Hydrolytic (In)stability of Methacrylate Esters in Covalently Cross-Linked Hydrogels Based on Chondroitin Sulfate and Hyaluronic Acid Methacrylate

• Published in: ACS omega 2021-10, Vol.6 (40), p.26302-26310
• Main Authors: Schuurmans, Carl C. L, Brouwer, Arwin J, Jong, Jacobus A. W, Boons, Geert-Jan P. H, Hennink, Wim E, Vermonden, Tina
• Format: Article
• Language: English
• ISSN: 2470-1343; 2470-1343
• DOI: 10.1021/acsomega.1c03395

Chondroitin sulfate (CS) and hyaluronic acid (HA) methacrylate (MA) hydrogels are under investigation for biomedical applications. Here, the hydrolytic (in)­stability of the MA esters in these polysaccharides and hydrogels is investigated. Hydrogels made with glycidyl methacrylate-derivatized CS (CSGMA) or methacrylic anhydride (CSMA) degraded after 2–25 days in a cross-linking density-dependent manner (pH 7.4, 37 °C). HA methacrylate (HAMA) hydrogels were stable over 50 days under the same conditions. CS­(G)­MA hydrogel degradation rates increased with pH, due to hydroxide-driven ester hydrolysis. Desulfated chondroitin MA hydrogels also degrade, indicating that sulfate groups are not responsible for CS­(G)­MA’s hydrolytic sensitivity (pH 7.0–8.0, 37 °C). This sensitivity is likely because CS­(G)­MA’s N-acetyl-galactosamines do not form hydrogen bonds with adjacent glucuronic acid oxygens, whereas HAMA’s N-acetyl-glucosamines do. This bond absence allows CS­(G)­MA higher chain flexibility and hydration and could increase ester hydrolysis sensitivity in CS­(G)­MA networks. This report helps in biodegradable hydrogel development based on endogenous polysaccharides for clinical applications.