CoChat
Sign Up
Cited by 215Adenosine and Purinergic SignalingWound Healing and TreatmentsBiochemical and Molecular Research

Pharmacological Activity and Clinical Use of PDRN

Open access
Squadrito, Francesco, Bitto, Alessandra, Irrera, Natasha, Pizzino, Gabriele, Pallio, Giovanni, Minutoli, Letteria, Altavilla, Domenica·2017·Frontiers in Pharmacology
DOI 10.3389/fphar.2017.00224PMC PMC5405115
Open this paper in CoChat — free accountOpen PDF

Abstract

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 A 2A receptors. Besides engaging the A 2A receptor, PDRN offers nucleosides and nucleotides for the so called “salvage pathway.” The binding to adenosine A 2A 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 A 2A 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.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.3389/fphar.2017.00224

Cites

1 of 1 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • PDRN has demonstrated a strong safety profile in both acute and chronic toxicity studies, with no significant immunogenic responses.

    “PDRN has demonstrated a strong safety profile in both acute and chronic toxicity studies, where no significant immunogenic responses were observed [11,17,19].”

    From Comparison of Polynucleotide and Polydeoxyribonucleotide in Dermatology: Molecular Mechanisms and Clinical Perspectives (2025) · cites this paper as [19]

    The Safety section reports no organ toxicity or mortality in acute and chronic studies in mice and rats, and describes PDRN’s overall safety profile as excellent. The Discussion says a lack of effects on the immune system contributes to that profile, but the paper does not report that the toxicity studies measured immunogenic responses or observed none. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • PDRNs are classified as prescription medications approved for injectable use for wound healing/tissue repair and knee osteoarthritis.

    “PDRNs are classified as prescription medications approved for injectable use for wound healing/tissue repair and knee osteoarthritis [19,173,174].”

    From Comparison of Polynucleotide and Polydeoxyribonucleotide in Dermatology: Molecular Mechanisms and Clinical Perspectives (2025) · cites this paper as [19]

    The Abstract calls PDRN a registered drug, and the Safety section reports dispensed prescriptions. The clinical-studies section describes injectable PDRN improving healing of diabetic foot ulcers. It does not establish approval for injectable treatment of wound healing or tissue repair, and its osteoarthritis example concerns a topical gel, not an approved knee injection (page numbers unavailable). (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • PDRNs have been approved by the Ministry of Food and Drug Safety in South Korea for use as pharmaceutical agents for tissue regeneration and wound healing, particularly for skin graft-associated injuries.

    “PDRNs have been approved by the Ministry of Food and Drug Safety in South Korea for use as pharmaceutical agents for tissue regeneration and wound healing, particularly for skin graft-associated injuries [19,152,153].”

    From Comparison of Polynucleotide and Polydeoxyribonucleotide in Dermatology: Molecular Mechanisms and Clinical Perspectives (2025) · cites this paper as [19]

    The clinical-studies section (page unavailable) reports improved healing at autologous skin-graft donor sites, and the pharmacological-properties section calls PDRN a registered, approved drug. Neither passage identifies South Korea’s Ministry of Food and Drug Safety or says it approved PDRN for the stated uses; searches for the regulator and Korean approval found no such passage. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Clinical dosing regimens for PDRN vary depending on indication, with low-dose/low-level protocols often used for cosmetic and esthetic purposes and high-dose/high-level protocols reserved for regenerative therapies and wound repair.

    “Clinical dosing regimens vary depending on the indication, and low-dose/low-level protocols are often used for cosmetic and esthetic purposes, where high-dose/high-level protocols are reserved for regenerative therapies and wound repair [19,144,176,177].”

