scholarly journals Fibroblast Growth Factor in Diabetic Foot Ulcer: Progress and Therapeutic Prospects

2021 ◽  
Vol 12 ◽  
Author(s):  
Ye Liu ◽  
Yiqiu Liu ◽  
Junyu Deng ◽  
Wei Li ◽  
Xuqiang Nie

Diabetic foot ulcer (DFU) is a combination of neuropathy and various degrees of peripheral vasculopathy in diabetic patients resulting in lower extremity infection, ulcer formation, and deep-tissue necrosis. The difficulty of wound healing in diabetic patients is caused by a high glucose environment and various biological factors in the patient. The patients’ skin local microenvironment changes and immune chemotactic response dysfunction. Wounds are easy to be damaged and ulcerated repeatedly, but difficult to heal, and eventually develop into chronic ulcers. DFU is a complex biological process in which many cells interact with each other. A variety of growth factors released from wounds are necessary for coordination and promotion of healing. Fibroblast growth factor (FGF) is a family of cell signaling proteins, which can mediate various processes such as angiogenesis, wound healing, metabolic regulation and embryonic development through its specific receptors. FGF can stimulate angiogenesis and proliferation of fibroblasts, and it is a powerful angiogenesis factor. Twenty-three subtypes have been identified and divided into seven subfamilies. Traditional treatments for DFU can only remove necrotic tissue, delay disease progression, and have a limited ability to repair wounds. In recent years, with the increasing understanding of the function of FGF, more and more researchers have been applying FGF-1, FGF-2, FGF-4, FGF-7, FGF-21 and FGF-23 topically to DFU with good therapeutic effects. This review elaborates on the recently developed FGF family members, outlining their mechanisms of action, and describing their potential therapeutics in DFU.

2021 ◽  
Vol 10 (7) ◽  
pp. 1495
Author(s):  
Yu-Chi Wang ◽  
Hsiao-Chen Lee ◽  
Chien-Lin Chen ◽  
Ming-Chun Kuo ◽  
Savitha Ramachandran ◽  
...  

Diabetic foot ulcers (DFUs) are a serious complication in diabetic patients and lead to high morbidity and mortality. Numerous dressings have been developed to facilitate wound healing of DFUs. This study investigated the wound healing efficacy of silver-releasing foam dressings versus silver-containing cream in managing outpatients with DFUs. Sixty patients with Wagner Grade 1 to 2 DFUs were recruited. The treatment group received silver-releasing foam dressing (Biatain® Ag Non-Adhesive Foam dressing; Coloplast, Humlebaek, Denmark). The control group received 1% silver sulfadiazine (SSD) cream. The ulcer area in the silver foam group was significantly reduced compared with that in the SSD group after four weeks of treatment (silver foam group: 76.43 ± 7.41%, SSD group: 27.00 ± 4.95%, p < 0.001). The weekly wound healing rate in the silver foam group was superior to the SSD group during the first three weeks of treatment (p < 0.05). The silver-releasing foam dressing is more effective than SSD in promoting wound healing of DFUs. The effect is more pronounced in the initial three weeks of the treatment. Thus, silver-releasing foam could be an effective wound dressing for DFUs, mainly in the early period of wound management.


2018 ◽  
Vol 24 (8) ◽  
pp. 6136-6139
Author(s):  
Maria Francisca Ham ◽  
Pradana Soewondo ◽  
Saphora Dien ◽  
Kusmardi Kusmardi ◽  
Mpu Kanoko

Diabetic foot ulcer (DFU) is a kind of chronic vascular complications in diabetes. Wound healing in DFU is a complex process where reduced proangiogenic growth factor is an important factor. We studied angiogenesis factors which may contribute to the healing of DFU. Twenty five type 2 diabetes patients with acute DFU were treated with hospital standard procedure and closely observed for 1 month. Biopsies from wound edges were subjected to histopathology assessment and immunohistochemical staining of CD34, bFGF and VEGF. All examination was performed two times consecutively. We observed that granulation tissues developed faster at proximal site of the foot. Weak tissue VEGF was expressed before treatment. Interestingly, VEGF expression in epidermis increased significantly after patients received treatment. Increased VEGF is consistent with increased number of CD34 positive endothelial cells. These data suggest that epidermal VEGF is an important angiogenesis factor and may improve healing in acute DFU receiving standard treatment.


