Chemistry and engineering of the alginate-based inks for the (bio)printing of osteochondral tissue grafts

Osteochondral tissue exhibits a complex multilayered structure with distinct structural and physiological properties. Recent advancements in extrusion bioprinting have enabled the layer-by-layer assembly of multilayered osteochondral constructs. Alginate, a natural polysaccharide widely used in bioinks, offers tunable properties for supporting cellular functions and engineering tissues. Alginate derived from different sources differ in β-D-mannuronate and α-L-guluronate contents, as well as the length of each block, possesses carboxylate groups that facilitate cross-linking with divalent cations and further functionalization. Several chemical and processing routes can be envisioned to achieve desired processability, mechanical, and biological versatility. Despite its potential, challenges remain in meeting the mechanical and biological requirements for osteochondral grafts. Herein, we examine the technical challenges associated with osteochondral tissue repair and discuss extrusion bioprinters’ requirements and advances in bioprinting methods to address these challenges. We highlight the last decade's key findings dealing with the chemistry and functionalization of alginate-based (bio)inks for osteochondral tissue engineering. Engineering strategies for modulating alginate-based (bio)inks with optimized rheological features, printability, and shape fidelity are overviewed. Finally, obstacles, opportunities, and emerging solutions for better developing alginate (bio)inks for osteochondral tissue engineering are explored, considering advances in artificial intelligence and machine learning.