Search Results (40)

Polydeoxyribonucleotides (PDRN), highly purified DNA-derived polymers, were approved by the Italian Medicines Agency (AIFA) in 1994 to treat superficial wounds, skin ulcers, and dystrophic connective tissue disorders. Since then, PDRN have gained considerable attention as regenerative biomaterials. Beyond their established role in wound healing, they have also been approved as dermal fillers in several countries, with growing clinical evidence supporting their benefits for facial skin health. Recent clinical and preclinical studies suggest that PDRN may improve various skin conditions, including wrinkles, dryness, hyperpigmentation, hair loss, and barrier dysfunction. These findings have generated interest in their broader dermatological applications beyond traditional indications. This review aims to explore the therapeutic potential of PDRN for the treatment of skin disorders. We examine the efficacy and safety of PDRN-based drugs and medical devices in dermatology, with a focus on their clinical applications, pharmacological effects, and underlying molecular mechanisms. Given that PDRN consists of over 90% purified DNA, we further examine the biological functions of extracellular DNA (exDNA) and propose potential mechanisms by which PDRN may function as exDNA, beyond its classical action via the A2A receptor pathway. Collectively, current evidence highlights PDRN as safe and effective biopolymers with promising potential as DNA-based therapeutics in dermatology. Full article

Background: Polydeoxyribonucleotide (PDRN) is increasingly used in dermatology and cosmetic applications owing to its regenerative and anti-aging properties. However, its topical use is limited by its high molecular weight and anionic charge, which restrict skin penetration. Methods: In this study, we employed a nitrogen-oxygen plasma treatment to PDRN to overcome these limitations and characterized its physicochemical properties and in vitro efficiency. Results: Upon plasma treatment, PDRN’s surface charge was attenuated and its hydrodynamic size decreased, leading to improved uptake and markedly increased cell migration activity. Conclusions: These findings suggest that plasma treatment can transform PDRN into a cosmetically viable active ingredient and may provide a general strategy for adapting other high-molecular-weight bioactives for topical delivery. Full article

Polynucleotide (PN) and polydeoxyribonucleotide (PDRN) are DNA-derived biopolymers increasingly recognized for their potential in dermatology. Despite their structural similarities, PN and PDRN exhibit distinct functions due to differences in polymer length and molecular weight. PN, composed of longer DNA fragments, plays a key role in extracellular matrix remodeling. Conversely, PDRN, composed of relatively shorter oligonucleotide sequences than those of PN, enhances skin condition through adenosine receptor activations and supports nucleotide synthesis via both the salvage and de novo pathways. This review provides a critical comparison of the molecular characteristics and functions of PN and PDRN with particular emphasis on their dermatological applications. By delineating their respective roles in esthetic and regenerative medicine, we aim to highlight recent advances that may guide the development of optimized treatment strategies and foster evidence-based clinical practice. Full article

The cosmetic industry faces a critical need to balance commercial innovation with scientific validation, especially regarding the safety and efficacy of raw materials. Plant-derived materials (PDMs) offer a promising alternative to animal-derived ingredients in cosmetics, particularly due to their safety and compliance with vegan and ethical standards. Unlike compounds such as polydeoxyribonucleotide (PDRN), which is derived from the testis or seminal fluid of Salmonidae species and raises concerns regarding its origin, sustainability, and consumer acceptability, PDMs provide a cleaner, ethically preferable profile. In this study, we evaluated 50 PDM candidates using in vitro cell viability, wound healing, and immunocytochemistry assays, along with primary skin irritation tests in human participants. None of the samples showed harmful effects. Notably, sample Nos. 38 and 42 demonstrated significant wound-healing capacity and upregulated filaggrin expression without causing notable irritation in clinical testing. These findings support the biological activity and safety of specific PDMs as functional cosmetic ingredients. This study presents scientifically validated evidence for plant-based alternatives to animal-derived materials and offers a new milestone in the shift toward sustainable and ethical cosmetic development. By bridging the gap between consumer demand and scientific rigor, this study provides a robust platform for future innovations in vegan cosmetics. Full article

