Search Results (60)

Skin aging is a complex biological process characterized by progressive alterations in the dermal microenvironment, including extracellular matrix (ECM) disorganization, fibroblast dysfunction, and changes in the biomechanical properties of the tissue. In this context, biomaterials used in regenerative aesthetic medicine have been widely employed with the aim of stimulating dermal remodeling processes. This review aimed to analyze the main biomaterials currently used in clinical practice, including calcium hydroxyapatite, poly-L-lactic acid, polycaprolactone, polynucleotides, polydeoxyribonucleotide, and nano-hydroxyapatite, focusing on their biological mechanisms and interactions with the cutaneous microenvironment. The available literature suggests that the effects of these materials are not limited to collagen induction, but also involve modulation of fibroblast activity, extracellular matrix reorganization, and progressive tissue remodeling processes. However, relevant limitations remain in the scientific literature, including methodological heterogeneity among studies and the scarcity of evidence directly clarifying the cellular mechanisms involved. Therefore, advances in this field depend on the integration of experimental research, histological analysis, and well-controlled clinical investigation, as well as a deeper understanding of cellular biology and extracellular matrix dynamics. Full article

Conventional cosmetic human studies rely on pre–post mean comparisons, which have limitations in explaining where and how facial skin changes occur. This pilot single-arm study proposed a privacy-preserving three-dimensional (3D) facial mesh mapping framework and demonstrated its application using an illustrative dataset obtained from participants who used a polydeoxyribonucleotide (PDRN)-containing cosmetic. Twenty-two participants underwent facial skin assessments before and after product use. Conventional analysis included pre–post comparisons of elasticity-related parameters. Additionally, 3D facial images obtained via stereophotogrammetry were converted into de-identified mesh surfaces, spatially aligned between time points, and visualized using color-coded heatmaps. For each participant, the left facial panel displayed changes in a skin hydration permittivity index, while the right panel displayed changes in the R2 gross elasticity parameter (Ua/Uf). Overall mean values tended to increase after product use; however, the 3D visualization revealed heterogeneous spatial patterns undetectable via mean values. This method improved spatial matching, enabled intuitive regional comparison, and reduced privacy concerns by removing identifiable facial features. The privacy-preserving 3D facial mesh mapping (P3DMM) framework may serve as a complementary tool for cosmetic human studies, enabling the generation of structured, de-identified spatial datasets for future skin response research. Full article

Background/Objectives: Ulcerative colitis (UC) is a type of inflammatory bowel disease characterized by abdominal pain, diarrhea, and bleeding. Polydeoxyribonucleotide (PDRN), an adenosine A_2A receptor (A_2AR) agonist, exhibits anti-inflammatory properties. In the present study, we evaluated the therapeutic effects of PDRN in a dextran sodium sulfate (DSS)-induced murine model of UC. Methods: UC was induced by administering 2% DSS in drinking water for 7 days. One day after DSS administration, mice received intraperitoneal injections of PDRN (8 mg/kg) for 7 days. To investigate the involvement of A_2AR, the selective antagonist 3,7-dimethyl-1-propargylxanthine (DMPX, 8 mg/kg) was co-administered with PDRN. Results: DSS administration induced colonic tissue damage and increased disease activity index (DAI) and histological scores. DSS also elevated pro-inflammatory cytokines while reducing anti-inflammatory cytokine levels. PDRN treatment reduced histological damage, restored body weight, colon weight, and colon length, and decreased DAI scores. Furthermore, PDRN treatment inhibited nuclear factor kappa B (NF-κB) activation through suppression of NF-κB inhibitor-α phosphorylation and was associated with activation of the cAMP/PKA/CREB signaling pathway. PDRN treatment attenuated inflammation and was associated with increased expression of vascular endothelial growth factor (VEGF) in colonic tissues. Given the context-dependent role of VEGF in inflammatory bowel disease, this increase is interpreted as contributing to mucosal repair rather than exacerbating inflammation. Co-administration of DMPX abolished these effects, suggesting the involvement of A_2AR-dependent signaling pathways. Conclusions: PDRN attenuated colonic inflammation and improved disease outcomes in DSS-induced UC, potentially through modulation of the PKA/CREB/NF-κB signaling pathway and VEGF-mediated tissue repair mechanisms. Full article

