Periodic Reporting for period 5 - Living Bionics (Living bioelectronics: Bridging the interface between devices and tissues)
Reporting period: 2024-07-01 to 2025-06-30
To overcome this, Living Bionics proposed a new strategy, creating living neural interfaces composed of soft, tissue-like materials partly made from living cells. These “biohybrid” systems are designed to grow into the brain, connect with surrounding tissues, and support two-way communication between biological and electronic systems.
This approach enables new solutions across a range of neurological disorders including paralysis, epilepsy, sensory loss, and neurodegenerative diseases. By improving biocompatibility and functional integration, the project aimed to develop neural interfaces that are more stable, adaptive, and long-lasting.
This project combined expertise in bioengineering, neuroscience, biomaterials, and electronics to pursue three goals:
1. Design a custom biomaterial scaffold for neural engineering.
2. Engineer neural constructs that can self-organise and integrate with brain tissue.
3. Explore the use of these living systems as next-generation neural interfaces.
Using this hydrogel system, neural progenitor cells were co-encapsulated with primary astrocytes to guide self-organisation into synaptically active tissue constructs. These 3D systems demonstrated robust neuronal development, neurite outgrowth, and spontaneous activity in vitro.
Multi-layered “living electrodes” were engineered by combining these neural constructs with a conductive hydrogel substrate to enable controlled electrical stimulation. A high-throughput version of this platform allowed for systematic studies on how electrical stimuli influence neural cell development.
To assess integration with native tissue, constructs were co-cultured with organotypic brain slices. Structural and synaptic continuity across the interface was confirmed using immunofluorescence staining, highlighting the potential for functional integration in vivo. Building on these findings, constructs were integrated into electrocorticography (ECoG) arrays developed with the PIE Foundry at USC. These biohybrid devices are now undergoing long-term testing in rodent models for safety and performance.
Alongside these technical milestones, the project published high-impact papers in Advanced Functional Materials, Journal of Materials Chemistry B, and Tissue Engineering Part A, with additional manuscripts in preparation. Findings were presented at major international conferences and in interdisciplinary forums, including the Hybrid Minds initiative linking neurotechnology with ethics and policy.
The platform laid the groundwork for two follow-on programmes funded by the ERC and ARIA, which are advancing biohybrid neural interfaces for translational applications in deep brain and peripheral nerve modulation.
A central innovation was the use of glia-guided self-organisation to drive the differentiation and maturation of neural progenitors into functional neural networks. This developmental, bottom-up approach mirrors how brain circuits form in vivo and represents a new strategy in neural tissue engineering. The hydrogel system is also a notable advance in biomaterial science, by allowing precise tuning of mechanical and biochemical properties while maintaining cell viability and compatibility with electronics for developing implantable biohybrid systems.The project pioneered multi-layered living electrode constructs, combining biological and electronic components in a modular format. Supported by high-throughput stimulation and computational modelling, these tools enabled systematic investigation into how electrical cues shape tissue formation. Another key breakthrough was the demonstration of synaptic integration between engineered constructs and brain tissue ex vivo, providing early proof-of-concept for functional connectivity. The integration of these constructs into implantable ECoG arrays and their ongoing testing in animal models marks an important translational milestone.
Living Bionics advanced the field beyond the current state of the art by introducing a regenerative, biologically informed design paradigm for neural interfaces. The results offer a path toward future neurotechnologies that are not only mechanically and electrically compatible but also capable of integrating into the nervous system.