This paper explores the enhancement of pharmacological outcomes through the combined use of melatonin and polydeoxyribonucleotide (PDRN), hypothesizing that their simultaneous application might surpass the effectiveness of individual use. Melatonin is a hormone that modulates sleep, oxidative stress and inflammation, and exerts analgesic and anti-inflammatory effects. Conversely, PDRN is well-known for its significant contributions to tissue regeneration and its role in promoting angiogenesis. This article details the pharmacological effects and mechanisms of each compound, suggesting that their integration could amplify their individual benefits, particularly in the realms of wound healing and various medical applications. This paper seeks to provide a comprehensive analysis of the interactions between melatonin and PDRN by reviewing existing studies, thereby paving the way for novel therapeutic strategies. It emphasizes the need for further clinical trials and research to optimize the use of this combination for the improved treatment of diverse cellular or tissue conditions. In conclusion, further research is needed to optimize combination therapies involving melatonin and PDRN, with the goal of confirming their enhanced benefits when used together. In conclusion, further research is necessary to optimize combination therapies involving melatonin and PDRN to confirm their enhanced benefits when used in conjunction. This review emphasizes the importance of exploring their potential synergistic effects and developing effective therapeutic strategies across various medical disciplines. Full article

Emerging evidence highlights the biological risks associated with electromagnetic fields (EMFs) generated by electronic devices. The toxic effects and mechanisms induced by exposure to EMFs on microglial cells and natural substances that inhibit them are limited to date. Here, we investigated whether exposure to 3.5 GHz EMF radiation, potentially generated by smartphones working in 5G communication or cooking using microwave ovens, affects the growth of BV2 mouse microglial cells and polydeoxyribonucleotide (PDRN), a DNA preparation derived from salmon sperm, inhibits it. Of note, exposure to 3.5 GHz EMF radiation for 2 h markedly inhibited the growth and triggered apoptosis in BV2 cells, characterized by the reduced number of surviving cells, increased genomic DNA fragmentation, increased reactive oxygen species (ROS) levels, and altered phosphorylation and expression levels of JNK-1/2, p38 MAPK, ERK-1/2, eIF-2α, and procaspase-9. Pharmacological inhibition studies revealed that JNK-1/2 and p38 MAPK activation and ROS generation were crucial for 3.5 GHz EMF-induced BV2 cytotoxicity. Of interest, PDRN effectively countered these effects by inhibiting the activation of JNK-1/2, p38 MAPK, and caspase-9, and the production of ROS, although it did not affect eIF-2 phosphorylation. In conclusion, this study is the first to report that PDRN protects against 3.5 GHz EMF-induced toxicities in BV2 microglial cells, and PDRN’s protective effects on 3.5 GHz EMF-induced BV2 cytotoxicity are mediated primarily by modulating ROS, JNK-1/2, p38 MAPK, and caspase-9. Full article

Background/Objectives: The regeneration of the facial nerve using low-level laser therapy (LLLT) has been infrequently reported. Polydeoxyribonucleotides (PDRNs), a blend of short deoxyribonucleotide polymers known for their non-toxic and non-allergic properties, are recognized as a stimulator of cell growth that enhances cell proliferation and supports wound healing. This study investigates the synergistic effect of the topical sustained release of PDRN/F-127 and LLLT on facial nerve regeneration following crush injury-induced paralysis in rats. Methods: The main trunk of the facial nerve was compressed for 1 min using a hemostat. Animals were divided into five groups: a control group (n = 4), group I (Pluronic F-127 only, n = 4), group II (Pluronic F-127/PDRN, n = 4), group III (Pluronic F-127 + LLLT, n = 4), and group IV (Pluronic F-127/PDRN + LLLT, n = 4). We measured the recovery of vibrissa fibrillation, action potential, and facial nerve blood flow (FNBF). Results: Group IV exhibited a comparatively faster development of vibrissa fibrillation over time than the other groups. After the intervention, significant differences in vibrissa fibrillation values were observed at all time points (p = 0.0028) according to the repeated one-way ANOVA. Regarding the threshold of action potential, all five groups revealed a significant difference (one-way ANOVA, p < 0.0001; multiple comparisons via Tukey’s test). Among the groups, group IV showed a significantly reduced threshold of action potential compared to the other groups. Group IV showed the most notable recovery in FNBF compared to the other groups. One-way ANOVA showed a significant difference (p < 0.0001; multiple comparisons by Dunnett’s test). Conclusions: These findings suggest that PDRN and LLLT may work together synergistically to enhance peripheral nerve regeneration. Future studies should investigate the underlying molecular mechanisms and evaluate the potential clinical applications of this combined treatment strategy. Full article

