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      Polydeoxyribonucleotides Improve Diabetic Wound Healing in Mouse Animal Model for Experimental Validation

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      https://www.riss.kr/link?id=A106302719

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      다국어 초록 (Multilingual Abstract)

      Background: Wound healing mechanisms is believed to have effects similar to wound healing disorders in diabetic patients, including abnormal inflammatory cells, angiogenesis disorders, and reduced collagen synthesis. Therefore, reestablishment of structural and promoted angiogenesis could be beneficial to promote wound healing process. Objective: Therefore, we investigated whether the polydeoxyribonucleotide (PDRN) that was self-production in Korea, could be useful as an intradermal injection for promoting wound healing. Also, we validate for wound healing effect of PDRN using healing-impaired (db/db) mice.
      Methods: In this study, we confirmed the effects of PDRN by creating wound models in in vitro and in vivo model. Using an in vitro wound healing assay, we observed that PDRN stimulated closure of wounded monolayers of human fibroblast cells. PDRN (8.25 mg/ml) or phosphate-buffered saline (0.9% NaCl) was injected once daily into the dermis adjacent to the wound for 12 days after skin injury. Results: Time course observations revealed that mice treated with PDRN showed accelerated wound closure and epidermal and dermal regeneration, enhanced angiogenesis. The wound area and depth decreased at 3, 6, 9, and 12 days after skin injury.
      Histological evaluation showed an increase of vascular endothelial growth factor, CD31, and collagen fibers in the PDRN group compared with the control group, indicating that PDRN was effective in the treatment of delayed wound healing caused by diabetes. Conclusion: This study suggests that our PDRN has a wound healing effect in transgenic animal models with cells and diabetes through angiogenesis.
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      Background: Wound healing mechanisms is believed to have effects similar to wound healing disorders in diabetic patients, including abnormal inflammatory cells, angiogenesis disorders, and reduced collagen synthesis. Therefore, reestablishment of stru...

      Background: Wound healing mechanisms is believed to have effects similar to wound healing disorders in diabetic patients, including abnormal inflammatory cells, angiogenesis disorders, and reduced collagen synthesis. Therefore, reestablishment of structural and promoted angiogenesis could be beneficial to promote wound healing process. Objective: Therefore, we investigated whether the polydeoxyribonucleotide (PDRN) that was self-production in Korea, could be useful as an intradermal injection for promoting wound healing. Also, we validate for wound healing effect of PDRN using healing-impaired (db/db) mice.
      Methods: In this study, we confirmed the effects of PDRN by creating wound models in in vitro and in vivo model. Using an in vitro wound healing assay, we observed that PDRN stimulated closure of wounded monolayers of human fibroblast cells. PDRN (8.25 mg/ml) or phosphate-buffered saline (0.9% NaCl) was injected once daily into the dermis adjacent to the wound for 12 days after skin injury. Results: Time course observations revealed that mice treated with PDRN showed accelerated wound closure and epidermal and dermal regeneration, enhanced angiogenesis. The wound area and depth decreased at 3, 6, 9, and 12 days after skin injury.
      Histological evaluation showed an increase of vascular endothelial growth factor, CD31, and collagen fibers in the PDRN group compared with the control group, indicating that PDRN was effective in the treatment of delayed wound healing caused by diabetes. Conclusion: This study suggests that our PDRN has a wound healing effect in transgenic animal models with cells and diabetes through angiogenesis.

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      참고문헌 (Reference)

      1 Wu CH, "Wound healing effects of porcine placental extracts on rats with thermal injury" 148 : 236-245, 2003

      2 Lima MH, "Topical insulin accelerates wound healing in diabetes by enhancing the AKT and ERK pathways : a double-blind placebo-controlled clinical trial" 7 : e36974-, 2012

      3 Yan Y, "The impact of ranibizumab on the level of intercellular adhesion molecule type 1 in the vitreous of eyes with proliferative diabetic retinopathy" 94 : 358-364, 2016

      4 Jeong W, "Scar prevention and enhanced wound healing induced by polydeoxyribonucleotide in a rat incisional wound-healing model" 18 : E1698-, 2017

      5 Powell RJ, "Safety and efficacy of patient specific intramuscular injection of HGF plasmid gene therapy on limb perfusion and wound healing in patients with ischemic lower extremity ulceration : results of the HGF-0205 trial" 52 : 1525-1530, 2010

      6 Veronesi F, "Polydeoxyribonucleotides(PDRNs)from skin to musculoskeletal tissue regeneration via adenosine A2A receptor involvement" 232 : 2299-2307, 2017

      7 Altavilla D, "Polydeoxyribonucleotide(PDRN) : a safe approach to induce therapeutic angiogenesis in peripheral artery occlusive disease and in diabetic foot ulcers" 7 : 313-321, 2009