    From Comparison of Polynucleotide and Polydeoxyribonucleotide in Dermatology: Molecular Mechanisms and Clinical Perspectives (2025) · cites this paper as [19]

    The clinical-studies section (page unavailable) reports different PDRN administration routes and schedules for different indications, including skin-graft donor sites and diabetic foot ulcers. It does not describe low-dose protocols as common for cosmetic use or high-dose protocols as reserved for regeneration and wound repair; both cited wound-healing treatments use 5.625 mg per administration. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • PDRN sources mainly include the sperm of Oncorhynchus mykiss and Oncorhynchus keta.

    “Furthermore, its sources mainly include the sperm of species such as Oncorhynchus mykiss (salmon trout) and Oncorhynchus keta (chum salmon) [11,19].”

    From Comparison of Polynucleotide and Polydeoxyribonucleotide in Dermatology: Molecular Mechanisms and Clinical Perspectives (2025) · cites this paper as [19]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 42

  1. Al Jaroudi W. Iskandrian A. E. (2009). Regadenoson: a new myocardial stress agent. J. Am. Coll. Cardiol. 54, 1123– 1130. 10.1016/j.jacc.2009.04.089 19761931 · DOI
  2. Altavilla D. Bitto A. Polito F. Marini H. Minutoli L. Di Stefano V.. (2009). Polydeoxyribonucleotide (PDRN): a safe approach to induce therapeutic angiogenesis in peripheral artery occlusive disease and in diabetic foot ulcers. Cardiovasc. Hematol. Agents Med. Chem. 7, 313– 321. 10.2174/187152509789541909 19860658 · DOI · Paper page
  3. Altavilla D. Squadrito F. Polito F. Irrera N. Calò M. Lo Cascio P.. (2011). Activation of adenosine A2A receptors restores the altered cell-cycle machinery during impaired wound healing in genetically diabetic mice. Surgery 149, 253– 261. 10.1016/j.surg.2010.04.024 20570301 · DOI
  4. Arena S. Minutoli L. Arena F. Nicotina P. A. Romeo C. Squadrito F.. (2012). Polydeoxyribonucleotide administration improves the intra-testicular vascularization in rat experimental varicocele. Fertil. Steril. 97, 165– 168. 10.1016/j.fertnstert.2011.10.007 22100172 · DOI
  5. Avantaggiato A. Palmieri A. Carinci F. Trapella G. Sollazzo V. Lauritano D. (2014). Effects of glucosamine and nucleotide association on fibroblast: extracellular matrix gene expression. Int. J. Immunopathol. Pharmacol. 27, 689– 693. 10.1177/039463201402700428 25572752 · DOI
  6. Belletti S. Uggeri J. Gatti R. Govoni P. Guizzardi S. (2007). Polydeoxyribonucleotide promotes cyclobutane pyrimidine dimer repair in UVB-exposed dermal fibroblasts. Photodermatol. Photoimmunol. Photomed. 23, 242– 249. 10.1111/j.1600-0781.2007.00320.x 17986061 · DOI · Paper page
  7. Bengalorkar G. M. Bhuvana K. Sarala N. Kumar T. N. (2012). Regadenoson. J. Postgrad. Med. 58, 140– 146. 10.4103/0022-3859.97177 22718059 · DOI
  8. Bitto A. Galeano M. Squadrito F. Minutoli L. Polito F. Dye J. F.. (2008a). Polydeoxyribonucleotide improves angiogenesis and wound healing in experimental thermal injury. Crit. Care Med. 36, 1594– 1602. 10.1097/CCM.0b013e318170ab5c 18434887 · DOI · Paper page
  9. Bitto A. Oteri G. Pisano M. Polito F. Irrera N. Minutoli L.. (2013). Adenosine receptor stimulation by polynucleotides (PDRN) reduces inflammation in experimental periodontitis. J. Clin. Periodontol. 40, 26– 32. 10.1111/jcpe.12010 23033941 · DOI
  10. Bitto A. Polito F. Altavilla D. Minutoli L. Migliorato A. Squadrito F. (2008b). Polydeoxyribonucleotide (PDRN) restores blood flow in an experimental model of peripheral artery occlusive disease. J. Vasc. Surg. 48, 1292– 1300. 10.1016/j.jvs.2008.06.041 18971038 · DOI
  11. Bitto A. Polito F. Irrera N. D'Ascola A. Avenoso A. Nastasi G. (2011). Polydeoxyribonucleotide reduces cytokine production and the severity of collagen-induced arthritis by stimulation of adenosine A(2A) receptor. Arthritis Rheum. 63, 3364– 3371. 10.1002/art.30538 21769841 · DOI · Paper page
