An effective range of polydeoxyribonucleotides is critical for wound healing quality

Abstract

Wound healing is a physiological restorative response to tissue and cell injury. This process occurs in collaboration with a complex cascade of cellular events, including biochemical alterations to the extracellular matrix. Polydeoxyribonucleotide (PDRN) is a fragmented DNA mixture from Oncorhynchus mykiss or Oncorhynchus keta sperm known to promote tissue regeneration under different pathophysiological conditions. However, the most effective molecular size of PDRNs for promoting the wound healing process and quality has not been established. In the present study, the regeneration quality with low (<50 kDa), middle [classic PDRN; 50-1,500 kDa] and high (>1,500 kDa) molecular weight PDRNs in a skin wound healing mouse model was examined using hematoxylin and eosin, as well as Masson's trichrome stain. A 4 mm biopsy punch was used to produce wounds in the skin of the mice. PDRN-mediated cellular behavior and signaling were evaluated by in vitro scratch assay and western blot analysis, respectively. It was observed that the apparent surface wound healing processes were not significantly different between PDRN molecular sizes. Immunohistochemical analysis revealed that classic PDRN-injected mice exhibited less lipid accumulation with increased collagen composition. These results suggested that 50-1,500 kDa PDRN offers an effective DNA mixture to improve wound healing quality. Furthermore, classic PDRN increased cell migration via c-Jun N-terminal kinase signaling in human fibroblasts. The present study suggests an optimal PDRN molecular weight to promote wound healing, and novel approaches for therapeutic strategies to improve tissue regeneration quality.

Applications of Marine Organism-Derived Polydeoxyribonucleotide: Its Potential in Biomedical Engineering

“…The wound healing properties of Ok-PDRN have also been assessed using several cell lines [ 8 , 26 , 27 , 28 ]. Ok-PDRN significantly increased the cell migration ability on all cell lines, including osteosarcoma cells, CDD-686sk, normal and diabetic human dermal fibroblasts (HDFs), and human umbilical vein endothelial cells (HUVEC).…”

“…A total of nine studies have evaluated the wound healing activity of Ok- (six studies) and Om-PDRNs (three studies) [ 4 , 8 , 9 , 27 , 28 , 45 , 46 , 47 ]. In the case of Ok-PDRN, one study has evaluated the effective range of Ok-PDRN for wound healing as a function of molecular weight distributions (under 50 kDa, between 50 and 1500 kDa, over 1500 kDa) [ 27 ]. Regardless of MW distribution, daily i.p.…”

“…Regarding the modes of PDRN administration, most studies have injected these compounds directly at the wound site. Finally, the underlying mechanisms of PDRN were demonstrated by only five articles as MAPK activation [ 20 , 21 , 27 , 29 , 40 ]. Despite the limitations of PDRN, it has recently garnered much attention as a promising drug for several diseases.…”

Polydeoxyribonucleotide Regulation of Inflammation

“…Immunohistochemistry revealed that the molecular weight of PDRN did not affect wound closure but did affect the quality of wound regeneration. 64 Among the examined sizes, mid-molecular-weight PDRN promoted earlier collagen deposition as well as better wound closure and increased re-epithelialization.…”

Dynamics of Regenerative Processes in Patients with Trophic Ulcers against the Background of Chronic Venous Hemodynamic Disturbances Using Therapy with Polydesoxyrinobonucleotides

“…The drug was administered via subcutaneous and intracutaneous injections one time in 6 days along the periphery of the wound with a supplied 30G 0.3×13 mm needle (about 20 injections of 0.05 ml each). (14) The injections were made at a distance of 1 cm from the edge of the TU every 5 mm around the perimeter, distributing evenly the dose of the drug at the rate of 1 ml per 10 cm 2 of skin defect.…”