Hyaluronic Acid Fillers as Injectable Biomaterials: Relationships Among Network Architecture, Rheology, and Hyaluronidase Response

Abstract

Objective: To critically reinterpret contemporary evidence on hyaluronic acid fillers through a biomaterials framework that links network architecture, rheology, and hyaluronidase response.

Sources and interpretive strategy: This narrative review prioritized comparative and material-characterization studies published between 2018 and 2026, with greater interpretive weight assigned to studies that compared technological platforms and reported analytically useful physicochemical or degradation data.

Synthesis: Available evidence consistently shows that hyaluronic acid fillers are materially heterogeneous. Differences in crosslinking chemistry, molecular-weight composition, gel-phase organization, cohesivity, and viscoelastic profile translate into non-equivalent dissolution patterns under standardized hyaluronidase exposure. Susceptibility to hyaluronidase cannot be inferred from a single rheological parameter or from commercial taxonomy alone; it emerges from the interaction among network architecture, gel concentration, crosslink density and distribution, and experimental variables such as enzyme source, dose, dilution, exposure time, and readout method.

Conclusion: Current evidence supports a materially explicit reading of filler performance and argues against treating enzymatic reversibility as a generic class property. Further progress will depend on more standardized and auditable study designs integrating advanced rheology, microstructural characterization, and reproducible degradation assays.