Thermo-sensitive, injectable, and tissue adhesive sol-gel transition hyaluronic acid/pluronic composite hydrogels prepared from bio-inspired catechol-thiol reaction

Hyaluronic acid (HA) hydrogels are widely pursued as tissue regenerative and drug delivery materials due to their excellent biocompatibility and biodegradability. Inspired by mussel adhesion, we report here a novel class of thermo-sensitive and injectable HA/Pluronic F127 composite tissue-adhesive hydrogels applicable for various biomedical applications. HA conjugated with dopamine (HA-DN) was mixed with thiol end-capped Pluronic F127 copolymer (Plu-SH) to produce a lightly cross-linked HA/Pluronic composite gel structure based on Michael-type catechol-thiol addition reaction. The HA/Pluronic hydrogels exhibited temperature-dependent sol-gel phase transition behaviors different from Pluronic hydrogels. Rheological studies showed that the sol-gel transitions were rapid and reversible in response to temperature. The HA/Pluronic hydrogels could be injected in vivo in a sol state at room temperature using a syringe, but immediately became a robust gel state at body temperature. The in situ formed hydrogels exhibited excellent tissue-adhesion properties with superior in vivo gel stability and are potentially useful for drug and cell delivery.