Polydeoxyribonucleotide stimulates angiogenesis and wound healing in the genetically diabetic mouse

Abstract

Healing of diabetic wounds still remains a critical medical problem. Polydeoxyribonucleotide (PDRN), a compound having a mixture of deoxyribonucleotide polymers, stimulates the A2 purinergic receptor with no toxic or adverse effect. We studied the effects of PDRN in diabetes-related healing defect using an incisional skin-wound model produced on the back of female diabetic mice (db1/ db1) and their normal littermates (db1/1m). Animals were treated daily for 12 days with PDRN (8 mg/kg/ip) or its vehicle (100 mL 0.9%NaCl). Mice were killed 3, 6, and 12 days after skin injury to measure vascular endothelial growth factor (VEGF) mRNA expression and protein synthesis, to assay angiogenesis and tissue remodeling through histological evaluation, and to study CD31, Angiopoietin-1 and Transglutaminase-II. Furthermore, we measured wound breaking strength at day 12. PDRN injection in diabetic mice resulted in an increased VEGF message (vehicle51.0 AE 0.2 n-fold vs. b-actin; PDRN51.5 AE 0.09 n-fold vs. b-actin) and protein wound content on day 6 (vehicle50.3 AE 0.07 pg/wound; PDRN50.9 AE 0.1 pg/wound). PDRN injection improved the impaired wound healing and increased the wound-breaking strength in diabetic mice. PDRN also caused a marked increase in CD31 immunostaining and induced Transglutaminase-II and Angiopoietin-1 expression. Furthermore, the concomitant administration of 3,7-dimethyl-1-propargilxanthine, a selective adenosine A2A receptor antagonist, abolished PDRN positive effects on healing. However, 3,7-dimethyl-1-propargilxanthine alone did not affect wound healing in both diabetic mice and normal littermates. These results suggest that PDRN might be useful in wound disorders associated with diabetes.

Polydeoxyribonucleotide (PDRN) restores blood flow in an experimental model of peripheral artery occlusive disease

“…A 2A receptors are expressed on different cell types, especially under ischemic conditions. [23][24][25][26][27] These observations, together with our previous findings on the ability of PDRN to induce VEGF expression during altered healing conditions such as diabetes 11 and burn injury, 12 acting through the A 2A receptor, led us to hypothesize that PDRN could be also efficacious in stimulating VEGF and revascularization in the ischemic limb. Indeed, in this study we demonstrated the beneficial role of Femoral artery ligation and excision provoked an immediate impairment in perfusion, as revealed by laser Doppler flowmetry that persisted after 21 days after the surgical procedures.…”

“…10 Polydeoxyribonucleotide (PDRN) is a compound that, acting through adenosine receptors, is able to stimulate VEGF production during pathologic conditions of low tissue perfusion such as diabetes mellitus and thermal injury. 11,12 PDRN is the active fraction of a preparation used in therapy as an agent to stimulate tissue repair and is extracted from the sperm of trout bred for human consumption. The drug is obtained by an extraction process with purifying and high temperature sterilizing procedures to obtain an Ͼ95% pure active principle without pharmacologically active proteins and peptides (Registration Dossier, Italian Ministry of Health).…”

Polyethylene Glycol Formulations Show Different Soft Tissue Remodeling and Angiogenesis Features

“…3 Angiogenesis plays a fundamental role in the wound healing process, so wherever the vascular conditions are lacking at the surgical site, consistent neoangiogenetic stimuli could enhance the healing of the wound. [13][14][15] The results described here suggest that PEG is able to interact with the host tissue without any inflammatory reaction, regardless of the previous preconditioning of the material with other substances. In addition, we have demonstrated an increase in blood flow and angiogenesis in the area where PEG was inserted in combination with EMD, which was able to further improve PEG integration in the host tissues as well as the angiogenic response for up to 8 weeks.…”

Effectiveness of Autogenous Tooth Bone Graft Combined with Growth Factor: Prospective Cohort Study

“…PDRN is helpful for normal matrix formation by shortening the healing period through its prompt tissue regeneration and wound healing and by promoting the creation of collageneous/ noncollageneous protein. Also, it is characterized by being effective in tissue regeneration by promoting cell regeneration in cellular stage [9][10][11][12][13][14] . In 2008, an autogenous bone graft material was developed from extracted teeth, and subjected to many basic and clinical studies.…”