Injectable and\n3D-Printable Semi-Interpenetrating\nPolymer Networks Based on Modified Sodium Alginate for Cell Spheroid\nFormation

We report on 3D-printable polymer networks based on the\ncombination\nof modified alginate-based polymer blends; two alginate polymers were\nprepared, namely, a thermoresponsive polymer grafted with P(NIPAM<sub>86</sub>-<i>co</i>-NtBAM<sub>14</sub>)-NH<sub>2</sub> copolymer\nchains and a second polymer modified with diol/pH-sensitive 3-aminophenylboronic\nacid. The gelation properties were determined by the hydrophobic association\nof the thermosensitive chains and the formation of boronate esters.\nAt a mixing ratio of 70/30 wt % of the thermo/diol-responsive polymers,\nthe semi-interpenetrating network exhibited an optimum storage modulus\nranging from ca. 150 Pa at 20 °C up to ca. 480 Pa at 37 °C\ndue to the stimulated cross-linking synergism. The resulting bioink\nblends could promote the rapid formation of cell spheroids with an\naverage diameter of 62.5 μm within 24 h. The network could easily\nbe dissociated by the addition of free glucose, acting as an antagonistic\ndisruptor of the cross-links. The proposed material was found to be\nnontoxic, with adequate injectability and 3D printability.