Dermal senescence is associated with reduced fibroblast activity, decreased extracellular matrix synthesis, and impaired tissue repair. Commercial injectable formulations containing poly-L-lactic acid (PLLA), hyaluronic acid (HA), and polydeoxyribonucleotide (PDRN)-associated compounds have been proposed for dermal remodeling approaches and modulate tissue-response pathways; however, comparative studies evaluating commercially available formulations under standardized experimental conditions remain limited. This study aimed to characterize the morphology of formulations containing PLLA, HA, and PDRN, used alone or in combination, by environmental scanning electron microscopy (ESEM), and to investigate formulation-associated histological and collagen-related molecular responses in a murine model. Formulations containing PLLA, HA, HA + PDRN, and PLLA, HA and PDRN were administered into the dorsal subcutaneous tissue of 14 Mus musculus mice (Swiss strain). After 30 days, tissue response was assessed by ultrasound, histological analysis with Masson’s trichrome staining, and RT-qPCR quantification of collagen-related gene expression. ESEM analysis revealed distinct morphological characteristics among the biomaterials, and the combined PLLA, HA and PDRN formulation exhibited a more complex and integrated multiphase structure. Histological analysis showed preserved tissue architecture in all groups, with no evidence of marked inflammatory response or structural disruption. RT-qPCR demonstrated significantly higher COL1A1 expression in the PLLA-only and PLLA, HA, and PDRN groups compared with controls (p < 0.05), whereas no significant differences were observed for COL2A1 or COL3A1. These findings indicate that PLLA-containing formulations were associated with selective COL1A1 upregulation under the evaluated conditions, suggesting formulation-associated collagen-related molecular responses in this short-term model. Full article

Polydeoxyribonucleotide (PDRN) activates the adenosine A2A receptor (A2AR), triggering anti-inflammatory signaling and providing essential nucleotides for the salvage pathway, thereby helping bypass metabolic bottlenecks and promoting tissue repair. Combining PDRN with biochemical agents and physical stimuli represents a significant shift in medical treatment, moving from monotherapy to an integrated, multi-target regenerative approach. These combinatorial strategies effectively address the limitations of PDRN, such as its rapid degradation and diffusion, by simultaneously meeting the structural, metabolic, and signaling needs of injured tissues. The mechanism of action for PDRN involves a synergistic effect with hyaluronic acid, amplification of growth factors (e.g., Platelet-Rich Plasma (PRP), Epidermal Growth Factor (EGF), Platelet-Derived Growth Factor (PDGF)), and enhancements from extracorporeal shockwave therapy (ESWT) and lasers. This results in a notable acceleration of the repair process for chronic wounds, musculoskeletal disorders, and neurological injuries. As intelligent delivery systems like responsive hydrogels and sustainable L-PDRN production continue to advance, these synergistic protocols are poised to redefine global standards of care in regenerative medicine and esthetic dermatology. Future clinical success will hinge on the standardization of sequence-specific protocols and large-scale validation to ensure long-term safety and efficacy. Full article

Developing novel anabolic agents for bone regeneration remains a clinical priority. Polydeoxyribonucleotide (PDRN) exhibits tissue-regenerative properties, but its direct cellular effects on bone remodeling remain unclear. This in vitro study investigated PDRN’s effects on osteoblast (MC3T3-E1) and osteoclast (primary bone marrow-derived macrophages) differentiation. We evaluated metabolic activity, gene/protein expression, and specific differentiation markers using MTS, qRT-PCR, Western blotting, and functional assays (ALP, Alizarin Red S, TRAP, pit formation). In osteoblasts, PDRN dose-dependently modulated metabolic activity while upregulating the early transcription factor Runx2. PDRN significantly enhanced osteoblast differentiation, evidenced by increased ALP activity, elevated mineralized matrix deposition, and robust upregulation of osteocalcin and Runx2. Conversely, PDRN exhibited no direct effect on osteoclast precursor metabolic activity, differentiation, or resorptive function. These findings support a working hypothesis in which PDRN selectively promotes osteoblast differentiation without directly affecting osteoclastogenesis. While further pharmacological investigations are required to definitively elucidate the specific purinergic receptor mechanisms, our results highlight PDRN as a promising candidate anabolic agent for bone regeneration. Full article

