Effects of Poly‐L‐Lactic Acid Fillers on Inflammatory Response and Collagen Synthesis in Different Animal Models

ABSTRACT Background The responses to poly‐L‐lactic acid (PLLA) filler implantation exhibit variability across various animal models. This study aimed to investigate these differences in order to identify suitable animal models for diverse experimental applications. Methods PLLA fillers were implanted into two distinct skin layers (periosteum and subcutaneous tissue), in rabbits, guinea pigs, rats, and mice. At 1, 2, 4, and 12 weeks postimplantation, biopsy samples were collected for hematoxylin and eosin staining, Masson's trichrome staining, and enzyme‐linked immunosorbent assay (ELISA) to evaluate the differential responses among the animals. Results All four animal models exhibited significant inflammatory responses and collagen regeneration following PLLA injection. However, the magnitude of these responses varied across species, with guinea pigs and rabbits displaying the most pronounced inflammatory responses, whereas mice exhibited the mildest. The degree of response also differed between tissue layers, with rats and mice showing stronger inflammatory responses in the periosteum compared to the subcutaneous tissue; a phenomenon not observed in rabbits and guinea pigs. ELISA analysis revealed upregulated TNF‐α, IL‐12, and TGF‐β expression in rats and mice at 12 weeks. Conclusions Varying levels of tissue responses are observed following PLLA injections in different animals and within different tissue layers within a single animal. These findings suggest a careful selection of appropriate animal models is necessary for specific research objectives.