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Bioactive peptide-bearing polylactic acid fibers as a model of the brain tumor-stimulating microenvironment

Abstract

Malignant glioblastoma multiforme (GBM), with an aggressive growth pattern and unpredictable tumor location within the brain, causes a deadly disease with an extremely poor prognosis. Laminin, a typical matrix in the basement membranes of the brain vasculature and GBM-remodeled extracellular matrix (ECM), exhibits a tumor-promoting effect. Here, a poly(L–lactic acid) (PLLA) fiber substrate was modified with an IKVAV peptide derived from laminin to construct an in vitro model for investigating the effect of the ECM on GBM in white matter tracts. A heterofunctional compound composed of oligo(D–lactic acid) (ODLA) and the IKVAV peptide was synthesized and linked with a hydrophilic diethylene glycol linker (ODLA–diEG–IKVAV) to form PLLA/ODLA–diEG–IKVAV aligned fibers. The hydrophilicity and IKVAV surface density were improved by heating, enhancing human astrocytoma (U-251MG) cell adhesion. The bioactive peptide scaffold constructed in this study is a promising platform that can be used to investigate the effects of the ECM on brain tumors.

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Acknowledgements

This work was supported by JSPS KAKENHI (grant number 16H03186).

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HW-Y: Writing—original draft, conceptualization, methodology, investigation, visualization, and validation. AO: Conceptualization, methodology, investigation, project administration, validation, writing—review, and editing. SF: Methodology, investigation, validation, writing—review, and editing. TY: Conceptualization, methodology, resources, supervision, writing—review, and editing.

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Correspondence to Tetsuji Yamaoka.

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Huang, WY., Otaka, A., Fujita, S. et al. Bioactive peptide-bearing polylactic acid fibers as a model of the brain tumor-stimulating microenvironment. Polym J 55, 273–281 (2023). https://doi.org/10.1038/s41428-022-00743-8

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