Nanoengineered Micellar Hydrogel with Controllable Strain‐Dependent Behavior for Brain Slice‐Like Tissue Patch Bioprinting

The advancement of bioink tailored for extrusion-based bioprinting (EBB) unveils the critical importance of the structure-property relationship that calls for advanced characterization techniques. Particularly for soft hydrogel in printing central nervous tissues, it is essential to ensure cell viability and differentiation with customized architecture. This study introduces a nanoengineered chitosan micelle-crosslinked hydrogel (CDP) system, achieving three distinct rheological properties by regulating the relative contribution of dynamic covalent crosslinking vs. micelle stacking through high shear-induced crystallization to the final printing performance. The optimized CDP-II bioink exhibits balanced shear strain tolerance and stability within 200% strain. Rheo-SAXS analysis reveals the reversible lyotropic liquid crystal (LLC) structures, while SANS fitting identifies the radius (8.1 nm) and packing ratio (36%) for the micelles. The CDP-II bioink with 0.6 kPa shear modulus demonstrates proper mechanical properties and biocompatibility for neural stem cells. The bioink supports the differentiation of neural stem cells while protecting cell death from extrusion. The brain slice-like tissue patch printed from the CDP-II bioink can be picked up, manipulated, and moved to the culture vessel, underscoring its potential in neural tissue engineering. The structure-property relationship established through the model system can be used in the precise structure design of a binary hydrogel for bioprinting.