2020 ◽  
Vol 11 (SPL4) ◽  
pp. 158-161
Author(s):  
Meena P ◽  
Monisha V

Diabetes is previously known as the disease of the rich people, but now there is  no partiality between the rich and poor and it has become the third leading cause of  death. Diabetic Mellitus (DM) is a metabolic issue that is characteristics by  chronic hyperglycemia; it is a typical and conceivably persistent disease. The  aims of the present study to assess the effectiveness of insulin dressing of the diabetic foot ulcer among diabetic patients. A quasi-experimental research design with  purposive sampling technique was adopted to conduct a study among 30 diabetic foot ulcer patients. Demography data was collected and wound was measured and insulin dressing was done. After one week the wound was measured. Confidentiality was maintained throughout the procedure. The collected data were analyzed by using descriptive and inferential statistics. Among 30 samples pretest mean score of wound healing among patients with diabetic foot ulcer in the topical insulin dressing was 2.67±0.66 and the post test mean score was 1.43±0.57. The calculated paired ‘t’ test  value of t = 15.703 was found to be statistically highly significant at p<0.001 level.  The above finding clearly infers that topical insulin dressing to patients with diabetic foot ulcer had significant effect which resulted in the improvement in the level of  wound healing among patients with diabetic foot ulcer.


2014 ◽  
Vol 63 (10) ◽  
pp. 1377-1385 ◽  
Author(s):  
Thokur S. Murali ◽  
Shettigar Kavitha ◽  
Jain Spoorthi ◽  
Deepika V. Bhat ◽  
Alevoor S. Bharath Prasad ◽  
...  

While virulence factors and the biofilm-forming capabilities of microbes are the key regulators of the wound healing process, the host immune response may also contribute in the events following wound closure or exacerbation of non-closure. We examined samples from diabetic and non-diabetic foot ulcers/wounds for microbial association and tested the microbes for their antibiotic susceptibility and ability to produce biofilms. A total of 1074 bacterial strains were obtained with staphylococci, Pseudomonas, Citrobacter and enterococci as major colonizers in diabetic samples. Though non-diabetic samples had a similar assemblage, the frequency of occurrence of different groups of bacteria was different. Gram-negative bacteria were found to be more prevalent in the diabetic wound environment while Gram-positive bacteria were predominant in non-diabetic ulcers. A higher frequency of monomicrobial infection was observed in samples from non-diabetic individuals when compared to samples from diabetic patients. The prevalence of different groups of bacteria varied when the samples were stratified according to age and sex of the individuals. Several multidrug-resistant strains were observed among the samples tested and most of these strains produced moderate to high levels of biofilms. The weakened immune response in diabetic individuals and synergism among pathogenic micro-organisms may be the critical factors that determine the delicate balance of the wound healing process.


2020 ◽  
Vol 54 (3) ◽  
pp. 207-216
Author(s):  
Ignatius U. Ezeani ◽  
Ejiofor T. Ugwu ◽  
Funmi O. Adeleye ◽  
Ibrahim D. Gezawa ◽  
Innocent O. Okpe ◽  
...  

