Mechanistic insights into the calcium-mediated gelation of poly(4-tert-butylstyrene-alt-maleic acid)-block-poly(N-acryloylmorpholine) double hydrophilic block copolymers

• Double hydrophilic block copolymers with an anionic block can form hydrogels. • Higher anionic-to-neutral block ratios lead to enhanced mechanical properties. • The hydrogels show shear-thinning and self-healing properties. • The hydrogels may have potential as injectable h. Stimuli responsive double hydrophilic block copolymers (DHBCs) are ubiquitous in water-based applications, such as drug/gene delivery, nanoreactor and sensor development, photocatalysis, 3D inkjet printing, etc. DHBC-based gels, cross-linked with calcium ions, are particularly valuable for the development of biomedically relevant materials (such as wound dressings or injectable formulations), due to the benignity of Ca 2+ in biological systems. Therefore, gels formed via the calcium-mediated crosslinking of poly(4- tert -butylstyrene- alt -maleic acid)- block -poly( N -acryloylmorpholine) (P t BuSMA- b -PNAM), which in itself constitutes polymers with established biomedical relevance, are promising candidates for the development of the aforementioned biomedical materials. To this end, P t BuSMA- b -PNAM diblock copolymers were synthesized with different block ratios (1:1, 1:2 and 2:1) and treated with Ca 2+ , whereby the concentration of the two constituents, the pH or the block copolymer architecture was varied, in order to tune the mechanical properties of the P t BuSMA- b -PNAM/Ca 2+ gels. P t BuSMA- b -PNAM/Ca 2+ with the lowest P t BuSMA composition (1:2 block ratio) could not form gels and rather formed micelles, whereas P t BuSMA- b -PNAM/Ca 2+ with the highest P t BuSMA composition (2:1 block ratio) exhibited enhanced mechanical properties compared to the 1:1 block ratio. The overall amphiphilic balance of the P t BuSMA- b -PNAM/Ca 2+ complexes was therefore proven vital for the design and formation of gels with desirable mechanical properties. P t BuSMA- b -PNAM/Ca 2+ gels exhibited shear thinning when subjected to high shear conditions and demonstrated some self-healing properties, suggesting these materials have value in the formulation of injectable gels.