The Effect of Polydeoxyribonucleotide on Ischemic Rat Skin Flap Survival

Lee, Jun Young; Hong, Hyun Joon; Roh, Huyn; Lee, Won Jai

doi:10.1097/sap.0000000000000053

Cited by 19 publications

(14 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Finally, PDRN has been proven effective in the treatment (intradermal administration) of chronic plantar fasciitis (Kim and Chung, 2015) and in the therapeutic management (topical application) of female pattern hair loss (Lee et al, 2015). …”

Section: Introductionmentioning

confidence: 99%

Pharmacological Activity and Clinical Use of PDRN

et al. 2017

View full text Add to dashboard Cite

PDRN is a proprietary and registered drug that possesses several activities: tissue repairing, anti-ischemic, and anti-inflammatory. These therapeutic properties suggest its use in regenerative medicine and in diabetic foot ulcers. PDRN holds a mixture of deoxyribonucleotides with molecular weights ranging between 50 and 1,500 KDa, it is derived from a controlled purification and sterilization process of Oncorhynchus mykiss (Salmon Trout) or Oncorhynchus keta (Chum Salmon) sperm DNA. The procedure guarantees the absence of active protein and peptides that may cause immune reactions. In vitro and in vivo experiments have suggested that PDRN most relevant mechanism of action is the engagement of adenosine A2A receptors. Besides engaging the A2A receptor, PDRN offers nucleosides and nucleotides for the so called “salvage pathway.” The binding to adenosine A2A receptors is a unique property of PDRN and seems to be linked to DNA origin, molecular weight and manufacturing process. In this context, PDRN represents a new advancement in the pharmacotherapy. In fact adenosine and dipyridamole are non-selective activators of adenosine receptors and they may cause unwanted side effects; while regadenoson, the only other A2A receptor agonist available, has been approved by the FDA as a pharmacological stress agent in myocardial perfusion imaging. Finally, defibrotide, another drug composed by a mixture of oligonucleotides, has different molecular weight, a DNA of different origin and does not share the same wound healing stimulating effects of PDRN. The present review analyses the more relevant experimental and clinical evidences carried out to characterize PDRN therapeutic effects.

show abstract

Section: Introductionmentioning

confidence: 99%

Pharmacological Activity and Clinical Use of PDRN

et al. 2017

View full text Add to dashboard Cite

show abstract

“…As observed in Figures and , the 20 skin regeneration studies were: (1) six in vitro studies on skin fibroblasts (FBs) or biopsies (Muratore et al, ; Sini et al, ; Thellung et al, ; Belletti et al, ; Pleshkanyova et al, ; Avantaggiato et al, ); (2) six in vivo studies in animal models of thermal injuries (Bitto et al, ), back skin or ischemic flap (Polito et al, ; Chung et al, ; Lee et al, ), and back full‐thickness incisions (Galeano et al, ; Altavilla et al, ) in diabetic or healthy animals; (3) in healthy or diabetic patients affected by ulcers (Kim et al, ; Squadrito et al, ; De Caridi et al, ), benign cervical lesions (Perino et al, ) or subjected to autologous skin grafts (Rubegni et al, ; De Aloe et al, ; Valdatta et al, ) (seven clinical studies). In addition, one study included in vitro and an in vivo parts regarding the effects of PDRNs in biopsies from foot ulcers of diabetic patients and back full‐thickness wounds of diabetic mice (Gennero et al, ).…”

Section: Resultsmentioning

confidence: 99%

“…In four animal models of thermal injury (Bitto et al, ), dorsal skin flap (Chung et al, ), and ischemic flap (Polito et al, ; Lee et al, ), an intraperitoneal injection of 8 mg/kg of PDRNs increased VEGF, nitric oxide (NO) production, microvessel density and blood flow, promoting re‐epithelialization, and reducing hypoxia‐inducible factor 1‐alpha (HIF‐1α). The same conclusions were also reached in two other in vivo studies, conducted in genetically diabetic mice with incisions of the dorsum, where PDRN amount and way of administration were the same as the four previous ones (Galeano et al, ; Altavilla et al, ).…”

Section: Resultsmentioning

confidence: 99%

“…Even if different PDRN dosages were evaluated, the authors agreed a dose‐response effect of PDRNs up to 100 μg/ml (Muratore et al, ; Sini et al, ; Thellung et al, ; Belletti et al, ; Pleshkanyova et al, ; Gennero et al, ; Avantaggiato et al, ). In all in vivo studies, the amount and the way of administration were the same, 8 mg/kg in 100 μl of vehicle solution by intraperitoneal injection (Bitto et al, ; Galeano et al, ; Altavilla et al, ; Polito et al, ; Chung et al, ; Lee et al, ) and only one study employed PDRNs in the form of cream (Gennero et al, ). Through the examination of these in vivo studies, PDRNs showed their ability in inducing tissue regeneration by the increase of VEGF, NO, ECM protein, blood flow, epidermal regeneration, wound closure, and cell cycle in mice and rat models.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Polydeoxyribonucleotides (PDRNs) From Skin to Musculoskeletal Tissue Regeneration via Adenosine A_2A Receptor Involvement

