Thermally Stable Microporous Microgels for Cell Encapsulation and Tissue Engineering

Microgel-based injectable hydrogels, which are produced by crosslinking (or annealing) the microgels, have recently received a lot of attention due to their ability to induce rapid cell adhesion and promote cell-cell interactions within the interstitial space. Although these approaches showed significantly improved cellular responses compared to the conventional nonporous injectable hydrogels, porosity of the hydrogel is limited by the interstitial pore space and the cellular growth is mostly excluded from the microgel phase. Use of microporous microgels and their assembly can increase porosity of the hydrogel and serve as better scaffolds for tissue engineering. However, most microgels are thermally unstable and the pore structures are lost during the cell encapsulation process at physiological temperature. In this research, we report a novel method of producing thermally stable microporous gelatin/alginate microgels that can be enzymatically crosslinked to form a highly porous bulk hydrogel. The porous structure of microporous microgels and of the crosslinked bulk hydrogel was characterized by scanning electron microscope (SEM) and confocal microscopy. When human dermal fibroblasts (hDFs) were encapsulated in the assembly of microporous microgels, hDFs were found to grow within the pores of microgels with high viability over 7 days.