One-step cross-linked injectable hydrogels with tunable properties for space-filling scaffolds in tissue engineering

Abstract

Developments in tissue engineering have led to the fabrication and refinement of a wide variety of injectable space-filling agents, as they can be injected to the tissue defect sites in a minimally invasive manner. Hydrogels are promising since the native tissue composed of cells and extracellular matrix can be well simulated by hydrogels encapsulating therapeutic cells and drugs. In this study, aldehyde dextran (ald-dex) and amino gelatin (ami-gel) were prepared through reaction with sodium periodate and ethane diamine to fabricate in situ gelable ald-dex/ami-gel hydrogel. The gelation process was monitored rheologically and the microstructure was revealed under scanning electron microscopy (SEM). The tunable porous structures were obtained through simply altering the ratio of aldehyde dextran and amino gelatin. Gelation time and swelling ratio of the ald-dex/ami-gel hydrogels were shown to be related to the crosslinking density of the hydrogels, which can be modulated through simply changing the proportion of ald-dex/ami-gel. The degradation rate could also be modulated by altering the content of aldehyde dextran. Then biocompatibility evaluation was performed on both two-dimensional (2D) and three-dimensional (3D) environments by using mouse pre-osteoblast cells (MC3T3-E1). According to the results, beneficial cell responses such as the attachment, spreading and proliferation of cells were exhibited with the increase of the gelatin content. Furthermore, MC3T3-E1 cells encapsulated inside the hydrogel assumed a round shape initially and gradually adapted to the microenvironment to spread out. Therefore, the ability to support cell adhesion and spreading on the surface and long-term viability of encapsulated cells enabled the tunable ald-dex/ami-gel hydrogel to be an effective space-filling scaffold for tissue engineering.