Veronesi

Carubbi

Martini

et al. 2017

Journal Cellular Physiology

View full text Add to dashboard Cite

Polydeoxyribonucleotides (PDRNs) are low molecular weight DNA molecules of natural origin that stimulate cell migration and growth, extracellular matrix (ECM) protein production, and reduce inflammation. Most preclinical and clinical studies on tissue regeneration with PDRNs focused on skin, and only few are about musculoskeletal tissues. Starting from an overview on skin regeneration studies, through the analysis of in vitro, in vivo, and clinical studies (1990-2016), the present review aimed at defining the effects of PDRN and their mechanisms of action in the regeneration of musculoskeletal tissues. This would also help future researches in this area. A total of 29 studies were found by PubMed and www.webofknowledge.com searches: 20 were on skin (six in vitro, six in vivo, one vitro/vivo, seven clinical studies), while the other nine regarded bone (one in vitro, two in vivo, one clinical studies), cartilage (one in vitro, one vitro/vivo, two clinical studies), or tendon (one clinical study) tissues regeneration. PDRNs improved cell growth, tissue repair, ECM proteins, physical activity, and reduced pain and inflammation, through the activation of adenosine A receptor. PDRNs are currently used for bone, cartilage, and tendon diseases, with a great variability regarding the PDRN dosage to be used in clinical practice, while the dosage for skin regeneration is well established. PDRNs are usually administered from a minimum of three to a maximum of five times and they act trough the activation of A receptor. Further studies are advisable to confirm the effectiveness of PDRNs and to standardize the PDRN dose. J. Cell. Physiol. 232: 2299-2307, 2017. © 2016 Wiley Periodicals, Inc.

show abstract

“…The technique is easy to use, standardized and enables to model a wound identical to human pathology. Therefore, the aim of the present study was to develop an ischemic animal skin flap able to adequately demonstrate ischemic evidence, however, necrosis development will not be rampant, and will result in no total flap loss within several days [6]. The model enables to study various pathological processes occurring in skin under ischemia, particularly, cell death, as well as Figure 1.…”

Section: Introductionmentioning

confidence: 99%

Ischemic Non-Healing Skin Wound Model: Cell Death and Wound Healing Mechanisms

Morgun¹,

Rogovaya²,

Vorotelyak³

2018

Sovrem Tehnol Med

View full text Add to dashboard Cite

The aim of the study was to develop an ischemic skin flap model in laboratory mice with the description of necrotic and apoptotic processes in time course, and demonstrate the regenerative characteristics of non-healing skin wound under the conditions of a formed flap. Materials and Methods. The study involved 20 BALB/c mice. The first experimental stage describes an ischemic flap on day 1, 2, 3, and 5 after flap formation using histology, immunofluorescence, morphometry, and TUNEL. At the second stage a non-healing wound was modeled on the flap, and its pathogenesis was histologically compared with an acute wound. Results. A formed flap showed such histological ischemic features as blood-filled vessels, micro blood clots in blood vessels, coagulation necrosis, migration of inflammatory cells, as well as extravasation, true skin edema and hyperproliferation of epithelial cells. Maximum pathological changes were found on the third postoperative day, and by day 5 the wound partially healed. Morphometry demonstrated a significant increase in blood-filled vessels and the tendency for epithelial layer reduction in a skin flap of experimental animals compared to the control ones. Apoptotic cells were observed on days 1, 2, 3, and 5 of a formed flap. Some areas showed cell clusters around hair follicles. No apoptotic cells were revealed in control animals. By the moment of complete regeneration of acute wounds, non-healing wounds exhibited no epithelialization and a formed mature cicatrix that enables to interpret the difference in wound healing as significant. Conclusion. Ischemia causes major pathological skin changes, as well as results in delayed wound healing. A developed non-healing wound model can be used to study wound healing mechanisms and the ways to influence them.

show abstract

The Effect of Polydeoxyribonucleotide on Ischemic Rat Skin Flap Survival

Cited by 19 publications

References 34 publications

Pharmacological Activity and Clinical Use of PDRN

Pharmacological Activity and Clinical Use of PDRN

Polydeoxyribonucleotides (PDRNs) From Skin to Musculoskeletal Tissue Regeneration via Adenosine A_2A Receptor Involvement

Ischemic Non-Healing Skin Wound Model: Cell Death and Wound Healing Mechanisms

Contact Info

Product

Resources

About

The Effect of Polydeoxyribonucleotide on Ischemic Rat Skin Flap Survival

Cited by 19 publications

References 34 publications

Pharmacological Activity and Clinical Use of PDRN

Pharmacological Activity and Clinical Use of PDRN

Polydeoxyribonucleotides (PDRNs) From Skin to Musculoskeletal Tissue Regeneration via Adenosine A2A Receptor Involvement

Ischemic Non-Healing Skin Wound Model: Cell Death and Wound Healing Mechanisms

Contact Info

Product

Resources

About

Polydeoxyribonucleotides (PDRNs) From Skin to Musculoskeletal Tissue Regeneration via Adenosine A_2A Receptor Involvement