Stimuli-responsive hydrogels composed of modified cellulose nanocrystal and gelatin with oriented channels for guiding axonal myelination

Myelination is modulated by neuron-glial communication, which is an essential physiological process during nerve regeneration. However, available scaffold for myelination of oriented axons is still challenging and lack of sufficient attention in neural tissue engineering. Here, we fabricate an extracellular matrix-mimic hydrogel (GB-SH), which was composed of cellulose nanocrystal grafted with sulfated hyperbranched polyglycerols (SHC) and 3-aminophenylboronic acid modified GelMA (GMPB) for stimuli-responsive release of sodium Danshensu (DSS). SHC with a “lubricative coating” maintained the crystalline core with a uniform size and 17.27 % of sulfation degree. GMPB having a grafting ratio of 14.94 % displayed a glucose-responsive release of dye. GB-SH hydrogels displaying oriented microchannels with controllable pore sizes were constructed by combining directional freeze-casting and photo-crosslinking strategies, which performed improved strengths, high water contents and slow degradation. It also exhibited stimulus (glucose, pH, H 2 O 2 ) triggered release of DSS. In vitro studies revealed that DSS loaded GB-SH enhanced the cellular viability, proliferation and orientation on fibroblast and oligodendrocyte precursor cells (OPCs). This scaffold induced OPCs differentiated into matured oligodendrocytes, which myelinated the extensive axons of hippocampal neurons successfully. The multi-functional hydrogel is a promising platform for studying myelination in vitro and a potential neural transplant in treating traumatic nerve injury.