*Article* **3D Bioprinted Human Cortical Neural Constructs Derived from Induced Pluripotent Stem Cells**

**Federico Salaris 1,2, Cristina Colosi 1, Carlo Brighi 1, Alessandro Soloperto 1, Valeria de Turris 1, Maria Cristina Benedetti 2, Silvia Ghirga 1, Maria Rosito 1, Silvia Di Angelantonio 1,3,\* and Alessandro Rosa 1,2,\***


Received: 6 September 2019; Accepted: 24 September 2019; Published: 2 October 2019

**Abstract:** Bioprinting techniques use bioinks made of biocompatible non-living materials and cells to build 3D constructs in a controlled manner and with micrometric resolution. 3D bioprinted structures representative of several human tissues have been recently produced using cells derived by differentiation of induced pluripotent stem cells (iPSCs). Human iPSCs can be differentiated in a wide range of neurons and glia, providing an ideal tool for modeling the human nervous system. Here we report a neural construct generated by 3D bioprinting of cortical neurons and glial precursors derived from human iPSCs. We show that the extrusion-based printing process does not impair cell viability in the short and long term. Bioprinted cells can be further differentiated within the construct and properly express neuronal and astrocytic markers. Functional analysis of 3D bioprinted cells highlights an early stage of maturation and the establishment of early network activity behaviors. This work lays the basis for generating more complex and faithful 3D models of the human nervous systems by bioprinting neural cells derived from iPSCs.

**Keywords:** 3D bioprinting; biofabrication; 3D cultures; iPSCs; cortical neurons; calcium imaging; patch clamp
