New goals for cross-linked hyaluronic acid application

The understanding of hyaluronic acid's potential in aesthetic medicine has expanded significantly. While cross-linked hyaluronic acid was previously associated primarily with volume restoration and the correction of deep folds, today more attention is being paid to its impact on skin quality. This concept encompasses a combination of characteristics, including hydration, microrelief smoothness, pore visibility, and the overall visual perception of the skin surface.

This is the core idea behind the study under discussion [1]. The authors questioned whether low-cross-linked hyaluronic acid fillers could be used not only for volumization but also to improve skin quality, specifically to reduce the appearance of enlarged pores. To investigate this, the study compared two products: a cohesive polydensified matrix hyaluronic acid (20.0 mg/mL) and a similar formula additionally containing glycerol (17.5 mg/mL). The choice of glycerol was based on its properties as a humectant; earlier studies have demonstrated that this combination improves hydration, elasticity, and density, while reducing roughness and signs of skin fatigue, and enhancing skin tone and radiance [2–4].

Study design and injection technique

This was a prospective, randomized, double-masked, split-face study that included 30 patients with enlarged facial pores. Each participant received the hyaluronic acid and glycerol product on one side of the medial (anterior, adjacent to the nose) cheek, and the hyaluronic acid-only product on the opposite side. Procedures were performed in three sessions: at day 0, week 4, and week 8.

From a practical standpoint, the injection technique is of utmost importance. Instead of deep filler placement in 1–2 points as used for volume correction, the study employed a superficial intradermal technique of multiple micro-injections. On each side of the face, 20 injection points of 0.05 mL (totaling 1 mL of product) were performed using a 30 G 1/2 needle in the medial cheek area. This method is aimed at improving relief and hydration rather than creating volume. The mechanism of action is explained by the fact that hyaluronic acid not only fills the extracellular matrix but also indirectly stimulates collagen and elastin production by mechanically stretching fibroblasts [5].

Results: pores, hydration, and safety

Both regimens showed a positive effect: on both sides of the face, the mean pore volume decreased compared to baseline throughout the 32-week observation period.

Impact on pores and hydration
The glycerol formula proved more effective for the key parameter. On the glycerol-treated side, the relative reduction in mean pore volume over 32 weeks was 24.2% higher than on the side treated with the product without the additive (p=0.038). The most significant reduction in pore volume was observed by week 12. The authors attribute this to two mechanisms: the restoration of the extracellular matrix by hyaluronic acid and the additional moisture-retaining action of glycerol, which improves the structural support of follicular structures [2, 3].

Regarding hydration, both products also showed improvement. At week 4, the advantage of the glycerol-containing product was statistically significant: the increase in hydration was 12.3% higher (p=0.029). By week 32, a positive trend in favor of the glycerol combination persisted, although the difference no longer reached statistical significance. According to the physician's visual assessment, the reduction in pore severity score over time was, on average, twice as high on the glycerol side (p=0.009). In contrast, there was no difference between the sides in patient self-assessment.

Other parameters and safety
No significant differences between the groups were found in transepidermal water loss or skin elasticity parameters. The safety profiles of both formulas were similar: the most common reactions were mild pain, swelling, bruising, or papules immediately after the procedures, which resolved spontaneously within 1–2 weeks. The addition of glycerol was not associated with decreased tolerability or increased frequency of adverse events.

Interpretation for practice

The study illustrates a shift in clinical logic: cross-linked hyaluronic acid can now be used successfully as a biorevitalizer rather than just as a filler for volume. The injection technique is crucial—superficial intradermal microdose injections improve visual skin uniformity, relief, and hydration. The combination with glycerol in this study showed an advantage in reducing pore volume with comparable safety. This suggests that the inclusion of additional active substances further unlocks the biorevitalizing potential of cross-linked hyaluronic acid. Thus, today, not only native but also cross-linked hyaluronic acid has its place in the arsenal of biorevitalizing techniques—and the addition of components such as glycerol opens further opportunities to improve skin quality [4].

References

1. Rutnumnoi T., Palakornkitti P., Anuntrangsee T,. et al. Superficial intradermal injections of cohesive polydensified matrix hyaluronic acid fillers for the improvement of facial pores and skin quality: A split-face randomized study. J Cosmet Dermatol 2025; 24: e70209. https://doi.org/10.1111/jocd.70209
2. Hertz-Kleptow D., Hanschmann A., Hofmann M. et al. Facial skin revitalization with CPM-HA20G: An effective and safe early intervention treatment. Clin Cosmet Investig Dermatol 2019; 12: 563–572.
3. Kerscher M., Prager W., Fischer T.C. et al. Facial skin revitalization with cohesive polydensified matrix-HA20G: Results from a randomized multicenter clinical study. Plast Reconstr Surg Glob Open 2021; 9(12): e3973.
4. Kleine-Borger L., Hofmann M., Kerscher M. Microinjections with hyaluronic acid in combination with glycerol: How do they influence biophysical viscoelastic skin properties? Skin Res Technol 2022; 28(4): 633–642.
5. Roh M., Han M., Kim D., Chung K. Sebum output as a factor contributing to the size of facial pores. Br J Dermatol. 2006; 155(5): 890–894.