Modular, synthetic, thiol-ene mediated hydrogel networks as potential scaffolds for 3D cell cultures and tissue regeneration

Abstract

Natural polymers such as collagen are popular materials for tissue engineering scaffolds due to their innate bioactivity and biocompatibility. Being derived from animal sources, however, means that batch-to-batch consistency is often low and the extraction of collagen is costly. This conundrum facilitates the need for synthetic alternatives as scaffolding materials. In this study, a system of poly(ethylene glycol) (PEG)-based thiol-ene coupled (TEC) hydrogel scaffolds is presented for tissue engineering purposes. The platform includes several necessary features, namely cytocompatibility, high swelling ability, biodegradability, tunable stiffness, and fast, straightforward fabrication. The swelling ability is provided by the hydrophilicity of the ether-links of PEG, which facilitated the formation of high water content hydrogels that match the water content of soft tissues for the proper diffusion of nutrients and waste compounds. TEC ensures fast and facile fabrication, with cross-linking moieties that allow for the biodegradation of the hydrogel network through hydrolytic cleavage. The mechanical properties of the scaffolds are made tunable in the range of storage moduli spanning <1 kPa to >100 kPa. It is also shown that despite the synthetic nature of the hydrogels, human dermal fibroblasts and murine macrophages, Raw 264.7, were able to survive and produce extracellular protein excretions while embedded in the 3D hydrogels.