Bidirectional cell-matrix interaction dictates neuronal network formation in a brain-mimetic 3D scaffold
Samanta, S., Ylä-Outinen, L., Rangasami, V. K., Narkilahti, S., & Oommen, O. P. (2022). Bidirectional cell-matrix interaction dictates neuronal network formation in a brain-mimetic 3D scaffold. Acta Biomaterialia, 140, 314-323. https://doi.org/10.1016/j.actbio.2021.12.010
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Acta BiomaterialiaAuthors
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2022Copyright
© 2021 The Author(s). Published by Elsevier Ltd on behalf of Acta Materialia Inc.
Human pluripotent stem cells (hPSC) derived neurons are emerging as a powerful tool for studying neurobiology, disease pathology, and modeling. Due to the lack of platforms available for housing and growing hPSC-derived neurons, a pressing need exists to tailor a brain-mimetic 3D scaffold that recapitulates tissue composition and favourably regulates neuronal network formation. Despite the progress in engineering biomimetic scaffolds, an ideal brain-mimetic scaffold is still elusive. We bioengineered a physiologically relevant 3D scaffold by integrating brain-like extracellular matrix (ECM) components and chemical cues. Culturing hPSCs-neurons in hyaluronic acid (HA) gels and HA-chondroitin sulfate (HA-CS) composite gels showed that the CS component prevails as the predominant factor for the growth of neuronal cells, albeit to modest efficacy. Covalent grafting of dopamine (DA) moieties to the HA-CS gel (HADA-CS) enhanced the scaffold stability and stimulated the gel's remodeling properties by entrapping cell-secreted laminin, and binding brain-derived neurotrophic factor (BDNF). Neurons cultured in the scaffold expressed Col1, Col11, and ITGB4; important for cell adhesion and cell-ECM signaling. Thus, the HA-CS scaffold with integrated chemical cues (DA) supported neuronal growth and network formation. This scaffold offers a valuable tool for tissue engineering and disease modeling and helps in bridging the gap between animal models and human diseases by providing biomimetic neurophysiology.
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The work was supported by the Imaging Facility and iPS Cells Facility (Faculty of Medicine and Health Technology, Tampere University). The authors also thank Biocenter Finland for the support of Imaging and iPS cell facilities. This work was supported by the Academy of Finland (grant number 336665 to SN; grant numbers 286990, 326436, and 301824 to LY), the European Union's Horizon 2020 Marie Sklodowska-Curie Grant Program (Agreement No. 713645 to SS). ...License
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