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Minimally invasive hyaluronan (HA) tissue fillers are routinely employed to provide tissue projection and correct age-related skin depressions. HA fillers can advantageously be degraded by hyaluronidase (HAase) administration in case of adverse events. However, clear guidelines regarding the optimal dosage and mode of administration of HAase are missing, leaving a scientific gap for practitioners in their daily practice. In this study, we implemented a novel rheological procedure to rationally evaluate soft tissue filler degradability and optimize their degradation kinetics. TEOSYAL RHA® filler degradation kinetics in contact with HAase was monitored in real-time by rheological time sweeps. Gels were shown to degrade as a function of enzymatic activity, HA concentration, and BDDE content, with a concomitant loss of their viscoelastic properties. We further demonstrated that repeated administration of small HAase doses improved HA degradation kinetics over large single doses. Mathematical analyses were developed to evaluate the degradation potential of an enzyme. Finally, we tuned the optimal time between injections and number of enzymatic units, maximizing degradation kinetics. In this study, we have established a scientific rationale for the degradation of HA fillers by multidose HAase administration that could serve as a basis for future clinical management of adverse events.

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