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 linking network architecture, rheology, and hyaluronidase response.

Data sources: Comparative degradation studies, material-characterization papers, and platform-level experimental investigations published between 2018 and 2026 were prioritized, with emphasis on studies that enabled interpretable comparison among filler technologies.

Eligibility criteria: Studies were retained when they clarified how network architecture, viscoelastic behavior, physicochemical attributes, or enzymatic conditions influenced comparative performance or hyaluronidase-mediated degradation. Greater interpretive weight was given to studies with explicit reporting of enzyme formulation, dose, dilution, exposure time, and readout method.

Methods of synthesis: This narrative review applied a structure-property-processing-performance framework and read the literature comparatively rather than descriptively. Priority was assigned to studies reporting analytically useful rheological or microstructural attributes, standardized degradation conditions, or material features capable of supporting platform-level interpretation.

Main findings: Current evidence consistently shows that HA fillers are materially heterogeneous. Differences in crosslinking strategy, molecular-weight composition, gel-phase organization, cohesivity, and viscoelastic behavior translate into non-equivalent dissolution patterns under exposure to hyaluronidase. Dynamic rheology, especially amplitude sweeps, linear viscoelastic range analysis, and frequency sweeps, provides a more diagnostic account of network architecture than static G′ values alone. Comparative interpretation is further conditioned by enzyme formulation, endpoint definition, and the transparency of the analytical workflow used to assess degradation.

Conclusion: The literature supports a materially explicit reading of filler performance and argues against treating enzymatic reversibility as a generic class property. Further progress will depend on standardized and auditable comparative designs integrating advanced rheology, microstructural characterization, digitally assisted metrology, and, where prospectively validated, computational approaches that improve traceability, reduce observer dependence, and strengthen platform-level comparison within translational biomaterials research.