Poly-D,L-Lactic Acid Filler Increases Hair Growth by Modulating Hair Follicular Stem Cells in Aged Skin

Area of Science:

• Dermatology and Regenerative Medicine
• Immunology
• Stem Cell Biology

Background:

• Age-associated hair loss stems from diminished hair follicle stem cell (HFSC) function and proliferation, often worsened by inhibitory signals and niche alterations.
• Macrophage polarization towards the anti-inflammatory M2 phenotype is recognized for its capacity to boost stem cell proliferation.

Purpose of the Study:

• To investigate the effects of poly-D,L-lactic acid (PDLLA) on hair growth in middle-aged skin.
• To explore PDLLA's role in modulating macrophage polarization and HFSC activity, focusing on Piezo1 signaling.

Main Methods:

• Senescent macrophages were treated with PDLLA to analyze Piezo1 activity, M2 polarization, and secretion of growth factors (HGF, IGF-1).
• Downstream effects on HFSC proliferation, stemness, and Wnt signaling were assessed, including Piezo1 inhibition experiments.
• In vivo studies in middle-aged mice evaluated hair follicle metrics and coverage following PDLLA administration.

Main Results:

• PDLLA treatment enhanced Piezo1 activity in senescent macrophages, promoting M2 polarization and increasing HGF/IGF-1 secretion.
• This led to activation of the RAS/ERK pathway, boosting HFSC proliferation and stemness, and upregulating Wnt signaling.
• In vivo, PDLLA significantly increased hair follicle number, diameter, length, prolonged anagen phase, and improved hair coverage in middle-aged mice.

Conclusions:

• PDLLA rejuvenates the middle-aged skin microenvironment by enhancing Piezo1-mediated M2 macrophage polarization and improving HFSC function.
• PDLLA presents a potential therapeutic strategy for age-related hair loss by targeting both immune and stem cell compartments.