A natural composite hydrogel laden with mesenchymal stromal cells for osteochondral repair: Comparison between casting and 3D bioprinting

Synovial joints, and particularly the osteochondral unit, are prone to lesions, with high risk of degeneration towards osteoarthritis. Various treatment strategies have been developed, including surgical techniques and cellular therapies, but they all show limitations. In this context, tissue engineering approaches, particularly 3D bioprinting, are promising for generating osteochondral tissue substitutes for joint repair. In this work, two biofabrication techniques, casting and extrusion-based 3D bioprinting, of an optimized formulation of a gelatin/alginate/fibrinogen bioink loaded with murine mesenchymal stromal cells (MSCs) were compared for the generation of cartilage and bone substitutes. Cell viability, proliferation and differentiation were characterized. Both techniques showed similar results in terms of viability and proliferation, but only the 3D bioprinted constructs allowed for differentiation towards the chondrogenic or osteogenic lineage using specific culture media. Bioprinting of biphasic osteochondral constructs comprising a cartilage compartment on top of a bone compartment was also explored. The study highlights the potential of our natural composite hydrogel bioink and extrusion-based 3D bioprinting for the generation of osteochondral tissue substitutes. Although further optimizations are needed, the study laid the groundwork for future advancements in osteochondral tissue engineering.