Speaker
Description
The fabrication of large, perfusable tissue constructs remains a major challenge in regenerative medicine due to the complexity of translating vascular networks across multiple scales. Here, we present an agentic generative AI (GenAI) platform capable of autonomously generating STL files for bioprinting macro-to-millimeter-scale architectures that are subsequently colonized by self-organizing cells to form functional microvascular networks. Our approach integrates GenAI-driven design of a hexagonally arrayed macrofluidic scaffold with computationally optimized branching patterns that direct flow from portal-like inlets to central venous-like outlets, mirroring the hepatic lobule’s geometry. The scaffolds are bioprinted and seeded with GATA6+ hepatic progenitor organoids, which establish parenchymal domains, followed by ETV2+ endothelial progenitors that line the macro- and millimeter-scale channels. At the microscale, endothelial sprouting and tissue-derived morphogens drive emergent self-assembly of capillary-level networks that bridge between printed channels, achieving full perfusability without additional external patterning. This multi-scale design strategy closes the gap between macroengineered perfusion conduits and cell-autonomous microvascularization, enabling the generation of large, metabolically active hepatic tissues. The platform highlights how AI-guided macro-to-millimeter structural design coupled with emergent cell-driven microarchitecture formation can be leveraged to accelerate the biomanufacturing of organ-scale tissues.
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