Catechol-modified hyaluronic acid: in situ-forming hydrogels by auto-oxidation of catechol or photo-oxidation using visible light

Mussel-inspired polymers have emerged as attractive candidates for the synthesis of injectable hydrogels with tissue-adhesive properties. In these systems, polymer crosslinking occurs via the oxidative coupling of catechol groups grafted on the polymer backbone, performed in the presence of an enzyme or a chemical oxidant. Here, we show that catechol-modified hyaluronic acid (HA-CA) can self-crosslink in physiological conditions without any requirement of oxidizing reagents. A careful rheological analysis of gelation of HA-CA solutions indicated that both the degree of substitution and the molar mass of HA-CA are key parameters controlling the gelation kinetics. Interestingly, the gelation time could be dramatically lowered by photo-oxidation of catechol using visible light in the presence of eosin Y as a photosensitizer. This strategy can be advantageously used to manage viscosity and gelation kinetics during injection, which paves the way for various biomedical applications of HA-CA including wound closure and healing as well as drug delivery.