Development of a 3D printable in vitro vascular model for therapeutic applications

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dc.contributor.advisorVeiseh, Omiden_US
dc.creatorRoyse, Madison K.en_US
dc.date.accessioned2022-09-23T18:15:58Zen_US
dc.date.created2022-08en_US
dc.date.issued2022-08-08en_US
dc.date.submittedAugust 2022en_US
dc.date.updated2022-09-23T18:15:58Zen_US
dc.descriptionEMBARGO NOTE: This item is embargoed until 2024-08-01en_US
dc.description.abstractThe process of drug discovery and development is long and costly, often resulting in limited or expensive treatment options for patients. The translation of drug candidates and therapeutic strategies from preclinical screening to clinical studies is a substantial hurdle in the field and has underscored the need for technologies that can accurately predict therapeutic outcomes in vitro before translation to clinical studies. Recent advances in 3D printing have enabled the fabrication of in vitro models that more accurately recapitulate physiologic forces and material composition in comparison to traditional in vitro methods such as 2D cell culture and microfluidic devices. Here, we demonstrate the development of a 3D-printed perfusable gelatin-based hydrogel as an in vitro vascular model for screening therapeutics in an accelerated and cost-effective manner. Biocompatible hydrogels of gelatin methacrylate (GelMA) and poly(ethylene glycol) diacrylate (PEGDA) with hollow vascular architectures were fabricated via projection stereolithography, endothelialized with human umbilical vein endothelial cells (HUVECs), and subjected to fluid flow with varying biochemical stimuli to promote endothelial maturation and stability. The ability of these endothelialized channels to respond to external barrier-disrupting stimuli was validated by showing a significant increase in vascular permeability after ultrasound treatment, demonstrating the utility of this model in assessing therapeutic strategies targeting vasculature. Finally, this model was adapted to recreate the highly restrictive vasculature of the central nervous system, the blood-brain barrier (BBB), via incorporation of human brain microvascular endothelial cells, human brain microvascular pericytes, and human brain astrocytes. The presence of essential blood-brain barrier junctional complexes and transporters were confirmed, and pilot work demonstrated the capacity of this in vitro BBB model to be used as a tool for evaluating the transport of therapeutics across the blood-brain barrier. This 3D printed perfusable vascular model offers an alternative route to assess vascular-focused therapies, providing a preclinical model that bridges less physiologic in vitro methods and more complex, costly in vivo animal studies.en_US
dc.embargo.lift2024-08-01en_US
dc.embargo.terms2024-08-01en_US
dc.format.mimetypeapplication/pdfen_US
dc.identifier.citationRoyse, Madison K.. "Development of a 3D printable in vitro vascular model for therapeutic applications." (2022) Diss., Rice University. <a href="https://hdl.handle.net/1911/113266">https://hdl.handle.net/1911/113266</a>.en_US
dc.identifier.urihttps://hdl.handle.net/1911/113266en_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.subject3D printingen_US
dc.subjectbioprintingen_US
dc.subjectin vitro vascular modelen_US
dc.subjectendothelial barrier functionen_US
dc.subjectultrasound-enhanced permeabilityen_US
dc.subjectblood-brain barrier modelen_US
dc.titleDevelopment of a 3D printable in vitro vascular model for therapeutic applicationsen_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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