  12. Chung K. I. Kim H. K. Kim W. S. Bae T. H. (2013). The effects of polydeoxyribonucleotide on the survival of random pattern skin flaps in rats. Arch. Plast. Surg. 40, 181– 186. 10.5999/aps.2013.40.3.181 23730590 PMC3665858 · DOI
  13. De Caridi G. Massara M. Acri I. Zavettieri S. Grande R. Butrico L.. (2016). Trophic effects of polynucleotides and hyaluronic acid in the healing of venous ulcers of the lower limbs: a clinical study. Int. Wound J. 13, 754– 758. 10.1111/iwj.12368 25224018 PMC7949893 · DOI
  14. Di Nicola V. Pierpaoli W. (2013). Biological baseline of joint self-repair procedures. Curr. Aging Sci. 6, 206– 214. 10.2174/18746098112059990029 23746041 · DOI
  15. Falanga V. (2005). Wound healing and its impairment in the diabetic foot. Lancet 366, 1736– 1743. 10.1016/S0140-6736(05)67700-8 16291068 · DOI
  16. Galeano M. Bitto A. Altavilla D. Minutoli L. Polito F. Calò M.. (2008). Polydeoxyribonucleotide stimulates angiogenesis and wound healing in the genetically diabetic mouse. Wound Repair Regen. 16, 208– 217. 10.1111/j.1524-475X.2008.00361.x 18318806 · DOI
  17. Gennero L. Denysenko T. Calisti G. F. Vercelli A. Vercelli C. M. Amedeo S.. (2013). Protective effects of polydeoxyribonucleotides on cartilage degradation in experimental cultures. Cell Biochem. Funct. 31, 214– 227. 10.1002/cbf.2875 23001693 · DOI
  18. Guglielmelli T. Bringhen S. Palumbo A. (2012). Update on the use of defibrotide. Expert Opin. Biol. Ther. 12, 353– 361. 10.1517/14712598.2012.657623 22283742 · DOI
  19. Guizzardi S. Galli C. Govoni P. Boratto R. Cattarini G. Martini D.. (2003). Polydeoxyribonucleotide (PDRN) promotes human osteoblast proliferation: a new proposal for bone tissue repair. Life Sci. 73, 1973– 1983. 10.1016/S0024-3205(03)00547-2 12899922 · DOI · Paper page
  20. Guizzardi S. Martini D. Bacchelli B. Valdatta L. Thione A. Scamoni S.. (2007). Effects of heat deproteinate bone and polynucleotides on bone regeneration: an experimental study on rat. Micron 38, 722– 728. 10.1016/j.micron.2007.05.003 17587587 · DOI
  21. Jeong E. K. Jang H. J. Kim S. S. Lee S. Y. Oh M. Y. Kim H. J.. (2016). Protective effect of polydeoxyribonucleotide against renal ischemia-reperfusion injury in mice. Transplant. Proc. 48, 1251– 1257. 10.1016/j.transproceed.2016.01.028 27320598 · DOI
  22. Keating G. M. (2014). Defibrotide: a review of its use in severe hepatic veno-occlusive disease following haematopoietic stem cell transplantation. Clin. Drug Investig. 34, 895– 904. 10.1007/s40261-014-0242-x 25351934 · DOI
  23. Kim I. Kim H. Park K. Karki S. Khadka P. Jo K.. (2016a). Viscoelastic interactions between polydeoxyribonucleotide and ophthalmic excipients. Drug Dev. Ind. Pharm. 42, 231– 237. 10.3109/03639045.2015.1040417 26023993 · DOI
  24. Kim J. K. Chung J. Y. (2015). Effectiveness of polydeoxyribonucleotide injection versus normal saline injection for treatment of chronic plantar fasciitis: a prospective randomised clinical trial. Int. Orthop. 39, 1329– 1334. 10.1007/s00264-015-2772-0 25920599 · DOI · Paper page
  25. Kim S. K. Huh C. K. Lee J. H. Kim K. W. Kim M. Y. (2016b). Histologic study of bone-forming capacity on polydeoxyribonucleotide combined with demineralized dentin matrix. Maxillofac. Plast. Reconstr. Surg. 38: 7. 10.1186/s40902-016-0053-5 26913276 PMC4752573 · DOI
  26. Laino L. Suetti S. Sperduti I. (2013). Polydeoxyribonucleotide dermal infiltration in male genital lichen sclerosus: adjuvant effects during topical therapy. Dermatol. Res. Pract. 2013: 654079. 10.1155/2013/654079 24489537 PMC3893745 · DOI
  27. Lazzarotto M. Tomasello E. M. Caporossi A. (2004). Clinical evaluation of corneal epithelialization after photorefractive keratectomy in a patients treated with polydeoxyribonucleotide (PDRN) eye drops: a randomized, double-blind, placebo-controlled trial. Eur. J. Ophthalmol. 14, 284– 289. 10.5301/EJO.2008.2105 15309972 · DOI
