Photopatterned Sacrificial Vascular Architectures for Large Tissue-Scale Oxygenation

The engineering of thick, metabolically active tissues is constrained by the lack of scalable methods to create perfusable vasculature. This hinders effective metabolite transport in large tissue volumes, posing a critical barrier for regenerative tissue applications. In this study, we introduce photopatterned Channel Architectures with Sacrificial Templates (pCAST), an additive manufacturing strategy for generating three dimensional (3D), interconnected vascular networks with precisely defined negative space. Water-soluble sacrificial templates were fabricated using scalable Continuous Liquid Interface Production (CLIP), embedded within tissue constructs, and flushed away to yield 50 {micro}m perfusable channels spanning centimeter-scale tissue constructs. We then apply experimental oxygen mapping and viability analysis to pCAST constructs to build finite-element models that predict patterns of oxygen availability and tissue survival are governed by the balance between metabolic demand and vascular architecture, consistent with reaction-diffusion theory. This computational framework quantitatively predicts oxygen distributions and viability boundaries across vascular geometries and is validated experimentally. Together, these results establish pCAST as a scalable design framework linking vascular architecture, perfusion, and metabolic support for engineering large, 3D perfused tissue constructs. SignificanceThe ability to engineer thick, living tissues is limited by poor oxygen and nutrient delivery, which causes cell death before tissues can function or integrate with the body. This work addresses that fundamental barrier by introducing photopatterned Channel Architecture with Sacrificial Templates (pCAST), a scalable manufacturing strategy that creates precisely defined, perfusable vascular networks inside 3D tissues. By combining high-resolution 3D printing, sacrificial templating, and quantitative oxygen mapping, this research establishes design rules that link vascular geometry, perfusion, and tissue viability. These insights provide a general framework for building large, metabolically active tissues, with direct relevance to cardiac patches and other regenerative medicine applications.