Engineering functional tissues by spatiotemporal patterning: 3D bioprinting and optogenetics for directing the organization of cell spheroid building blocks (OPTO-BIOPRINTING) (360G-Wellcome-309435_Z_24_Z)

Each day, 17 people die waiting for organ transplants. Artificial organs or synthetic implants, if available, cannot sustain long-term use. Tissue engineering holds promise for providing living replacements, but existing strategies cannot produce fully native-like tissues with biomimetic organization and physiological function. In normal development, finely coordinated spatiotemporal gradients of morphogens dictate cell fate. Next- generation tissue engineering will leverage emerging technologies to provide permissive environmental cues harnessing the innate regenerative potential of stem/progenitor cells to organize into structurally complex and functional tissues. The goal of OPTO-BIOPRINTING is to establish a novel platform for spatiotemporally guided tissue engineering, combining a bioprinting technique whereby growth factor gradients mimicking physiological development are patterned alongside cellular spheroids (Aim 1), with an optogenetics approach whereby light can trigger cellular production of regionally specific proteins on demand (Aim 2). These complementary patterning strategies will enable spatiotemporal cue specification both pre- and post-biofabrication, allowing unprecedented control over engineered tissue development (Aim 3). Human induced pluripotent stem cell-derived spheroids will serve as minimally invasive, patient-specific, cell-dense, and self-assembling building blocks to form larger tissue constructs. The cartilage-bone unit will be used for proof- of-concept, but the project impact extends broadly to functional tissue engineering, regenerative medicine, and disease modelling.