Comparative Effects of Two Hyaluronic Acid-Based Formulations on Cellular Repair Mechanisms in Human Keratinocytes

Hyaluronic acid formulations are widely used in aesthetic and regenerative medicine, yet molecular weight-dependent effects on cellular repair remain incompletely characterized. This study investigated two hyaluronic acid formulations-low- and medium-high-molecular-weight ranges with trehalose (LMHMW-HA; 200-400 and 1200-1500 kDa) and high-molecular-weight range (HMW-HA; 1800-2600 kDa)-on keratinocyte repair using an in vitro scratch assay. Human keratinocyte monolayers were treated with various concentrations, and repair dynamics were monitored over 48 h through microscopy and quantitative inter-edge distance analysis. Both formulations significantly enhanced gap closure compared to controls without cytotoxic effects. LMHMW-HA promoted gradual closure over 48 h with increased cellular density, indicating sustained proliferation and migration. HMW-HA induced faster closure at approximately 30 h, accompanied by transient pericellular swelling consistent with hydration-mediated edge approximation. These findings indicate that LMHMW-HA and HMW-HA promote repair through distinct patterns: LMHMW-HA was associated with gradual closure and increased cellular density consistent with proliferation-driven repair, while HMW-HA induced rapid closure with transient pericellular swelling consistent with hydration-mediated effects. These preliminary observations suggest complementary repair mechanisms and provide a foundation for future mechanistic investigations. The molecular weight-tailored approach combining HA with trehalose offers therapeutic potential for aesthetic and regenerative medicine applications requiring enhanced tissue repair.