Red microalga Porphyridium cruentum produces a sulfated exopolysaccharide (EPS), which enables its survival in challenging intertidal and spray zones. Extracellular polysaccharide hyaluronic acid (HA) plays important roles in skin hydration, elasticity, and volume. However, with aging, HA decreases and loses effectiveness, reducing skin moisture retention and firmness, and increasing signs of aging. An effective topical alternative to injectable HA replacement remains a largely unmet need. An extract of Porphyridium cultivated in natural sunlight, rich in EPS and polydeoxyribonucleotides (PDRNs), significantly activated the ADORA2A receptor in a CHO model, as well as reduced inflammation and increased collagen and HA production, autophagic flux, and key autophagy gene expression in dermal fibroblast cultures. In a double-blind clinical trial with placebo and HA benchmark controls, the Porphyridium extract delivered significant HA-like skin plumpness, hydration, and radiance benefits, and reduced signs of aging. The extract generally equaled or exceeded the HA benchmark. Its meaningful, swift HA-like activity shows potential for a safe, natural, and arguably more powerful HA-like alternative. Full article

Background/Objectives: Guang Chenpi, the aged pericarp of Citrus reticulata ‘Chachi’, is a traditional Chinese medicinal food with documented health benefits. This study aimed to systematically evaluate the multifaceted bioactivity of a standardized Guang Chenpi extract (GCE), both alone and in combination with ergothioneine (EGT) and polydeoxyribonucleotide (PDRN), using in vitro and in vivo models. Methods: GCE quality was characterized by LC-MS/MS. Combination regimens of GCE with EGT or PDRN were assessed in UVB-irradiated 3D MelaKutis^® skin tissue for ROS levels, antioxidation defense markers (NNT, GSH-PX1), and melanocyte protein (Pmel17). In zebrafish, GCE was evaluated for toxicity, antioxidant activity, tail fin regeneration, skin barrier protection, melanogenesis inhibition, and expression of collagen (col1a1a, col1a1b, and col1a2) and elastin (elna) genes. Results: In 3D skin models, GCE combined with EGT or PDRN significantly enhanced antioxidant defenses (NNT increased by 113–186%; GSH-PX1 by 173–231%), reduced ROS by 46.27–57.76%, and decreased melanocyte protein (Pmel17) by 23.44–44.27%. In zebrafish, GCE showed low toxicity (≤0.63 mg/mL) and exhibited dose-dependent antioxidant activity (ROS reduction: 27.57–61.85%), enhanced tail fin regeneration (11.35–27.84%), and strengthened skin barrier function (65.20–89.32% protection). GCE also upregulated collagen and elastin gene expression, improved blood circulation, and suppressed melanogenesis. Conclusions: GCE is a promising multifunctional natural ingredient with significant antioxidant, regenerative, and skin-protective properties. Its combination with EGT or PDRN results in enhanced protective effects against UVB-induced skin damage, supporting its potential use in advanced pharmaceutical and cosmeceutical formulations. Full article

Acute lung injury (ALI) is a severe inflammatory condition with high mortality rates, necessitating the development of effective therapeutic agents. Polydeoxyribonucleotide (PDRN), a DNA-derived compound known for its tissue repair and anti-inflammatory properties, has gained attention as a potential therapeutic agent. However, the efficacy of PDRN derived from marine sources, particularly Porphyra sp. (laver), remains unexplored in respiratory inflammation. In this study, we investigated the protective effects of Porphyra sp.-derived PDRN (Ps-PDRN) against LPS-induced ALI in mice through two administration routes: intranasal (IN) and oral (PO). Ps-PDRN treatment significantly attenuated fever, pulmonary edema, and histopathological changes in LPS-challenged mice. Both IN and PO administration of Ps-PDRN markedly reduced proinflammatory cytokines (TNF-α, IL-1β, and IL-6) and chemokines (MCP-1, RANTES, CXCL1, and MIP-2) in bronchoalveolar lavage fluid (BALF) and serum. Comparative analysis of the two administration routes revealed distinct efficacy profiles, with oral administration demonstrating superior chemokine inhibition, while intranasal delivery showed advantages in certain cytokine suppression. Histological examination revealed that Ps-PDRN preserved alveolar architecture and reduced inflammatory cell infiltration. Furthermore, in vitro studies using RAW 264.7 macrophages demonstrated that Ps-PDRN inhibited LPS-induced production of proinflammatory cytokines, such as TNF-α and IL-6, in a dose-dependent manner. These findings suggest that Ps-PDRN exerts potent anti-inflammatory effects against ALI through both local and systemic administration routes, highlighting its potential as a novel therapeutic agent for inflammatory lung diseases. Full article