PDRN, polydeoxyribonucleotide, which is used as a tissue-regeneration material, is present in human cells under physiological conditions and stimulates regeneration and metabolic activity. PDRN can be used as a biomaterial for several types of regeneration, including wound healing, to promote cell growth and growth-factor production. The aims of this study were to determine the effect of PDRN derived from human placenta-derived mesenchymal stem cells (hPD-MSCs) on cellular regeneration through A2A receptor signaling and to investigate its therapeutic effects in a mouse model of wound healing. Human PDRN (UNIPlax) was extracted from hPD-MSCs fragmented via a sonication system and evaluated for its effect on the migration of HaCaT cells in an in vitro system and in a wound-healing mouse model in vivo. Compared with the sham treatment, UNIPlax treatment significantly increased the migration of injured HaCaT cells (p < 0.05). Additionally, the tube formation of human umbilical vein endothelial cells (HUVECs) was greater than that of the sham group (p < 0.05), and the effects of this treatment were mediated through the A2A receptor. Furthermore, UNIPlax treatment led to a decrease in wound size; in addition, the area of granulation and the rate of collagen formation at the wound site were significantly greater than those in the sham group in the wound-healing mouse model (p < 0.001). We also confirmed that UNIPlax promoted tissue regeneration and the expression of VEGF through the A2A receptor. Taken together, these findings indicate that UNIPlax has potential for regeneration of damaged tissues, including during wound healing. Full article

Polydeoxyribonucleotides (PDRNs) and polynucleotides (PNs) are similar DNA-derived biopolymers that have garnered significant scientific attention since the 1990s for their potential applications in wound healing and skin rejuvenation. These biopolymers exhibit a broad molecular weight (MW) range, typically spanning from 50 to 1500 kDa. However, recent studies have expanded this range to encompass fragments as small as 1 kDa and as large as 10,000 kDa. Clinically, PDRN/PN formulations, commercially available in various galenic forms (gels, creams, serums, masks, and injectables), have demonstrated promising effects in significantly promoting skin regeneration, reducing inflammation, improving skin texture, preventing scar formation, and mitigating wrinkles. Importantly, despite their widespread use in cosmetology and aesthetic dermatology, the interchangeable use of the terms “PDRN” and “PN” in the scientific literature (to describe polymers of varying lengths) has led to considerable confusion within the medical and scientific communities. To specifically address this PDRN/PN ambiguity, this narrative review proposes a standardized structure-based nomenclature for these DNA-derived polymers, the “Marques Polynucleotide Cutoff”, set at 1500 kDa. Thus, we propose that the term “PDRN” should be exclusively reserved for small- and medium-chain polymers (MW < 1500 kDa), while the term “PN” should specifically be used to denote longer-chain polymers (MW ≥ 1500 kDa). In a broader perspective, this classification is based on the distinct physicochemical properties and therapeutic effects of these DNA fragments of various MWs, which are comprehensively discussed in the present review. Full article

Polydeoxyribonucleotide (PDRN) has emerged as a potent bioactive compound with proven efficacy in wound healing, tissue regeneration, and anti-inflammatory applications and is predominantly derived from salmonid gonads. However, this study presents a groundbreaking advancement by successfully extracting and characterizing PDRN from microbial sources, specifically Lactobacillus rhamnosus, marking the first report to utilize microbial-, biome-, or Lactobacillus-derived PDRN (L-PDRN). The findings demonstrate the enhanced biological properties of L-PDRN over traditional salmon-derived PDRN across several assays. L-PDRN exhibited superior antioxidant activity, with significantly higher SOD-like and DPPH radical scavenging activities compared to PDRN, particularly at higher concentrations. In wound-healing assays, L-PDRN demonstrated superior efficacy in promoting cell migration and wound closure, even under inflammatory conditions induced by tumor necrosis factor (TNF-α). Additionally, L-PDRN demonstrated the potential for enhanced immunostimulatory effects under non-inflammatory conditions while maintaining anti-inflammatory properties under lipopolysaccharide (LPS) stimulation. Electrophoretic analysis revealed that L-PDRN consists of smaller DNA fragments (under 100 bp) compared to salmon-derived PDRN (200–800 bp), suggesting greater bioavailability and skin absorption. Mechanistic studies confirmed that L-PDRN activates the focal adhesion kinase (FAK) and protein kinase B (AKT) signaling pathway through the A2A receptor, similar to PDRN, while also engaging alternative pathways for p38 and ERK phosphorylation, highlighting its signaling versatility. This study underscores the potential of L-PDRN as a multifunctional and sustainable alternative to salmon-derived PDRN, offering enhanced bioactivity, scalability, and environmental benefits. The novel approach of utilizing microbial-derived PDRN opens new avenues for therapeutic applications in oxidative stress management, tissue regeneration, and immune modulation, paving the way for a paradigm shift in PDRN sourcing and functionality. Full article

