Engineering in vitro human neural tissue analogs by 3D bioprinting and electrostimulation

Abstract

There is a fundamental need for clinically relevant, reproducible, and standardized in vitro human neural tissue models, not least of all to study heterogenic and complex human-specific neurological (such as neuropsychiatric) disorders. Construction of three-dimensional (3D) bioprinted neural tissues from native human-derived stem cells (e.g., neural stem cells) and human pluripotent stem cells (e.g., induced pluripotent) in particular is appreciably impacting research and conceivably clinical translation. Given the ability to artificially and favorably regulate a cell's survival and behavior by manipulating its biophysical environment, careful consideration of the printing technique, supporting biomaterial and specific exogenously delivered stimuli, is both required and advantageous. By doing so, there exists an opportunity, more than ever before, to engineer advanced and precise tissue analogs that closely recapitulate the morphological and functional elements of natural tissues (healthy or diseased). Importantly, the application of electrical stimulation as a method of enhancing printed tissue development in vitro , including neuritogenesis, synaptogenesis, and cellular maturation, has the added advantage of modeling both traditional and new stimulation platforms, toward improved understanding of efficacy and innovative electroceutical development and application.

Photothermal Agarose Microfabrication Technology for Collective Cell Migration Analysis

“…Recent advancements in microfabrication technologies enabled researchers to examine the dynamics of singe-cell-based cellular networks in the confined microstructures [ 1 , 2 ]. Microetching and microprinting are two major complementary approaches to form the confined spatial arrangement of cells.…”

Induced Pluripotent Stem Cells for Treatment of Alzheimer’s and Parkinson’s Diseases

“…A scaffold takes the place of the ECM in the context of an engineered construct; its mechanical properties should correspond to those specifically required by the desired cell type. It has also been shown that development of some cell types, namely neurons, benefits from electrical stimulation [ 63 ], which should undoubtedly be taken on board when developing a tissue-engineered neural construct. Bioprinting is an exciting new field that shows great promise in manufacturing such constructs by spatially depositing the scaffold material as well as cells, all the while allowing for controlled encapsulation of soluble cell signaling ligands.…”

“…Crosslinking has the potential to damage the cells within the bioink, as it exerts stresses on them in the form of mechanical shear, temperature variation, ionic changes, and laser radiation. This should especially be considered when using iPSCs, which are extremely sensitive to mechanical stresses [ 63 ]. A higher stiffness usually yields higher print resolution [ 55 ], but requires more extrusion force to print, putting cells at higher risk of damage.…”

“…Nonetheless, the in vivo efficacy of 3D-printed neural constructs for ND remains incomplete. Future directions will entail the optimization of biomaterials to develop optimal bioinks for guiding neural cell differentiation [ 63 ]. Ideally, the scaffold of a 3D-printed implant should gradually be replaced by native ECM.…”

“…Ideally, the scaffold of a 3D-printed implant should gradually be replaced by native ECM. This prospect relies on advances in biomaterial science geared towards matching the biodegradation rate of bioinks to ECM deposition rate [ 63 ]. Taken together, as this review has outlined, fundamental advantages offered by iPSCs, especially coupled with the exciting new prospects of 3D bioprinting and its endless modalities, show promise in understanding and treating Alzheimer’s and Parkinson’s through in vitro modeling and personalized regenerative cell therapy in the future.…”