Enhanced hyaline cartilage formation and continuous osteochondral regeneration via 3D-Printed heterogeneous hydrogel with multi-crosslinking inks.

The unique gradient structure and complex composition of osteochondral tissue pose significant challenges in defect regeneration. Restoration of tissue heterogeneity while maintaining hyaline cartilage components has been a difficulty of an osteochondral tissue graft. A novel class of multi-crosslinked polysaccharide-based three-dimensional (3D) printing inks, including decellularized natural cartilage (dNC) and nano-hydroxyapatite, was designed to create a gradient scaffold with a robust interface-binding force. Herein, we report combining a dual-nozzle cross-printing technology and a gradient crosslinking method to create the scaffolds, demonstrating stable mechanical properties and heterogeneous bilayer structures. Biofunctional assessments revealed the remarkable regenerative effects of the scaffold, manifesting three orders of magnitude of mRNA upregulation during chondrogenesis and the formation of pure hyaline cartilage. Transcriptomics of the regeneration site in vivo and scaffold cell interaction tests in vitro showed that printed porous multilayer scaffolds could form the correct tissue structure for cell migration. More importantly, polysaccharides with dNC provided a hydrophilic microenvironment. The microenvironment is crucial in osteochondral regeneration because it could guide the regenerated cartilage to ensure the hyaline phenotype.

The different composites of cellulose nanocrystals with d- or l-histidine.

Cellulose nanocrystals (CNCs) are inherently right-handed nanostructures that originate from nature, showing chirality in their fibrils, bundles, and self-assembled films. However, the enantio-specific interaction between CNCs and other chiral molecules has not been explored so far. In this study, we first demonstrated a chirality-related difference in the composite films of cellulose nanocrystals and histidine with a d- or l-configuration. The distinction is not only presented in the self-assembled nanostructures of CNCs, optical properties, and the thermal decomposition of composites but also in the crystallization of the amino acid. We suppose that it might have originated from the packing of amino acids on the twisted surface of CNCs. The knowledge about the enantio-specific interaction between the chiral amino acid and polysaccharide nanostructure is of significant importance for developing a new strategy for enantiomeric separation.