Application of Electrospun Nanofiber Membrane in the Treatment of Diabetic Wounds

Diabetic wounds are complications of diabetes which are caused by skin dystrophy because of local ischemia and hypoxia. Diabetes causes wounds in a pathological state of inflammation, resulting in delayed wound healing. The structure of electrospun nanofibers is similar to that of the extracellular matrix (ECM), which is conducive to the attachment, growth, and migration of fibroblasts, thus favoring the formation of new skin tissue at the wound. The composition and size of electrospun nanofiber membranes can be easily adjusted, and the controlled release of loaded drugs can be realized by regulating the fiber structure. The porous structure of the fiber membrane is beneficial to gas exchange and exudate absorption at the wound, and the fiber surface can be easily modified to give it function. Electrospun fibers can be used as wound dressing and have great application potential in the treatment of diabetic wounds. In this study, the applications of polymer electrospun fibers, nanoparticle-loaded electrospun fibers, drug-loaded electrospun fibers, and cell-loaded electrospun fibers, in the treatment of diabetic wounds were reviewed, and provide new ideas for the effective treatment of diabetic wounds.

Dissatisfaction Risk Factors of Patients after Laminectomy for Thoracic Ossification of Ligamentum Flavum: A Retrospective Cohort Study of Different Follow-Up Periods

Objectives. To explore the influencing factors of satisfaction with postoperative treatment in patients diagnosed with thoracic ossification of the ligamentum flavum during different follow-up periods. Methods. This was a retrospective study of 57 patients who were diagnosed with thoracic ossification of ligamentum flavum (TOLF) and treated with laminectomy in the Spine Surgery Department of the Third Hospital of Hebei Medical University from January 2010 to January 2017. The Patient Satisfaction Index (PSI) was collected at discharge and at 6-month, 1-year, and the last follow-up. According to the evaluation results, the patients could be divided into a satisfied group and a dissatisfied group. The patient’s Japanese Orthopaedic Association (JOA) score improvement rate was evaluated at the last follow-up. Possible influencing factors of the two groups of patients were compared and the related influencing factors of satisfaction with postoperative treatment in patients during different follow-up periods were summarized. Results. At the time of discharge, the dissatisfied and satisfied groups had significant differences in variables of diabetes mellitus, duration of preoperative symptoms, urination disorder, intramedullary signal change on MRI, dural ossification, residual rate of cross-sectional spinal canal area on CT, shape on the sagittal MRI, hospital stay, hospitalization expenses, postoperative pain in LE VAS, delayed wound healing, postoperative depression, and intercostal pain ( P < 0.05 ). There were also significant differences in urination disorder, postoperative pain according to the LE VAS, JOA score, and postoperative depression during the 6-month follow-up ( P < 0.05 ). There were no significant differences in other variables between the two groups ( P > 0.05 ). One year after the operation, there were significant differences between the dissatisfied group and the satisfied group in urination disorder, JOA score, and symptom recurrence ( P < 0.05 ). There were also significant differences in the JOA score and symptom recurrence at the final follow-up ( P < 0.05 ). For further analysis, the duration of preoperative symptoms in the satisfied group was less than 24 months and the duration of preoperative symptoms in the dissatisfied group was more than 24 months. The JOA scores of patients in the satisfied group and the dissatisfied group increased gradually with the improvement of neurological function in different follow-up periods, but, at the last follow-up, the JOA scores of patients in the satisfied group were significantly higher than those in the dissatisfied group. Conclusions. In conclusion, for thoracic ossification of ligamentum flavum patients who received laminectomy, dissatisfaction with the early and medium-term postoperative results may be related to diabetes, the duration of preoperative symptoms, hospitalization expenses, delayed wound healing, intercostal pain, and urination disorder, and dissatisfaction with the long-term postoperative results might be related to the low JOA score improvement rate and symptom recurrence.