Plant-derived polynucleotides (PNs) have emerged as promising regenerative biomolecules; however, their mechanisms remain less defined than those of salmon-derived polydeoxyribonucleotides (S-PDRNs). Here, we extracted polynucleotides from Paeonia lactiflora callus (PL-PN) and evaluated their biological effects on human dermal fibroblasts. PL-PN treatment increased cell viability and pro-collagen I α1 secretion. PL-PN enhanced adenosine A2A receptor expression and activated the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA)/cAMP response element-binding protein (CREB) pathway, accompanied by increased Cyclin D1 levels, retinoblastoma protein (Rb) phosphorylation, and nuclear proliferating cell nuclear antigen (PCNA) levels, indicating an accelerated G1/S transition. PL-PN also significantly reduced nuclear NF-κB localization and downregulated MMP1, MMP3, MMP9, and MMP13, suggesting attenuation of inflammatory and catabolic signaling. Furthermore, PL-PN increased TGF-β maturation, Smad2/3 phosphorylation, and the transcription of COL1A1, COL3A1, and elastin, resulting in enhanced collagen and elastin deposition. These effects are comparable to those of S-PDRN. Although the pathway specificity and in vivo relevance require further studies, our findings provide evidence that PL-PN promotes extracellular matrix regeneration via coordinated proliferative, anabolic, and anti-inflammatory actions. Thus, PL-PN represents a potential sustainable plant-based alternative to S-PDRN for dermatological regeneration. Full article

Polydeoxyribonucleotide (PDRN), a DNA fragment mixture, exerts biological effects via adenosine A2A receptor and salvage pathway activation. Here, Paeonia lactiflora-derived PDRN (Peony PDRN) is proposed as a plant-based alternative to salmon-derived PDRN. While P. lactiflora is known for its medicinal properties, the biological functions of Peony PDRN have not been characterized. To validate and optimize its efficacy, we systematically compared the biological activities of three molecular weight groups of Peony PDRN (high, medium, and low) using in vitro assays and clinical studies. The low-molecular-weight fraction (Low-Peony PDRN) markedly enhanced skin cell proliferation and migration, upregulated extracellular matrix-related genes (COL1A1, COL5A1, ELN, and FBN1), and promoted keratinocyte differentiation and epidermal barrier formation by increasing COL7A1, IVL, FLG, and OCLN expression. It also reduced reactive oxygen species levels and suppressed key inflammatory mediators. Clinically, topical application of Low-Peony PDRN for 2 weeks markedly reduced transepidermal water loss in a sodium lauryl sulfate-induced skin damage model, enhancing barrier recovery (n = 10). Periorbital skin elasticity improved after 4 weeks of treatment (Approval No. Intertek IRB-202505-HR(1)-0001, 20 June 2025). These results indicate that Low-Peony PDRN is a promising plant-derived biomaterial of pharmacological and cosmetic significance, with potential to address skin aging. Full article

