Controlling renal epithelial cell behavior by tuning the mechanical and biological characteristics of bioinks

Bioprinting is an emerging technology with the potential to fabricate functional in vitro 3D models of different tissues, enabling more predictive and physiological relevant drug development. However, suitable bioinks that fulfil good printability and biofunctionality, e.g., allowing cell adhesion and self-organization, are still limited. We therefore tested how the addition of nanofibrillated cellulose (NFC) and/or decellularized extracellular matrix (dECM) can help to solve the mentioned issues by tuning the viscosity and providing cell attachment sites, respectively, for two commonly used biomaterials, namely alginate (Alg) and gelatine methacryloyl (GelMA). Investigations on the printability showed that NFC addition improved printability for GelMA and alginate. Initial cell attachment of renal proximal tubule epithelial cells could be successfully increased by adding dECM to GelMA/NFC and Alg/NFC, although cell arrangements were only observed within the GelMA-based bioinks. Significant induced 3D cell migration was observed through GelMA/NFC and GelMA/NFC/dECM. To demonstrate the application potential of this material, a microfluidic chip model was created, showing good viability and epithelial like morphology after 7 days of cultivation under perfusion. Taken together, this study covers a full range of assessments of bioink physicochemical properties, printability and cell behavior. The innovative integration of NFC and dECM balances printing performance and biological function, solving the key problems in the field. The successful application in a microfluidic chip and dynamic perfusion model demonstrates the translational potential of this research.