Free Functional Latissimus Dorsi Reconstruction of the Quadriceps and Hamstrings following Oncologic Resection of Soft Tissue Sarcomas of the Thigh

Background. Limb-salvage surgery combined with radiotherapy has become the primary treatment for soft tissue sarcomas of the extremity. Free functional latissimus flaps (FFLF) are an option to restore function in the setting of volumetric muscle loss. The purpose of the current study was to examine the use of FFLF in patients undergoing resection of thigh sarcoma. Methods. Twelve patients with a sarcoma involving the hamstring (n = 6), quadriceps (n = 5), or combined (n = 1) defects which included multiple muscle groups were reviewed. This included 9 males and 3 females with a mean age and body mass index of 56 ± 12 years and 31.3 ± 5.7 kg/m2. Results. The mean defect volume and operative time was 3,689 ± 2,314 cm3 and 587 ± 73 minutes. Following reconstruction, the mean knee range of motion (ROM), MSTS93 score, and muscle strength was 89 ± 24°, 90 ± 15%, and 4 ± 1; with 75% of patients ambulating without gait aids. Seven (58%) patients sustained a complication, namely, delayed wound healing (n = 2). Conclusion. Although there was a high incidence of complications, FFLF can restore active knee ROM and function, with most patients ambulating without gait aids following reconstruction of large oncologic defects in the thigh.

MicroRNA-133b Inhibition Restores EGFR Expression and Accelerates Diabetes-Impaired Wound Healing

Diabetic foot ulcers (DFUs) are caused by impairments in peripheral blood vessel angiogenesis and represent a great clinical challenge. Although various innovative techniques and drugs have been developed for treating DFUs, therapeutic outcomes remain unsatisfactory. Using the GEO database, we obtained transcriptomic microarray data for DFUs and control wounds and detected a significant downregulation of epidermal growth factor receptor (EGFR) in DFUs. We cultured human umbilical vein endothelial cells (HUVECs) and noted downregulated EGFR expression following high-glucose exposure in vitro. Further, we observed decreased HUVEC proliferation and migration and increased apoptosis after shRNA-mediated EGFR silencing in these cells. In mice, EGFR inhibition via focal EGFR-shRNA injection delayed wound healing. Target prediction analysis followed by dual-luciferase reporter assays indicated that microRNA-133b (miR-133b) is a putative upstream regulator of EGFR expression. Increased miR-133b expression was observed in both glucose-treated HUVECs and wounds from diabetes patients, but no such change was observed in controls. miR-133b suppression enhanced the proliferation and angiogenic potential of cultured HUVECs and also accelerated wound healing. Although angiogenesis is not the sole mechanism affected in DFU, these findings suggest that the miR-133b-induced downregulation of EGFR may contribute to delayed wound healing in diabetes. Hence, miR-133b inhibition may be a useful strategy for treating diabetic wounds.

Porphyromonas gingivalis Gingipains-Mediated Degradation of Plasminogen Activator Inhibitor-1 Leads to Delayed Wound Healing Responses in Human Endothelial Cells

Plasminogen activator inhibitor-1 (PAI-1), a serine protease inhibitor, is constitutively produced by endothelial cells and plays a vital role in maintaining vascular homeostasis. Chronic periodontitis is an inflammatory disease characterized by bleeding of periodontal tissues that support the tooth. In this study, we aimed to determine the role of PAI-1 produced by endothelial cells in response to infections caused by the primary periodontal pathogen Porphyromonas gingivalis. We demonstrated that P. gingivalis infection resulted in significantly reduced PAI-1 levels in human endothelial cells. This reduction in PAI-1 levels could be attributed to the proteolysis of PAI-1 by P. gingivalis proteinases, especially lysine-specific gingipain-K (Kgp). We demonstrated the roles of these degradative enzymes in the endothelial cells using a Kgp-specific inhibitor and P. gingivalis gingipain-null mutants, in which the lack of the proteinases resulted in the absence of PAI-1 degradation. The degradation of PAI-1 by P. gingivalis induced a delayed wound healing response in endothelial cell layers via the low-density lipoprotein receptor-related protein. Our results collectively suggested that the proteolysis of PAI-1 in endothelial cells by gingipains of P. gingivalis might lead to the deregulation of endothelial homeostasis, thereby contributing to the permeabilization and dysfunction of the vascular endothelial barrier.

