Skin aging is a multifactorial and progressive biological process resulting from both intrinsic (chronological) and extrinsic (environmental) factors. Intrinsically, it is driven by genetic programming, hormonal changes, and the gradual decline in cellular function, while extrinsic aging is largely caused by ultraviolet radiation, pollution and lifestyle factors such as smoking and diet [1]. These processes lead to cumulative damage to skin structures, resulting in dermal thinning, loss of elasticity, decreased hydration, uneven pigmentation, and the formation of fine lines and wrinkles. The aging skin is characterized by reduced fibroblast activity, fragmentation of collagen and elastin fibers and alterations in the extracellular matrix (ECM) [2,3]. Additionally, oxidative stress and chronic low-grade inflammation, commonly referred to as “inflammaging,” contribute to cellular senescence and ECM degradation [4].

Another hallmark of aging skin is the decline in hyaluronic acid (HA) content. HA is a key molecule for water retention and volume maintenance in the dermis. Its reduction compromises skin turgor and hydration, contributing to the dry and dull appearance often seen in aged skin [5]. Furthermore, dermal microcirculation becomes impaired with age, leading to reduced nutrient and oxygen delivery to the skin and impairing tissue repair mechanisms [6].

Collectively, these changes result in visible and functional deterioration of the skin, creating a growing demand for targeted therapies that not only address structural support but also stimulate biological regeneration and cellular rejuvenation. In this context, the use of HA-polyrevitalizing solutions and neuromodulators such as botulinum toxin A, has emerged as an innovative approach in multi-layered facial rejuvenation strategies [7].

Given the multifactorial nature of skin aging, regenerative strategies that combine structural support with dermal revitalization are increasingly favored. One such approach involves the use of polyrevitalizing solutions, like NCTF® 135 HA, a sterile injectable formulation composed of non-crosslinked hyaluronic acid (5 mg/mL) and a complex of 59 active ingredients, including amino acids, vitamins, minerals, nucleotides, coenzymes, and antioxidants [8]. Its purpose is to restore optimal skin physiology by stimulating fibroblast activity, promoting extracellular matrix remodeling, and enhancing microcirculation. These effects reflect its ability to reactivate dermal metabolism, increase collagen and elastin synthesis, and improve cutaneous density — making it ideal for intradermal biorevitalization protocols, particularly in photodamaged or aging skin [9,10].

Complementing this, the intradermal and intramuscular use of botulinum toxin type A (BoNT-A) offers both functional and aesthetic benefits. While traditionally used to reduce dynamic wrinkles via neuromuscular blockade, recent literature highlights a second mechanism: “Botulinum toxin A has also demonstrated efficacy through intradermal (‘microbotox’, ‘mesobotox’) injection for skin rejuvenation; improving texture, tone, pore size, and elasticity” [11]. This cutaneous action is attributed to modulation of sebaceous activity, reduction in superficial muscle contraction, and potential effects on dermal fibroblasts and vascular regulation [12].

Therefore, a layered approach — combining intramuscular BoNT-A, intradermal mesobotox, and Poly-HA-biorevitalization — provides a synergistic effect, targeting multiple aspects of facial aging in a single protocol: muscular overactivity, structural dermal depletion and cellular metabolic decline.