2026-09-19T00:25:02Zhttps://ecommons.cornell.edu/server/oai/request

oai:ecommons.cornell.edu:1813/1159562026-05-15T19:52:01Zcom_1813_35col_1813_47

Lu, Renhao Lee, Esak Ma, Minglin Kurpios, Natasza 2024-11-05T19:46:39Z 2024-05 ProQuest Submission ID: 14223 ProQuest Publication ID: 31239443 https://hdl.handle.net/1813/115956 https://doi.org/10.7298/nj8j-5913 16575646 151 pages The lymphatic system is a network consisting of lymphatic vessels and lymphoid organs such as lymph nodes (LNs), which drain excess interstitial fluid and eventually return it to the blood circulatory system via the thoracic duct and subclavian veins. It plays a key role in interstitial fluid homeostasis, adaptive immune response, biomolecular uptake (dietary lipid, albumin, amyloid beta, etc.), and tumor metastasis. Dysfunction of the lymphatic system thus can lead to various diseases, including lymphedema, lipedema, inflammatory diseases, autoimmune diseases, neurodegenerative diseases, cancer, and glaucoma. Despite the significant roles of lymphatics, its morphogenesis, pathogenesis, and drug delivery strategies are still not completely understood. Organ-on-chip systems combine microfabrication technology with biology, which enables in vitro models to recapitulate key aspects of human physiology and disease. In this dissertation, I discuss organ-on-chip models for studying different compartments of lymphatic vessels (initial lymphatics and collecting lymphatics) and organ-specific ocular lymphatics under physiological and pathological conditions. Specifically, I first describe the aqueous humor outflow model that incorporates trabecular meshwork and Schlemm’s canal, and TGF-β1/ALK5/VEGFC signaling axis in steroid-induced glaucoma. Then, I discuss the double-casting sacrificial 3D printing method to study lymphatic valve morphogenesis and inflammation-induced lymphatic valve dysfunction. Finally, I discuss the use of initial lymphatic vessel-on-chip devices to study nanoparticle delivery to lymphatic systems, revealing previously unappreciated size-dependent intracellular accumulation of nanoparticles in lymphatic endothelial cells. 2026-06-17 en Attribution 4.0 International https://creativecommons.org/licenses/by/4.0/ 3D bioprinting Drug delivery Glaucoma Lymphatics Nanoparticle Tissue engineering Tissue-engineered in vitro models for studying lymphatic morphogenesis, pathogenesis, and drug delivery dissertation or thesis https://newcatalog.library.cornell.edu/catalog/16575646 application/pdf Biomedical Engineering Cornell University Doctor of Philosophy Ph. D., Biomedical Engineering https://hdl.handle.net/1813/59810.2 Publication Cornell Theses and Dissertations Lu, Renhao 5893a6ea-7af3-41d7-abc6-04bcd26ab5df embargo embargo <Publication xmlns="https://www.openaire.eu/cerif-profile/1.1/" id="0c479e03-6030-4154-912c-e680068622ac"> <Type xmlns="https://www.openaire.eu/cerif-profile/vocab/COAR_Publication_Types">http://purl.org/coar/resource_type/c_1843</Type> <Language>en</Language> <Title>Tissue-engineered in vitro models for studying lymphatic morphogenesis, pathogenesis, and drug delivery</Title> <PublishedIn> <Publication> </Publication> </PublishedIn> <PublicationDate>2024-05</PublicationDate> <DOI>https://doi.org/10.7298/nj8j-5913</DOI> <Authors> <Author> <DisplayName>Lu, Renhao</DisplayName> <Affiliation> <OrgUnit> </OrgUnit> </Affiliation> </Author> </Authors> <Editors> </Editors> <Publishers> <Publisher> <OrgUnit /> </Publisher> </Publishers> <License>https://creativecommons.org/licenses/by/4.0/</License> <Keyword>3D bioprinting</Keyword> <Keyword>Drug delivery</Keyword> <Keyword>Glaucoma</Keyword> <Keyword>Lymphatics</Keyword> <Keyword>Nanoparticle</Keyword> <Keyword>Tissue engineering</Keyword> <Abstract>The lymphatic system is a network consisting of lymphatic vessels and lymphoid organs such as lymph nodes (LNs), which drain excess interstitial fluid and eventually return it to the blood circulatory system via the thoracic duct and subclavian veins. It plays a key role in interstitial fluid homeostasis, adaptive immune response, biomolecular uptake (dietary lipid, albumin, amyloid beta, etc.), and tumor metastasis. Dysfunction of the lymphatic system thus can lead to various diseases, including lymphedema, lipedema, inflammatory diseases, autoimmune diseases, neurodegenerative diseases, cancer, and glaucoma. Despite the significant roles of lymphatics, its morphogenesis, pathogenesis, and drug delivery strategies are still not completely understood. Organ-on-chip systems combine microfabrication technology with biology, which enables in vitro models to recapitulate key aspects of human physiology and disease. In this dissertation, I discuss organ-on-chip models for studying different compartments of lymphatic vessels (initial lymphatics and collecting lymphatics) and organ-specific ocular lymphatics under physiological and pathological conditions. Specifically, I first describe the aqueous humor outflow model that incorporates trabecular meshwork and Schlemm’s canal, and TGF-β1/ALK5/VEGFC signaling axis in steroid-induced glaucoma. Then, I discuss the double-casting sacrificial 3D printing method to study lymphatic valve morphogenesis and inflammation-induced lymphatic valve dysfunction. Finally, I discuss the use of initial lymphatic vessel-on-chip devices to study nanoparticle delivery to lymphatic systems, revealing previously unappreciated size-dependent intracellular accumulation of nanoparticles in lymphatic endothelial cells.</Abstract> <Access xmlns="http://purl.org/coar/access_right" > </Access> </Publication>