A facile one-step gelation approach simultaneously combining physical and chemical cross-linking for the preparation of injectable hydrogels

Abstract

Injectable hydrogels are promising substrates for tissue engineering and drug delivery applications, while the existing hydrogels and gelation approaches usually have unsatisfactory mechanical strength, notable cytotoxicity, limited controllability, and complex and time-consuming gelation process. Herein, an ultra-facile and versatile approach is reported to overcome these problems via a simultaneously occurring physical (hydrogen bond and π–π stacking) and chemical (transesterification) cross-linking between the polyamidoamine (PAMAM) and N-hydroxysuccinimide/maleimide dual-functionalized PEG (NHS-PEG-MAL). Because of skillfully integrated major advantages of individual physical and chemical cross-linking, as well as due to the simplification of the complex and time-consuming gelation process of sequential multi-step cross-linking, this approach displays various advantages over traditional ones, including excellent mechanical strength, good homogeneity and plasticity, good controllability in gelation rate (tens of seconds to several minutes), porosity and storage modulus (several kPa to several MPa). Moreover, this approach demonstrates a relatively gentle and safe gelation process accompanied by favorable biocompatibility for 3D cell culture. The cell viability of all the resultant hydrogels is >80% after culturing for 2 days, which even increases to >90% for 10% w/v hydrogels. Taken together, this study reports an ultra-facile and versatile approach for the preparation of injectable hydrogels with numerous advanced features enabling various biomedical applications.