Bio-inspired hydrogel composed of hyaluronic acid and alginate as a potential bioink for 3D bioprinting of articular cartilage engineering constructs.

Bioprinting is a promising tool to fabricate well-organized cell-laden constructs for repair and regeneration of articular cartilage. The selection of a suitable bioink, in terms of composition and mechanical properties, is crucial for the development of viable cartilage substitutes. In this study, we focused on the use of one of the main cartilage components, hyaluronic acid (HA), to design and formulate a new bioink for cartilage tissue 3D bioprinting. Major characteristics required for this application such as printability, biocompatibility, and biodegradability were analyzed. To produce cartilage constructs with optimal mechanical properties, HA-based bioink was co-printed with polylactic acid (PLA). HA-based bioink was found to improve cell functionality by an increase in the expression of chondrogenic gene markers and specific matrix deposition and, therefore, tissue formation. These results indicate that it is a promising bioink candidate for cartilage tissue engineering based in 3D bioprinting. STATEMENT OF SIGNIFICANCE: The recent appearance of 3D printing technology has enabled great advances in the treatment of osteochondral disorders by fabrication of cartilage tissue constructs that restore and/or regenerate damaged tissue. In this attempt, the selection of a suitable biomaterial, in terms of composition and mechanical properties, is crucial. In this study, we describe for first time the development of a bioink based on the main component of cartilage, HA, with suitable biological and mechanical properties, without involving toxic procedure, and its application  in cartilage tissue bioprinting. Hybrid constructs prepared by co-printing  this  bioink and thermoplastic polymer PLA provided an optimal niche for chondrocyte growth and maintenance as well as mechanical properties necessary to support load forces exerted in native tissue. We highlight the translation potential of this HA-based bioink in the clinical arena.