Injectable and 3D-Printable Semi-Interpenetrating Polymer Networks Based on Modified Sodium Alginate for Cell Spheroid Formation

We report on 3D-printable polymer networks based on the combination of modified alginate-based polymer blends; two alginate polymers were prepared, namely, a thermoresponsive polymer grafted with P(NIPAM₈₆-<i>co</i>-NtBAM₁₄)-NH₂ copolymer chains and a second polymer modified with diol/pH-sensitive 3-aminophenylboronic acid. The gelation properties were determined by the hydrophobic association of the thermosensitive chains and the formation of boronate esters. At a mixing ratio of 70/30 wt % of the thermo/diol-responsive polymers, the semi-interpenetrating network exhibited an optimum storage modulus ranging from ca. 150 Pa at 20 °C up to ca. 480 Pa at 37 °C due to the stimulated cross-linking synergism. The resulting bioink blends could promote the rapid formation of cell spheroids with an average diameter of 62.5 μm within 24 h. The network could easily be dissociated by the addition of free glucose, acting as an antagonistic disruptor of the cross-links. The proposed material was found to be nontoxic, with adequate injectability and 3D printability.