AbstractObjective. The high amputation rates from diabetic foot ulcer (DFU) in Nigeria and prolonged hospitalization due to poor wound healing is a source of concern. Furthermore, factors that affect wound healing of DFUs have not yet been well studied in Nigeria, whereas knowing these factors could improve DFU outcomes. Therefore, the objective of this study was to determine the factors that are associated with the wound healing in patients hospitalized for DFU.Methods. The Multi-Center Evaluation of Diabetic Foot Ulcer in Nigeria (MEDFUN) was an observational study involving 336 diabetic patients hospitalized for DFU and managed by a multi-disciplinary team until discharge or death. Demographic, clinical, and biochemical characteristics were documented. Test statistics used were chi square, t-test, univariate, and multivariate logistic regression. The study endpoints were ulcer healing, LEA, duration of hospitalization, and mortality. Here we present data on wound healing.Results. The mean ± SD age was 55.9±12.5 years. Univariate predictors of wound healing were ulcer duration more than 1 month prior to hospitalization (p<0.001), peripheral arterial disease (PAD) (p<0.001), foot gangrene (p<0.001), Ulcer grade ≥3 (p=0.002), proteinuria (p=0.005), anemia (p=0.009), renal impairment (p=0.021), glycated hemoglobin ≥7% (0.012), and osteomyelitis (p<0.001). On multivariate regression, osteomyelitis was the strongest independent predictor of wound healing after adjusting for all other variables (OR 0.035; 95% CI 0.004–0.332). This was followed by PAD (OR 0.093; 95% CI 0.028–0.311), ulcer duration >1 month (OR 0.109; 95% CI 0.030–0.395), anemia (OR 0.179; 95% CI 0.056–0.571).Conclusion. Presence of osteomyelitis, duration of ulcer greater than 1 month, PAD, Wagner grade 3 or higher, proteinuria, presence of gangrene, anemia, renal impairment, and HbA1c ≥7% were the significant predictors of wound healing in patients hospitalized for DFU. Early identification and prompt attention to these factors in a diabetic foot wound might significantly improve healing and reduce adverse outcomes such as amputation and death.


Planta Medica ◽  
2019 ◽  
Vol 85 (08) ◽  
pp. 657-669 ◽  
Author(s):  
Zhang Pengzong ◽  
Li Yuanmin ◽  
Xiong Xiaoming ◽  
Deng Shang ◽  
Xiong Wei ◽  
...  

AbstractThe aim of the present study was to evaluate the wound healing potential and possible mechanism of action of the standardized extract of Boswellia serrata against the experimental model of diabetic foot ulcer. α-Boswellic acid was isolated from the standardized extract of B. serrata and characterized (HPLC, 1H-NMR, 13C-NMR, ESI-MS). Diabetes was induced in Sprague-Dawley rats by streptozotocin (55 mg/kg, i. p.), and wounds were created on the dorsal surface of the hind paw. B. serrata (100, 200, and 400 mg/kg, p. o.) was administered to the rats for 16 days. The HPLC analysis showed a single peak with a retention time of 12.51 min. The compound was identified with ESI-MS [M + Na]+ = 455.37 as α-boswellic acid. Treatment with B. serrata (200 and 400 mg/kg) significantly increased the rate of wound contraction via modulation of oxido-nitrosative stress and elevated the hydroxyproline level at the wound area. reverse transcription-PCR analysis revealed that streptozotocin-induced increases in TNF-α, interleukin-1β, interleukin-6, nuclear factor-kappa-light-chain-enhancer of activated B cells, and Bcl-2-associated X protein, and decreases in angiopoietin-1, Tie2, transforming growth factor beta 1, vascular endothelial growth factor, and collagen-1 mRNA expression were significantly inhibited by B. serrata. It also significantly reduced wound cellular necrosis as evaluated by flow cytometry using propidium iodide fluorescence intensity. Streptozotocin-induced histopathological alterations were also significantly ameliorated by B. serrata. In conclusion, standardized extracts of B. serrata exert its wound healing potential via orchestrating mechanisms, which include the inhibition of oxido-inflammatory markers (oxido-nitrosative stress, TNF-α, interleukins, and nuclear factor-kappa-light-chain-enhancer of activated B cells), increased collagen synthesis (hydroxyproline and collagen-1) and angiogenesis (Ang-1/Tie2), promoting growth factors (transforming growth factor beta 1 and vascular endothelial growth factor), and inhibition of apoptosis (Bcl-2-associated X protein) to accelerate wound healing in experimental delayed diabetic foot ulcer.


2021 ◽  
Author(s):  
Mariarosa Ruffo ◽  
Ortensia Ilaria Parisi ◽  
Marco Dattilo ◽  
Francesco Patitucci ◽  
Rocco Malivindi ◽  
...  

