Stretchable and self-healable hyaluronate-based hydrogels for three-dimensional bioprinting

Abstract

Hydrogels have been widely exploited as inks for three-dimensional (3D) bioprinting, a useful technique for building complex biological structures with living cells. However, hydrogels have inherently limited mechanical properties (e.g., brittleness) and printability. Thus, we hypothesized that hyaluronate-based hydrogels with stretchable and self-healing properties would be useful for 3D bioprinting. Oxidized hyaluronate (oHA) and hydrazide-modified hyaluronate (hHA) formed stretchable and flexible hydrogels because of double network formation via chemical cross-linking (i.e., acylhydrazone bond formation) and physical cross-linking (i.e., charge interaction). The addition of adipic acid dihydrazide (ADH) to oHA/hHA hydrogels enhanced the self-healing capability of the gels, which were useful for fabricating 3D constructs with various shapes maintaining their stretchability even after 3D printing (about two times its original length). ATDC5 cells were viable within the 3D-printed constructs in vitro. This hydrogel system, consisting of hyaluronic acid (HA)-based polymers, may have potential for many tissue engineering applications via 3D bioprinting.

Keywords: 3D bioprinting; Hydrazide-modified hyaluronate; Oxidized hyaluronate; Self-healing; Stretchable hydrogel.