Multiple Crosslinking Hyaluronic Acid Hydrogels with Improved Strength and 3D Printability.

Abstract

Hyaluronic acid (HA) hydrogel is preferred for biomedicine applications, as it possesses biodegradability, biocompatibility, and cell-regulated capacity as well as high hydration nature similar to the native extracellular matrix. However, HA hydrogel fabricated via a 3D printing technique often faces poor printing properties. In this study, maleiated sodium hyaluronate (MHA) with a high substituted degree of the acrylate group (i.e., 2.27) and thiolated sodium hyaluronate (SHHA) were synthesized. By blending these modified HAs, the MHA/SHHA hydrogels were prepared via pre-crosslinking through thiol-acrylate Michael addition and subsequently covalent crosslinking using thiol-acrylate and acrylate-acrylate photopolymerization mechanisms. Rheological properties, swelling behaviors, and mechanical properties can be modulated by altering the molar ratio of the thiol group and acrylate group. The results showed that the MHA/SHHA hydrogel precursors have rapidly gelling capacity and improved compressive strength. Based on these results, high-resolution hydrogel scaffolds with good structural stability were prepared by extrusion-based 3D printing. This HA hydrogel is cytocompatible and capable of supporting adherence of L929 cells, indicating its great potential for tissue engineering scaffolds.