Abstract

Hyaluronic acid (HA), a naturally occurring glycosaminoglycan (GAG), has emerged as a pivotal bioactive ingredient in modern cosmeceuticals due to its remarkable biocompatibility, hydrophilicity, and multifunctional dermatological benefits. This review explores the structural, pharmacological, and therapeutic dimensions of HA, particularly in the context of skin hydration, repair, and anti-aging. HA’s molecular weight (MW) plays a critical role in its bioactivity. High molecular weight (HMW) HA offers surface-level hydration and anti-inflammatory effects, while low MW-HA penetrates deeper to promote collagen synthesis and tissue regeneration. Topical formulations, injectable dermal fillers, and advanced delivery systems such as nanoparticles and microneedles have broadened HA’s clinical utility and consumer appeal. Mechanistically, HA interacts with receptors such as cluster of differentiation 44 (CD44) and the receptor for hyaluronic acid-mediated motility (RHAMM), influencing the functions of keratinocytes and fibroblasts, while also regulating immune responses through Toll-like receptors 2 and 4 (TLR2/TLR4). These receptor-mediated pathways enhance skin elasticity, accelerate wound healing, and mitigate oxidative stress. Recent advances include cross-linked and bioengineered HA derivatives with improved stability and prolonged activity. Moreover, combination therapies incorporating HA with peptides, retinoids, or vitamins exhibit synergistic benefits in anti-aging and scar treatments. Safety assessments affirm HA’s excellent tolerability, reinforcing its dominant role in both cosmetic and therapeutic dermatology. Emerging frontiers in personalized HA-based skincare and its potential role in regulating the skin microbiome signal forward-looking strategies for innovation. Overall, HA continues to redefine cosmeceutical science by offering multifunctional, evidence-based solutions for skin health and rejuvenation.

Keywords

anti-aging, extracellular matrix, collagen synthesis, Cosmeceuticals, dermal fillers, nanoparticles, transdermal delivery, artificial intelligence