Abstract In diabetic patients, the presence of neuropathy, peripheral vascular diseases and ischemia, leads to the formation of foot ulcerations with a higher risk of infection because the normal response to bacterial infection is missing. In the aim to control and treat Diabetic Foot Ulcerations (DFUs), wound dressings able to absorb exudate, to prevent infections and to promote wound healing, are needed. For this reason, the aim of the present research was to synthetize a biocompatible hydrogel composed by Carboxymethylcellulose (HyDrO-DiAb) loaded with Silver nanoparticles (AgNPs) for the treatment of diabetic foot ulcer. In this study, AgNPs were obtained by a green synthesis and, then, were dissolved in CMC hydrogel that, after freeze drying process become a flexible and porous structure. The in vitro and in ex-vivo wound healing activity of the obtained HyDrO-DiAb hydrogel was evaluated.


2018 ◽  
Vol 108 (5) ◽  
pp. 419-429
Author(s):  
Isabelle J. Dumont ◽  
Marc Lepeut ◽  
Coralie Segalen ◽  
Yannis Guillemin ◽  
Jean Noel Gouze

The number of people with diabetes is expected to reach 592 million in the year 2035. Diabetic foot lesions are responsible for more hospitalizations than any other complication of diabetes. The aims of this study were to examine for the first time a new biocompatible and biodegradable tridimensional collagen-based matrix, GBT013, in humans for diabetic foot ulcer wound healing and to evaluate its ease of use to better define a protocol for a future clinical trial. Seven adult patients with a diabetic foot ulcer of grade 1A to 3D (University of Texas Diabetic Wound Classification) were treated using GBT013, a new collagen-based advance dressing and were monitored in two specialized foot care units for a maximum of 9 weeks. Five of seven wounds achieved complete healing in 4 to 7 weeks. Nonhealed ulcers showed a significant reduction of the wound surface (&gt;44%). GBT013 was well tolerated and displayed positive wound healing outcomes as a new treatment strategy of chronic foot ulcers in diabetic patients.


2018 ◽  
Vol 16 ◽  
pp. 205873921877525 ◽  
Author(s):  
Li Wang ◽  
Ting He ◽  
Adan Fu ◽  
Zhijin Mao ◽  
Lan Yi ◽  
...  

One of the most devastating consequences of diabetes mellitus is a chronic condition, diabetic foot ulcer. Numerous investigations are being targeted to explore newer compounds for treatment of diabetic foot ulcer wounds in diabetic patients. Hesperidin (HSP), an isoflavone glycoside has been established to exhibit antidiabetic and antioxidant potential. In the current investigation, diabetes was induced in rats by administration by streptozotocin (STZ) intraperitoneally (50 mg/kg). Wound-healing capacity was estimated in hind paw of rats by artificially initiating wound injury on the paw dorsal surface. The injured animals were administered with incremental doses of HSP suspension orally (10, 20, 40, 60, and 80 mg/kg) and insulin subcutaneously (10 IU/kg). Parameters such as wound area were estimated every 2 days, and at the end of 20 days of study, biochemical estimations in serum and histopathological observations of the wound were made. HSP (60 and 80 mg/kg) revealed statistically significant ( P < 0.05) improvement in wound dimension, glucose and insulin concentration, and glycated hemoglobin (HbA1C). Administration of HSP indicated significant ( P < 0.05) modulation of mRNA associated with expression of vascular endothelial growth factor (VEGF), whereas the levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6 levels were lowered compared to the control group of animals. Real-time quantitative polymerase chain reaction (RT-qPCR) indicated expression of vascular endothelial growth factor receptors 1 and 2 (VEGFR1 and VEGFR2) compared to glyceraldehyde 3-phosphate dehydrogenase (GAPDH). Histological observations indicated higher expression of VEGF in the groups receiving HSP, indicative of angiogenesis stimulation in the diabetic wound. The results advocate angiogenesis activity of HSP was enhanced owing to reduction in hyperglycemia and oxidative stress–induced damage, reduced expression of inflammatory mediators, and enhanced expression of growth-related factors, thereby promoting healing of diabetic foot ulcer.


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