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.

Skin aging is a complex and multifactorial process influenced by both intrinsic and extrinsic factors. The periorbital area of the face is particularly susceptible to premature aging signs due to its delicate skin structure, and is a major concern for many individuals. While hyaluronic acid (HA)-based dermal filler products are commonly used for periorbital rejuvenation, novel approaches to effectively locally address the visible signs of aging are available. This study aimed to investigate Innovyal Regenerative Action (IRA), an injectable polynucleotide–HA (PN-HA) regenerative complex designed for periocular prejuvenation. Firstly, PN-HA was compared to other commercially available HA-based dermbooster products (Profhilo^®, Suisselle Cellbooster^® Glow, and NCTF^® 135 HA) in terms of rheological properties, in vitro antioxidant capacity, and total collagen production stimulation in human fibroblasts. Secondly, the clinical effects of the IRA PN-HA complex were evaluated in two case reports (monotherapy for periorbital prejuvenation). It was shown that the PN-HA complex outperformed its comparators in terms of relative rheological behavior (biophysical attributes normalized to polymer contents), intrinsic antioxidant activity (CUPRAC, FRAP, and ORAC assays), as well as total collagen level induction (72-h in vitro dermal fibroblast induction model). Generally, the results of this study provided mechanistic and preliminary clinical insights into the potential benefits of the IRA PN-HA complex for periocular cutaneous treatment. Overall, it was underscored that combining the structural support and regenerative properties of PN with the hydrating and volumizing effects of HA bares tangible potential for multifactorial skin quality enhancement and for periocular prejuvenation in particular.

Facial aging is a complex process manifesting as skin hyperpigmentation, textural irregularities, and a diminished elasticity, hydration, and evenness of tone. The escalating demand for minimally invasive aesthetic interventions has driven the development of advanced hydrogel-based injectable formulations. This clinical study assessed the safety and efficacy of Hydragel A1, an injectable hydrogel containing hyaluronic acid (HA), niacinamide, and tranexamic acid (TXA), designed to simultaneously address multiple facets of facial skin aging. A cohort of 49 female participants underwent a series of objective and subjective assessments, including the Global Aesthetic Improvement Scale (GAIS), instrumental measurements (Antera 3D, Chromameter, Cutometer, Dermascan, Corneometer), and standardized photographic documentation at baseline (Day 0) and 14, 28, and 70 days post-treatment. The results demonstrated statistically significant improvements in skin hydration, texture, elasticity, and pigmentation following Hydragel A1 administration. Notably, no serious adverse events or significant injection site reactions were observed, confirming the favorable safety profile of the investigated device. Collectively, these findings underscore the potential of a combined HA, niacinamide, and TXA injectable formulation to provide a comprehensive approach to facial skin rejuvenation, effectively targeting multiple aging-related mechanisms.

Background: The growing demand for minimally invasive aesthetic procedures highlights the need for innovative injectable solutions that target skin aging beyond volumization. Hyaluronic acid (HA)-based fillers remain a cornerstone of aesthetic treatments, but traditional formulations often offer limited benefits in improving skin quality parameters such as elasticity. This study evaluated the efficacy and safety of an injectable formulation composed of 2.6% high molecular weight hyaluronic acid (H-HA) and 3.2% sorbitol, designed to improve skin biomechanical properties through subcutaneous administration. Methods: In this single-center, open-label, single-arm clinical trial, 86 participants aged 35 to 70 years received a single injection in the facial region. Clinical outcomes were assessed at baseline (day 0), one month (M1), and four months (M4) post-injection using the Global Aesthetic Improvement Scale (GAIS), instrumental Cutometer^® measurements of skin elasticity and recovery, and patient satisfaction questionnaires. Results: Significant improvements in skin elasticity and recovery were observed at M4 following a single administration. The product was well tolerated, with only mild and transient injection site reactions observed. Conclusions: These exploratory findings support the clinical benefit of combining high-concentration H-HA with sorbitol to enhance skin quality in a safe and minimally invasive manner. These preliminary results position this formulation as a promising option for facial rejuvenation, targeting biomechanical improvement through a single-session injectable protocol.

Hair loss, or alopecia, constitutes a significant and prevalent concern affecting individuals worldwide. Despite the availability of numerous commercial solutions, many individuals continue to experience substantial psychological distress, leading to adverse impact on personal relationships, social interactions, and occupational performance. The limitations of conventional treatments, such as oral medication with potential systemic side effects and topical applications with localized adverse events, have driven the exploration of alternative therapies. Emerging localized injectable treatments for hair regrowth (PRP, stem cells, exosomes) offer a promising avenue for addressing this persistent issue. These injectable therapies hold the potential to minimize the systemic side effects often associated with oral medications, while also mitigating the localized adverse events that can arise from topical applications. This narrative review provides a comprehensive overview of the medical state-of-the-art in off-label injectable hair regrowth treatments, delving into the diverse range of available options. A critical component of this narrative review involves a thorough evaluation of relevant clinical studies, assessing the efficacy and safety profiles of these emerging therapies. Furthermore, detailed attention is given to injection techniques and administration protocols, crucial factors in optimizing treatment outcomes. These evolving therapies represent a significant advancement in the field of scalp regenerative medicine. By stimulating hair follicle reactivation, these treatments aim to promote sustained and natural hair growth, providing individuals with more effective and durable solutions. The enhanced safety profiles of these injectable therapies, compared to conventional systemic pharmacological treatments (minoxidil, finasteride), offer a substantial improvement in patient care, addressing a widespread clinical need.

This study evaluated the safety and effectiveness of HYDRAGEL A2, an injectable medical device containing hyaluronic acid (HA), polynucleotides (PN), and niacinamide, for improving facial skin quality. These ingredients are increasingly recognized for their synergistic effects in aesthetic medicine, with HA and PN providing hydration and skin support, and niacinamide offering anti-inflammatory and antioxidant properties. A prospective, open-label clinical investigation was conducted on 42 female subjects (mean age 45 ± 1 years, Fitzpatrick skin phototypes II-V) to assess skin elasticity, hydration, and mild skin depression correction following cheek area injections. Efficacy was measured using the Global Aesthetic Improvement Scale (GAIS), Antera 3D^® (texture), Cutometer^® (elasticity/firmness), Corneometer^® (hydration), and Dermascan^® (density/thickness) devices at baseline (D0), week 2 (W2/D14), and week 6 (W6/D42). GAIS values showed significant overall facial improvement (p < 0.001) by both investigators and subjects, where 100% of subjects rated their appearance as improved immediately post-injection (D0), with sustained improvements at D42. Objective measurements revealed significant improvements in skin texture (reduced roughness), elasticity, firmness, hydration (p < 0.001), density, and thickness, demonstrating the combined benefits of the HA, PN, and niacinamide blend. Injection site reactions, primarily mild and transient, were reported immediately post-injection. Investigators and subjects reported high satisfaction with the product’s ease of use and aesthetic outcomes. Globally, HYDRAGEL A2, leveraging the established benefits of HA, PN, and niacinamide, was well-tolerated and effectively enhanced facial skin quality, demonstrating significant and sustained improvements in monitored skin parameters. The study concludes that this combination of ingredients, formulated in HYDRAGEL A2, provides a well-tolerated approach associated with improvements in skin quality.