Gatekeeper – Bioprinting in vitro mini-models with recapitulating in vivo anatomy of the blood-brain barrier using remodelable elastin-like protein bioinks and neural progenitor cells
Final Report Abstract
Human tissues, both in health and disease, are exquisitely organized into complex three-dimensional architectures that inform tissue function. In biomedical research, specifically in drug discovery and personalized medicine, novel human-based 3D models are needed to provide information with higher predictive value compared to state-of-the-art 2D preclinical models. However, current in vitro models remain inadequate to recapitulate the complex and heterogenous architectures that underlie biology. Therefore, it would be beneficial to develop novel models that could capture both the 3D heterogeneity of tissue (e.g. through 3D bioprinting) and integrate vascularization that is necessary for tissue viability (e.g. through culture in tissue-on-chips). The blood-brain-barrier (BBB) is a highly complex, multi-layered structure that serves as the gatekeeper between the central nervous system and the rest of the body. Three-dimensional BBB in vitro mini-models are potential platforms for understanding how the BBB functions, evaluating drug penetration across the barrier and investigating personalized therapies for progressive diseases, such as neurodegeneration and cancer. In this project, elastin-like protein (ELP) engineered hydrogels were used as bioinks for constructing in vitro models of the BBB. The use of ELP hydrogels as bioinks is an advancement in this field, given that previous bioprinting studies mostly used physically cross-linked hydrogels (e. g. agarose) that allowed little to no cell-driven matrix remodeling. Moreover, this project demonstrated a first step towards combining 3D bioprinting technologies with on-chip platforms containing vascular-like channels. In the future, these platforms may be further developed for in vitro studies of interactions between the vascular interface and patterned, three-dimensional tissue mimics. Functional tissue models, such as neural, corneal, dental, and cardiovascular, and disease models like neurodegenerative and cancer models, can be fabricated using technologies and materials that have been developed during this funded DFG project.
Publications
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(2019). Bioprinting an in vitro model of the blood brain barrier with elastin-like protein-engineered hydrogels and neural progenitor cells. 30th Conference of the European Society for Biomaterials (ESB) together with the 26th Conference of the German Society for Biomaterials (DGBM), 9-13.9.2019, Dresden, Germany
Duarte Campos DF, Lindsay CD, Roth JG, LeSavage BL, Blaeser A, Heilshorn SC
