3D bioprinting of tyramine modified hydrogels under visible light for osteochondral interface.

Recent advancements in tissue engineering have demonstrated a great potential for the fabrication of three-dimensional tissue structures such as cartilage and bone. However, achieving structural integrity between different tissues and fabricating tissue interfaces are still great challenges. In this study, an in situ crosslinked hybrid, multi-material three-dimensional (3D) bioprinting approach was used for the fabrication of hydrogel structures based on an aspiration-extrusion microcapillary method. Different cell-laden hydrogels were aspirated in the same microcapillary glass and deposited in the desired geometrical and volumetric arrangement directly from a computer model. Alginate and carboxymethyl cellulose (CMC) were modified with tyramine to enhance cell bioactivity and mechanical properties of human bone marrow Mesenchymal Stem Cells (hBMSC)-laden bioinks. Hydrogels were prepared for extrusion by gelling in microcapillary glass utilizing an in situ crosslink approach with ruthenium (Ru) and sodium persulfate (SPS) photo-initiating mechanisms under visible light. The developed bioinks were then bioprinted in precise gradient composition for cartilage-bone tissue interface using microcapillary bioprinting technique. The biofabricated constructs were co-cultured in chondrogenic/osteogenic culture media for three weeks. After cell viability and morphology evaluations of the bioprinted structures, biochemical and histological analyses, and a gene expression analysis for the bioprinted structure were carried out. Analysis of cartilage and bone formation based on cell alignment and histological evaluation indicated that mechanical cues in conjunction with chemical cues successfully induced MSC differentiation into chondrogenic and osteogenic tissues with a controlled interface.