Abstract
ABSTRACTAlthough the process by which the cortical tissues of the brain fold has been the subject of considerable study and debate over the past few decades, a single mechanistic description of the phenomenon has yet to be fully accepted. Rather, two competing explanations of cortical folding have arisen in recent years; known as the axonal tension and the differential tangential expansion models. In the present review, these two models are introduced by analyzing the computational, theoretical, materials-based, and cell studies which have yielded them. Then Four-dimensional bioprinting is presented as a powerful technology which can not only be used to test both models of cortical folding de novo, but can also be used to explore the reciprocal effects that folding associated mechanical stresses may have on neural development. Therein, the fabrication of ‘smart’ tissue models which can accurately simulate the in vivo folding process and recapitulate physiologically relevant stresses are introduced. We also provide a general description of both cortical neurobiology as well as the cellular basis of cortical folding. Our discussion also entails an overview of both 3D and 4D bioprinting technologies, as well as a brief commentary on recent advancements in printed central nervous system tissue engineering.
Highlights
The process by which the cortical tissues of the brain enfold in order to form its wrinkled topology has been the subject of extensive study over the past several decades, yet the exact mechanisms which guide this process remain poorly understood
It is believed that each micro-complex receives sensory-motor information originating from elsewhere in the brain as well as the peripheral nervous system (PNS), and is in turn responsible for actuating unique modulatory controls directly corresponding to specific motor regions of the body
Whereas there is some evidence which suggests that axonal tension may play some role in the formation of cortical folds, the microdissection work of Xu et al (2010) has demonstrated that axonal tension is not directed across areas undergoing gyration, challenging the speculation that axonal tension is the key driving force of cortical folding [61]
Summary
The process by which the cortical tissues of the brain enfold in order to form its wrinkled topology has been the subject of extensive study over the past several decades, yet the exact mechanisms which guide this process remain poorly understood. Abiotic materials-based studies have challenged, verified, and extended existing theoretical models of cortical folding [17,18] Since these materials-based studies do not incorporate living cells, they largely cannot account for the potential unforeseen effects that cells and their physiological processes might have on the mechanics of tissue development such as stiffening and folding [14,19,20,21]. In order to obtain a more comprehensive and physiologically relevant model of the neuraldevelopmental process of cortical tissue folding, future studies should likely focus on using models constructed from cell-laden ‘smart’- materials These so-called smart materials can artificially simulate the mechanical stresses associated with cortical folding in order to observe the potential effects these forces might have on neural-cell maturation and functionality. We conclude our discussion with a brief overview of recent advancements in 3D- and 4D bioprinting of nervous system tissues, and discuss plausible directions future research might take towards a robust 4D-bioprinted platform for studying the motile aspects of neurodevelopment and disease
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
