Multifunctional Roles of Polydeoxyribonucleotide in Tissue Regeneration and Repair

Introduction

Polydeoxyribonucleotide (PDRN) consists of DNA fragments with molecular weights ranging from 50 to 1 500 kDa, which are mainly extracted from the sperm cells of salmon trout or chum salmon. Many preclinical and clinical studies have demonstrated the properties of PDRN. These include anti-inflammatory, anti-apoptotic, anti-osteoporotic, anti-melanogenetic, anti-allodynic, anti-osteonecrotic, bone regenerative, tissue damage preventive, anti-ulcerative, and wound healing properties, which are mediated by the activation of the adenosine A2A receptor and salvage pathways. Moreover, PDRN promotes angiogenesis, cellular activity, collagen synthesis, soft tissue regeneration, and skin priming and revitalization and can be used to treat hyperpigmentation. [1]

A Promising Skin Anti-aging Agent

As aging progresses, collagen, the most abundant protein, undergoes organizational and structural changes, and undesired skin wrinkles become evident. There are many solutions available in the market to improve skin conditions. All of these procedures have a common goal, which is to enhance collagen production. Treatment with polydeoxyribonucleotide does improve collagen synthesis. A recent study investigated the increase in fibroblast collagen and elastin synthesis via the inhibition of MMP-1; the decrease in MMP activity resulted in an increase in collagen synthesis.44 MMPs play an important role in elastin degradation,45 and an increase in MMPs is associated with damage to ECM components. As mentioned above, polydeoxyribonucleotide inhibits the expression of MMP-1 and elastase. These two factors play a key role in skin aging and wrinkling. [1]

One of the key factors contributing to skin aging is the accumulation of DNA damage. UV light plays a significant role in DNA damage. A study showed that UV-induced DNA damage initiates the release of MMP-1. Exposure to sunlight can trigger an increase in MMP-1 expression. As mentioned above, polydeoxyribonucleotide can inhibit MMP-1. Furthermore, polydeoxyribonucleotide has the advantage of promoting angiogenesis and tissue regeneration. Blood vessels are the highways transporting oxygen and nutrients to the cells, but vascular growth requires VEGF. Polynucleotides stimulate VEGF production by activating the adenosine A2A receptor to promote angiogenesis. Damaged and/or hypoxic tissue often cannot undergo de novo DNA synthesis. The nucleotides derived from polydeoxyribonucleotide provide purines and pyrimidine rings for the “salvage pathways.” Salvage pathways help recover bases and nucleosides generated from DNA and RNA degradation, convert them back to nucleotides, and finally reincorporate them into DNA. [1]

A Promising Platform for Impaired Skin Wound Healing

The normal wound healing process is characterized by a complex, highly integrated cascade of events, requiring the interactions of many cell types, including inflammatory cells, fibroblasts, keratinocytes and endothelial cells, as well as the involvement of growth factors and enzymes. Polydeoxyribonucleotide (PDRN) has been used to improve wound healing through local and systemic administration thanks to its ability to promote cell migration and growth, angiogenesis, and to reduce inflammation on impaired wound healing models in vitro, in vivo and clinical studies. Polydeoxyribonucleotide improved healing of burn wounds by reducing inflammatory infiltration and burn edema, and by stimulating dermal and epidermal regeneration, proliferation of fibroblasts, and neoangiogenesis as suggested by the marked increase in microvessel density and the robust expression of PECAM-1 in the skin samples. Polydeoxyribonucleotide also showed a marked systemic effect by reducing the serum levels of the pleiotropic cytokine tumor necrosis factor (TNF-α) and by augmenting wound VEGF, eNOS, iNOS expression and the wound content of nitric oxide products. [2]

A New Proposal for Bone Tissue Repair

Polydeoxyribonucleotide (PDRN) acts as osteoblast growth stimulator. In recent work, studies evaluated the effects of polydeoxyribonucleotide on human cultured osteoblasts, focusing attention on cell proliferation and alkaline phosphatase activity. Polydeoxyribonucleotide at a concentration of 100 μg/ml induce an increase in osteoblasts growth after 6 days as compared to control (+21%). The addition of DMPX 50 μM and suramine (P2 inhibitor) 10 μM give different results: suramine has no significant effect, while DPMX reduce, even if partially, the polydeoxyribonucleotide induced cell growth. The alkaline phosphatase activity shows a gradual enhancement starting from day 0 to day 10, even if polydeoxyribonucleotide treated cells, examined at day 6, present a sensibly lower phosphatase activity when compared to controls. The data demonstrate that polydeoxyribonucleotide acts as an osteoblast growth stimulator. Its action is partially due to a stimulation of the purinergic system mediated by A2 purinoreceptors, however the involvement of other mechanism like salvage pathway can not be excluded. For these reasons polydeoxyribonucleotide may be a useful osteoblast stimulator, and play an important role in repairing bone defects. [3]

References:

[1] Khan, A., Wang, G., Zhou, F., Gong, L., Zhang, J., Qi, L., & Cui, H. (2022). Polydeoxyribonucleotide: A promising skin anti-aging agent. Chinese Journal of Plastic and Reconstructive Surgery, 4(4), 187-193.

[2] Galeano, M., Pallio, G., Irrera, N., Mannino, F., Bitto, A., Altavilla, D., ... & Squadrito, F. (2021). Polydeoxyribonucleotide: a promising biological platform to accelerate impaired skin wound healing. Pharmaceuticals, 14(11), 1103.

[3] Guizzardi, S., Galli, C., Govoni, P., Boratto, R., Cattarini, G., Martini, D., ... & Scandroglio, R. (2003). Polydeoxyribonucleotide (PDRN) promotes human osteoblast proliferation: a new proposal for bone tissue repair. Life sciences, 73(15), 1973-1983.