Functional Blood–Brain Barrier Model with Tight Connected Minitissue by Liquid Substrates Culture. Issue 4 (30th November 2022)

• Record Type: Journal Article
• Authors: Liu, Nian; Zhu, Yuanbo; Yu, Kang; Gu, Zeming; Lv, Shang; Chen, Yuewei; He, Chaofan; Fu, Jianzhong; He, Yong
• Is Part Of: Advanced healthcare materials. Volume 12:Issue 4(2023)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-11-30
• Subjects: biofabrication -- blood−brain barrier models -- liquid substrate cultures -- tissue engineering; Biomedical materials -- Periodicals; 610.28
• DOI: 10.1002/adhm.202201984
• Languages: English
• ISSNs: 2192-2640

Abstract

Abstract: The functional blood–brain barrier (BBB) model can provide a reliable tool for better understanding BBB transport mechanisms and in vitro preclinical experimentation. However, recapitulating microenvironmental complexities and physiological functions in an accessible approach remains a major challenge. Here, a new BBB model with a high‐cell spatial density and tightly connected biomimetic minitissue is presented. The minitissue, pivotal functional structure of the BBB model, is fabricated by a novel and easy‐to‐use liquid substrate culture (LSC) method, which allows cells to self‐assemble and self‐heal into macrosized, tightly connected membranous minitissue. The minitissue with uniform thickness can be easily harvested in their entirety with extracellular matrix. Attributed to the tightly connected minitissue formed by LSC, the fabricated BBB biomimetic model has 1 to 2 orders of magnitude higher transendothelial electric resistance than the commonly reported BBB model. It also better prevents the transmission of large molecular substances, recapitulating the functional features of BBB. Furthermore, the BBB biomimetic model provides feedback regarding BBB‐destructive drugs, exhibits selective transmission, and shows efflux pump activity. Overall, this model can serve as an accessible tool for life science or clinical medical researchers to enhance the understanding of human BBB and expedite the development of new brain‐permeable drugs. Abstract : A new blood–brain barrier (BBB) model with a high‐cell spatial density and tightly connected biomimetic minitissue is presented. The minitissue, pivotal functional structure of the BBB model, is fabricated by a novel and easy‐to‐use liquid substrate culture method, which allows cells to self‐assemble and self‐heal into macrosized, tightly connected membranous minitissue.