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.
Highlights
Biomedical research is benefiting from innovative in vitro engineered live-human neural tissue modeling
From our own research relating to electrical stimulation (ES) for human neural stem cell (NSC) and induced pluripotent stem cells (iPSCs) differentiation, we have shown stem cell fate determination and guided differentiation toward neuronal cells without the use of exogenous chemical inducers.[45]
This review considers ES applied to neural tissue models, with a view toward combining both ES and 3D bioprinting to create enhanced and even more relevant and reproducible in vitro neural tissue analogs
Summary
Biomedical research is benefiting from innovative in vitro engineered live-human neural tissue modeling. Notwithstanding the value of conventional human ex vivo tissue studies and in vivo animal models, the extrapolation of findings to live-human in vivo processes is relatively limited.[1,2] For example, human postmortem brain tissue only provides a snapshot of in vivo tissue function and cellular processes, while animal modeling of disease is often centered on a particular phenotype or partial underlying pathology, thereby failing to capture the whole spectrum of important processes or account for possible comorbidities These limitations explicate some of the findings of comparative studies between homologous human and animal (e.g., murine) cell types that have observed extensive differences, ranging from alterations of the intrinsic membrane and electrical properties over altered laminar distribution to distinct gene expression and morphological variations.[3,4] In addition to the significant ethical considerations, there is clearly a need for accessible and valid (biologically relevant) human neural tissue models with the ability to track normal and aberrant cellular and molecular interactions, as well as whole system interconnectivity.[2,5] The recapitulation of cellular disease models is challenging for heterogeneous diseases such as neuropsychiatric disorders (e.g., schizophrenia, autism, or bipolar disorder), with complex and variable phenotypes, where the underlying pathology and causation are not well understood.[5,6]. The promise of ES as a means to enhance printed tissue formation and maturation is considered, with a view to promulgating the interfacing of 3D printed material-matrices and cells with modern bioelectronics for a most optimal and clinical compatible approach (Fig. 1)
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