      8 Galeano M, "Polydeoxyribonucleotide stimulates angiogenesis and wound healing in the genetically diabetic mouse" 16 : 208-217, 2008

      9 Polito F, "Polydeoxyribonucleotide restores blood flow in an experimental model of ischemic skin flaps" 55 : 479-488, 2012

      10 Bitto A, "Polydeoxyribonucleotide improves angiogenesis and wound healing in experimental thermal injury" 36 : 1594-1602, 2008

      1 Wu CH, "Wound healing effects of porcine placental extracts on rats with thermal injury" 148 : 236-245, 2003

      2 Lima MH, "Topical insulin accelerates wound healing in diabetes by enhancing the AKT and ERK pathways : a double-blind placebo-controlled clinical trial" 7 : e36974-, 2012

      3 Yan Y, "The impact of ranibizumab on the level of intercellular adhesion molecule type 1 in the vitreous of eyes with proliferative diabetic retinopathy" 94 : 358-364, 2016

      4 Jeong W, "Scar prevention and enhanced wound healing induced by polydeoxyribonucleotide in a rat incisional wound-healing model" 18 : E1698-, 2017

      5 Powell RJ, "Safety and efficacy of patient specific intramuscular injection of HGF plasmid gene therapy on limb perfusion and wound healing in patients with ischemic lower extremity ulceration : results of the HGF-0205 trial" 52 : 1525-1530, 2010

      6 Veronesi F, "Polydeoxyribonucleotides(PDRNs)from skin to musculoskeletal tissue regeneration via adenosine A2A receptor involvement" 232 : 2299-2307, 2017

      7 Altavilla D, "Polydeoxyribonucleotide(PDRN) : a safe approach to induce therapeutic angiogenesis in peripheral artery occlusive disease and in diabetic foot ulcers" 7 : 313-321, 2009

      8 Galeano M, "Polydeoxyribonucleotide stimulates angiogenesis and wound healing in the genetically diabetic mouse" 16 : 208-217, 2008

      9 Polito F, "Polydeoxyribonucleotide restores blood flow in an experimental model of ischemic skin flaps" 55 : 479-488, 2012

      10 Bitto A, "Polydeoxyribonucleotide improves angiogenesis and wound healing in experimental thermal injury" 36 : 1594-1602, 2008

      11 Cianfarani F, "Placenta growth factor in diabetic wound healing : altered expression and therapeutic potential" 169 : 1167-1182, 2006

      12 Squadrito F, "Pharmacological activity and clinical use of PDRN" 8 : 224-, 2017

      13 Brem H, "Molecular markers in patients with chronic wounds to guide surgical debridement" 13 : 30-39, 2007

      14 Emmerson E, "Insulin-like growth factor-1 promotes wound healing in estrogen-deprived mice : new insights into cutaneous IGF-1R/ERα cross talk" 132 : 2838-2848, 2012

      15 김석곤, "Histologic study of bone-forming capacity on polydeoxyribonucleotide combined with demineralized dentin matrix" 대한악안면성형재건외과학회 38 (38): 1-5, 2016

      16 Christman AL, "Hemoglobin A1c predicts healing rate in diabetic wounds" 131 : 2121-2127, 2011

      17 Barrientos S, "Growth factors and cytokines in wound healing" 16 : 585-601, 2008

      18 Smiell JM, "Efficacy and safety of becaplermin(recombinant human platelet-derived growth factor-BB)in patients with nonhealing, lower extremity diabetic ulcers : a combined analysis of four randomized studies" 7 : 335-346, 1999

      19 Oryan A, "Effects of insulin on wound healing : a review of animal and human evidences" 174 : 59-67, 2017

      20 Han G, "Chronic wound healing : a review of current management and treatments" 34 : 599-610, 2017

      21 Brem H, "Cellular and molecular basis of wound healing in diabetes" 117 : 1219-1222, 2007

      22 Ebrahimian TG, "Cell therapy based on adipose tissue-derived stromal cells promotes physiological and pathological wound healing" 29 : 503-510, 2009

      23 Reiber GE, "Causal pathways for incident lower-extremity ulcers in patients with diabetes from two settings" 22 : 157-162, 1999

      24 Montesinos MC, "Adenosine promotes wound healing and mediates angiogenesis in response to tissue injury via occupancy of A(2A)receptors" 160 : 2009-2018, 2002

      25 Altavilla D, "Activation of adenosine A2A receptors restores the altered cell-cycle machinery during impaired wound healing in genetically diabetic mice" 149 : 253-261, 2011

      26 Lee SJ, "1, 2, 3, 4, 6-Penta-O-galloyl-beta-D-glucose blocks endothelial cell growth and tube formation through inhibition of VEGF binding to VEGF receptor" 208 : 89-94, 2004

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