Microfluidic‐Based Reconstitution of Functional Lymphatic Microvasculature: Elucidating the Role of Lymphatics in Health and Disease
Abstract The knowledge of the blood microvasculature and its functional role in health and disease has grown significantly attributable to decades of research and numerous advances in cell biology and tissue engineering; however, the lymphatics (the secondary vascular system) has not garnered simila...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2024-02-01
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| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202302903 |
| _version_ | 1827361395343097856 |
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| author | Jean C. Serrano Mark R. Gillrie Ran Li Sarah H. Ishamuddin Emad Moeendarbary Roger D. Kamm |
| author_facet | Jean C. Serrano Mark R. Gillrie Ran Li Sarah H. Ishamuddin Emad Moeendarbary Roger D. Kamm |
| author_sort | Jean C. Serrano |
| collection | DOAJ |
| description | Abstract The knowledge of the blood microvasculature and its functional role in health and disease has grown significantly attributable to decades of research and numerous advances in cell biology and tissue engineering; however, the lymphatics (the secondary vascular system) has not garnered similar attention, in part due to a lack of relevant in vitro models that mimic its pathophysiological functions. Here, a microfluidic‐based approach is adopted to achieve precise control over the biological transport of growth factors and interstitial flow that drive the in vivo growth of lymphatic capillaries (lymphangiogenesis). The engineered on‐chip lymphatics with in vivo‐like morphology exhibit tissue‐scale functionality with drainage rates of interstitial proteins and molecules comparable to in vivo standards. Computational and scaling analyses of the underlying transport phenomena elucidate the critical role of the three‐dimensional geometry and lymphatic endothelium in recapitulating physiological drainage. Finally, the engineered on‐chip lymphatics enabled studies of lymphatic‐immune interactions that revealed inflammation‐driven responses by the lymphatics to recruit immune cells via chemotactic signals similar to in vivo, pathological events. This on‐chip lymphatics platform permits the interrogation of various lymphatic biological functions, as well as screening of lymphatic‐based therapies such as interstitial absorption of protein therapeutics and lymphatic immunomodulation for cancer therapy. |
| first_indexed | 2024-03-08T07:04:33Z |
| format | Article |
| id | doaj.art-3ca350d9bc7c43e6b481257893b212af |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-03-08T07:04:33Z |
| publishDate | 2024-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-3ca350d9bc7c43e6b481257893b212af2024-02-03T05:02:44ZengWileyAdvanced Science2198-38442024-02-01115n/an/a10.1002/advs.202302903Microfluidic‐Based Reconstitution of Functional Lymphatic Microvasculature: Elucidating the Role of Lymphatics in Health and DiseaseJean C. Serrano0Mark R. Gillrie1Ran Li2Sarah H. Ishamuddin3Emad Moeendarbary4Roger D. Kamm5Department of Mechanical Engineering Massachusetts Institute of Technology Cambridge MA 02139 USADepartment of Biological Engineering Massachusetts Institute of Technology Cambridge MA 02139 USACenter for Systems Biology Massachusetts General Hospital Research Institute Boston MA 02114 USADepartment of Biological Engineering Massachusetts Institute of Technology Cambridge MA 02139 USADepartment of Biological Engineering Massachusetts Institute of Technology Cambridge MA 02139 USADepartment of Mechanical Engineering Massachusetts Institute of Technology Cambridge MA 02139 USAAbstract The knowledge of the blood microvasculature and its functional role in health and disease has grown significantly attributable to decades of research and numerous advances in cell biology and tissue engineering; however, the lymphatics (the secondary vascular system) has not garnered similar attention, in part due to a lack of relevant in vitro models that mimic its pathophysiological functions. Here, a microfluidic‐based approach is adopted to achieve precise control over the biological transport of growth factors and interstitial flow that drive the in vivo growth of lymphatic capillaries (lymphangiogenesis). The engineered on‐chip lymphatics with in vivo‐like morphology exhibit tissue‐scale functionality with drainage rates of interstitial proteins and molecules comparable to in vivo standards. Computational and scaling analyses of the underlying transport phenomena elucidate the critical role of the three‐dimensional geometry and lymphatic endothelium in recapitulating physiological drainage. Finally, the engineered on‐chip lymphatics enabled studies of lymphatic‐immune interactions that revealed inflammation‐driven responses by the lymphatics to recruit immune cells via chemotactic signals similar to in vivo, pathological events. This on‐chip lymphatics platform permits the interrogation of various lymphatic biological functions, as well as screening of lymphatic‐based therapies such as interstitial absorption of protein therapeutics and lymphatic immunomodulation for cancer therapy.https://doi.org/10.1002/advs.202302903immune cellslymphaticsmicrofluidicstissue engineeringtransport phenomena |
| spellingShingle | Jean C. Serrano Mark R. Gillrie Ran Li Sarah H. Ishamuddin Emad Moeendarbary Roger D. Kamm Microfluidic‐Based Reconstitution of Functional Lymphatic Microvasculature: Elucidating the Role of Lymphatics in Health and Disease Advanced Science immune cells lymphatics microfluidics tissue engineering transport phenomena |
| title | Microfluidic‐Based Reconstitution of Functional Lymphatic Microvasculature: Elucidating the Role of Lymphatics in Health and Disease |
| title_full | Microfluidic‐Based Reconstitution of Functional Lymphatic Microvasculature: Elucidating the Role of Lymphatics in Health and Disease |
| title_fullStr | Microfluidic‐Based Reconstitution of Functional Lymphatic Microvasculature: Elucidating the Role of Lymphatics in Health and Disease |
| title_full_unstemmed | Microfluidic‐Based Reconstitution of Functional Lymphatic Microvasculature: Elucidating the Role of Lymphatics in Health and Disease |
| title_short | Microfluidic‐Based Reconstitution of Functional Lymphatic Microvasculature: Elucidating the Role of Lymphatics in Health and Disease |
| title_sort | microfluidic based reconstitution of functional lymphatic microvasculature elucidating the role of lymphatics in health and disease |
| topic | immune cells lymphatics microfluidics tissue engineering transport phenomena |
| url | https://doi.org/10.1002/advs.202302903 |
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