As we age, hair becomes thinner, sparser, and duller. Behind these changes lies a cascade of processes: oxidative stress accumulates, dermal papilla cells grow "tired" and slide into senescence, insulin-like growth factor-1 (IGF-1) secretion declines, proliferation of hair matrix keratinocytes slows, and keratin synthesis drops [1].

Poly-D, L-lactic acid (PDLLA) is already well studied as a biostimulatory filler for facial skin rejuvenation, known for reducing oxidative stress and kickstarting tissue repair processes. It was a logical next step to ask whether the same mechanism could apply to the hair follicle. That is exactly the hypothesis a team of researchers set out to test in a new laboratory study [2].

What the researchers did

The goal was to determine whether a PDLLA filler could slow age-related changes in the structures responsible for hair growth and quality. The study had two stages.

The first stage was conducted in vitro: cultures of human dermal papilla cells (hDPCs) and human hair follicle keratinocytes (hHFKs) were aged with hydrogen peroxide (H₂O₂), then treated with PDLLA at 300 μg/mL.

The second stage moved in vivo, using 17-month-old female C57BL/6 mice — a model of naturally aged animals. The mice received intradermal injections of either the PDLLA filler or saline (500 μL across five sites on the back, 27G needle), with 5 animals per group; outcomes were assessed 3 weeks after injection.

One important detail: the filler tested was a clinical-grade formulation containing a small amount of hyaluronic acid (HA) as a suspending agent alongside PDLLA — meaning the study examined a finished product rather than "pure" PDLLA polymer.

Results

At the cellular level (in vitro)

Treating H₂O₂-aged dermal papilla cells with PDLLA produced the following effects:

• lower levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of oxidative DNA damage;
• reduced cell-cycle arrest, a hallmark of senescent cells;
• increased secretion of insulin-like growth factor-1 (IGF-1).

The effect also carried further down the chain: conditioned media from PDLLA-treated dermal cells boosted proliferation and keratin production in aged follicle keratinocytes.

In the animal model (in vivo)

In mice receiving PDLLA injections, the pattern repeated and expanded:

• lower 8-OHdG levels in dermal papilla cells;
• restored proliferative activity of dermal papilla cells, as shown by PCNA expression, a marker of cell division;
• increased IGF-1 levels in the dermal papilla;
• enhanced keratinocyte division in the hair matrix;
• a marked rise in expression of hair cortex keratins (K35, K85) and inner root sheath markers (AE15, K25, K71);
• a more intact hair cuticle structure and fewer signs of follicle miniaturization;
• reduced signs of sebaceous gland aging, reflected in higher PCNA and PPAR-γ receptor expression;
• increased hair shaft shine, correlating with the changes observed in the sebaceous glands.

The article does not report specific p—values for each outcome; it reports only general significance thresholds (p<0.05 and p<0.01) relative to control groups.

Safety

Data here are limited: the methods section notes that no animals were excluded from analysis after group allocation, but the article does not separately describe adverse events or injection tolerability.

Limitations

The authors themselves candidly list several weaknesses of the study.

First, the in vivo data come from an aged mouse model. Clinical studies are needed to confirm efficacy and determine dosing in humans—particularly given substantial differences between mice and humans in skin thickness and hair growth cycle dynamics: the cycle is synchronized in mice, whereas human follicles cycle independently in a "mosaic" pattern.

Second, the authors did not assess the long-term safety and durability of the effect with repeated or prolonged PDLLA injections.

Third, although the authors showed increased expression of NRF2 and antioxidant enzymes (SOD, catalase, GSH-Px), a direct causal link between NRF2 activation and reduced 8-OHdG still needs confirmation using pathway inhibitors.

Fourth, hHFKs serve only as a surrogate for hair matrix keratinocytes, so further studies using primary cells or organoid models are needed.

Finally, because the tested filler contains HA and no HA-only comparison group was included, the authors cannot precisely separate PDLLA's contribution from HA's to the observed effect.

What this means for practice

For practicing specialists, this study is notable primarily as support for a hypothesis: the biostimulatory properties of PDLLA, already familiar from soft-tissue augmentation and facial skin rejuvenation, may extend to the hair follicle—through reduced oxidative stress, support for dermal papilla function, and stimulation of keratin synthesis [3].

The study broadens our understanding of how PDLLA filler works and opens a new avenue for research into its role in trichology.

That said, these are currently laboratory findings from cells and animals, not an established clinical technique for the human scalp. It is premature to speak of a ready-made treatment for age-related hair thinning: as the authors themselves acknowledge, clinical trials on the human scalp, an HA-only comparison group, and long-term safety data are all needed before these findings can be translated into practice.

References

1. Trüeb R.M. The impact of oxidative stress on hair. Int J Cosmet Sci 2015; 37: 25–30.
2. Oh S., Seo S.B., Kim G., Batsukh S. et al. Poly-D, L-lactic acid filler restores hair thickness and shine by ameliorating age-associated follicular decline. Int J Mol Sci 2026; 27(5): 2098.
3. Zhang H.L., Qiu X.X., Liao X.H. Dermal papilla cells: from basic research to translational applications. Biology 2024; 13: 842.