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

January 2025 | Volume 24 | Issue 1 | 34 | Copyright © January 2025


Published online December 18, 2024

doi:10.36849/JDD.8464R1

Jill Waibel MDa, Thu Q. Nguyen PhDb, Jennifer H.T.D. Le PharmD RPhb, Aamir Qureshi MD MBAb, Mary Ziegler PhDc, Alan Widgerow MBBCh MMed FCS FACSb,c, Matthew Meckfessel PhDb

aMiami Dermatology and Laser Institute, Miami, FL
bGalderma Laboratories, L.P., Dallas, TX
cALASTIN, a Galderma Company, Carlsbad, CA

Abstract
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

INTRODUCTION

Aging skin is characterized by dermal thinning with collagen, elastin loss, and altered fat volume and distribution.1,2 These changes occur due to the degradation of the skin's structural components with function alteration due to intrinsic and extrinsic factors.3,4

The epidermis and dermis atrophy are due to decreased and inefficient mast cells and fibroblasts, which are key to structural alterations, including diminished collagen, proteoglycans, and elastin.3,4 Senescent fibroblasts create a pro-aging microenvironment.5 In pro-aging environments, matrix metalloproteinases (MMPs) are activated, accelerating extracellular matrix (ECM) breakdown and suppressing growth factor release.3 In addition, complex negative feedback loops occur due to abnormal collagen and elastin metabolism, increasing MMPs and furthering ECM degradation.3,6 Superficial and deep facial fat compartments are also altered.7 Fat can reposition, which is most apparent in the jowl, lateral nasolabial fold (NLF), and labiomental crease.7

When selecting treatments, it is important to consider regeneration. Regenerative pathways activate multiple systems that help restore the tissue's natural architecture and function. Treatments that offer tissue replacement primarily result in connective tissue deposition, which does not translate to natural morphology or function.3 Regenerative aesthetics focuses on the recreation of normal/youthful functioning tissue.3 An important step toward regenerative aesthetics approaches includes identifying potentially regenerative treatments.3 Regenerative approaches use cells, bio-cues, and scaffolds.3 Scaffolds may be regenerative or non-regenerative. Regenerative scaffolding can stimulate structural tissue components, while non-regenerative scaffolds lead to narrow tissue-type formation.3

Poly-L-lactic acid (PLLA) and calcium hydroxylapatite (CaHA) are both commonly used aesthetic treatments.4 Soft-tissue injectables are popular because they are minimally invasive and are effective for restoring volume and correcting contour deficiencies.8 PLLA-SCATM (Sculptra®, Galderma Laboratories,

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