PH-Responsive Gallol-Functionalized Hyaluronic Acid-Based Tissue Adhesive Hydrogels for Injection and Three-Dimensional Bioprinting.

Abstract

The major challenges of hyaluronic acid-based bioinks in extrusion-based three-dimensional bioprinting are poor printability and low printing accuracy. To tackle the challenges, we developed a bioink in which two components are blended: gallic acid-functionalized hyaluronic acid (HAGA) and hyaluronic acid methacrylate (HAMA). In the precursor phase, the blend's HAGA component enables pH-dependent viscosity modulation that results in improved injectability and printability at physiological temperature. Postprinting, the blend's HAMA component is photocrosslinked to create a true hydrogel with a complementary network of both HAGA and HAMA. The ready structures of the HAGA-HAMA hydrogel showed sufficient printing quality and accuracy compared to plain HAMA. The blend also displayed enhanced viscoelastic properties and stable swelling behavior. In addition to the pH tunability, the HAGA component also imparted tissue adhesion and antioxidant activity. This bioink has the potential to be printed directly on an infected wound site due to its adhesiveness to tissue and dimensional stability in situ.