Failure rate after chronic rotator cuff repair is considerably high. Moreover, diabetes mellitus is known as a compromising factor of rotator cuff tear. The effect of Polydeoxyribonucleotide (PDRN) and polynucleotide (PN) on tendon healing and fatty infiltration is unclear as tissue regeneration activator in diabetic state. Therefore, a diabetic rat model with chronic rotator cuff tear was made for mechanical, histologic and blood tests. In the animal study using a diabetic rat cuff repair model, the administration of PDRN and PN increased the load to failure of repaired cuffs and improved tendon healing and decreased fatty infiltration. Also, the plasma levels of vascular endothelial growth factor and fibroblast growth factor were elevated in PDRN and PN administrated groups. We concluded that PDRN and PN appear to boost tendon recovery and reduce the presence of fatty infiltration following cuff repair in diabetic state. Also, PN showed a later onset and a longer duration than PDRN associated with the mean plasma growth factors.

BACKGROUND: Regenerative aesthetics claims to enhance cosmetic outcomes through advanced biological interventions like Stem cell and Exosome therapy, Polydeoxyribonucleotide (PDRN), Photobiomodulation, bioactive peptides and treatment for cellular senescence yet lacks substantial scientific and regulatory validation.
OBJECTIVE: To evaluate the scientific and clinical foundations of regenerative medicine techniques in non-surgical aesthetics and assess the legitimacy of regenerative aesthetics as a medical specialty.
METHODS: A systematic review was conducted according to PRISMA guidelines, searching databases including PubMed, Scopus, and Web of Science for studies published in the last ten years. We included 19 studies, comprising 14 randomized controlled trials (RCTs) and 5 prospective studies, focusing on interventions that purportedly use regenerative medicine principles in aesthetic applications.
RESULTS: The review highlights a prevalent gap in molecular and clinical evidence supporting the efficacy and safety of regenerative aesthetics. Despite the robust design of the included RCTs and prospective studies, there remains a significant lack of consistent, high-quality evidence proving the effectiveness of these interventions. Issues such as inadequate reporting, unclear molecular mechanisms, and absence of long-term safety data were common.
CONCLUSIONS: The field of regenerative aesthetics lacks the necessary scientific rigour and regulatory compliance to be recognized as a legitimate medical specialty. This review underscores the need for stringent scientific validation and regulatory oversight to ensure patient safety and treatment efficacy before these techniques can be recommended for clinical use.
METHODS: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Sea cucumber viscera contain various naturally occurring active substances, but they are often underutilized during sea cucumber processing. Polydeoxyribonucleotide (PDRN) is an adenosine A2A receptor agonist that activates the A2A 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.

There has been a growing interest in skin recovery in both the medical and cosmetics fields, leading to an increasing number of studies reporting diverse materials being utilized for this purpose. Among them, polydeoxyribonucleotide (PDRN) is known for its efficacy in skin repair processes, while Hibiscus sabdariffa (HS) is recognized for its antioxidant, hypolipidemic, and wound healing properties, including its positive impact on mammalian skin and cells. We hypothesized that these characteristics may have a germane relationship during the healing process. Consequently, we induced calli from HS and then extracted PDRN for use in treating human keratinocytes. PDRN (5 μg/mL) had considerable wound healing effects and wrinkle improvement effects. To confirm its function at the molecular level, we performed real-time polymerase chain reaction, western blotting, and immunocytochemistry. Furthermore, genes related to wound healing (MMP9, Nrf2, KGF, VEGF, SOD2, and AQP3) were significantly upregulated. Additionally, the protein expression of MMP9, AQP3, and CAT, which are closely related to wound healing and antioxidant cascades, was considerably enhanced. Based on cellular morphology and molecular-level evidence, we propose that PDRN from calli of HS can improve wound healing in human keratinocytes. Furthermore, its potential to serve as a novel material in cosmetic products is demonstrated.

