Decellularized kidney extracellular matrix bioinks recapitulate renal 3D microenvironment in vitro

Abstract

Decellularized extracellular matrices (ECMs) are able to provide the necessary and specific cues for remodeling and maturation of tissue-specific cells. Nevertheless, their use for typical biofabrication applications requires chemical modification or mixing with other polymers, mainly due to the limited viscoelastic properties. In this study, we hypothesize that a bioink exclusively based on decellularized kidney ECM (dKECM) could be used to bioprint renal progenitor cells. To address these aims, porcine kidneys were decellularized, lyophilized and digested to yield a viscous solution. Then, the bioprinting process was optimized using an agarose microparticle support bath containing transglutaminase for enzymatic crosslinking of the dKECM. This methodology was highly effective to obtain constructs with good printing resolution and high structural integrity. Moreover, the encapsulation of primary renal progenitor cells resulted in high cell viability, with creation of 3D complex structures over time. More importantly, this tissue-specific matrix was also able to influence cellular growth and differentiation over time. Taken together, these results demonstrate that unmodified dKECM bioinks have great potential for bioengineering renal tissue analogs with promising translational applications and/or for in vitro model systems. Ultimately, this strategy may have greater implications on the biomedical field for the development of bioengineered substitutes using decellularized matrices from other tissues.