Speaker
Description
Vasculature plays a crucial role in tissue engineering since it is essential for maintaining tissue viability by efficient nutrient and oxygen exchange as well as waste removal. The creation of biomimetic vascular networks is therefore critical for the development of functional tissue constructs. Sacrificial strategy has emerged as an effective method for engineering vascular structures by creating temporary templates that are subsequently removed to form well-defined vascular channels. By utilizing 3D printing technology, microvasculature with various designs has been fabricated. However, all previous sacrificial techniques entailed first constructing the hollow channels, with subsequent cell seeding. This two-step process often involves delicate experiment steps including sacrificial gel removal and subsequent cell seeding by perfusion, and hence cannot achieve spatial and density control of the seeded cells. Moreover, the uncontrollable cell perfusion in the microchannels affects the cell adhesion and the integrity of the resulting microvasculature, resulting in low reproducibility. At present, fabrication of endothelialized microvasculature with a diameter smaller than 100 μm is still a significant challenge.
Here, we developed a general PRINting Cell Embedded Sacrificial Strategy (PRINCESS) and successfully fabricated microvasculatures using degradable DNA biolubricant. This is the first demonstration of direct cell printing to fabricate microvasculature, which eliminates the need for a subsequent cell seeding process and the associated deficiencies. Utilizing the shear-thinning property of DNA hydrogels as a novel sacrificial, cell-laden biolubricant, we can print a 70 μm endothelialized microvasculature, breaking the limit of 100 μm. To our best knowledge, this is the smallest endothelialized microvasculature that has ever been bioprinted so far. This strategy provides a new platform for constructing complex hierarchical vascular networks and offers new opportunity towards engineering thick tissues.
In PRINCESS, the degradation rate of sacrificial materials and the cell adhesion process are complex yet critical for vascularization. Traditional experimental methods struggle to comprehensively investigate these dynamics. Artificial intelligence (AI) offers a powerful alternative, providing a systematic framework to uncover non-intuitive relationships between material parameters and cell behavior through computational modeling and predictive analytics. By leveraging AI to predict material degradation and cell adhesion, the underlying mechanisms of vascularization are elucadated, which can be further used to guide the selection of sacrificial materials and the optimization bioprinting process.
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