Advances in Hydrogel-Based Microfluidic Blood–Brain-Barrier Models in Oncology Research

Abstract

The intrinsic architecture and complexity of the brain restricts the capacity of therapeutic molecules to reach their potential targets, thereby limiting therapeutic possibilities concerning neurological ailments and brain malignancy. As conventional models fail to recapitulate the complexity of the brain, progress in the field of microfluidics has facilitated the development of advanced in vitro platforms that could imitate the in vivo microenvironments and pathological features of the blood–brain barrier (BBB). It is highly desirous that developed in vitro BBB-on-chip models serve as a platform to investigate cancer metastasis of the brain along with the possibility of efficiently screening chemotherapeutic agents against brain malignancies. In order to improve the proficiency of BBB-on-chip models, hydrogels have been widely explored due to their unique physical and chemical properties, which mimic the three-dimensional (3D) micro architecture of tissues. Hydrogel-based BBB-on-chip models serves as a stage which is conducive for cell growth and allows the exchange of gases and nutrients and the removal of metabolic wastes between cells and the cell/extra cellular matrix (ECM) interface. Here, we present recent advancements in BBB-on-chip models targeting brain malignancies and examine the utility of hydrogel-based BBB models that could further strengthen the future application of microfluidic devices in oncology research.

Electrospun Scaffolds as Cell Culture Substrates for the Cultivation of an In Vitro Blood–Brain Barrier Model Using Human Induced Pluripotent Stem Cells

“…A reduction in the fiber diameter further allows for tuning of the pore size of the respective cultivation substrate to obstruct or encourage the migration of cells into the fiber network. With respect to the BBB, small pore sizes and subsequent migration of hiPSCs on the surface of the scaffold are desirable to achieve a tight endothelial barrier [28][29][30]. The electrospun gelatin scaffold has an average pore area of 0.21 µm 2 , whereas the pore area of PCL increased more than 10-fold compared to gelatin to an average pore area of 3.59 µm 2 .…”

Breaking the clean room barrier: exploring low-cost alternatives for microfluidic devices

“…Additionally, these hydrogels exhibit optical transparency, allowing visualization of internal microfluidic device components. These features render hydrogels particularly well-suited for use in lab-on-a-chip and organs-on-a-chip systems, especially in the context of biosensing and drug delivery applications ( Hou et al, 2017 ; Nie et al, 2020 ; Ma et al, 2022 ; Sood et al, 2022 ; Cao et al, 2023 ).…”

Current progress and challenges in the development of brain tissue models: How to grow up the changeable brain in vitro?

“…The reader is referred to the reviews for additional information. 17 , 31 , 33 , 213 , 226 – 231 The most representative works were analyzed and systematically reproduced in Tables 2 and 3 . Timeline of technology evolution with key excerpts is visualized in Figure 3 .…”