Stabilization and improved functionality of three-dimensional perfusable microvascular networks in microfluidic devices under macromolecular crowding

Biomaterials Research

卷:27

Research Article

Susan K. Nilsson¹  Benjamin Cao¹  Roger D. Kamm²  Jack Chun Hin Chen³  Yi-Ping Ho³  Qinru Xiao³  Boguang Yang⁴  Michael Raghunath⁵  Christy Wingtung Wong⁶  Ho-Ying Wan⁶  Rocky S. Tuan⁷  Anna Blocki⁸ 

[1] Biomedical Manufacturing Commonwealth Scientific and Industrial Research Organisation (CSIRO), Melbourne, Australia;Australian Regenerative Medicine Institute, Monash University, Melbourne, Australia;

[2] Department of Biology and Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA;

[3] Department of Biomedical Engineering, Faculty of Engineering, The Chinese University of Hong Kong, Hong Kong SAR, China;

[4] Department of Orthopaedics & Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China;

[5] Institute for Chemistry and Biotechnology, Zurich University of Applied Sciences, Wädenswil, Switzerland;

[6] Institute for Tissue Engineering and Regenerative Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China;School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China;

[7] Institute for Tissue Engineering and Regenerative Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China;School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China;Center for Neuromusculoskeletal Restorative Medicine (CNRM), Hong Kong Science Park, Shatin, New Territories, Hong Kong SAR, China;

[8] Institute for Tissue Engineering and Regenerative Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China;School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China;Department of Orthopaedics & Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China;Center for Neuromusculoskeletal Restorative Medicine (CNRM), Hong Kong Science Park, Shatin, New Territories, Hong Kong SAR, China;

关键词: Microvascular networks;    Microfluidic device;    Macromolecular crowding;    Vessel retraction;    Basement membrane;    Vascular barrier function;   

DOI  :  10.1186/s40824-023-00375-w

 received in 2022-11-06, accepted in 2023-04-04,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundThere 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.MethodsHerein, 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.ResultsMMC 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.ConclusionApplication of MMC to MVNs in microfluidic devices provides a reliable, flexible and versatile approach to stabilize engineered microvessels under simulated physiological conditions.

【 授权许可】

CC BY   
© The Author(s) 2023

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