Three-dimensional extrusion bioprinting of self-healing hydrogel for tissue regeneration

Abstract

Statement of Purpose: Three-dimensional (3D) bioprinting with living cells provides a useful means to fabricate artificial tissues and organs. Extrusion-based bioprinting is a widely used method due to its low cost and high compatibility with various bioinks. Hydrogels are often employed in extrusion-based bioprinting as they can mimic the structures and functions of extracellular matrices in the body. Inspired by the autonomous healing exhibited by living tissues after damage, self-healing hydrogels have been proposed for 3D bioprinting and have been extensively investigated in recent years. In this study, hyaluronate (HA) was chosen as a base material, as it is an excellent biomaterial for tissue engineering. Glycol chitosan (GC) was also utilized as a polymeric cross-linker to form the network of partially oxidized hyaluronate (OHA) under physiological conditions. We hypothesized that the addition of adipic acid dihydrazide (ADH), a species capable of dynamic and reversible bond formation, to OHA/GC hydrogel would improve autonomous healing of the gel due to the bond exchange reaction. Various characteristics of OHA/GC/ADH hydrogel, including physicochemical properties, biocompatibility, and 3D-printability, were investigated in vitro. In addition, the potential use of OHA/GC/ADH self-healing hydrogel for cartilage regeneration was investigated.