Dynamic Alginate Hydrogel as an Antioxidative Bioink for Bioprinting

Abstract

3D bioprinting holds great potential for use in tissue engineering to treat degenerative joint disorders, such as osteoarthritis. However, there is a lack of multifunctional bioinks that can not only support cell growth and differentiation, but also offer protection to cells against injuries caused by the elevated oxidative stress; this conditions is a common characteristic of the microenvironment of the osteoarthritis disease. To mitigate oxidative stress-induced cellular phenotype change and malfunction, an anti-oxidative bioink derived from an alginate dynamic hydrogel was developed in this study. The alginate dynamic hydrogel gelated quickly via the dynamic covalent bond between the phenylboronic acid modified alginate (Alg-PBA) and poly (vinyl alcohol) (PVA). It presented good self-healing and shear-thinning abilities because of the dynamic feature. The dynamic hydrogel supported long-term growth of mouse fibroblasts after stabilization with a secondary ionic crosslinking between introduced calcium ions and the carboxylate group in the alginate backbone. In addition, the dynamic hydrogel showed good printability, resulting in the fabrication of scaffolds with cylindrical and grid structures with good structural fidelity. Encapsulated mouse chondrocytes maintained high viability for at least 7 days in the bioprinted hydrogel after ionic crosslinking. Most importantly, in vitro studies implied that the bioprinted scaffold could reduce the intracellular oxidative stress for embedded chondrocytes under H2O2 exposure; it could also protect the chondrocytes from H2O2-induced downregulation of extracellular matrix (ECM) relevant anabolic genes (ACAN and COL2) and upregulation of a catabolic gene (MMP13). In summary, the results suggest that the dynamic alginate hydrogel can be applied as a versatile bioink for the fabrication of 3D bioprinted scaffolds with an innate antioxidative ability; this technique is expected to improve the regenerative efficacy of cartilage tissues for the treatment of joint disorders.