EFFECT OF CHANNA MICROPELTES IN THE GRANULATION, FIBROSIS AND NECROSIS OF DIABETIC WOUND HEALING

Background: Diabetes mellitus (DM) is characterized by persistent hyperglycemia. The symptoms of DM is delayed wound healing. Delayed wound healing in diabetes will increase the risk of wound complications that will hinder the healing process, and lead to complications such as fibrosis and necrosis. The use of Channa Micropeltes (CM) extract at a dose of 16 mL/kg BW orally is proven to general optimal wound closure and wound contraction clinically in Wistar rats as diabetic model on day 14.However, the histopathological description of wound healing is yet to be known. Objective: To analyze the effect of 16 mL/kg BW dose of CM extract on histopathological changes of wound healing granulation tissue, fibrosis and necrosis in diabetic Wistar rats on day 14. Materials and Methods: This study was a true experimental design with a post-test only control group design. The samples were divided into two groups, namely the diabetic model group given CM extract at 16 mL/kg BW dose for 14 days, and the diabetic model group given BR2 feed only for 14 days. Results: The results of Mann-Whitney U test showed p = 0.003 for granulation tissue, p = 0.411 for fibrosis and p = 1 for necrosis, with the level of significance was p<0.05. Conclusion: The CM extract at 16 mL/kg BW dose affects the histopathological description of granulation tissue which presents a better result than those in the control group but did not affect the features of fibrosis and necrosis in diabetic Wistar rats on day 14. Keywords: Channa Micropeltes, Diabetic wound, Fibrosis, Granulation tissue, Necrosis.

The emerging roles of neutrophil extracellular traps in wound healing

Delayed wound healing causes problems for many patients both physically and psychologically, contributing to pain, economic burden, loss of function, and even amputation. Although many factors affect the wound healing process, abnormally prolonged or augmented inflammation in the wound site is a common cause of poor wound healing. Excessive neutrophil extracellular trap (NET) formation during this phase may amplify inflammation and hinder wound healing. However, the roles of NETs in wound healing are still unclear. Herein, we briefly introduce NET formation and discuss the possible NET-related mechanisms in wound healing. We conclude with a discussion of current studies, focusing on the roles of NETs in diabetic and normoglycemic wounds and the effectiveness of NET-targeting treatments in wound healing.

Use of a Negative-Pressure Wound Dressing to Prevent Surgical Site Complications after Revision Knee Arthroplasty—A Randomized Controlled Trial

The aim of this study was to determine if a negative pressure wound therapy (NPWT) system can facilitate wound healing and withstand mechanical stress owing to the high range of motion of the knee joint in total knee arthroplasty. The benefits of NPWT include aiding wound granulation and a reduction in wound edema and secretion; our goal is to investigate its benefits in primary wound closure. Within an eight-day duration of treatment, we compared standard wound dressing (gauze and compression) with the disposable NPWT system (PICO)TM. A total of 79 patients were recruited in a controlled, randomized, prospective, single-institution clinical trial. A total of 40 patients were allocated to the study group and 39 to the control group. In terms of blood loss and infection parameters, there was no significant difference between both groups. In the NPWT group, we determined a significant reduction in wound edema but none in wound secretion. While the NPWT dressings survived the mechanical effects of movement during postoperative physiotherapy, conventional compressive dressings were often renewed. Even though the risk factors that could lead to delayed wound healing were reduced in the test group, we could not identify any significant difference pertaining to delayed wound healing that required surgical treatment.

Biofilm and Equine Limb Wounds

In chronic wounds in humans, biofilm formation and wound chronicity are linked, as biofilms contribute to chronic inflammation and delayed healing. Biofilms are aggregates of bacteria, and living as biofilms is the default mode of bacterial life; within these aggregates, the bacteria are protected from both antimicrobial substances and the immune response of the host. In horses, delayed healing is more commonly seen in limb wounds than body wounds. Chronic inflammation and hypoxia are the main characteristics of delayed wound healing in equine limbs, and biofilms might also contribute to this healing pattern in horses. However, biofilm formation in equine wounds has been studied to a very limited degree. Biofilms have been detected in equine traumatic wounds, and recent experimental models have shown that biofilms protract the healing of equine limb wounds. Detection of biofilms within wounds necessitates advanced techniques that are not available in routine diagnostic yet. However, infections with biofilm should be suspected in equine limb wounds not healing as expected, as they are in human wounds. Treatment should be based on repeated debridement and application of topical antimicrobial therapy.