Hybrid polypeptide hydrogels produced via native chemical ligation

Biocompatible crosslinking is a key approach for developing biomedical hydrogels and scaffolds. In this report, native chemical ligation (NCL) was utilized to prepare biocompatible and biodegradable hydrogel using naturally derived poly(γ-glutamic acid) and e-poly-lysine as the backbone without any additive and byproduct. First, thiolactone grafted poly(γ-glutamic acid) (PGA-HC) and cysteine grafted e-poly-lysine (EPL-C) precursors were synthesized. Their structure was confirmed by nuclear magnetic resonance (NMR). After that, NCL crosslinking of PGA-HC and EPL-C precursors was triggered by simply blending their buffer solutions without any additive at room temperature, resulting in a hybrid polypeptide hydrogel. The crosslinking approach was verified by Fourier transform infrared spectroscopy (FTIR) analysis. The equilibrium water content, morphology, degradation rate and mechanical properties of the hybrid hydrogels were characterized in detail. The results revealed the NCL hybrid hydrogels had tunable gelation time, water content and mechanical properties by adjusting precursor composition. Furthermore, the biocompatibility of hybrid hydrogels was confirmed by MTT assay. These characteristics provide a potential opportunity for the NCL hybrid polypeptide hydrogels as wound dressings, skin fillings, drug delivery vehicles and tissue regeneration matrices.