Bioink Composition and Printing Parameters for 3D Modeling Neural Tissue

Abstract

Neurodegenerative diseases (NDs) are a broad class of pathologies characterized by the progressive loss of neurons in the central nervous system. The main problem in the study of NDs is the lack of an adequate realistic experimental model to study the pathogenic mechanisms. Induced pluripotent stem cells (iPSCs) partially overcome the problem, with their capability to differentiate into almost every cell types; even so, these cells alone are not sufficient to unveil the mechanisms underlying NDs. 3D bioprinting allows to control the distribution of cells such as neurons, leading to the creation of a realistic in vitro model. In this work, we analyzed two biomaterials: sodium alginate and gelatin, and three different cell types: a neuroblastoma cell line (SH-SY5Y), iPSCs, and neural stem cells. All cells were encapsulated inside the bioink, printed and cultivated for at least seven days; they all presented good viability. We also evaluated the maintenance of the printed shape, opening the possibility to obtain a reliable in vitro neural tissue combining 3D bioprinting and iPSCs technology, optimizing the study of the degenerative processes that are still widely unknown.

Biomaterials in Neurodegenerative Disorders: A Promising Therapeutic Approach

“…Viability was maintained and the hydrogel printed in a 3D structure allowed for the 3D organization of the cells, mimicking the environment of the tissue. These results open the possibility of a new model for the study of ALS, especially in the neuromuscular plaque [70].…”

3D Bioprinting Pluripotent Stem Cell Derived Neural Tissues Using a Novel Fibrin Bioink Containing Drug Releasing Microspheres

“…Our results suggested that microsphere incorporated scaffolds could potentially generate dopaminergic neurons and a number of committed differentiated neurons. Once optimized, these 3D bioprinted neural tissues could be used to model neurodegenerative diseases using patient-specific hiPSC lines, as currently done in 2D (Poon et al, 2017;Fantini et al, 2019). This study provides an approach to generate 3D neural tissues containing dopaminergic neurons as a clinically relevant model for drug discovery as well as a potential way to generate tissue to replace the lost neurons that die off during Parkinson's disease.…”

Bioprinting Neural Systems to Model Central Nervous System Diseases

“…hiPSC-derived neuronal and glial precursor cells Neurons (MAP2+); Astrocytes (GFAP+) [35] hiPSC-derived NSCs NSCs (Nestin+/SOX2+/SOX1+/PAX6+) [135] hiPSC-derived neural aggregates Neurons (TUBB3+) [36] hiPSC-derived NPCs Spinal cord motor neurons (TUBB3+/ChaT+); Astrocytes (GFAP+) [136] has made it possible to derive large amounts of human neural cells in vitro. [121] This has largely bypassed the ethical issues of neural cells obtained from either human embryos or embryonic stem cells.…”