HIGH-SPEED VOLUMETRIC BIOPRINTING APPROACH FOR BIOFABRICATION OF COMPLEX LIVING TISSUE STRUCTURES

Abstract

The generation of tissue‐mimetic living structures of clinically‐relevant size remains a major challenge in tissue engineering. 3D‐bioprinting is a promising approach to shape cell‐laden biomaterials into complex architectures, but current techniques like extrusion bioprinting (EB) and digital‐light processing (DLP), operating in a layer‐wise fashion, pose scalability challenges and struggle to resolve certain free‐form geometrical features typical of biological tissues. Herein, the concept of volumetric bioprinting (VBP) by ultra‐fast visible‐light tomography‐inspired fabrication is introduced, demonstrating the fabrication of complex, cell‐laden, cm‐scale biological structures within seconds. A gelatin‐based photosensitive bioresin was developed for VBP. Centimeter‐scale auricle constructs were printed in 22.7s with high volume accuracy (5.71 ± 2.31% mismatch vs. CAD design) exposing the bioresin to visible‐light (λ = 405nm) shaped as multiple tomographic filtered backprojections. Printing time remained constant for samples of 1.23 and 4.14cm3, in contrast to EB (∼30‐90min) and DLP (∼20‐30min) printing. VBP‐printed cells maintained high viability (>80%). Complex, mesenchymal stromal cell‐laden trabecular bone models with convoluted porous networks were accurately resolved with features down to 144.69 ± 13.55μm. After endothelial cell seeding, constructs showed enhanced neo‐vessel formation. Finally, printed meniscus constructs cultured for 28‐days produced fibrocartilage‐like matrix and exhibited increasing compressive properties over time, approaching values comparable to native meniscal fibrocartilage (∼300kPa).[1] This study established a novel approach for bioprinting complex, tissue‐like architectures within seconds. Short printing times and design freedom make this technique appealing for biomedical applications like patient‐specific grafts and in vitro models. The findings shown here open new avenues for designing the next generation of biomaterial‐based bioprinted constructs of clinically‐relevant sizes.