Articular cartilage faces challenges in self-repair due to the lack of blood vessels and limited chondrocyte concentration. Polydeoxyribonucleotide (PDRN) shows promise for promoting chondrocyte growth and cartilage regeneration, but its delivery has been limited to injections. Continuous PDRN delivery is crucial for effective cartilage regeneration. This study explores using gelatin methacrylate (gelMA) hydrogel, crosslinked with visible light and riboflavin 5′-phosphate sodium (RF) as a photoinitiator, for sustained PDRN release. GelMA hydrogel’s synthesis was confirmed through spectrophotometric techniques, demonstrating successful methacrylate group incorporation. PDRN-loaded gelMA hydrogels displayed varying pore sizes, swelling ratios, degradation rates, and mechanical properties based on gelMA concentration. They showed sustained PDRN release and biocompatibility, with the 14% gelMA-PDRN composition performing best. Glycosaminoglycan (GAG) activity was higher in PDRN-loaded hydrogels, indicating a positive effect on cartilage formation. RT-PCR analysis revealed increased expression of cartilage-specific genes (COL2, SOX9, AGG) in gelMA-PDRN. Histological assessments in a rabbit cartilage defect model demonstrated superior regenerative effects of gelMA-PDRN hydrogels. This study highlights the potential of gelMA-PDRN hydrogels in cartilage tissue engineering, providing a promising approach for effective cartilage regeneration. Full article

Background and Objectives: Polydeoxyribonucleotides (PDRN), composed of DNA fragments derived from salmon DNA, is widely recognized for its regenerative properties. It has been extensively used in medical applications, such as dermatology and wound healing, due to its ability to enhance cellular metabolic activity, stimulate angiogenesis, and promote tissue regeneration. In the field of dentistry, PDRN has shown potential in promoting periodontal healing and bone regeneration. This study aims to investigate the effects of PDRN on the morphology, survival, and osteogenic differentiation of gingiva-derived stem cell spheroids, with a focus on its potential applications in tissue engineering and regenerative dentistry. Materials and Methods: Gingiva-derived mesenchymal stem cells were cultured and formed into spheroids using microwells. The cells were treated with varying concentrations of PDRN (0, 25, 50, 75, and 100 μg/mL) and cultivated in osteogenic media. Cell morphology was observed over seven days using an inverted microscope, and viability was assessed with Live/Dead Kit assays and Cell Counting Kit-8. Osteogenic differentiation was evaluated by measuring alkaline phosphatase activity and calcium deposition. The expression levels of osteogenic markers RUNX2 and COL1A1 were quantified using real-time polymerase chain reaction. RNA sequencing was performed to assess the gene expression profiles related to osteogenesis. Results: The results demonstrated that PDRN treatment had no significant effect on spheroid diameter or cellular viability during the observation period. However, a PDRN concentration of 75 μg/mL significantly enhanced calcium deposition by Day 14, suggesting increased mineralization. RUNX2 and COL1A1 mRNA expression levels varied with PDRN concentration, with the highest RUNX2 expression observed at 25 μg/mL and the highest COL1A1 expression at 75 μg/mL. RNA sequencing further confirmed the upregulation of genes involved in osteogenic differentiation, with enhanced expression of RUNX2 and COL1A1 in PDRN-treated gingiva-derived stem cell spheroids. Conclusions: In summary, PDRN did not significantly affect the viability or morphology of gingiva-derived stem cell spheroids but influenced their osteogenic differentiation and mineralization in a concentration-dependent manner. These findings suggest that PDRN may play a role in promoting osteogenic processes in tissue engineering and regenerative dentistry applications, with specific effects observed at different concentrations. Full article

