and pathways involved in this process. For this purpose, a total of 320 articles were collected. All experimental studies, systematic or narrative reviews, studies and clinical trials included in this paper were searched on PubMed, Medline, Embase, Science Direct, and Scopus databases in English using the following terms: Wound Healing, wound regeneration, Gene Transfer, and Gene Therapy were used to search the mentioned databases. Unfortunately, we didn’t find a large sample cohort study on this topic. A total amount of 330 articles were collected based on the guidelines of the PRISMA method. Both inclusion and exclusion criteria were settled.
   Results: During the last decade, different models of gene delivery have been introduced, which include viral transfection and Non-viral techniques. In this regard, TIMP-2 protein and VEGF mutants such as VEGF165, CARP, and HIF-1 are the genes that accelerate the rate of tissue repair.
   Conclusion: The process of wound healing is mainly related to the change of expression of genes that have a role in the parts of inflammation and repair. In our study, some of the most suitable genes involved in the wound-healing process are mentioned.
 

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Background: The skin is the biggest organ in the body and has several important functions in protection and regulation. However, wound development can disrupt the natural healing process, leading to challenges such as chronic wounds, persistent infections, and impaired angiogenesis. These issues not only affect individuals' well-being but also pose significant economic burdens on healthcare systems. Despite advancements in wound care research, managing chronic wounds remains a pressing concern, with obstacles such as persistent infection and impaired angiogenesis hindering the healing process. Understanding the complex genetic pathways involved in wound healing is crucial for developing effective therapeutic strategies and reducing the socio-economic impact of chronic wounds. Weighted Gene Co-Expression Network Analysis (WGCNA) offers a promising approach to uncovering key genes and modules associated with different stages of wound healing, providing valuable insights for targeted interventions to enhance tissue repair and promote efficient wound healing.
   Methods: Data collection involved retrieving microarray gene expression datasets from the Gene Expression Omnibus website, with 65 series selected according to inclusion and exclusion criteria. Preprocessing of raw data was performed using the Robust MultiArray Averaging approach for background correction, normalization, and gene expression calculation. Weighted Gene Co-Expression Network Analysis was employed to identify co-expression patterns among genes associated with wound healing processes. This involved steps such as network construction, topological analysis, module identification, and association with clinical traits. Functional analysis included enrichment analysis and identification of hub genes through gene-gene functional interaction network analysis using the GeneMANIA database.
   Results: The analysis using WGCNA indicated significant correlations between wound healing and the black, brown, and light green modules. These modules were further examined for their relevance to wound healing traits and subjected to functional enrichment analysis. A total of 16 genes were singled out as potential hub genes critical for wound healing. These hub genes were then scrutinized, revealing a gene-gene functional interaction network within the module network based on the KEGG enrichment database. Noteworthy pathways such as MAPK, EGFR, and ErbB signaling pathways, as well as essential cellular processes including autophagy and mitophagy, emerged as the most notable significant pathways.
   Conclusion: We identified consensus modules relating to wound healing across nine microarray datasets. Among these, 16 hub genes were uncovered within the brown and black modules. KEGG enrichment analysis identified co-expression genes within these modules and highlighted pathways most closely associated with the development of wound healing traits, including autophagy and mitophagy. The hub genes identified in this study represent potential candidates for future research endeavors. These findings serve as a stepping stone toward further exploration of the implications of these co-expressed modules on wound healing traits.