Stabilization and improved functionality of three-dimensional perfusable microvascular networks in microfluidic devices under macromolecular crowding
Abstract Background There is great interest to engineer in vitro models that allow the study of complex biological processes of the microvasculature with high spatiotemporal resolution. Microfluidic systems are currently used to engineer microvasculature in vitro, which consists of perfusable microv...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Association for the Advancement of Science (AAAS)
2023-04-01
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| Series: | Biomaterials Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40824-023-00375-w |
| _version_ | 1797280586034839552 |
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| author | Ho-Ying Wan Jack Chun Hin Chen Qinru Xiao Christy Wingtung Wong Boguang Yang Benjamin Cao Rocky S. Tuan Susan K. Nilsson Yi-Ping Ho Michael Raghunath Roger D. Kamm Anna Blocki |
| author_facet | Ho-Ying Wan Jack Chun Hin Chen Qinru Xiao Christy Wingtung Wong Boguang Yang Benjamin Cao Rocky S. Tuan Susan K. Nilsson Yi-Ping Ho Michael Raghunath Roger D. Kamm Anna Blocki |
| author_sort | Ho-Ying Wan |
| collection | DOAJ |
| description | Abstract Background There is great interest to engineer in vitro models that allow the study of complex biological processes of the microvasculature with high spatiotemporal resolution. Microfluidic systems are currently used to engineer microvasculature in vitro, which consists of perfusable microvascular networks (MVNs). These are formed through spontaneous vasculogenesis and exhibit the closest resemblance to physiological microvasculature. Unfortunately, under standard culture conditions and in the absence of co-culture with auxiliary cells as well as protease inhibitors, pure MVNs suffer from a short-lived stability. Methods Herein, we introduce a strategy for stabilization of MVNs through macromolecular crowding (MMC) based on a previously established mixture of Ficoll macromolecules. The biophysical principle of MMC is based on macromolecules occupying space, thus increasing the effective concentration of other components and thereby accelerating various biological processes, such as extracellular matrix deposition. We thus hypothesized that MMC will promote the accumulation of vascular ECM (basement membrane) components and lead to a stabilization of MVN with improved functionality. Results MMC promoted the enrichment of cellular junctions and basement membrane components, while reducing cellular contractility. The resulting advantageous balance of adhesive forces over cellular tension resulted in a significant stabilization of MVNs over time, as well as improved vascular barrier function, closely resembling that of in vivo microvasculature. Conclusion Application of MMC to MVNs in microfluidic devices provides a reliable, flexible and versatile approach to stabilize engineered microvessels under simulated physiological conditions. |
| first_indexed | 2024-03-07T16:42:23Z |
| format | Article |
| id | doaj.art-8769e87eb188420c9a3ff4b8d9840c21 |
| institution | Directory Open Access Journal |
| issn | 2055-7124 |
| language | English |
| last_indexed | 2024-03-07T16:42:23Z |
| publishDate | 2023-04-01 |
| publisher | American Association for the Advancement of Science (AAAS) |
| record_format | Article |
| series | Biomaterials Research |
| spelling | doaj.art-8769e87eb188420c9a3ff4b8d9840c212024-03-03T07:34:50ZengAmerican Association for the Advancement of Science (AAAS)Biomaterials Research2055-71242023-04-0127111610.1186/s40824-023-00375-wStabilization and improved functionality of three-dimensional perfusable microvascular networks in microfluidic devices under macromolecular crowdingHo-Ying Wan0Jack Chun Hin Chen1Qinru Xiao2Christy Wingtung Wong3Boguang Yang4Benjamin Cao5Rocky S. Tuan6Susan K. Nilsson7Yi-Ping Ho8Michael Raghunath9Roger D. Kamm10Anna Blocki11Institute for Tissue Engineering and Regenerative Medicine, The Chinese University of Hong KongDepartment of Biomedical Engineering, Faculty of Engineering, The Chinese University of Hong KongDepartment of Biomedical Engineering, Faculty of Engineering, The Chinese University of Hong KongInstitute for Tissue Engineering and Regenerative Medicine, The Chinese University of Hong KongDepartment of Orthopaedics & Traumatology, Faculty of Medicine, The Chinese University of Hong KongBiomedical Manufacturing Commonwealth Scientific and Industrial Research Organisation (CSIRO)Institute for Tissue Engineering and Regenerative Medicine, The Chinese University of Hong KongBiomedical Manufacturing Commonwealth Scientific and Industrial Research Organisation (CSIRO)Department of Biomedical Engineering, Faculty of Engineering, The Chinese University of Hong KongInstitute for Chemistry and Biotechnology, Zurich University of Applied SciencesDepartment of Biology and Mechanical Engineering, Massachusetts Institute of TechnologyInstitute for Tissue Engineering and Regenerative Medicine, The Chinese University of Hong KongAbstract Background There is great interest to engineer in vitro models that allow the study of complex biological processes of the microvasculature with high spatiotemporal resolution. Microfluidic systems are currently used to engineer microvasculature in vitro, which consists of perfusable microvascular networks (MVNs). These are formed through spontaneous vasculogenesis and exhibit the closest resemblance to physiological microvasculature. Unfortunately, under standard culture conditions and in the absence of co-culture with auxiliary cells as well as protease inhibitors, pure MVNs suffer from a short-lived stability. Methods Herein, we introduce a strategy for stabilization of MVNs through macromolecular crowding (MMC) based on a previously established mixture of Ficoll macromolecules. The biophysical principle of MMC is based on macromolecules occupying space, thus increasing the effective concentration of other components and thereby accelerating various biological processes, such as extracellular matrix deposition. We thus hypothesized that MMC will promote the accumulation of vascular ECM (basement membrane) components and lead to a stabilization of MVN with improved functionality. Results MMC promoted the enrichment of cellular junctions and basement membrane components, while reducing cellular contractility. The resulting advantageous balance of adhesive forces over cellular tension resulted in a significant stabilization of MVNs over time, as well as improved vascular barrier function, closely resembling that of in vivo microvasculature. Conclusion Application of MMC to MVNs in microfluidic devices provides a reliable, flexible and versatile approach to stabilize engineered microvessels under simulated physiological conditions.https://doi.org/10.1186/s40824-023-00375-wMicrovascular networksMicrofluidic deviceMacromolecular crowdingVessel retractionBasement membraneVascular barrier function |
| spellingShingle | Ho-Ying Wan Jack Chun Hin Chen Qinru Xiao Christy Wingtung Wong Boguang Yang Benjamin Cao Rocky S. Tuan Susan K. Nilsson Yi-Ping Ho Michael Raghunath Roger D. Kamm Anna Blocki Stabilization and improved functionality of three-dimensional perfusable microvascular networks in microfluidic devices under macromolecular crowding Biomaterials Research Microvascular networks Microfluidic device Macromolecular crowding Vessel retraction Basement membrane Vascular barrier function |
| title | Stabilization and improved functionality of three-dimensional perfusable microvascular networks in microfluidic devices under macromolecular crowding |
| title_full | Stabilization and improved functionality of three-dimensional perfusable microvascular networks in microfluidic devices under macromolecular crowding |
| title_fullStr | Stabilization and improved functionality of three-dimensional perfusable microvascular networks in microfluidic devices under macromolecular crowding |
| title_full_unstemmed | Stabilization and improved functionality of three-dimensional perfusable microvascular networks in microfluidic devices under macromolecular crowding |
| title_short | Stabilization and improved functionality of three-dimensional perfusable microvascular networks in microfluidic devices under macromolecular crowding |
| title_sort | stabilization and improved functionality of three dimensional perfusable microvascular networks in microfluidic devices under macromolecular crowding |
| topic | Microvascular networks Microfluidic device Macromolecular crowding Vessel retraction Basement membrane Vascular barrier function |
| url | https://doi.org/10.1186/s40824-023-00375-w |
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