Synthesis and Evaluation of Cytocompatible Alkyne-Containing Poly(β-amino ester)-Based Hydrogels Functionalized via...

Although poly(β-amino esters) (PAEs) have been widely applied in nonviral gene transfection, drug delivery systems, and regenerative medicine, the multifunctional modification of PAEs and bio-orthogonal strategies of PAE-based hydrogel functionalization is still a challenge. Herein, a strategy of poly(β-amino ester)-based hydrogel functionalization was developed via bio-orthogonal reactions in this study. Acrylate-terminated poly(β-amino esters) containing alkyne groups were synthesized by Michael addition reaction. Alkyne groups on poly(β-amino esters) could conjugate bioactive molecules with azide of K(N₃)RGD via copper-catalyzed azide-alkyne cycloaddition, and terminal acrylate groups could in situ polymerize to prepare a hydrogel. A biomimetic peptide K(N₃)RGD functionalized hydrogel was prepared by polymerization of acrylate-terminated poly(β-amino esters) containing conjugated peptide and polyethylene glycol diacrylate (PEGDA). The storage modulus and mechanical properties exhibited an increased trend with the increased concentration; nevertheless, swelling ratio and surface wetting properties demonstrated a decreased tendency by increased concentrations. Cell proliferation and live/dead staining showed that Schwann cells plated on the hydrogel with an elastic modulus of 25.39 KPa are more suitable for proliferation and function exertion of Schwann cells compared with that of 42.11 and 57.86 KPa, and KRGD-conjugated hydrogel could increase the elongation of Schwann cells relative to nonconjugated hydrogels. This azide-alkyne strategy may be a promising candidate for hydrogel functionalization in tissue engineering and other biomedical applications.