Comparative Bulk RNA-Seq Analysis of Poly-l-Lactic Acid Versus Calcium Hydroxylapatite Reveals a Novel, Adipocyte-Mediated Regenerative Mechanism of Action Unique to PLLA

BACKGROUND Injectable biostimulators are widely used to improve facial aging signs. This study was performed to compare the genetic pathways affected by 2 different injectable biostimulators. METHODS Randomized 13-week study ( n = 21) comparing gene expression after poly l -lactic acid (PLLA-SCA) and calcium hydroxylapatite (CaHA-R) injections (baseline [BL] and Day 28) as treatment of nasolabial fold wrinkles. Punch biopsy was performed at BL and day 90; RNA was isolated, gene expression was analyzed, and bulk RNA sequencing performed. Data from both pathways were studied using the Search Tool for Retrieval of Interacting Genes/Proteins and Reactome databases. RESULTS Analysis at Day 0 and Day 90 showed differing gene regulation for PLLA-SCA and CaHA-R (after accounting for minor differences at BL, p < .05 at Day 90 for 9–12 genes). PLLA-SCA uniquely correlates with genes involved in adipocyte regeneration, while CaHA-R did not affect these genes. Clinically, this could translate to healthy fat replacement with an enhanced effect beyond the improvement of the collagen structure and a longer-lasting effect with PLLA-SCA. Furthermore, the adipokines that appear to be upregulated are regenerative with a positive impact on skin health. CONCLUSION PLLA-SCA has a novel and unique signature, which supports a potential regenerative mechanism of action through its role in the modulation of adipocyte function.