  28. Lee D. W. Hong H. J. Roh H. Lee W. J. (2015). The effect of polydeoxyribonucleotide on ischemic rat skin flap survival. Ann. Plast. Surg. 75, 84– 90. 10.1097/SAP.0000000000000053 25954843 · DOI
  29. Minutoli L. Antonuccio P. Squadrito F. Bitto A. Nicotina P. A. Fazzari C.. (2012). Effects of polydeoxyribonucleotide on the histological damage and the altered spermatogenesis induced by testicular ischaemia and reperfusion in rats. Int. J. Androl. 35, 133– 144. 10.1111/j.1365-2605.2011.01194.x 21651579 · DOI
  30. Minutoli L. Arena S. Antonuccio P. Romeo C. Bitto A. Magno C.. (2015). Role of inhibitors of apoptosis proteins in testicular function and male fertility: effects of polydeoxyribonucleotide administration in experimental varicocele. Biomed. Res. Int. 2015: 248976. 10.1155/2015/248976 26347229 PMC4539425 · DOI
  31. Minutoli L. Arena S. Bonvissuto G. Bitto A. Polito F. Irrera N.. (2011). Activation of adenosine A2A receptors by polydeoxyribonucleotide increases vascular endothelial growth factor and protects against testicular damage induced by experimental varicocele in rats. Fertil. Steril. 95, 1510– 1513. 10.1016/j.fertnstert.2010.07.1047 20797711 · DOI
  32. Pallio G. Bitto A. Pizzino G. Galfo F. Irrera N. Squadrito F.. (2016). Adenosine receptor stimulation by polydeoxyribonucleotide improves tissue repair and symptomology in experimental colitis. Front. Pharmacol. 7: 273. 10.3389/fphar.2016.00273 27601997 PMC4993775 · DOI
  33. Pescador R. Capuzzi L. Mantovani M. Fulgenzi A. Ferrero M. E. (2013). Defibrotide: properties and clinical use of an old/new drug. Vascul. Pharmacol. 59, 1– 10. 10.1016/j.vph.2013.05.001 23680861 · DOI
  34. Polito F. Bitto A. Galeano M. Irrera N. Marini H. Calò M.. (2012). Polydeoxyribonucleotide restores blood flow in an experimental model of ischemic skin flaps. J. Vasc. Surg. 55, 479– 488. 10.1016/j.jvs.2011.07.083 22051873 · DOI
  35. Raposio E. Guida C. Coradeghini R. Scanarotti C. Parodi A. Baldelli I.. (2008). In vitro polydeoxyribonucleotide effects on human pre-adipocytes. Cell Prolif. 41, 739– 754. 10.1111/j.1365-2184.2008.00547.x 18673371 PMC6496018 · DOI
  36. Reyes E. (2016). Regadenoson stress for myocardial perfusion imaging. Future Cardiol. 12, 59– 67. 10.2217/fca.15.70 26639775 · DOI
  37. Richardson P. G. Corbacioglu S. Ho V. T. Kernan N. A. Lehmann L. Maguire C.. (2013). Drug safety evaluation of defibrotide. Expert Opin. Drug Saf. 12, 123– 136. 10.1517/14740338.2012.749855 23228043 · DOI
  38. Sini P. Denti A. Cattarini G. Daglio M. Tira M. E. Balduini C. (1999). Effect of polydeoxyribonucleotides on human fibroblasts in primary culture. Cell Biochem. Funct. 17, 107– 114. 10377956
  39. Squadrito F. Bitto A. Altavilla D. Arcoraci V. De Caridi G. De Feo M. E.. (2014). The effect of PDRN, an adenosine receptor A2A agonist, on the healing of chronic diabetic foot ulcers: results of a clinical trial. J. Clin. Endocrinol. Metab. E746– E753. 10.1210/jc.2013-3569 24483158 · DOI
  40. Thellung S. Florio T. Maragliano A. Cattarini G. Schettini G. (1999). Polydeoxyribonucleotides enhance the proliferation of human skin fibroblasts: involvement of A2 purinergic receptor subtypes. Life Sci. 64, 1661– 1674. 10.1016/S0024-3205(99)00104-6 10328526 · DOI · Paper page
  41. Valdatta L. Thione A. Mortarino C. Buoro M. Tuinder S. (2004). Evaluation of the efficacy of polydeoxyribonucleotides in the healing process of autologous skin graft donor sites: a pilot study. Curr. Med. Res. Opin. 20, 403– 408. 10.1185/030079904125003116 15025849 · DOI · Paper page
  42. Zucchi A. Cai T. Cavallini G. D'Achille G. Pastore A. L. Franco G.. (2016). Genital lichen sclerosus in male patients: a new treatment with polydeoxyribonucleotide. Urol. Int. 97, 98– 103. 10.1159/000443184 26828936 · DOI

