ABSTRACT

Organ shortage has been a major problem in the United States, and the number of people on organ donor wait lists continues to be much larger than both the number of donors and transplants. Recent estimates suggest that 22 people die every day waiting for an organ transplant, mainly due to the scarcity of donors. Advances in three-dimensional (3D) bioprinting could provide a solid base for the future creation of implantable, bioengineered tissues and organs, obviating the need of immunosuppression and other shortcomings associated with transplants. Printable organs have remained elusive, however, and a main reason is the limited life of cells after printing. This project will investigate a new process, called "Aspiration-assisted Bioprinting," in order to precisely position tissue building blocks in a rapid manner, with the intent to increase throughput to allow fabrication of scalable tissues. If successful, the research will establish a method for bioprinting of tissues or tissue models, which can be used for drug development, lesion studies, or even for replacement of body parts. This research directly impacts the medical products and health industries, and also has direct impact on the quality of life of wounded veterans, and therefore is directly applicable to economic welfare and national security of the United States. Broader impacts activities will include education and participation of underrepresented populations and woman students through training and laboratory tours and demonstrations, as well as the integration of next-generation bioprinting science into both graduate and undergraduate education.

Despite the great progress in bioprinting of cells in scaffolds, such as their encapsulation in hydrogels during bioprinting, fabrication of native-like tissues is quite challenging. Achieving cell densities similar to that of native tissues is not quite feasible using hydrogels. Cellular aggregates are considered a promising bioink with certain measurable and controllable properties, and are self-assembled into tissues with specific features through layer-by-layer stacking or direct assembly. Despite a few attempts, bioprinting of cellular aggregates, most commonly known as "tissue spheroids," have been rarely applied due to lack of robust and practical bioprinting processes. Current processes have major limitations such as (i) poor control on the localization of bioprinted spheroids resulting in tissues with air gaps, (ii) significant damages to the cell viability and structural integrity of spheroids, (iii) poor repeatability of the process when the spheroids are non-uniform in shape and size. The goal of this project is to explore Aspiration-assisted Bioprinting process and study its underlying physical mechanism in order to understand the interactions between physical governing forces and aspirated tissue building blocks. The research objective of this project is to test five sets of hypothesis: 1) cell type and spheroid culture duration influences surface tension and viscoelastic properties of spheroids but cell density does not, 2) spheroids with more viscous properties need less pressure to lift while they are subject to more cell death during lifting, 3) increasing the surface tension of support gel or decreasing the surface tension of spheroids increases the bioprintability of spheroids, 4) larger interspace between spheroids and longer spheroid incubation duration reduces the speed of tissue self-assembly, and 5) larger interspace between spheroids decreases the mechanical properties and graft integration of bioprinted osteochondral tissues. Accomplishing this objective will allow the exploration of advanced bioprinting processes for fabrication of native-like tissues for various application areas such as but not limited to tissue engineering and regenerative medicine, drug screening and disease modeling.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

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