OBJECTIVE: The aims of this study were 1) to investigate the effects of a subepithelial connective tissue graft (SCTG) and a volume-stable collagen matrix (VCMX) on soft-tissue volume gain in the immediate implant placement protocol, and 2) to determine whether polydeoxyribonucleotide (PDRN) can enhance the effects of a VCMX.
METHODS: Dental implants were placed in 4 mongrel dogs immediately after extracting the distal roots of their third and fourth mandibular premolars. The gap between the implant and the buccal bone plate was filled with synthetic bone substitute particles. The following soft-tissue augmentation modalities were applied buccally: 1) control (no augmentation), 2) SCTG, 3) VCMX, and 4) VCMX/PDRN. After 4 months, histomorphometric analysis was performed. Tissue changes were evaluated using superimposed standard tessellation language (STL) files.
RESULTS: Wound dehiscence was found in more than half of the test groups, but secondary wound healing was successfully achieved in all groups. Histomorphometrically, tissue thickness was favored in group SCTG at or above the implant platform level (IP), and group SCTG and the groups with VCMX presented similar tissue thickness below the IP. However, the differences in such thickness among the groups were minor. The keratinized tissue height was greater in group VCMX/PDRN than in groups SCTG and VCMX. Superimposing the STL files revealed a decrease in soft-tissue volume in all groups.
CONCLUSIONS: Wound dehiscence after soft-tissue volume augmentation might be detrimental to obtaining the expected outcomes. PDRN appears not to have a positive effect on the soft-tissue volume gain.

OBJECTIVE: This study investigated the adjunctive effect of polydeoxyribonucleotide (PDRN) on bone formation in alveolar ridge preservation (ARP) sockets.
METHODS: Both mandibular second, third and fourth premolars of eight beagle dogs were randomly divided into ARP and ARP/PDRN groups. Following tooth extraction, ARP procedures were conducted using collagenized alloplastic graft material and bilayer collagen membrane soaked with normal saline (ARP group) or PDRN (ARP/PDRN group) for 10 min before application. Both groups were also randomly allocated to 2-, 4- or 12-week healing subgroups. The primary endpoint of this study was to compare histomorphometric differences between ARP and ARP/PDRN. The secondary endpoints of this study were to compare micro-CT analysis and three-dimensional volumetric measurement between the two groups.
RESULTS: In the histomorphometric analysis, the ARP/PDRN group exhibited greater new bone formation at coronal, middle and total position compared with the ARP group at 2-week healing. The number of newly formed blood vessels was higher in the ARP/PDRN group than in the ARP group at 2- and 4-week healing. In micro-CT analysis, the mean new bone volume/total bone volume between ARP and ARP/PDRN was statistically significant at 2-week healing. Ridge volume alterations were significantly decreased in the ARP/PDRN group during entire healing time compared with the ARP group, especially on the buccal side.
CONCLUSIONS: The application of PDRN in ARP might provide additional benefits for early bone regeneration and maintenance of buccal ridge volume.

BACKGROUND: Polynucleotides (PN) are becoming more prominent in aesthetic medicine. However, the structural characteristics of PN have not been published and PN from different companies may have different structural characteristics. This study aimed to elucidate the structural attributes of DOT™ PN and distinguish differences with polydeoxyribonucleotides (PDRN) using high-resolution scanning electron microscopy (SEM) imaging.
METHODS: DOT™ PN was examined using a Quanta 3-D field emission gun (FEG) Scanning Electron Microscope (SEM). Sample preparation involved cryogenic cooling, cleavage, etching, and metal coating to facilitate high-resolution imaging. Cryo-FIB/SEM techniques were employed for in-depth structural analysis.
RESULTS: PDRN exhibited an amorphous structure without distinct features. In contrast, DOT™ PN displayed well-defined polyhedral shapes with smooth, uniformly thick walls. These cells were empty, with diameters ranging from 3 to 8 micrometers, forming a seamless tessellation pattern.
CONCLUSIONS: DOT™ PN\'s distinct geometric tessellation design conforms to the principles of biotensegrity, providing both structural reinforcement and integrity. The presence of delicate partitions and vacant compartments hints at possible uses in the field of pharmaceutical delivery systems. Within the realms of beauty enhancement and regenerative medicine, DOT™ PN\'s capacity to bolster cell growth and tissue mending could potentially transform approaches to rejuvenation treatments. Its adaptability becomes apparent when considering its contributions to drug administration and surgical procedures.
CONCLUSIONS: This study unveils the intricate structural scaffold features of DOT™ PN for the first time, setting it apart from PDRN and inspiring innovation in biomedicine and materials science. DOT™ PN\'s unique attributes open doors to potential applications across healthcare and beyond.

