Spatiotemporally dynamic therapy with shape-adaptive drug-gel for the improvement of tissue regeneration with ordered structure.

A spatiotemporally dynamic therapy (SDT) is proposed as a powerful therapeutic modality that provides spatially dynamic responses of drug-carriers for adapting to the wound microenvironment. Herein, dynamic chitosan-poly (ethylene glycol) (CP) Schiff-base linkages are employed to perform SDT by directly converting a liquid drug (KFX) into a gel formation. The obtained KFX-CP drug-gel with shape-adaptive property is used to treat a representative oral mucositis (OM) model in a spatiotemporally dynamic manner. The KFX-CP drug-gel creates an instructive microenvironment to regulate signaling biomolecules and endogenous cells behavior, thereby promoting OM healing by the rule of dynamically adjusting shape to fit the irregular OM regions first, and then provides space for tissue regeneration, over KFX potion control and the general hydrogel group of CP hydrogel and KFX-F127. Most interestingly, the regenerated tissue has ordered structure like healthy tissue. Therefore, the SDT provides a new approach for the design of next generation of wound dressing and tissue engineering materials.