Insights into the alkaline degradation of oxidized chondroitin sulfate: Implications in Schiff base formation for hydrogel fabrication

Abstract

Chondroitin sulfate (CS) shows great promise for hydrogels and scaffolds in tissue engineering due to its biocompatibility and compressive strength. However, its chemical structure limits its use, necessitating modifications like oxidation to render CS with aldehyde groups (oxCS) and enabling hydrogel formation via Schiff base chemistry with amines. While an alkaline pH is essential for this crosslinking, high alkalinity affects the stability of oxCS. Despite extensive studies on CS, the extent of this in oxCS has not been thoroughly explored. This study examines oxCS degradation under alkaline conditions using spectrometric and spectroscopic techniques, suggesting possible pathways associated with decreased aldehyde functionality and reduced potential for Schiff base formation. At pH 10, aldehyde groups diminish by 50 % within 2 h, accompanied by enhanced chain scission compared to CS. These findings are applied as proof of concept in the development of two hydrogel families using 8-arm PEG-amines with varying pKa values, demonstrating the critical impact on oxCS stability and affecting the hydrogels' mechanical properties and performance. All in all, the present work provides essential insights into the design of glycosaminoglycan-based hydrogels and scaffolds. These findings advance the development of tailored biomaterials for tissue engineering, addressing the challenges posed by oxCS's stability under alkaline conditions.