Cited by

Sorted by citations

Authors
Squadrito, F., Bitto, A., Irrera, N., Pizzino, G., Pallio, G., Minutoli, L., & Altavilla, D.
Affiliations
University of Messina (IT)
Corresponding author
Squadrito, Francesco
ORCID
Venue
Frontiers in Pharmacology
Publisher
Frontiers Media SA
Published
2017-04-26
Volume
8
Pages
224-224
ISSN
1663-9812 (ISSN-L)
DOI
10.3389/fphar.2017.00224
PMC
PMC5405115
OpenAlex
W2610140566
Cited by
215
References
1
Citations by year
2026: 48 · 2025: 53 · 2024: 26 · 2023: 26 · 2022: 14 · 2021: 15 · 2020: 15 · 2019: 11 · 2018: 7
FWCI
0.94
Type
journal article
Language
en
Update notices
corrigendum (2022-11-21)
Open access
Licence
Locations
  • Frontiers in Pharmacology (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
  • Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
Keywords
polydeoxyribonucleotide, deoxyribonucleotides, adenosine A2A receptor, wound healing, diabetic foot ulcer, regenerative medicine, anti-inflammatory activity, anti-ischemic activity, salvage pathway, defibrotide, regadenoson, dipyridamole, oligonucleotides, tissue repair

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review