Engineered tissues supported by convection and diffusion through dendritic vascular networks

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dc.contributor.advisorMiller, Jordan Sen_US
dc.creatorKinstlinger, Ian S.en_US
dc.date.accessioned2020-11-03T20:05:21Zen_US
dc.date.available2021-12-01T06:01:10Zen_US
dc.date.created2020-12en_US
dc.date.issued2020-10-22en_US
dc.date.submittedDecember 2020en_US
dc.date.updated2020-11-03T20:05:21Zen_US
dc.description.abstractMetabolic function in mammalian tissues is sustained by the delivery of oxygen and nutrients as well as the removal of waste through complex, three-dimensional (3D) networks of hierarchically organized blood vessels. However, fabrication of such 3D vascular networks within soft hydrogels remains one of the greatest challenges in tissue engineering. Sacrificial templates have proven useful for patterning perfusable vascular networks in engineered tissues, but such templates have been constrained in architectural complexity by limitations in the techniques which have been used to fabricate them. We hypothesized that these architectural limitations could be overcome by creating sacrificial vascular templates via selective laser sintering (SLS), an additive manufacturing process which uses a laser to fabricate solid structures from powdered raw materials. We developed an open-source SLS system and demonstrated its capacity to pattern biomimetic scale models of vascular topology. To adapt SLS fabrication for biocompatible and water-soluble materials which could be used sacrificially in the presence of cells, we identified carbohydrate powders formulations which are compatible with SLS and demonstrated laser sintering of carbohydrates into elaborate branched structures, including algorithmically-generated biomimetic branching networks which we term dendritic networks. Laser sintered carbohydrate templates were used to pattern perfusable vascular networks in a range of materials including natural and synthetically-derived biocompatible hydrogels, which can support cells in both the lumenal and parenchymal spaces. We leveraged this methodology to establish a complete pipeline encompassing generative vascular design, additive fabrication, perfusion culture, and volumetric spatial analysis of tissue performance. We identify heterogeneous zones of metabolic activity that emerge in perfused cell-laden hydrogels and we demonstrate that dendritic vascular networks can sustain cell metabolism deep within model tissues greater than 1 cm thick. We also seed endothelial cells, characterize convective transport through dendritic networks, and explore strategies to modulate the dynamics of changing cell densities within perfused gels. Finally, we demonstrate that perfusion culture through dendritic networks can support the survival and function of primary hepatocyte cultures. This approach for rapid design and biofabrication of engineered volumetric tissues offers an experimental strategy for interrogating the relationship between vascular network architecture, metabolite transport, and tissue function.en_US
dc.embargo.terms2021-12-01en_US
dc.format.mimetypeapplication/pdfen_US
dc.identifier.citationKinstlinger, Ian S.. "Engineered tissues supported by convection and diffusion through dendritic vascular networks." (2020) Diss., Rice University. <a href="https://hdl.handle.net/1911/109499">https://hdl.handle.net/1911/109499</a>.en_US
dc.identifier.urihttps://hdl.handle.net/1911/109499en_US
dc.language.isoengen_US
dc.rightsCopyright is held by the author, unless otherwise indicated. Permission to reuse, publish, or reproduce the work beyond the bounds of fair use or other exemptions to copyright law must be obtained from the copyright holder.en_US
dc.subjectBiomaterialsen_US
dc.subjectTissue Engineeringen_US
dc.subjectSelective Laser Sinteringen_US
dc.subject3D Printingen_US
dc.subjectVascular Networken_US
dc.subjectEndothelial Cellen_US
dc.subjectPerfusionen_US
dc.subjectHydrogelen_US
dc.subjectSacrificial Templatingen_US
dc.titleEngineered tissues supported by convection and diffusion through dendritic vascular networksen_US
dc.typeThesisen_US
dc.type.materialTexten_US
thesis.degree.departmentBioengineeringen_US
thesis.degree.disciplineEngineeringen_US
thesis.degree.grantorRice Universityen_US
thesis.degree.levelDoctoralen_US
thesis.degree.nameDoctor of Philosophyen_US
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