Driven by cell intrinsic organization, cell biology-based models are superior at mimicking early developmental details. Given its closer physiological relevance, 3D neural models are thought to be a better in vitro complement to the animal models.ĭifferent 3D culture systems, such as cell biology-based models (spheroids and organoids), and engineering-based models (scaffold and microfluidic platforms), have been widely explored for their ability to generate more faithful neural tissue-like structures that incorporate diverse cell types and materials, and both physical and biochemical signals,. In contrast, 3D cultures, which culture cells in an artificially established 3D environment, provide more complex environment with longer lifespan, and tend to be more informative and predictive. However, 2D cultures are generally inadequate in recapitulating specific physiological features due to insufficient cell-cell and cell-extracellular matrix (cell-ECM) interactions. Indeed, 2D neural culture studies have been very popular and successful, particularly in the areas of axon/dendrite growth, neuronal survival and synapse formation. 2D monolayer cultures, which culture cells on a thin surface-coated petri dish, are most commonly used, largely owing to its cost effectiveness, ease of handling, and robustness across diverse cell types. Here, 2D and 3D refer to the dimension into which cells grow over time. However, numerous limitations exist notably, significant functional loss occurs rapidly once slices are separated from the body.Īpart from animal models and ex vivo culture systems, cell-based in vitro models are extensively explored through both two-dimensional (2D) and three-dimensional (3D) cultures. In addition, they are more easily amendable to image analysis, and preserve the local cellular organization. Compared with intact animals, tissue slices are easier to manipulate experimentally. Alternatively, ex vivo models using slice cultures of nerve tissues have been widely adopted. Moreover, it is technically challenging to monitor what is going on inside the animals, and ethical issues are frequently raised. Yet animal experiments are time consuming, costly, and usually cannot fully reflect the actual conditions in human patients due to the apparent genetic, biochemical, and metabolic differences between species. Such dismal progress likely results from the lack of suitable models that recapitulate the complex cell-cell and cell-environmental interactions in vivo.Īnimal models provide the greatest extent of physiological relevance and therefore, are still considered to be the gold standard. This hinders the development of novel therapeutic interventions. Although great efforts have been devoted to promote functional restoration and neural regeneration, ,, , our molecular understanding of the pathogenic mechanisms remains very limited. In almost all cases, effective treatments are lacking. ![]() Parkinson's disease, Alzheimer's disease, Huntington's disease) or neurodevelopmental disorders (e.g. traumatic brain injury (TBI), spinal cord injury (SCI)), neurodegenerative diseases (e.g. Typical examples of neural disorders include acute traumatic injuries (e.g. Further advances in bioprinting research would likely consolidate existing models and generate complex neural tissue structures bearing higher fidelity, which is ultimately useful for probing disease-specific mechanisms, facilitating development of novel therapeutics and promoting neural regeneration.ĭisorders of the nervous system are estimated to affect more than one billion people worldwide. Bioprinting offers a revolutionary approach for constructing repeatable and controllable 3D in vitro neural tissues with diverse cell types, complex microscale features and tissue level responses. ![]() We draw on specific examples to describe the merits and limitations of each model, in terms of different applications. ![]() ![]() In this paper, we review the recent developments in 3D in vitro neural tissue models, with a particular focus on the emerging bioprinted tissue structures. Therefore, the former is believed to have great potential for both mechanistic and translational studies. Three-dimensional (3D) in vitro neural tissue models provide a better recapitulation of in vivo cell-cell and cell-extracellular matrix interactions than conventional two-dimensional (2D) cultures.
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