Improved and Highly Reproducible Synthesis of Methacrylated Hyaluronic Acid with Tailored Degrees of Substitution

Abstract

Methacrylated hyaluronic acid (HAMA) is a versatile material that has gained significant attention in various pharmaceutical and biomedical applications. This biocompatible material can be photo-cross-linked in the presence of Irgacure 2959 (I2959) to produce hydrogels. Controlling the degree of methacrylation (DM) is crucial since it plays a pivotal role in determining the properties and thus the potential applications of the gels. We report herein a new green approach for the highly controlled and tailored modification of hyaluronic acid (HA) with methacrylic anhydride (MA). The reaction conditions of previously reported procedures were optimized, leading to a decreased reaction time (3 h instead of 24 h) and consumption of fewer equivalents of MA (5 equiv instead of 20) and water as the sole solvent. By changing the amount of base added, HAMA with three different DMs was obtained: 19, 35, and 60%. The influence of the molecular weight of HA, degree of substitution, and concentration of the HAMA solution prior to photo-cross-linking on the rheological, swelling, and degradation properties of HAMA hydrogels was also studied in this work.