Conformationally constrained dipeptide-based hydrogel as a platform for 3D cell growth and tissue engineering applications

Abstract

Conventional two-dimensional culture has greatly assisted tissue engineering research but the absence of tissue-like architectures and availability of unidirectional cell growth limited its use in biomedical applications. Hydrogels, particularly peptide-based, due to their solid-like porous structures, high water content, and high biocompatibility offer tissue-like three-dimensional microenvironments for cell growth and help to mimic in vivo tissue-like conditions in in vitro. Here, we described spontaneous self-assembly of a conformationally constrained dipeptide, Leucine-α,β-dehydrophenylalanine (Leu-ΔPhe), into a strong hydrogel. Leu-ΔPhe hydrogel showed high mechanical strength in mega-pascal with self-healing properties. The hydrogel supported culture of three different mammalian cells including HEK293T, HeLa, and HepG2 in its matrix. Results of cell viability, confocal microscopy and protein expression for HEK293T cells cultured in the hydrogel have indicated that the cells were healthy and functional. In addition, Leu-ΔPhe hydrogel was stable against proteases which makes it a good candidate for use in tissue engineering applications.