Search Results (24)

Various biomaterials are currently employed for dermal biostimulation and filling purposes, with hyaluronic acid (HA)-based fillers among those with the most favorable safety profile, albeit exhibiting a limited biostimulatory effect. This study suggests that hyaluronic acid and succinic acid (SA) can significantly induce beneficial effects on skin cells by targeting key aging hallmarks. Human dermal senescent fibroblasts and aged adipocytes were treated with HA + SA, and various aging characteristics were examined through gene expression analysis and microscopy staining. HA was found to stimulate autophagy gene expression, while SA modulated senescence-gene expression, and the combination of these compounds induced mitophagy in senescent fibroblasts. Additionally, the HA + SA promoted adipogenesis, increased IGF1, and decreased TNFA gene expression in aged adipocytes. Furthermore, the conditioned medium from adipocytes treated with HA + SA upregulated key dermal genes such as COL3A1 and EGF. The findings of this study suggest that HA and SA compounds can be used for the biostimulation of aged skin through the regulation of senescence-associated gene expression and cell communication between dermal fibroblasts and subcutaneous adipocytes. Full article

Hyaluronic acid (HA) dermal fillers represent a cornerstone of modern esthetic medicine, providing a minimally invasive solution for facial volume restoration and skin rejuvenation. However, the diversity of available products, each utilizing distinct crosslinking technologies, presents a challenge for objective comparison and clinical decision making. This study introduces a scientific framework to evaluate and categorize the physicochemical properties of HA fillers based on two key parameter groups: dynamic parameters (e.g., rheology and gel content) and consistency parameters (e.g., extrusion force, water uptake, and gel particle size). Using standardized methodologies, 23 commercially available fillers from five major manufacturers were analyzed, enabling cross-technology comparisons. The findings reveal how specific crosslinking approaches influence the rheological behavior, handling characteristics, and potential clinical applications. By offering an integrated and reproducible assessment, this work helps practitioners select the most suitable filler for individualized treatment plans and encourages manufacturers to enhance product transparency through harmonized testing protocols. Full article

Background/Objectives: Calcium hydroxylapatite (CaHA)-based dermal fillers are widely used in esthetic medicine due to their dual volumizing and biostimulatory properties. Despite their rising popularity, comparative clinical outcome data evaluating different CaHA fillers remain limited. This prospective, single-center, unblinded study aimed to establish the effectiveness of the CaHA filler Rennova^® Diamond Intense via comparison to the well-established CaHA filler Radiesse^® in terms of clinical performance, safety, and patient satisfaction. Methods: Thirty patients (28 female, 2 male) underwent a single-session bilateral injection of Rennova^® Diamond Intense (right side) and Radiesse^® (left side) in the lower and medial posterior facial regions. Outcomes evaluated at multiple time points included dermal thickness, skin elasticity, transepidermal water loss, patient-reported outcomes (S-GAIS), physician-assessed outcomes (P-GAIS), and adverse events. Results: Both fillers showed improvements across all parameters. Patient-reported S-GAIS indicated predominantly “improved” outcomes at days 60 and 120, whereas physician assessments (P-GAIS) predominantly indicated “very improved” results at day 120. Ultrasound revealed increases in dermal thickness for both fillers. Similarly, improvements in skin elasticity and decreases in transepidermal water loss were observed bilaterally. Mild, transient adverse events (pain, swelling, redness, bruising) resolved spontaneously within 30 days post injection. Conclusions: Rennova^® Diamond Intense effectively increases dermal thickness, improves skin elasticity, and reduces transepidermal water loss, achieving high patient and physician satisfaction. These findings underscore its safety, versatility, and efficacy for esthetic facial rejuvenation, warranting further long-term evaluation. Full article

