Desenvolvimento de modelo de hipocampo humano com tecnologia de impressão em 3D

Abstract

Physiologically, cells find homeostasis in a complex three-dimensional environment that exposes them to circulating molecules, neighboring cells, and the extracellular matrix. The various existing models regarding scientific experimentation in translational medical research are based on the best possible simulation of the analyzed environment in relation to the clinical reality to be studied and treated. In this sense, it is vital to optimize the information produced to be more reliable in terms of anatomy and physiology, and 2D experimental models, usually with monolayer cell cultures, fail to represent the cell niche. 3D printers have enabled the transposition of a clinical imaging environment to an experimental one, such as cultured cells, with individual anatomical fidelity and control of cell layers which mimic real tissue. In particular, neuronal tissue presents many challenges in research due to its complexity, requiring an approximation with the clinic to overcome the experimental limitations of monolayer models of an organized tissue with distinct interconnected regions. Today we still lack an in vitro model capable of representing the connectivity of the hippocampus. The objective of this work is to create a negative model of human hippocampus with anatomical fidelity, printed with 3D technology in polymer and hydrogel for application in research. For that, we performed the screening of biomaterials regarding their hydrophobicity, through the contact angle, surface morphology, by scanning electron microscopy, and biocompatibility, through cell viability assays and direct and indirect adhesion. The materials evaluated, were PCL, blend of PLGA and PCL, PPY and PLA; PLA stood out as the best polymer to be used as the primary structure and we made the negative histological mold of the hippocampus in a 3D printer (that is, a structure whose space represents the measurements of the human hippocampus) with measurements from an MRI exam. Afterwards, a model of the human hippocampus was made in a hydrogel of decellularized pig brain.