BIOPRINTING BY LIGHT-SHEET LITHOGRAPHY: ENGINEERING COMPLEX TISSUES WITH HIGH RESOLUTION AT HIGH SPEED

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Engineered tissues are key elements in both in vitro and in vivo applications, strongly impacting the academy, pharma and clinical sectors. Bioprinting is considered the most promising method to produce such engineered tissues. However, current bioprinting methods are severely limited by both insufficient speed and spatial resolution. Long printing times decrease cell viability, while poor spatial resolution fails to recreate the heterogeneous nature of native tissues. BRIGHTER will develop a new bioprinting technology able to produce tissue surrogates with high spatial resolution at high printing speed using an original top-down lithography approach, in contrast with current bottom-up, layer-by-layer bioprinting methods. BRIGHTER will combine high-speed light-sheet illumination and high-resolution digital photomasks to selectively photocrosslink cell-laden hydrogels in confined voxels and produce three-dimensional complex geometries. This process will enable the bioprinting of key anatomical microfeatures of tissue such as invaginations, evaginations or wavy morphologies. It will also incorporate hollow vascular structures while maintaining tissue mechanical integrity without the need of additional sacrificial material. As a remarkable feature, matrix crosslinking density can be fine-tuned using BRIGHTER’s approach, allowing the fabrication of cellular compartments requiring specific matrix stiffness such as stem cell niches. The proof-of-concept application will be bioprinting viable engineered skin tissues exploiting the key features of the BRIGHTER device: skin appendix (hair follicles, sweat glands), stem cell niches and a vascular network. The ultimate goal is to provide a superior alternative to state-or-the art 3D bioprinting with a disruptive bioprinting technology that would create new scientific and business opportunities.