Brain Extracellular Matrix-Based Electronic Brain Biochip.

To monitor neuronal activity with high fidelity, in vitro models must recapitulate not only the cellular composition but also the three-dimensional (3D) microenvironment of the brain. Here, we present an electronic brain biochip that integrates animal-derived decellularized extracellular matrix (dECM) hydrogels with flexible, multichannel electrodes to build a multilayer 3D neural network in which each layer can be independently monitored. Brain dECM hydrogels provide tissue-like biochemical and structural cues that accelerate neurite outgrowth and neural connectivity between layers, enabling the formation of functionally active 3D networks within 3 weeks. We use a low-cost, readily available dECM source from porcine brain tissue, upcycling biological waste into high-value neural scaffolds without compromising biocompatibility. The dECM hydrogels are compatible with both rat primary neurons and hiPSC-derived neurons. Flexible electrode interfaces support real-time, multichannel electrophysiological recording and controlled chemical stimulation. The combination of dECM scaffolding and flexible electrode interfaces supports signal capture throughout the 3D network volume. Functional assays under chemical stimulation reveal bursting and synchronized activity in which all layers participate. By coupling a dECM-based, 3D neural architecture to flexible, multichannel electronics, this work establishes a scalable "electronic organoid" platform for the study of neuronal dynamics and neuropharmacology. Collectively, these advances represent an important step toward artificial brain models that bridge the gap between engineered neural tissues and functional neurobiology.