Influence of Hyaluronic Acid, Saline, and Sterile Water as Diluents on the Physicochemical Properties of Polycaprolactone Microsphere-Based Fillers.

OBJECTIVE

Diluting polycaprolactone (PCL) microsphere-based fillers is increasingly used in clinical practice to adjust handling and performance. However, how diluents affect the physical stability, injectability and rheological properties of these systems has not been systematically evaluated.

AIMS: This study aims to systematically investigate the sedimentation stability, extrusion force, and rheological behavior of diluted polycaprolactone (PCL) microsphere-based fillers prepared using three distinct diluents: non‑cross‑linked hyaluronic acid solution, saline, and sterile water. The findings are intended to provide experimental evidence for subsequent clinical handling and procedural planning.

METHODS

PCL microspheres-based fillers were diluted with non-cross-linked HA solution, sterile water, or saline at varying ratios. Sedimentation behavior was assessed both macroscopically and microscopically over a 20-minute period. Extrusion force was measured using 30 G and 32 G needles. Key rheological parameters, including storage modulus (G'), loss modulus (G''), and complex viscosity (η*), were systematically characterized.

RESULTS

Dilution with non-cross-linked HA significantly enhanced formulation stability. Representative HA-diluted formulation (PCL2HW2) maintained homogeneity for more than 20 minutes, while saline-diluted and water-diluted counterparts exhibited rapid phase separation. HA-diluted samples required higher extrusion forces (2.2-3.3 N) than saline-diluted and water-diluted formulations (1.1-2.0 N), though all remained readily injectable through fine needles under clinically relevant conditions. Rheological analysis showed that HA-diluted formulations exhibited a concentration-dependent decrease in moduli with increasing diluent volume, while maintaining a superior viscoelastic profile than saline and water controls, which displayed predominantly low-viscosity and liquid-like behavior.

CONCLUSION

Non-cross-linked HA solution serves as a superior diluent to saline and water, effectively stabilizing PCL microspheres and providing favorable rheological properties for superficial delivery. These findings confirm the technical feasibility of HA-diluted PCL fillers for hydro-shaping and mesotherapy indications and provide a scientific basis for optimizing clinical protocols in superficial aesthetic treatments due to inherently higher viscosity of HA, whereas saline and water can also be used as alternative dilution media. However, based on the stability kinetics, HA-diluted preparations should be used within 20 minutes, whereas saline- or water-diluted should be administered within 5 minutes to ensure optimal performance.

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