Zoledronic acid (ZA), a nitrogen-containing bisphosphonate, is widely used to treat osteoporosis and bone metastases. However, its clinical application is limited by adverse effects, notably bisphosphonate-related osteonecrosis of the jaw (BRONJ), which is associated with cytotoxicity in oral mucosal cells. Polydeoxyribonucleotide (PDRN), a salmon sperm-derived DNA polymer with regenerative and anti-inflammatory properties, has shown therapeutic potential in tissue repair; however, its ability to mitigate ZA-induced cytotoxicity remains poorly understood. Here, we investigated the molecular mechanisms of ZA-induced toxicity in HGF-1 cells, a human gingival fibroblast line, and evaluated the protective effects of PDRN. ZA treatment (50 µM, 48 h) significantly inhibited HGF-1 cell growth, accompanied by reduced phosphorylation of protein kinase B (PKB) and signal transducer and activator of transcription 3 (STAT-3), along with increased phosphorylation of TANK-binding kinase 1 (TBK1). TBK1 silencing restored cell growth under ZA exposure, whereas silencing PKB or STAT-3 further suppressed cell growth even without ZA. Co-treatment with PDRN (100 µg/mL) effectively prevented and reversed ZA-induced HGF-1 cytotoxicity. Mechanistically, PDRN inhibited ZA-induced TBK1 phosphorylation and partially restored PKB phosphorylation, though it did not reverse the reduction in p-STAT-3. Additionally, ZA significantly elevated intracellular reactive oxygen species (ROS) levels at 8 h, which were attenuated by PDRN. The antioxidant N-acetylcysteine (NAC) similarly reduced ZA-induced ROS and p-TBK1 levels and improved cell growth, although it had limited effects on p-PKB at 8 h. Importantly, delayed PDRN treatment following ZA exposure reversed ZA-induced cell growth inhibition and TBK1 activation in a dose- and time-dependent manner. In summary, these findings demonstrate that ZA suppresses HGF-1 cell growth through ROS production, TBK1 activation, and inhibition of PKB and STAT-3, whereas PDRN counteracts these effects primarily by suppressing TBK1 activation and oxidative stress. Full article

Environmental stressors such as pollution and ultraviolet (UV) radiation contribute significantly to skin aging and skin photo-aging, alongside intrinsic chronological factors. Recent insights into longevity science have emphasized mitochondrial health, proteostasis, and autophagic balance as critical processes for maintaining skin integrity. This study investigates the protective potential of a natural product, Rose-derived PolyDeoxyRiboNucleotide (PDRN), against mitochondrial dysfunction and dysregulated autophagy in primary human keratinocytes subjected to environmental stress (benzo-a-pyrene and UV-A). PDRN was evaluated at 0.1%, 0.05%, and 0.01% concentrations. Mitochondrial function was assessed through membrane polarization, ATP/ADP ratio, Complex V (CV-ATP5A) levels, and citrate synthase levels. LAMP2A levels were quantified to evaluate the autophagic pathway. Complementary analyses were performed on ex vivo human skin explants, evaluating oxidative protein damage (carbonylation), Collagen I/III integrity, MMP1 and IL1a levels, and mitophagy markers (PINK1, PARK2). The results confirm significant protection of mitochondrial function, attenuation of oxidative stress, and modulation of autophagy-related pathways by PDRN across all models tested. These findings underscore the capacity of this novel natural product, a plant-derived PDRN, to mitigate environmental skin aging (and photo-aging) through mitochondrial maintenance and proteostasis regulation, positioning Rose-PDRN as a key active ingredient for dermocosmetic formulations targeting skin longevity biomarkers. Full article

Polydeoxyribonucleotides (PDRNs) and polynucleotides (PNs) are biologically active DNA-derived polymers with emerging applications in regenerative dentistry. Acting through adenosine A₂A receptor activation and modulation of inflammatory responses, these biomolecules promote angiogenesis, enhance fibroblast proliferation, and stimulate extracellular matrix synthesis. In periodontal therapy, their potential to accelerate healing, reduce inflammation, and support the regeneration of gingival connective tissue, periodontal ligament, cementum, and alveolar bone is of increasing clinical interest. This review synthesizes current preclinical and clinical evidence regarding the use of PDRNs and PNs for tissue regeneration in dentistry, including their mechanisms of action, delivery strategies, synergistic effects with biomaterials and growth factors, and safety profile. Furthermore, recent advances in injectable formulations, scaffold integration, and combined therapies are discussed. The review also highlights gaps in evidence, methodological limitations in existing studies, and future research directions needed to establish standardized treatment protocols. A total of 21 studies (10 PDRNs and 11 PNs/ODNs) were analyzed. PDRNs and PNs consistently demonstrated preclinical regenerative efficacy, although robust clinical validation remains limited. Full article

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