Green Synthetic Approach for Photo-Cross-Linkable Methacryloyl Hyaluronic Acid with a Tailored Substitution Degree

The conventional synthesis of methacryloyl hyaluronic acid (HA-MA) requires an extremely high amount of modification reagents, the organic solvents, and strenuous purification steps. Herein, a new green synthetic approach for the methacryloyl hyaluronic acid preparation with a tailorable substitution degree (SD) is reported, in which methacryloyl hydrazide is used as a more reactive reagent and only water is used as the solvent. The new method significantly reduces the amount of functionalization reagents (as low as only 0.3 equiv) and avoids the use of any organic solvents. The substitution degree can be tailored from 26% to 86% in a facile controllable manner. The new HA-MA (termed as HA-MA-H) can be UV-cross-linked to form a biocompatible hydrogel.