A robust synthetic strategy where polysaccharide derivative precursors react through aqueous Diels–Alder chemistry without the involvement of catalysts and coupling reagents, allowing for the direct encapsulation of positive and negative proteins within biodegradable hydrogels. The results demonstrated that the aqueous Diels–Alder chemistry provides an extremely selective reaction and proceeds with high efficiency for polysaccharide bioconjugation. This synthetic approach uniquely allows for the direct fabrication of biologically functionalized gels with ideal structures, which provides a competitive alternative to conventional conjugation techniques such as click chemistry.
