Engineering functional tissues by spatiotemporal patterning: 3D bioprinting and optogenetics for directing the organization of cell spheroid building blocks (OPTO-BIOPRINTING)
Seventeen people die each day in the UK while waiting for an organ transplant, and existing artificial implants degrade over time. Tissue engineering could provide living replacements, but current methods cannot build tissues with the complex internal structure and function of natural organs. This project combines two technologies to solve that problem. First, a 3D bioprinter will deposit cell spheroids alongside growth factor gradients that mimic the chemical signals present during embryonic development. Second, an optogenetics system will use light to trigger cells within the printed construct to produce specific proteins on demand, after fabrication is complete. Together, these methods allow precise control over when and where cells receive developmental cues. If successful, the platform could produce patient-specific tissue grafts that integrate with the body and last a lifetime. The proof-of-concept uses cartilage-bone units, but the approach is designed to extend to other tissues and organs. Beyond transplantation, the same system could generate realistic disease models for drug testing, replacing some animal experiments and accelerating the development of new therapies.
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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.
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