2. Academic Validation
  3. High-yield extracellular vesicle production from HEK293T cells encapsulated in 3D auxetic scaffolds with cyclic mechanical stimulation for effective drug carrier systems

High-yield extracellular vesicle production from HEK293T cells encapsulated in 3D auxetic scaffolds with cyclic mechanical stimulation for effective drug carrier systems

  • Biofabrication. 2024 Sep 2;16(4). doi: 10.1088/1758-5090/ad728b.
Yi-Wen Chen 1 2,  Yen-Hong Lin 2 3,  Chia-Che Ho 4 5,  Cheng-Yu Chen 2,  Min-Hua Yu 6,  Alvin Kai-Xing Lee 7,  Shao-Chih Chiu 8,  Der-Yang Cho 1 2 8 9,  Ming-You Shie 2 3 4
Affiliations

Affiliations

  • 1 Graduate Institute of Biomedical Sciences, China Medical University, Taichung 406040, Taiwan.
  • 2 Research & Development Center for x-Dimensional Extracellular Vesicles, China Medical University Hospital, Taichung 404332, Taiwan.
  • 3 Department of Biomedical Engineering, China Medical University, Taichung 406040, Taiwan.
  • 4 Department of Bioinformatics and Medical Engineering, Asia University, Taichung 41354, Taiwan.
  • 5 High Performance Materials Institute for x-Dimensional Printing, Asia University, Taichung 41354, Taiwan.
  • 6 Institute of Translational Medicine and New Drug Development, China Medical University, Taichung 406040, Taiwan.
  • 7 Department of Orthopedics, China Medical University Hospital, Taichung 404332, Taiwan.
  • 8 Translational Cell Therapy Center, China Medical University Hospital, Taichung 404332, Taiwan.
  • 9 Department of Neurosurgery, China Medical University Hospital, Taichung 404332, Taiwan.
PMID: 39173665 DOI: 10.1088/1758-5090/ad728b
Abstract

Extracellular vesicles (EVs) show promise in drug loading and delivery for medical applications. However, the lack of scalable manufacturing processes hinders the generation of clinically suitable quantities, thereby impeding the translation of EV-based therapies. Current EV production relies heavily on non-physiological two-dimensional (2D) Cell Culture or bioreactors, requiring significant resources. Additionally, EV-derived ribonucleic acid cargo in three-dimensional (3D) and 2D culture environments remains largely unknown. In this study, we optimized the biofabrication of 3D auxetic scaffolds encapsulated with human embryonic kidney 293 T (HEK293 T) cells, focusing on enhancing the mechanical properties of the scaffolds to significantly boost EV production through tensile stimulation in bioreactors. The proposed platform increased EV yields approximately 115-fold compared to conventional 2D culture, possessing properties that inhibit tumor progression. Further mechanistic examinations revealed that this effect was mediated by the mechanosensitivity of YAP/TAZ. EVs derived from tensile-stimulated HEK293 T cells on 3D auxetic scaffolds demonstrated superior capability for loading doxorubicin compared to their 2D counterparts for Cancer therapy. Our results underscore the potential of this strategy for scaling up EV production and optimizing functional performance for clinical translation.

Keywords

HEK293T; auxetic scaffold; biofabrication; drug delivery; extracellular vesicles.

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