Gene Analysis of Biostimulators: Poly-L-Lactic Acid Triggers Regeneration While Calcium Hydroxylapatite Induces Inflammation Upon Facial Injection

BACKGROUND: Injectable biostimulator treatments stimulate endogenous collagen in aging skin, but whether they act through similar pathways is unknown. This study evaluates two biostimulatory agents' effects on genes, expressed proteins, and respective pathways as potential aging biomarkers and treatment outcomes. METHODS: This 13-week, randomized, single-center, comparative study compared volume change and gene expression stimulated by poly-L-lactic acid (PLLA-SCATM) and calcium hydroxylapatite (CaHA-R) via punch biopsy in the nasolabial fold (NLF). Subjects (n=21) had shallow NLF contour deficiencies on the wrinkle assessment scale (WAS) ≥2 and identical WAS scores on both sides of the nose. Biopsies at baseline and 90 days were analyzed for gene expression of targeted biomarkers. These results were assessed using the STRING and Reactome databases to determine functional pathways, as well as gene markers and their respective pathways. RESULTS: Gene analysis suggested unique processes for each biostimulator. PLLA-SCA stimulated more components of the extracellular matrix with less inflammatory response, translating to a more regenerative pathway. CaHA-R elicited a more inflammatory response that could diminish tissue regeneration, translating to a pro-inflammatory pathway. CONCLUSIONS: PLLA-SCA is associated with regenerative pathways, while CaHA-R did not show evidence of tissue regeneration and upregulated more genes in pro-inflammatory pathways. J Drugs Dermatol. 2025;24(1):34-40. doi:10.36849/JDD.8464R1.