In Vivo Effectiveness of Poly-L-Lactic Acid Microsphere Dermal Fillers in Stimulating Collagen Synthesis.

[BACKGROUND] Intradermal injections of fillers such as poly-L-lactic acid (PLLA) microspheres and hyaluronic acid (HA) offer the possibility of skin rejuvenation. However, the biological effects of these fillers and the mechanisms underlying collagen synthesis have not been fully elucidated. We investigated the histological effects of PLLA microsphere fillers on the rat dermis.

[METHODS] PLLA microspheres were used as the experimental group, while HA and saline served as the positive and negative controls, respectively. Equal doses of cross-linked HA, saline, and PLLA microspheres were intradermally injected into the backs of male Sprague-Dawley rats. Biopsy specimens were collected and histologically analyzed using hematoxylin and eosin, Ki-67, alpha-smooth muscle actin, Herovici, and Sirius scarlet staining. Immunofluorescence staining for types I and III collagen, CD68, and CD90 was also performed. Quantitative data were statistically analyzed using a two-way analysis of variance.

[RESULTS] PLLA microspheres increased collagen type I and III levels and maintained tissue homeostasis in rat dermis. The PLLA microspheres primarily stimulated type III collagen in the early stage, whereas type I collagen was predominantly stimulated in the later stages. After the PLLA microspheres were injected into the dermal tissue, early fibroblasts and macrophages surrounded the microspheres, followed by the transformation of fibroblasts into myofibroblasts, which positively affected the production of type I collagen. Notably, HA demonstrated a significant stimulatory effect on type I collagen synthesis (P < 0.05) but showed no statistically significant impact on type III collagen production. In contrast, the saline control group failed to show any measurable increase in either collagen subtype throughout the experimental period.

[CONCLUSIONS] HA and PLLA microspheres effectively increased type I collagen levels and maintained dermal tissue homeostasis. PLLA microspheres can be used as the main ingredient in intradermal collagen regenerative fillers due to their long degradation time and lasting effects.

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