A series of thermoresponsive graft copolymers, gelling at physiological conditions in aqueous solution and cell growth media, have been synthesized using quantitative coupling between a small set of amino-functionalized poly(alkylene oxide) copolymers (PAO) and the carboxylate of the biologically important polysaccharides (PSa) carboxymethylcellulose and the less reactive hyaluronate. Quantitative grafting enables the establishment of structure-function relationship which is imperative for controlling the properties of in situ gelling hydrogels. The EDC/NHS-mediated reaction was monitored using SEC-MALLS, which revealed that all PAOs were grafted onto the PSa backbone. Aqueous solutions of the graft copolymers were Newtonian fluids at room temperatures and formed reversible physical gels at elevated temperatures which were noncytotoxic toward chondrocytes. The established structure-function relationship was most clearly demonstrated by inspecting the thermogelling strength and the onset of thermogelling in a phase diagram. The onset of the thermogelling function could be controlled by the global PAO concentration, independent of graft ratio.
The Swedish Research Council FORMAS (2016–61 and 2018–02284), Vinnova (2017–04693), and the foundation Bengt Lundqvist minne (Postdoctoral Grant, no grant number available) are acknowledged for funding.