BACKGROUND: The concept of \"skin boosters\" has evolved, marking a shift from traditional uses of hyaluronic acid (HA) fillers primarily for augmenting skin volume to a more diverse application aimed at improving dermal conditions. Restylane Vital and other HA fillers have been repurposed to combat skin aging and wrinkles by delivering HA directly to the dermis.
OBJECTIVE: This review aims to define the term \"skin booster\" and to discuss the various components that constitute skin boosters. It seeks to provide a comprehensive overview of the different ingredients used in skin boosters, their roles, and their impact on enhancing dermal conditions.
METHODS: A comprehensive review was conducted, focusing on representative skin booster ingredients. The approach involved analyzing the different elements used in skin boosters and their specific roles in enhancing dermal improvement.
RESULTS: The findings indicate that skin boosters, encompassing a range of ingredients, are effective in improving the condition of the skin\'s dermis. The review identifies key ingredients in skin boosters and their specific benefits, including hydration, elasticity improvement, and wrinkle reduction.
CONCLUSIONS: Skin boosters represent a significant development in dermatological treatments, offering diverse benefits beyond traditional HA fillers. This review provides valuable insights into the constituents of skin boosters and their effectiveness, aiding readers in making informed decisions about these treatments. The potential of skin boosters in dermatological practice is considerable, warranting further research and application.

OBJECTIVE: Lithotomy position has been widely used in the various urologic surgery. Occasionally sensory and motor problems of the lower extremities are occurred due to the lithotomy position and these deficits may be related with sciatic nerve injury (SNI). Inflammatory process is a factor to induce functional impairment after SNI. Therefore, we evaluated the role of adenosine A2A receptor agonists, polydeoxyribonucleotide (PDRN) showing anti-inflammatory effect on locomotor function following SNI in rats.
METHODS: Sciatic nerve was compressed with surgical clips for 1 minute after exposing of right sciatic nerve. After 3 days of SNI, PDRN (2, 4, and 8 mg/kg) was applied to the damaged area of sciatic nerve once daily for 10 days. Walking track analysis was conducted for locomotor function and plantar test was performed for thermal pain sensitivity. Level of cyclic adenosine-3´,5´-monophosphate (cAMP) were measured using enzyme-linked immunosorbent assay. Western blot analysis was performed for tumor necrosis factor (TNF)-α, interleukin (IL)-1β, cAMP response element binding protein (CREP), vascular endothelial growth factor (VEGF). Immunofluorescence for neurofilament was also conducted.
RESULTS: Locomotor function was decreased and thermal pain sensitivity was increased by SNI. SNI enhanced proinflammatory cytokines\' production, such as TNF-α and IL-1β, while suppressed CREP phosphorylation and cAMP level. SNI also reduced the expression of VEGF and neurofilaments. However, treatment with PDRN inhibited proinflammatory cytokines\' production and upregulated CREP phosphorylation and cAMP expression. PDRN also enhanced the expression of VEGF and neurofilaments. As a result, PDRN improved locomotor function and alleviated thermal hyperalgesia after SNI.
CONCLUSIONS: PDRN has shown potential to be used as an effective treatment for neuropathic pain.

OBJECTIVE: 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.
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.