Injectable and Sprayable Polyphenol-Based Hydrogels for Controlling Hemostasis

Injectable and sprayable hydrogels have attracted considerable attention for application in the biomedical field owing to their high moldability and efficiency in encapsulating therapeutics and cells. Herein, we report the spontaneous assembly of injectable and sprayable hydrogels via a one-step mixing of solutions of tannic acid (TA) and O-carboxymethyl chitosan (CMCS) without an external stimulus. The presence of 1,4-benzenediboronic acid (BDBA) improves the mechanical properties and reduces the gelation time of the resulting hydrogels. The hydrogels assemble via hydrogen bonds between TA and CMCS as well as via dynamic boronate ester bonds between TA and BDBA, as confirmed by Fourier transform infrared spectroscopy. Balancing the interactions between the three components (CMCS/TA/BDBA) is essential for the construction of the hydrogels. The moduli of the CMCS-TA-BDBA hydrogels initially increase as the amount of BDBA increases and decrease after reaching a maximum value at a BDBA-to-TA molar ratio of 3:1. The CMCS-TA-BDBA hydrogels with interconnected porous morphologies display rapid gelation (similar to 10 s), biocompatibility, self-healing, injectable, and sprayable abilities. In addition, the hydrogels can be used for hemostasis. The extent of bleeding in mouse livers treated with the hydrogels could be reduced extensively from 240 (nontreated mouse livers) to 55 mg (77% reduction). The reported hydrogels coupled with the combination of functionality and biological activity make them promising hemostatic materials for biomedical applications.