Dynamic tuning of smart polymer stiffness with physiologically-relevant phenomena such as change in Ca2+ concentration and critical stress offered by the ECM. (I.) Modulation of stiffness via NIR radiation (A-B), , irradiation of specific regions (C-D), use of a photomask to produce stiff regions in a controlled region (E-F). (II.) A hybrid ECM consisting of covalent and ionic crosslinks was synthesized, where collagen type I (green) and CaCO3 (red) (a), were mixed with an alginate solution (b), The addition of glucono-delta-lactone and incubation at 37°C resulted in hydrogel formation first due to ionic crosslinks between Ca2+ and alginate backbone as and then due to Nb-Tz covalent crosslinking between Nb (purple)- and Tz (light blue)- functionalized alginate chains(c), Collagen self-assembles and gets increasingly crosslinked with time (d), Detailed reaction chemistry of the ionic and covalent crosslinks (e). A: Reproduced from reference [23] Copyright (2015) with permission from National Academy of Sciences, B: Reproduced from reference [52], Copyright (2019) with permission from Elsevier