Collagen fillers induce local adipogenesis

Objectives: After this session, participants will be able to: (1) describe how collagen-based fillers differ mechanistically from microsphere-based fillers in aged skin; (2) recognize that collagen can actively remodel the dermal microenvironment rather than acting solely through volume support; and (3) interpret the histological evidence linking collagen injection to local adipocyte formation, supporting individualized, evidence-based filler selection. Introduction: The anti-aging effects of dermal fillers are commonly attributed to volumetric augmentation, yet the biological differences among material classes within the aging dermal microenvironment remain poorly characterized at the histological level. In particular, whether different fillers can influence local adipocyte formation is unknown. This study compares collagen-based and microsphere-based materials in their capacity to remodel aged dermis and to induce local adipogenesis. Materials / method: Twelve-month-old C57BL/6 mice were randomized into a saline control and four groups (n=3): type bovine-derived collagen (35 mg/ml), diluted bovine-derived collagen (17.5 mg/ml), PLLA microspheres, or CaHA microspheres, given as dorsal subcutaneous injections. Skin was harvested at 1 and 3 months for HE and Masson trichrome staining and immunofluorescence (Col I, Col III, α-SMA, CD31, Perilipin-1,P16,P21). Dermal thickness, collagen density, follicular appendages, volume occupancy, and adipocyte distribution were quantified. Results: At 3 months, the diluted collagen group showed near-complete resolution of volume occupancy with significant increases in dermal thickness, Col I/III ratio, and follicular appendage density, achieving rejuvenation earlier than the other groups. Both collagen groups had higher α-SMA-positive fibroblast counts and CD31-positive microvascular density than microsphere and control groups. Perilipin-1-positive adipocytes were confirmed in both collagen groups by HE and immunofluorescence but were absent in microsphere groups. Conclusion: The anti-aging mechanisms of different filler classes are fundamentally distinct. Collagen-based materials act not merely through volume support but by actively remodeling the aged dermal microenvironment, accompanied by local adipocyte formation not observed with microsphere materials. These findings provide histological evidence to support individualized, mechanism-based filler selection and a basis for further study of collagen-associated adipogenesis via the pathway.