Niacinamide (or nicotinamide) is a small-molecule hydrosoluble vitamin with essential metabolic functions in mammalian cells. Niacinamide has become a key functional ingredient in diverse skincare products and cosmetics. This vitamin plays a pivotal role in NAD⁺ synthesis, notably contributing to redox reactions and energy production in cutaneous cells. Via diversified biochemical mechanisms, niacinamide is also known to influence human DNA repair and cellular stress responses. Based on decades of safe use in cosmetics, niacinamide recently gained widespread popularity as an active ingredient which aligns with the “Kligman standards” in skincare. From a therapeutic standpoint, the intrinsic properties of niacinamide may be applied to managing acne vulgaris, melasma, and psoriasis. From a cosmeceutical standpoint, niacinamide has been widely leveraged as a multipurpose antiaging ingredient. Therein, it was shown to significantly reduce cutaneous oxidative stress, inflammation, and pigmentation. Overall, through multimodal mechanisms, niacinamide may be considered to partially prevent and/or reverse several biophysical changes associated with skin aging. The present narrative review provides multifactorial insights into the mechanisms of niacinamide’s therapeutic and cosmeceutical functions. The ingredient’s evolving role in skincare was critically appraised, with a strong focus on the biochemical mechanisms at play. Finally, novel indications and potential applications of niacinamide in dermal fillers and alternative injectable formulations were prospectively explored.

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.

The injectability of cross-linked hyaluronic acid (HA) dermal fillers is influenced by polymer concentration, polymer cross-linking type and degree, the presence of lidocaine or other functional excipients, types of syringes, and injection techniques. Finished product injectability constitutes a critical quality attribute for clinical injectors, as it strongly influences product applicability and ease of use in aesthetic medicine. While injectable product extrusion force specifications are provided by the respective device manufacturers, the qualitative informative value of such datasets is low for injectors wishing to compare product brands and technologies from an injectability standpoint. Therefore, the present study comparatively assessed 28 cross-linked HA dermal fillers (JUVÉDERM^®, Restylane^®, BELOTERO^®, TEOSYAL RHA^®, and STYLAGE^® brands) using various injectability benchmarking setups for enhanced clinical-oriented relevance. Manual product injections were performed by three specialized and experienced clinicians, whereas automatic product extrusion was performed using a Texture Analyzer instrument. The various hydrogel products were injected into ex vivo human skin and into SimSkin^® cutaneous equivalents to appropriately account for injection-related counterpressure. The injectability results revealed important variability between and within product brands, with a strong influence of the local anesthetic lidocaine, HA contents, and needle gauge size. Critical appraisals of the investigated products were performed, notably from manufacturing process-based and clinical ease of application-based standpoints, centered on respective experimental injectability quality levels. Generally, it was confirmed that each HA-based dermal filler product requires specific expertise for optimal injection, mainly due to differing viscoelastic characteristics and injectability attributes. Overall, the present study set forth evidence-based and clinical-oriented rationale elements confirming the importance for injectors to work with injectable products with which they are experienced and comfortable to optimize clinical results.

Recent advancements in aesthetic medicine offer innovative cosmetic solutions to enhance patient skin quality and appearance. Advanced treatment options enable practitioners to effectively address skin aging signs, pigmentation imbalance, and loss of elasticity in ambulatory and home-based care regimens. Exosomes (nanoscale cell-derived vesicles) transport a variety of biomolecules and are pivotal in physiological intercellular communication. Importantly, exosomes have recently emerged as key endogenous players in tissular regeneration. More broadly (from an active ingredient purity standpoint), exosomes, stem cell secretomes, and cell culture-conditioned media have been clinically proven to exert multifaceted beneficial topical effects (anti-inflammatory, antioxidant, anti-aging, skin rejuvenation). Therefore, human, animal, and plant-derived exosomes or other refined sub-cellular biological fractions are gaining substantial interest within the aesthetic and cosmetic industries. Notably, such approaches are thought to be among the most promising novel contenders for advanced, biologically inspired skin prejuvenation and rejuvenation care. The present narrative review summarizes the latest clinically oriented research on exosomes and cell culture-conditioned media, highlighting their mechanisms of action in various topical applications. Furthermore, it explores the innovation landscape and currently commercially available products on the global cosmetic market and discusses the potential future applications of advanced, biologically inspired ingredients in the medical aesthetic industry.

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.

Thermo-responsive hyaluronan-based hydrogels and FE002 human primary chondroprogenitor cell sources have both been previously proposed as modern therapeutic options for the management of osteoarthritis (OA). For the translational development of a potential orthopedic combination product based on both technologies, respective technical aspects required further optimization phases (e.g., hydrogel synthesis upscaling and sterilization, FE002 cytotherapeutic material stabilization). The first aim of the present study was to perform multi-step in vitro characterization of several combination product formulas throughout the established and the optimized manufacturing workflows, with a strong focus set on critical functional parameters. The second aim of the present study was to assess the applicability and the efficacy of the considered combination product prototypes in a rodent model of knee OA. Specific characterization results (i.e., spectral analysis, rheology, tribology, injectability, degradation assays, in vitro biocompatibility) of hyaluronan-based hydrogels modified with sulfo-dibenzocyclooctyne-PEG4-amine linkers and poly(N-isopropylacrylamide) (HA-L-PNIPAM) containing lyophilized FE002 human chondroprogenitors confirmed the suitability of the considered combination product components. Specifically, significantly enhanced resistance toward oxidative and enzymatic degradation was shown in vitro for the studied injectable combination product prototypes. Furthermore, extensive multi-parametric (i.e., tomography, histology, scoring) in vivo investigation of the effects of FE002 cell-laden HA-L-PNIPAM hydrogels in a rodent model revealed no general or local iatrogenic adverse effects, whereas it did reveal some beneficial trends against the development of knee OA. Overall, the present study addressed key aspects of the preclinical development process for novel biologically-based orthopedic combination products and shall serve as a robust methodological basis for further translational investigation and clinical work.