Multi-scale hydrogel stereolithography for vascular tissue engineering & microphysiologic systems

Date
2021-09-17
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Abstract

Throughout all the known kingdoms of life, organisms must fight against entropy to build and maintain unique structural features that drive biological function. The field of tissue engineering seeks to recreate these structure-function relationships with carefully constructed assemblies of specialized cells and extracellular matrix components like polymers and proteins. Especially difficult to produce are the hollow tubes that shuttle fluids throughout the body in the form of blood vessels, airways, and ducts. Over the past 5 years, precision needles, lasers, and projectors have been used to build hollow vessels across the full range of biological scales. Critically though, each technology typically operates independently within its own optimal dimensional regime, and there does not currently exist a unified bioprinting technology that can endow large (>100 mL) tissues with multi-scale vascular hierarchies. Here we consider a light-based bioprinter that uses high-resolution 2D projections to build multi-scale hydrogel vessel networks with internal diameters of 50-2000 μm. In projection stereolithography, XY-resolution is limited by the projector’s physical pixel size and magnifying optics. In contrast, Z-resolution is limited by the bioink’s photoabsorbing properties, which if insufficient can lead to excess light penetration and vessel occlusion. Here we detail our efforts to identify and characterize biocompatible photoabsorbing compounds, which led to the successful fabrication of perfusable hydrogel vessel networks, including multi-vascular structures reminiscent of the lungs. We extend this work with technological innovations that enable higher resolution features, providing access to microvascular networks and advanced microphysiologic systems with vascularized microwell arrays. Finally, we highlight engineering advances that support multi-material projection stereolithography bioprinting, which has historically been limited by the difficulty of preventing different liquid bioinks from unintentional mixing. In each chapter, advantages and limitations of our technologies and strategies are addressed. Specific pain-points and troubleshooting guidelines are detailed, along with hypotheses for future experiments. We expect this work will provide unambiguous evidence of the rich architectural design space and novel microphysiologic applications that stereolithography bioprinting is able to provide for academic researchers, industry professionals, and clinicians.

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Doctor of Philosophy
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Thesis
Keywords
3D printing, bioprinting, biofabrication, biomaterials, vascular tissue engineering, pulmonary tissue engineering, endothelial cells, multicellular aggregates
Citation

Sazer, Daniel Warren. "Multi-scale hydrogel stereolithography for vascular tissue engineering & microphysiologic systems." (2021) Diss., Rice University. https://hdl.handle.net/1911/111360.

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