Natural Dual‐Crosslinked Self‐Healing Hydrogels for In Situ Wound Healing

Abstract Poly( l ‐glutamic acid) (PLGA), a polypeptide prepared by bacteria fermentation, has broad applications in tissue engineering. A natural host–guest pair of β ‐cyclodextrin ( β ‐CD) and bile acid molecules are attached covalently onto the PLGA backbones separately, and host–guest crosslinked self‐healing hydrogels can be easily formed by mixing these polymer solutions. Inspired by the adhesives of mussel foot proteins, a dopamine methyl acrylamide derivative is introduced into this system to prepare a PLGA‐based dual‐network hydrogel in situ through the combination of host–guest crosslinking and the photo‐crosslinking of the dopamine derivative. The mechanical properties of the hydrogels can be tuned by altering the molar ratios of β ‐CD and bile acid as well as the content of dopamine methyl acrylamide derivative. The dynamic inclusion complexation of β ‐CD and bile acid allows the hydrogel to self‐heal rapidly under ambient atmosphere and their mechanical properties can recover to original levels within 1 min as evidenced in rheological results. The dual‐network hydrogels exhibit stronger adhesion behavior to pig skin than the host–guest crosslinked hydrogels in vitro. The adhesion of the dual‐network hydrogels to rat whole cortical incision has promoted faster wound healing and tissue regeneration than that in sutured treatments in vivo.