Epidermal Vascular Endothelial Growth Factor Improved Wound Healing of Patients with Diabetic Foot Ulcer

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.

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 ◽  
Vol 13 (3) ◽  
pp. 332-6
Author(s):  
Ronald Winardi Kartika ◽  
Idrus Alwi ◽  
Franciscus Dhyanagiri Suyatna ◽  
Ferry Sandra ◽  
Em Yunir ◽  
...  

BACKGROUND: Hyaluronic acid (HA) is an essential component of extracellular matrix and mediates signaling in wound healing. HA could induce growth factor release from Advanced Platelet Rich Fibrin (A-PRF), including Vascular Endothelial Growth Factor (VEGF) and Platelet-derived Growth Factor (PDGF). However, concentrations of the released-VEGF and PDGF have not been clearly disclosed. Therefore, current study was conducted to measure the release of these growth factors in HA + A-PRF gel of diabetic foot ulcer (DFU) subjects.METHODS: Twenty DFU subjects were included in the study and treated with A-PRF or HA+A-PRF. A-PRF was derived from autologous peripheral blood and processed with low-speed centrifugation. HA was added with a ratio of 1:0.6. A-PRF or HA + A-PRF was applied topically on DFU. Upper tips of A-PRF or HA + A-PRF gels were collected on day 0, 3 and 7 for measurements of VEGF and PDGF concentrations with Enzyme-linked Immune-sorbent Assay (ELISA) methods.RESULTS: On day-3, both VEGF and PDGF concentrations of HA + A-PRF group were significantly higher than the VEGF (p=0.000) and PDGF (p=0.019) concentrations of A-PRF group. The VEGF and PDGF concentrations were continuously and significantly increased on day-7 of HA + A-PRF group, compared to the VEGF (p=0.000) and PDGF (p=0.004) concentrations of A-PRF group.CONCLUSION: Combination HA+A-PRF induces VEGF and PDGF release from A-PRF. A mixture of A-PRF and HA could be more effective than A-PRF alone for treatment of DFU.KEYWORDS: hyaluronic acid, advanced platelet rich fibrin, PRF, growth factor, VEGF, PDGF, diabetic foot ulcer


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.


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.


2019 ◽  
Vol 11 (2) ◽  
pp. 110
Author(s):  
Ekanova R. N. Sumarauw ◽  
Mendy J. Hatibie ◽  
Djony E. Tjandra ◽  
Fredrik G. Langi

Abstract: Diabetic foot ulcer (DFU) is still a health problem related to the extent amount of time in wound healing process hence increasing the treatment cost. Given any methods that are not sat-isfying, encourage the search of other methods that would increase the wound healing rate, in which hyperbaric oxygen therapy (HBOT) is amongst them. The DFU patient that receives HBOT shows a significant increase in angiogenesis process markedly by faster epithelialization and granulation process. This study was aimed to prove that HBOT could accelerate the wound healing process among DFU patients measured by wound size and depth of PEDIS score. This was a ran-domized controlled trial study, conducted at Surgery Department of Prof. Dr. R. D. Kandou Gen-eral Hospital from September 2018 to March 2019. There were 20 DFU patients divided into two groups, each of 10 patients. The control group received a holistic treatment, meanwhile the HBOT group received a holistic treatment added with the inclusion of HBOT. PEDIS score assessment of DFU in HBOT group was measured before and after the third HBOT session, meanwhile the con-trol group was measured on the first and the third day. The results showed that the difference in PEDIS score value was markedly found in HBOT group compared to the control group (2 vs. 0, P=0.001). Conclusion: HBOT could enhance the wound healing process in DFU patients based on the declined PEDIS score.Keywords: HBOT, PEDIS score, diabetic foot ulcerAbstrak: Ulkus kaki diabetik (UKD) masih merupakan masalah kesehatan terkait proses penyembuhan lama sehingga biaya pengobatan meningkat. Belum adanya metode penanganan yang memuaskan, mendorong pencarian metode percepatan penyembuhan luka, salah satunya ialah terapi oksigen hiperbarik (TOHB). Penderita UKD yang menjalani tambahan TOHB diketahui mengalami peningkatan proses angiogenesis yang menghasilkan proses epitelialisasi dan granulasi yang lebih cepat. Tujuan penelitian ialah untuk membuktikan bahwa TOHB dapat mempercepat proses penyembuhan UKD, dinilai berdasarkan ukuran dan kedalaman luka melalui skor PEDIS. Penelitian ini menggunakan randomized controlled trial dan dilaksanakan di Bagian Bedah RSUP Prof. Dr. R.D. Kandou Manado sejak September 2018 sampai dengan Maret 2019. Subyek penelitian sebanyak 20 penderita UKD, dibagi dalam dua kelompok, masing-masing 10 penderita. Kelompok kontrol menjalani penanganan holistik UKD, sedangkan kelompok TOHB menjalani penanganan holistik UKD dengan TOHB. Penilaian skor PEDIS terhadap UKD pada kelompok TOHB dilakukan sebelum dan sesudah TOHB sesi ke-3, sedangkan pada kelompok kontrol dilakukan penilaian pada hari ke-1 dan hari ke-3 sesudahnya. Hasil penelitian mendapatkan bahwa perubahan skor PEDIS yang terjadi antara kedua pengukuran terlihat lebih besar pada kelompok TOHB dibandingkan kelompok kontrol (2 vs 0, P=0,001). Simpulan. TOHB mempercepat proses penyembuhan UKD dinilai dari penurunan skor PEDIS.Kata kunci: TOHB, skor PEDIS, ulkus kaki diabetik


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