Polydeoxyribonucleotide restores blood flow in an experimental model of ischemic skin flaps.

Department of Biochemical, Physiological and Nutritional Sciences, Section of Physiology and Human Nutrition, University of Messina, Messina, Italy.
Journal of vascular surgery: official publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter (Impact Factor: 3.52). 11/2011; 55(2):479-88. DOI: 10.1016/j.jvs.2011.07.083
Source: PubMed

ABSTRACT Ischemia is a major factor contributing to failure of skin flap surgery, which is routinely used for coverage of wounds to prevent infection and to restore form and function. An emerging concept is that adenosine A(2A) receptors can improve tissue oxygenation by stimulating angiogenesis, likely through vascular endothelial growth factor (VEGF). This study assessed the ability of polydeoxyribonucleotide (PDRN) to restore blood flow and improve wound healing, acting through the A(2A) receptor, in a rat model of ischemic skin flaps.
The H-shaped double-flap model was used in male Sprague-Dawley rats. After surgical procedures, the animals were randomized to receive intraperitoneal PDRN (8 mg/kg) or vehicle (NaCl 0.9%). Rats were euthanized 3, 5, and 10 days after skin injury, after the evaluation of skin perfusion by laser Doppler. The wounds underwent histologic analysis and were measured for VEGF messenger RNA and protein expression, hypoxia inducible factor-1-α (HIF-1α), and inducible nitric oxide synthase (iNOS) protein expression, and nitrite content.
Blood flow markedly increased in blood flow in ischemic flaps treated with PDRN, with a complete recovery starting from day 5 (ischemic flap + vehicle, 1.80 ± 0.25; ischemic flap + PDRN, 2.46 ± 0.25; P < .001). Administration of PDRN enhanced the expression of VEGF (ischemic flap + vehicle, 5.3 ± 0.6; ischemic flap + PDRN, 6.2 ± 0.5; P < .01) at day 5, and iNOS (ischemic flap + vehicle, 3.9 ± 0.6; ischemic flap + PDRN, 5.3 ± 1; P < .01), but reduced HIF-1α expression (ischemic flap + vehicle, 7 ± 1.1; ischemic flap + PDRN, 4.8 ± 0.5; P < .05) at day 3. Histologically, the PDRN-treated group showed complete re-epithelialization and well-formed granulation tissue rich in fibroblasts.
These results suggest that PDRN restores blood flow and tissue architecture, probably by modulating HIF-1α and VEGF expression, and may be an effective therapeutic approach in improving healing of ischemic skin flaps.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Chronic radiation cystitis (CRC) is a serious complication that can arise in patients with pelvic malignancies treated with radiotherapy. Polydeoxyribonucleotides (PDRNs) are known to reduce inflammation and improve tissue perfusion and angiogenesis. In this manuscript, we describe our observational experience regarding intravesical instillation of PDRNs in improving symptoms of CRC in subjects unresponsiveness to conventional medical therapy. Eight patients with persistent and/or worsening CRC symptoms, despite conventional therapy, received biweekly intravesical instillation of PDRNs for two consecutive months. Symptoms were scored according to the Late Effects of Normal Tissues-Subjective, Objective, Management, Analytic (LENT-SOMA) scale, before, at the end, and after 4 months following the PDRNs treatment. Four months after instillations, a significant improvement in the subjective perception of CRC symptoms was experienced by participants. The mean LENT-SOMA score was reduced from 1.16 + 0.26 before to 0.34 + 0.035 after 4 months from instillations (p < 0.001). No adverse effect related to instillations was reported. Subjective perception of persistent and/or worsening CRC symptoms, despite conventional therapy, is improved after intravesical instillation with PDRNs without adverse events. Even though we deduced suggestive insights, the results need to be collected and verified from a large-scale study.
    Supportive Care in Cancer 12/2013; · 2.09 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Partial or complete necrosis of a skin flap is a common problem. Polydeoxyribonucleotide (PDRN) can be extracted from trout sperm and used as a tissue repair agent. The aim of this study was to investigate whether PDRN could improve the survival of random pattern skin flaps in rats. Twenty-two male Sprague-Dawley rats were randomly divided into two groups: the PDRN treatment group (n=11) and the control group (n=11). Caudally pedicled random pattern skin flaps were elevated on their dorsal skin and resutured. The treatment group received daily intraperitoneal administration of PDRN (8 mg/kg/day), and the control group received fluid vehicle (NaCl 0.9%, 8 mg/kg/day) from day 0 to day 6. On day 7, the flap survival was evaluated and the harvested tissue surrounding the demarcation line of the necrotic area was stained with H&E, anti-rat vascular endothelial cell growth factor (VEGF) antibody, and PECAM-1/CD31 antibody. The average necrotic area of the flap in the PDRN group was significantly smaller when compared with that of the control group. Histologic and immunohistochemical evaluation showed that granulation thickness score and VEGF-positive staining cells were marked higher in the PDRN group than in the control group. PECAM-1/CD31-positive microvascular densities were significantly higher in the PDRN group when compared with the control group. This study confirms that PDRN improves the survival of random pattern skin flaps in rats. These results may represent a new therapeutic approach to enhancing flap viability and achieving faster wound repair.
    Archives of plastic surgery. 05/2013; 40(3):181-6.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background. Lichen sclerosus (LS) is an autoimmune inflammatory skin disease that leads to tissue sclerosis. Actually, the first-line treatment consists of local steroid as clobetasol propionate (CP). Polydeoxyribonucleotide (PDRN) has demonstrated anti-inflammatory effects through the reduction of cytokine production and growth stimulation of fibroblast. Objective. To evaluate the efficacy of intradermal administration of PDRN in male patients suffering from genital lichen sclerosus in addition to topical 0.05% CP, as compared to administering 0.05% CP without PDRN injection. Patients/Methods. A group of male patients (n = 28; aged 25 to 65) suffering from LS were observed during topical therapy or subdermal in addition to topical therapy. Disease activity at baseline was evaluated on Investigator's Global Assessment (IGA) and the Dermatology Life Quality Index (DLQI). We used polydeoxyribonucleotide in a commercial preparation for human use and a topical CP emulsion. Results. After therapy, in all group A patients there has been a regression of most of clinical pathological signs, while there has been a moderate improvement in all group B patients. Conclusions. On site intradermal administration of PDRN, associated with CP 0.05% cream, seemed to be associated with a clinical improvement of lichen sclerosus better than CP used in single therapy.
    Dermatology Research and Practice 01/2013; 2013:654079.