Background: The attractiveness of the central area (the so-called mid-face area or middle third) has a strong impact on the observer, and the treatment of aging in this area is therefore considered a key component in facial rejuvenation. A standardized photographic and three-dimensional analysis was conducted in this observational study to determine the outcome of volumetric restoration procedures of the mid-face area with HA injection, providing an objective, repetitive, and reliable evaluation of this facial rejuvenation technique. Methods: In total, 47 patients were treated with two types of HA-based dermal fillers, and calibrated, stereoscopic images of the face were taken with volume reconstruction and analysis software performed before (t0), 45 days after HA implantation (t1), and at the check-up after the end of follow-up (t2). Results: In total, 39 out of 47 patients completed the study, which showed an overall volume restoration of 4.46 ± 1.34 mL at 45 days (t0–t1) after HA implantation, maintaining a value of 1.23 ± 0.68 mL at the end of the 318-day follow-up (t0–t2). Conclusions: The results of this study indicate that rejuvenation of the mid-facial region through volumetric restoration with an HA filler leads to an indirect volumetric effect that is clinically more significant than the actual injected volume and equally long-lasting. Full article

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. Full article

Lip augmentation has become increasingly popular in aesthetic medicine, driven by advancements in dermal filler technologies and injection techniques. This review provides a comprehensive overview of lip anatomy, age-related changes, and current best practices in lip augmentation using dermal fillers. The complex structure of the lips, including multiple layers of skin, muscle, and mucosa, contributes to their unique appearance and function. Age-related changes, such as volume loss, thinning of the vermilion border, and flattening of the philtrum, significantly impact lip aesthetics. Understanding these changes is crucial for developing effective treatment strategies. The review discusses the importance of tailoring treatments to individual patient needs, considering factors such as ethnic variations in lip structure and cultural preferences. It emphasizes the significance of proper filler selection, with hyaluronic acid-based products being the gold standard due to their biocompatibility and reversibility. Injection techniques, including needle and cannula approaches, are described in detail, with a focus on safety and optimal aesthetic outcomes. Anatomical considerations, particularly the vascular supply to the lips, are highlighted as critical for avoiding complications during filler injections. The review also addresses the evolving approach to lip augmentation, which now focuses on restoring natural contours and addressing age-related changes in the perioral region rather than simply increasing volume. Finally, the importance of managing patient expectations and the potential for future advancements in the field are discussed, including the development of more targeted filler products and refined injection techniques. Full article

This study presents the development of thiol–maleimide/thiol–thiol double self-crosslinking hyaluronic acid-based (dscHA) hydrogels for use as dermal fillers. Hyaluronic acid with varying degrees of maleimide substitution (10%, 20%, and 30%) was synthesized and characterized, and dscHA hydrogels were fabricated using two molecular weights of four-arm polyethylene glycol (PEG10K/20K)–thiol as crosslinkers. The six resulting dscHA hydrogels demonstrated solid-like behavior with distinct physical and rheological properties. SEM analysis revealed a decrease in porosity with higher crosslinker MW and maleimide substitution. The swelling ratios of the six hydrogels reached equilibrium at approximately 1 h and ranged from 20% to 35%, indicating relatively low swelling. Degradation rates decreased with increasing maleimide substitution, while crosslinker MW had little effect. Higher maleimide substitution also required greater injection force. Elastic modulus (G′) in the linear viscoelastic region increased with maleimide substitution and crosslinker MW, indicating enhanced firmness. All hydrogels displayed similar creep-recovery behavior, showing instantaneous deformation under constant stress. Alternate-step strain tests indicated that all six dscHA hydrogels could maintain elasticity, allowing them to integrate with the surrounding tissue via viscous deformation caused by the stress exerted by changes in facial expression. Ultimately, the connection between the clinical performance of the obtained dscHA hydrogels used as dermal filler and their physicochemical and rheological properties was discussed to aid clinicians in the selection of the most appropriate hydrogel for facial rejuvenation. While these findings are promising, further studies are required to assess irritation, toxicity, and in vivo degradation before clinical use. Overall, it was concluded that all six dscHA hydrogels show promise as dermal fillers for various facial regions. Full article

