Igniting Life with Sparks of Light: 3D Spatiotemporal Photoactivation of Angiogenesis via Radiational Kinesis (3D SPARK)

Replicating a human organ is a highly complex challenge both structurally and functionally. At the core of this grand challenge lies the critical need for vascularisation and more broadly the need for cellularisation. Cellular systems in our bodies are naturally programmed in a bottom-up fashion where structure is an evolutionary consequence of function.

For instance, the need for optimal exchange and transport drives morphogenesis, manifesting itself via dynamic signalling and secretion patterns during vascularisation, alveolarization and the formation of all self-organised tissue compartments. Tissue engineers have attempted the inverse hoping function will also follow form, with a laser focus on the structure problem: the ability to produce acellular architectures such as perfusable networks for transport and microporous scaffolds for cellular aggregation.

These top-down engineered matrices are intricate yet static and non-responsive, leaving us with rudimental means of bulk seeding, cellularisation and stimulation, and limiting cell-mediated bottom-up growth and remodelling. Organotypic growth patterns are a dynamic response to physiological needs, driven by the spatiotemporally controlled release of biochemical factors and stimuli, and require extremely soft and degradable cell encapsulated extracellular microenvironments capable of bottom-up remodelling, both of which are currently only afforded at small microfluidic footprints.

The 3D SPARK project offers a game-changing solution to large-scale volumetric tissue production via computed axial lithography (CAL) and computed axial stimulation (CAS) - the optical inverses of computed axial tomography (CAT). Volumetric processing challenges conventional wisdom in tissue engineering showing that complex and delicate 3D cellular architectures can be produced all-at-once without relying on slow, sequential processing of biological matter, and that large volumes of manufactured tissue can be accessible at a single cell level without a need for physical manipulation or slow optical scanning.

At its core, this revolutionary CAT-inspired method utilises a superposition of 2D angular light projections to construct a 3D spatial distribution of exposure dose, and volumetrically trigger photopolymerization (bioprinting), photorelease (biomodulation) and photoexcitation (imaging) to regulate and monitor key cellular events during tissue development in a photoactive cell-encapsulated hydrogel matrix.

With light-mediated volumetric processing and the ability to pattern light intensity in 3D at multiple wavelengths, we introduce a scalable solution to: (1) trigger photopolymerization and manufacture intact vascular structures in such soft (