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Engineered hydrogels for brain tumor culture and therapy

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Abstract

Brain tumors’ severity ranges from benign to highly aggressive and invasive. Bioengineering tools can assist in understanding the pathophysiology of these tumors from outside the body and facilitate development of suitable antitumoral treatments. Here, we first describe the physiology and cellular composition of brain tumors. Then, we discuss the development of three-dimensional tissue models utilizing brain tumor cells. In particular, we highlight the role of hydrogels in providing a biomimetic support for the cells to grow into defined structures. Microscale technologies, such as electrospinning and bioprinting, and advanced cellular models aim to mimic the extracellular matrix and natural cellular localization in engineered tumor tissues. Lastly, we review current applications and prospects of hydrogels for therapeutic purposes, such as drug delivery and co-administration with other therapies. Through further development, hydrogels can serve as a reliable option for in vitro modeling and treatment of brain tumors for translational medicine.

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Fig. 1

(Adapted from McNeill et al. [37]). b Multiple steps of metastatic colonization including pre-colonization phase, which occurs in minutes to hours, followed by colonization phase, which occurs in years. Pre-colonization steps include intravasation of cancer cells into the tumor vasculature, entry into the circulatory system, and extravasation into the parenchyma of target tissues or organs (Adapted from Massague et al. [40])

Fig. 2

(Adapted from Mao et al. [52]). b The glioma perivascular niche. Vascular endothelial cells provide chemotactic signals to migrating glioma cells in order to attract them to blood vessels. GSCs may also migrate to the site and differentiate to multiple cell types due to signals in the PVN (Adapted from Diksin et al. [56])

Fig. 3

(Adapted from Langhans et al. [58]). b Incorporation of brain glioblastoma spheroids within a microfluidic 3D culture platform of 96-well plates containing a tapered hole in the center of a rail for brain glioblastoma spheroids to generate angiogenic sprouting patterns (Adapted from Ko et al. [69]). c A 3D model generated by combination of transwell 96-well-plates and 96-well spheroid microplates to simulate penetration of anti-cancer drugs through the BBB (Adapted from Sherman et al. [71]). d Generation of brain organoids on a brain organoid-on-a-chip device to investigate the effect of nicotine on early brain development (Adapted from Wang et al. [74])

Fig. 4

(Adapted from Monzo et al. [111]). b Aligned PCL nanofibers promote directional contact guidance to glioma cells seeded on their surface, while randomly oriented fibers produce non-specific cell populations on their surface (Adapted from Agudelo-Garcia et al. [76]). c Microfluidic devices are compartmentalized and consist of wells which allow for GBM cell aggregation as the flow of media provides nutrients as cells proliferate (Adapted from Fan et al. [21]). d Bioprinting extrudes of alginate/gelatin/fibrin gel which encapsulates cells and causes them to grow in distinct arrays (Adapted from Wang et al. [112])

Fig. 5

(Adapted from Cha et al. [17])

Fig. 6

(Adapted from Li et al. [132] and Basso et al. [8]). b Insertion of a PCL/polyurethane carrier conduit containing aligned PCL nanofiber films, and cyclopamine (anti-cancer)-conjugated collagen hydrogel serving as an apoptotic tumor sink in the brain. Migration of tumor cells along the aligned films throughout the cross section of conduit was observed at different distances from the interface of the tumor in the brain (Adapted from Jain et al. [141]. c Stereotactical injection of drug-loaded magnetic hydrogel, and simultaneous magnetic resonance images of treated region over time by degradation of hydrogel and sustained release of drug (Adapted from Kim et al. [144])

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Acknowledgements

The authors have no competing interests. The authors also acknowledge funding from the National Institutes of Health (1U01CA214411-01A1).

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Authors and Affiliations

  1. Center for Minimally Invasive Therapeutics (C-MIT), University of California-Los Angeles, 570 Westwood Plaza, Los Angeles, CA, 90095, USA

    Jai Thakor, Samad Ahadian, Ali Niakan, Ethan Banton, Fatemeh Nasrollahi & Ali Khademhosseini

  2. Department of Bioengineering, University of California-Los Angeles, Los Angeles, CA, 90095, USA

    Jai Thakor, Samad Ahadian, Fatemeh Nasrollahi, Mohammad M. Hasani-Sadrabadi & Ali Khademhosseini

  3. Department of Materials Science and Engineering, University of California-Los Angeles, Los Angeles, CA, 90095, USA

    Ethan Banton

  4. Weintraub Center for Reconstructive Biotechnology, Division of Advanced Prosthodontics, School of Dentistry, University of California-Los Angeles, Los Angeles, CA, 90095, USA

    Mohammad M. Hasani-Sadrabadi

  5. Department of Radiological Sciences, University of California-Los Angeles, Los Angeles, CA, 90095, USA

    Ali Khademhosseini

  6. Department of Chemical and Biomolecular Engineering, University of California-Los Angeles, Los Angeles, CA, 90095, USA

    Ali Khademhosseini

  7. Terasaki Institute for Biomedical Innovation (TIBI), Los Angeles, CA, 90024, USA

    Ali Khademhosseini

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  1. Jai Thakor
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  2. Samad Ahadian
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  4. Ethan Banton
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Thakor, J., Ahadian, S., Niakan, A. et al. Engineered hydrogels for brain tumor culture and therapy. Bio-des. Manuf. 3, 203–226 (2020). https://doi.org/10.1007/s42242-020-00084-6

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