Hyaluronic acid (HA)-based dermal fillers are among the most popular non-invasive facial aesthetic treatments. To ensure an effective and safe treatment experience, knowledge of their biophysical and rheological characteristics, such as: HA concentration, molecular weight (MW), G′, and the degree of cross-linking is essential. Products with a higher MW, G′, and degree of cross-linking are more suitable for promoting volume and lift. Dermal fillers with a lower MW, G′, and degree of cross-linking can produce a soft filling effect that regulates hydration and elasticity. This review discusses how these rheological characteristics can inform treatment choice and their effects on clinical outcomes. The Aliaxin^® line of HA dermal fillers, which are tailored to different clinical applications due to their rheological characteristics, highlights that extensive knowledge of the product can provide very safe and effective procedures for patients, whilst respecting their natural facial aesthetics. This review discusses studies using Aliaxin^® dermal fillers for volumizing and hydrating treatments and fillers that can be used for lip augmentation. Treatment with Aliaxin^® was overall very effective, with no reported adverse events. A full facial treatment using tailored dermal fillers may be a future approach to achieve an effective and safe harmonized and natural aesthetic. Full article

Dermal filler injectability is a critical factor for commercial product adoption by medical aesthetic professionals and for successful clinical administration. We have previously reported (in vitro and ex vivo) cross-linked hyaluronic acid (HA)-based dermal filler benchmarking in terms of manual and automated injectability requirements. To further enhance the function-oriented product characterization workflows and the clinical relevance of dermal filler injectability assessments, the aim of this study was to perform in vivo evaluations. Therefore, several variants of the MaiLi^® product range (OxiFree™ technology) were characterized in vitro and in vivo in terms of injectability attributes, with a focus on hydrogel system homogeneity and ease of injection. Firstly, standardized in vitro assays were performed in SimSkin^® cutaneous equivalents, with variations of the clinical injector, injection site, and injection technique. Then, automated injections in SimSkin^® cutaneous equivalents were comparatively performed in a texture analysis setup to obtain fine-granulometry injection force profile results. Finally, five female participants were recruited for the in vivo arm of the study (case reports), with variations of the clinical injector, injection site, and injection technique. Generally, the obtained quantitative force values and injection force profiles were critically appraised from a translational viewpoint, based on discussions around the OxiFree™ manufacturing technology and on in-use specialized clinician feedback. Overall, the present study outlined a notable level of homogeneity across the MaiLi^® product range in terms of injectability attributes, as well as consistently high ease of administration by medical aesthetic clinicians. Full article

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. Full article

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. Full article

The aim of the case series was to determine the efficacy of a new medical device developed for adipose tissue restoration in the face. The medical device used the patented NAHYCO^® Hybrid Technology to deliver 45 mg of high- (1400 ± 200 kDa) and 45 mg of low- (100 ± 20 kDa) molecular-weight hyaluronan, in 2 mL. Patients and methods: Twenty-two volunteers, aged 36–60 years. Two mL of Profhilo^® Structura was injected using a 25 G cannula for each hemiface, into superficial fat compartment along the line from the preauricular area to the mandibular angle. Two injections were performed, and Profhilo Structura’s effect on restoring adipose tissue was evaluated immediately after treatment, and over a 6-month follow-up. The studied medical device revealed a pseudoplastic behavior and consistency that allowed easy extrusion from a syringe. It showed a lower viscosity compared to dermal fillers, based on crosslinked HA. Clinically, the soft tissue thickness increased immediately after injection, and the clinical improvement persisted across a 6-month follow-up. The self-reported satisfaction with the treatment showed an amelioration in the midface of all the subjects enrolled, with no adverse effects. Profhilo^® Structura demonstrated a peculiar fat compartment integration, with a regenerating effect on adipose tissue senescence. The skin thickening and compaction effects were similar to those obtained using chemically crosslinked dermal fillers, while a natural look was preserved, and the use of crosslinking agents was avoided. Full article

Recently, thanks to the greater discovery of the mechanisms of facial aging, an alternative to invasive plastic surgery has found space with less invasive aesthetic procedures, also based on an increasingly pressing request. We are specifically referring to dermal filler injection into or under the skin which leads to immediate rejuvenation and aesthetic improvements. In this study, we wanted to analyze the results obtained through the use of NEAUVIA Organic Stimulate, particularly with regard to its effectiveness, which is a cross-linked polymeric hydrogel, containing stabilized sodium hyaluronate 26 mg/mL and calcium hydroxyapatite (1%), glycine and L-proline in buffer pyrogen-free water, in its main indication, namely, the temporary correction of congenital and acquired deficiencies of the soft tissues of the face by intradermal injection. Initially, 70 patients were enrolled, but 10 did not complete the study due to non-observance of the investigation rules, so they were excluded from the protocol. The collected data demonstrate an efficient mechanical effect of the pegylated polymeric acid matrix enriched with low concertation of calcium hydroxyapatite and in accordance with other evidence in vitro and in vivo, and the mechanical support of the interstitial connective space improves the homestays of the anatomical layer rebalancing the physiological activity of the dermis cells. Full article

