A Clinical Histology Study Evaluating the Biostimulatory Activity Longevity of Injectable Poly-L-Lactic Acid for Facial Rejuvenation

September 2024 | Volume 23 | Issue 9 | 729 | Copyright © September 2024


Published online September 1, 2024

doi:10.36849/JDD.8057

Suleima Arruda MDa, Victor Prieto MD PhDb, Christopher Shea c, Alyssa Swearingen MDa, Zahyaa Elmadany BSa, Neil S. Sadick MDb

aSadick Dermatology and Research, New York, NY
bDepartment of Pathology, MD Anderson Cancer Center, University of Texas, Houston, TX
cDepartment of Dermatology, University of Miami, FL

Abstract
Background: Poly-L-lactic acid (PLLA) is an injectable filler used for restoring facial fat volume loss that improves skin quality.
Objective: To evaluate the histological changes underlying the observed improvement in skin quality after repeated PLLA injections.
Methods: Ten healthy women were enrolled in this randomized, placebo-controlled, single-center study. Eligible subjects received 3 treatments every 4 weeks with either PLLA (treatment group) or saline (control group) injections, into both sides of the face. Follow-up visits were at week 18 after the last treatment. Assessments included live ratings, patient questionnaires, three-dimensional microtopography imaging analysis, and histological analysis from biopsies taken before and after PLLA treatment.
Results: At the 18-week follow-up, there was a significant improvement in investigator- and subject-rated global aesthetic improvement (GAIS) scores, as well as a decrease in wrinkle severity in PLLA-treated but not placebo-treated patients. Skin quality parameters of erythema, pore size, and roughness were significantly improved from baseline and compared with placebo at the 18-week follow-up as assessed by microtopographic analysis and investigator ratings. Histologic analysis revealed increased tissue remodeling and angiogenesis in PLLA-treated tissues at the 18-week follow-up and decreased elastin fragmentation compared with baseline. No treatment-related adverse events occurred.
Conclusion: Repeated PLLA treatments may improve skin quality through tissue remodeling and neovascularization.

J Drugs Dermatol. 2024;23(9):729-734. doi:10.36849/JDD.8057

INTRODUCTION

The aging process is a complex phenomenon that is influenced by both internal (genetic) and external (environmental) factors. Bone resorption, fat pad repletion, ligament/muscle atrophy, and changes in skin tone, color, and texture all contribute to the loss of a youthful appearance. Injectable soft tissue fillers and neurotoxins are the gold standard in aesthetic medicine for correcting the facial changes associated with aging. These treatments can be used in conjunction with energy-based devices and a daily skincare regimen to achieve natural, long-lasting facial rejuvenation.1

Some fillers, such as hyaluronic acid, volumize the area of injection instantly. Others, such as poly-L-lactic acid (PLLA), are biostimulatory, meaning that they activate resident fibroblasts to produce autologous collagen over time. This leads to a more natural and long-lasting effect.2 The mechanism by which PLLA stimulates neocollagenesis is by triggering a foreign body reaction to the injected material demonstrated by neutrophil and macrophage infiltration from day 2 to day 10 after injection. This is followed by a cellular inflammatory response that leads to the formation of vascularized, connective tissue. PLLA is then hydrolyzed into lactate, converted to pyruvate, and oxidized into carbon dioxide. The inflammatory response subsides in 6 months, but the extracellular matrix production continues, leading to a gradual increase in dermal thickness that can last for at least 2 years.3

PLLA was approved by the US Food and Drug Administration (FDA) in 2004 for the treatment of HIV-associated lipoatrophy, and in 2009 for the correction of shallow to deep nasolabial folds and other facial wrinkles in healthy patients. In 2023, the FDA expanded the approval