Abstract
BACKGROUND: Superficial injection of hyaluronic acid (HA)-based gels is a widely used method to restore skin quality and achieve a more youthful appearance. While the clinical benefits of such procedures are well established, their biological mechanisms of action remain poorly understood. OBJECTIVE: This study aimed to evaluate the effectiveness of two cross-linked HA gels (IPN-12.5 and HA-X12) on skin rejuvenation, focusing on skin hydration and extracellular matrix quality. The evaluation was conducted using an innovative skin model that closely mimics native human skin. MATERIAL AND METHODS: A bioengineered scaffold composed of collagen, glycosaminoglycans, and chitosan was developed and seeded with aged human fibroblasts. This seeded scaffold has the ability to allow cellular migration, proliferation, and neo-synthesize its own extracellular matrix. Normal human keratinocytes were subsequently seeded on top of the newly formed dermal equivalent, thereby simulating the complex interactions that occur between the epidermis and dermis. Multipoint intradermal injections of the test products were administrated using a multipoint technique during the reconstruction protocol. RESULTS: Both products significantly decreased transepidermal water loss (TEWL), though histomorphological differences were observed. The IPN-12.5-hydrogel-injected models showed enhanced barrier integrity, water retention, epidermal renewal, and skin elasticity markers compared to the controls and HA-X12. CONCLUSION: IPN-12.5 hydrogel significantly improved hydration and elasticity-related skin markers when compared to a similar product (HA-X12). Despite similar clinical indications and concentrations, the products exhibited different biological effects, potentially due to differences in cross-linking technologies or HA molecular weights. These factors are likely to influence clinical outcomes achieved with the two formulations.