To evaluate the efficacy of human placenta hydrolysate (HPH) in a mice model of CFA-induced inflammatory pain. TNF-α, IL-1β, and IL-6 are key pro-inflammatory cytokine factors for relieving inflammatory pain. Therefore, this study investigates whether HPH suppresses CFA-induced pain and attenuates the inflammatory process by regulating cytokines. In addition, the relationship between neuropathic pain and HPH was established by staining GFAP and Iba-1 in mice spinal cord tissues. This study was conducted for a total of day 28, and inflammatory pain was induced in mice by injecting CFA into the right paw at day 0 and day 14, respectively. 100 μL of 20% glucose and polydeoxyribonucleotide (PDRN) and 100, 200, and 300 μL of HPH were administered intraperitoneally twice a week. In the CFA-induced group, cold and mechanical allodynia and pro-inflammatory cytokine factors in the spinal cord and plantar tissue were significantly increased. The five groups of drugs evenly reduced pain and gene expression of inflammatory factors, and particularly excellent effects were confirmed in the HPH 200 and 300 groups. Meanwhile, the expression of GFAP and Iba-1 in the spinal cord was increased by CFA administration but decreased by HPH administration, which was confirmed to suppress damage to peripheral ganglia. The present study suggests that HPH attenuates CFA-induced inflammatory pain through inhibition of pro-inflammatory cytokine factors and protection of peripheral nerves. Full article

Sea cucumber viscera contain various naturally occurring active substances, but they are often underutilized during sea cucumber processing. Polydeoxyribonucleotide (PDRN) is an adenosine A_2A receptor agonist that activates the A_2A receptor to produce various biological effects. Currently, most studies on the activity of PDRN have focused on its anti-inflammatory, anti-apoptotic, and tissue repair properties, yet relatively few studies have investigated its antioxidant activity. In this study, we reported for the first time that PDRN was extracted from the sperm of Apostichopus japonicus (AJS-PDRN), and we evaluated its antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid (ABTS), and hydroxyl radical scavenging assays. An in vitro injury model was established using H₂O₂-induced oxidative damage in RAW264.7 cells, and we investigated the protective effect of AJS-PDRN on these cells. Additionally, we explored the potential mechanism by which AJS-PDRN protects RAW264.7 cells from damage using iTRAQ proteomics analysis. The results showed that AJS-PDRN possessed excellent antioxidant activity and could significantly scavenge DPPH, ABTS, and hydroxyl radicals. In vitro antioxidant assays demonstrated that AJS-PDRN was cytoprotective and significantly enhanced the antioxidant capacity of RAW264.7 cells. The results of GO enrichment and KEGG pathway analysis indicate that the protective effects of AJS-PDRN pretreatment on RAW264.7 cells are primarily achieved through the regulation of immune and inflammatory responses, modulation of the extracellular matrix and signal transduction pathways, promotion of membrane repair, and enhancement of cellular antioxidant capacity. The results of a protein–protein interaction (PPI) network analysis indicate that AJS-PDRN reduces cellular oxidative damage by upregulating the expression of intracellular selenoprotein family members. In summary, our findings reveal that AJS-PDRN mitigates H₂O₂-induced oxidative damage through multiple pathways, underscoring its significant potential in the prevention and treatment of diseases caused by oxidative stress. Full article

Aim: Polydeoxyribonucleotide (PDRN) is a chain-like polymer derived from DNA. Recent in vitro and animal studies have showcased the beneficial impacts of PDRN on the process of bone mending, whether used on its own or in conjunction with other substances that aid in regeneration. This scoping review aims to synthesize the current understanding of how PDRNs influence bone healing. Materials and Methods: The studies included in the screening procedure were randomized controlled clinical trials (RCTs), both retrospective and prospective case–control studies, as well as in vitro and in vivo investigations. Articles were sourced from PubMed (MEDLINE), Scopus, EMBASE, Web of Science, and Google Scholar electronic databases using the following MeSH terms: (polydeoxyribonucleotide) and (bone) and (regeneration). Results: Initially, 228 articles were identified. Following the review process, a total of eight studies were ultimately examined. Among these, two were confined to laboratory studies, five were conducted on living organisms, and one encompassed both evaluations on living organisms and in vitro assessments. A descriptive qualitative approach was employed to present the data extracted from the studies that were included. Conclusions: PDRN has the potential to enhance the process of bone healing and the quantity of newly generated bone when combined with grafting materials. Future clinical studies are warranted to ascertain the appropriate clinical application of PDRN based on the dosage under consideration. Full article