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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.

Abstract Background and Aims Hyaluronic acid (HA)‐based injections are used worldwide to improve skin defects associated with aging and ultraviolet light/environmental exposure. HA formulations developed according to molecular weight or with additional components, for example, cross‐linking reagents, are limited by their low biological activity and concentration limit. NAHYCO™ technology has enabled the production of hybrid cooperative complexes (HCCs) of low and high molecular weight HA. Developed for injection into the fat compartments of the face and previously demonstrating potential benefits for adipose tissue restoration, Profhilo Structura® is a new 2 mL HCC formulation comprising low molecular weight HA (45 mg/mL) and high molecular weight HA (45 mg/mL). To evaluate the efficacy and tolerability of Profhilo Structura® to restore adipose tissue compartments in the lateral cheek fat compartment. Methods Fifty healthy enrolled subjects received two injections, 1 month apart, and were evaluated 3 months posttreatment. Investigators performed clinical evaluations (Facial Volume Loss Scale [FVLS] and Wrinkle Severity Rating Scale [WSRS]) at different time points. Subjects also completed self‐evaluation assessments following treatment. Results A significant improvement in FVLS and WSRS clinical scores after the first treatment was observed; treatment benefit was maintained 3 months after treatment completion and confirmed by subject self‐assessment. Most participants reported an improvement, particularly a marked reduction of wrinkles and increased skin firmness. No serious adverse events were reported, confirming the excellent safety profile of HCC injectable devices. Conclusions Overall, the study highlighted the efficacy and tolerability of the studied medical device proving its effect on adipose tissue.

Hyaluronic acid (HA) is a remarkably multifaceted biomacromolecule, playing a role in regulating myriad biological processes such as wound healing, tissue regeneration, anti-inflammation, and immunomodulation. Crosslinked high- and low-molecular-weight hyaluronic acid hydrogels achieve higher molar concentrations, display slower degradation, and allow optimal tissue product diffusion, while harnessing the synergistic contribution of different-molecular-weight hyaluronans. A recent innovation in the world of hyaluronic acid synthesis is represented by NAHYCO® Hybrid Technology, a thermal process leading to hybrid cooperative hyaluronic acid complexes (HCC). This review summarizes the current literature on the in vitro studies and in vivo applications of HCC, from facial and body rejuvenation to future perspectives in skin wound healing, dermatology, and genitourinary pathologies.

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.

Summary: Calcineurin (CN) inhibitors currently used to avoid transplant rejection block the activation of adaptive immune responses but also prevent the development of tolerance toward the graft, by directly inhibiting T cells. CN, through the transcription factors of the NFAT family, plays an important role also in the differentiation dendritic cells (DCs), the main cells responsible for the activation of T lymphocytes. Therefore, we hypothesized that the inhibition of CN only in DCs and not in T cells could be sufficient to prevent T cell responses, while allowing for the development of tolerance. Here, we show that inhibition of CN/NFAT pathway in innate myeloid cells, using a new nanoconjugate capable of selectively targeting phagocytes in vivo, protects against graft rejection and induces a longer graft acceptance compared to common CN inhibitors. We propose a new generation of nanoparticles-based selective immune suppressive agents for a better control of transplant acceptance.

Abstract Natural killer (NK) cells are critical players against tumors. The outcome of anti‐tumor vaccination protocols depends on the efficiency of NK‐cell activation, and efforts are constantly made to manipulate them for immunotherapeutic approaches. Thus, a better understanding of NK‐cell activation dynamics is needed. NK‐cell interactions with accessory cells and trafficking between secondary lymphoid organs and tumoral tissues remain poorly characterized. Here, we show that upon triggering innate immunity with lipopolysaccharide (LPS), NK cells are transiently activated, leave the lymph node, and infiltrate the tumor, delaying its growth. Interestingly, NK cells are not actively recruited at the draining lymph node early after LPS administration, but continue their regular homeostatic turnover. Therefore, NK cells resident in the lymph node at the time of LPS administration become activated and exert anti‐tumor functions. NK‐cell activation correlates with the establishment of prolonged interactions with dendritic cells (DCs) in lymph nodes, as observed by two‐photon microscopy. Close DC and NK‐cell contacts are essential for the localized delivery of DC‐derived IL‐18 to NK cells, a strict requirement in NK‐cell activation.

Natural killer (NK) cells have antitumor, antiviral, and antibacterial functions, and efforts are being made to manipulate them in immunotherapeutic approaches. However, their activation mechanisms remain poorly defined, particularly during bacterial infections. Here, we show that upon lipopolysaccharide or E. coli exposure, dendritic cells (DCs) produce three cytokines—interleukin 2 (IL-2), IL-18, and interferon β (IFN-β)—necessary and sufficient for NK cell activation. IFN-β enhances NK cell activation by inducing IL-15 and IL-15 receptor α not only in DCs but, surprisingly, also in NK cells. This process allows the transfer of IL-15 on NK cell surface and its cis presentation. cis-presented NK cell-derived and trans-presented DC-derived IL-15 contribute equally to optimal NK cell activation.

In order to minimize the impact of systemic toxicity of drugs in the treatment of local acute and chronic inflammatory reactions, the achievement of reliable and efficient delivery of therapeutics in/through the skin is highly recommended. While the use of nanoparticles is now an established practice for drug intravenous targeted delivery, their transdermal penetration is still poorly understood and this important administration route remains almost unexplored. In the present study, we have synthesized magnetic (iron oxide) nanoparticles (MNP) coated with an amphiphilic polymer, developed a water-in-oil emulsion formulation for their topical administration and compared the skin penetration routes with the same nanoparticles deposited as a colloidal suspension. Transmission and scanning electron microscopies provided ultrastructural evidence that the amphiphilic nanoparticles (PMNP) cream formulation allowed the efficient penetration through all the skin layers with a controllable kinetics compared to suspension formulation. In addition to the preferential follicular pathway, also the intracellular and intercellular routes were involved. PMNP that crossed all skin layers were quantified by inductively coupled plasma mass spectrometry. The obtained data suggests that combining PMNP amphiphilic character with cream formulation improves the intradermal penetration of nanoparticles. While PMNP administration in living mice via aqueous suspension resulted in preferential nanoparticle capture by phagocytes and migration to draining lymph nodes, cream formulation favored uptake by all the analyzed dermis cell types, including hematopoietic and non-hematopoietic. Unlike aqueous suspension, cream formulation also favored the maintenance of nanoparticles in the dermal architecture avoiding their dispersion and migration to draining lymph nodes via afferent lymphatics.