Most marketed HA-based dermal fillers use chemical cross-linking to improve mechanical properties and extend their lifetime in vivo; however, stiffer products with higher elasticity require an increased extrusion force for injection in clinical practice. To balance longevity and injectability, we propose a thermosensitive dermal filler, injectable as a low viscosity fluid that undergoes gelation in situ upon injection. To this end, HA was conjugated via a linker to poly(N-isopropylacrylamide) (pNIPAM), a thermosensitive polymer using “green chemistry”, with water as the solvent. HA-L-pNIPAM hydrogels showed a comparatively low viscosity (G′ was 105.1 and 233 for Candidate1 and Belotero Volume^®, respectively) at room temperature and spontaneously formed a stiffer gel with submicron structure at body temperature. Hydrogel formulations exhibited superior resistance against enzymatic and oxidative degradation and could be administered using a comparatively lower injection force (49 N and >100 N for Candidate 1 and Belotero Volume^®, respectively) with a 32G needle. Formulations were biocompatible (viability of L929 mouse fibroblasts was >100% and ~85% for HA-L-pNIPAM hydrogel aqueous extract and their degradation product, respectively), and offered an extended residence time (up to 72 h) at the injection site. This property could potentially be exploited to develop sustained release drug delivery systems for the management of dermatologic and systemic disorders. Full article

Angiogenesis promotes rejuvenation in multiple organs, including the skin. Heat shock protein 90 (HSP90), hypoxia-inducible factor-1 alpha (HIF-1α), and vascular endothelial growth factor (VEGF) are proangiogenic factors that stimulate the activities of phosphoinositide 3-kinase (PI3K), protein kinase B (AKT), and extracellular signal-regulated kinase 1/2 (ERK1/2). Poly-D,L-lactic acid (PDLLA), polynucleotide (PN), and calcium hydroxyapatite (CaHA) are dermal fillers that stimulate the synthesis of dermal collagen. However, it is not yet known whether these compounds promote angiogenesis, which leads to skin rejuvenation. Here, we evaluated whether PDLLA, PN, and CaHA stimulate angiogenesis and skin rejuvenation using H₂O₂-treated senescent macrophages and endothelial cells as an in vitro model for skin aging, and we used young and aged C57BL/6 mice as an in vivo model. Angiogenesis was evaluated via endothelial cell migration length, proliferation, and tube formation after conditioned media (CM) from senescent macrophages was treated with PDLLA, PN, or CaHA. Western blot showed decreased expression levels of HSP90, HIF-1α, and VEGF in senescent macrophages, but higher expression levels of these factors were found after treatment with PDLLA, PN, or CaHA. In addition, after exposure to CM from senescent macrophages treated with PDLLA, PN, or CaHA, senescent endothelial cells expressed higher levels of VEGF receptor 2 (VEGFR2), PI3K, phosphorylated AKT (pAKT), and phosphorylated ERK1/2 (pERK1/2) and demonstrated greater capacities for cell migration, cell proliferation, and tube formation. Based on the levels of 4-hydroxy-2-nonenal, the oxidative stress level was lower in the skin of aged mice injected with PDLLA, PN, or CaHA, while the tumor growth factor (TGF)-β1, TGF-β2, and TGF-β3 expression levels; the density of collagen fibers; and the skin elasticity were higher in the skin of aged mice injected with PDLLA, PN, or CaHA. These effects were greater in PDLLA than in PN or CaHA. In conclusion, our results are consistent with the hypothesis that PDLLA stimulates angiogenesis, leading to the rejuvenation of aged skin. Our study is the first to show that PDLLA, PN, or CaHA can result in angiogenesis in the aged skin, possibly by increasing the levels of HSP90, HIF-1α, and VEGF and increasing collagen synthesis. Full article