Rapidly Thermoreversible and Biodegradable Polypeptide Hydrogels with Sol-Gel-Sol Transition Dependent on Subtle...

Thermoreversible hydrogels are attractive materials for biomedical applications, but their applications are still limited by nonbiodegradability and/or slow temperature-dependent gel-to-sol transition rates. In this research, we prepared a range of amphiphilic diblock, triblock, and four-armed star block copolymers composed of poly(ethylene glycol) (PEG) and poly(γ-(2-(2-ethoxyethoxy)ethyl)-l-glutamate) (P(EEO₂LG)) segments, which can form rapidly thermoreversible hydrogels at physiological temperature. Intriguingly, the obtained hydrogels can transform from gel to sol within 10-70 s in response to the temperature decrease from 37 to 0 °C. The thermosensitive sol-gel-sol transitions are markedly faster than previously reported thermoreversible PEG-poly(l-glutamate) derivative hydrogels with subtle differences in the side groups and a widely studied poly(d,l-lactide-co-glycolide)-b-PEG-b-poly(d,l-lactide-co-glycolide) (PLGA-PEG-PLGA) hydrogel that required a much longer time of 40∼150 min. Further investigation of the relationship between the hydrogel property and polymer structure is performed, and the self-assembly mechanisms of different copolymers are proposed. Cytotoxicity assays and subcutaneous degradation experiments reveal that the PEG/P(EEO₂LG) block copolymers are biocompatible and biodegradable. The polypeptide hydrogel can therefore be used as a three-dimensional platform for facile cell culture and collection by regulating the temperature.