Subcutaneous Hyaluronic Acid Filler Injection Promotes Skin Regeneration and Modulates Immune Response in a Rat Model: A Histological and Hematological Study

Background: Hyaluronic acid (HA)-based dermal fillers are widely used in aesthetic and reconstructive dermatology. However, the temporal hematological and histological responses to subcutaneous HA injection remain incompletely characterized. Objective: This study aimed to evaluate the effects of a single subcutaneous injection of a hyaluronic acid-based dermal filler on skin tissue structure and hematological parameters in a female rat model over a 14-week period. Methods: Fifty female albino rats were divided into five groups (n=10/group), each with a treatment subgroup receiving a single 0.1 mL subcutaneous injection of a monophasic HA filler (Neuramis Volume Lidocaine) and a control subgroup. Animals were euthanized at 2, 4, 8, 10, and 14 weeks post-injection. Hematological analysis was performed on blood samples, and histopathological examination of skin tissues was conducted using H&E staining. Results: Early phases (2-8 weeks) showed a significant decrease in red blood cell count and hemoglobin, alongside increased white blood cell and lymphocyte counts, indicating an acute inflammatory response. Histology revealed collagen disorganization, dermal thickening, and inflammatory infiltration. By weeks 10-14, hematological parameters normalized. Histological assessment demonstrated tissue regeneration, characterized by reorganization of collagen fibers, reduced inflammation, epidermal renewal, and enhanced tissue remodeling. Conclusion: Subcutaneous HA injection induces a transient inflammatory immune response followed by progressive tissue regeneration and remodeling. The results confirm the biocompatibility and regenerative potential of HA fillers, supporting their safe use in clinical applications. Conclusion: Subcutaneous HA injection induces a transient inflammatory immune response followed by progressive tissue regeneration and remodeling. The results confirm the biocompatibility and regenerative potential of HA fillers, supporting their safe use in clinical applications.