Research Projects

Screening drugs and potential therapeutics for neurodegenerative diseases (NDD) remains a challenge due to lack of structural and functional complexity of blood-brain-barrier (BBB) platforms. Such platforms typically organize monolayers of different cell types (neuron and glial cells) and endothelial cells partitioned by synthetic non-biodegradable membrane. This limits barrier’s capability to remodel with cell growth and lacks selectivity in ionic and biomolecular transport. Further, current organ-on-a-chip (OOC) and BBB platforms rely on microscopy and biomarker quantification. However, additional real-time characterization with a higher spatial resolution is necessary. The local electrical properties measured in real-time can be a descriptor of the state of the BBB. We propose to mimic the BBB complexity with hydrogel interfaces that guide biomolecule transport. A novel microphysiological unit platform is proposed to combine biodegradable interface membranes capable of remodelling with cell growth and regulating biomolecule transport and an embedded electrode array for high spatial resolution electric potential capture. Zwitterionic interfaces are proposed to establish a BBB model exhibiting the permeability of in vivo mature BBB. Hypothesis and Approach – First, amino-acid functionalized hyaluronic photocrosslinkable bioinks will be synthesized to fabricate zwitterionic hydrogels. Using an extrusion/electrowriting system, these bioinks will be used to fabricate charged fibrous membranes followed by photocrosslinking to obtain mats with controlled pore morphology. Next, a device will be constructed using 3D printing methods, including an electrode array (EA) and fluid perfusion to mimic BBB model. The fabricated membrane will allow asymmetric transport. The EA will be placed on the fabricated chip for electric potential mapping. The hydrogel layer encapsulating cells will be bioprinted and placed above EA. Channels in the fluidic chip will be used to perfuse growth medium and will be analysed for biomarkers. Various drugs and injuries will be introduced in the fabricated BBB to study spatial response over time. Novelty – A brain-vasculature interface that mimics BBB capable of remodelling with cell growth. The real-time monitoring of spatial electric potentials can provide a look at the dynamic nature of degeneration. The selective biomolecular transport capability of hydrogel barrier will provide a real view of how therapeutics may fail and ways to improve drug transport. Novel biomaterials can be explored as carriers to cross the BBB to deliver drugs to injured brain tissue. Further, this can model critical tissue interfaces providing means to alter the tissue environment by electromechanical or biochemical stimulations. We envision capturing the intricacies of natural tissue functions as compared to highly simplified OOC models providing valuable tools for researchers, medical research facilities, and pharmaceutical firms.