Poly-L-Lactic Acid in Aesthetic Dermatology: A Decade Beyond Volume Restoration Toward Regenerative Biostimulation

Abstract Over the past decade, Poly-L-lactic acid (PLLA), a synthetic, biodegradable, and biocompatible polymer, has evolved from a volumizing solution for HIV-associated lipoatrophy into a foundational tool in regenerative aesthetic dermatology. This systematic review explores PLLA’s transformation across clinical generations, emphasizing its role as a biostimulatory scaffold rather than a conventional filler. Through an extensive literature review, we identify and analyze 67 studies published between January 2013 and March 2025. Findings confirm that PLLA induces a regenerative cascade marked by M2 macrophage polarization, TGF-β1-mediated fibroblast activation, and sustained neocollagenesis, thereby promoting long-term remodeling of the extracellular matrix (ECM), improved dermal density, and enhanced skin quality. The applications of PLLA have extended beyond facial volumization to full-body rejuvenation, with significant roles in post-GLP-1 therapy restoration and preventive ("prejuvenation") strategies. Protocol refinements, including optimized dilutions and cannula techniques, have enhanced safety and efficacy. This review also highlights emerging areas such as PLLA’s integration with energy-based devices, digital imaging, AI diagnostics, and microbiome-focused care. Collectively, the evidence supports PLLA’s utility as a versatile biostimulatory agent that bridges aesthetic innovation and regenerative dermatology.