Injectable, biomolecule-responsive polypeptide hydrogels for cell encapsulation and facile cell recovery through triggered degradation.

Injectable hydrogels have been widely investigated in biomedical applications, and increasing demand has been proposed to achieve the dynamic regulation of physiological properties of hydrogels. Herein, a new type of injectable and biomolecule-responsive hydrogel based on poly(L-glutamic acid) (PLG) grafted with disulfide bond modified phloretic acid (denoted as PLG-g-CPA) was developed. The hydrogels formed in situ via enzymatic crosslinking under physiological condition in the presence of horseradish peroxidase and hydrogen peroxide. The physiochemical properties, including gelation time and rheological property, of the hydrogels were measured. Particularly, the triggered degradation of the hydrogel in response to a reductive biomolecule, glutathione (GSH), was investigated in detail. The mechanical strength and inner porous structure of the hydrogel were influenced by the addition of GSH. The polypeptide hydrogel was used as a three-dimentional (3D) platform for cell encapsulation, which could release the cells through the triggered disruption of the hydrogel in response to the addition of GSH. The cells released from the hydrogel were found to maintained high viability. Moreover, after subcutaneous injection into rats, the PLG-g-CPA hydrogels with disulfide-containing crosslinks exhibited a markedly faster degradation behavior in vivo compared to the PLG hydrogels without disulfide crosslinks, implying an interesting accelerated degradation process of the disulfide-containing polypeptide hydrogels in the physiological environment in vivo. Overall, the injectable and biomolecule-responsive polypeptide hydrogels may serve as potential platform for 3D cell culture and easy cell collection.