02137nas a2200277   4500000000100000000000100001008004100002260001100043653001900054653001700073653001900090653001800109653003500127653002100162653001100183653001300194100002000207700001800227700002300245245011200268856004300380300000700423490000700430520140800437022001401845       2023                            d  c2023/110a3D bioprinting10abiomaterials10abrain organoid10adisease model10ainduced pluripotent stem cells10aneural stem cell10aneuron10ascaffold1 aPierre Layrolle1 aPierre Payoux1 aStéphane Chavanas00aMessage in a Scaffold: Natural Biomaterials for Three-Dimensional (3D) Bioprinting of Human Brain Organoids  uhttps://www.mdpi.com/2218-273X/13/1/25  a250 v133 aBrain organoids are invaluable tools for pathophysiological studies or drug screening, but there are still challenges to overcome in making them more reproducible and relevant. Recent advances in three-dimensional (3D) bioprinting of human neural organoids is an emerging approach that may overcome the limitations of self-organized organoids. It requires the development of optimal hydrogels, and a wealth of research has improved our knowledge about biomaterials both in terms of their intrinsic properties and their relevance on 3D culture of brain cells and tissue. Although biomaterials are rarely biologically neutral, few articles have reviewed their roles on neural cells. We here review the current knowledge on unmodified biomaterials amenable to support 3D bioprinting of neural organoids with a particular interest in their impact on cell homeostasis. Alginate is a particularly suitable bioink base for cell encapsulation. Gelatine is a valuable helper agent for 3D bioprinting due to its viscosity. Collagen, fibrin, hyaluronic acid and laminin provide biological support to adhesion, motility, differentiation or synaptogenesis and optimize the 3D culture of neural cells. Optimization of specialized hydrogels to direct differentiation of stem cells together with an increased resolution in phenotype analysis will further extend the spectrum of possible bioprinted brain disease models.  a2218-273X