Bioinspired In Vitro Brain Vasculature Model for Nanomedicine Testing Based on Decellularized Spinach Leaves

Nano Lett. 2021 Dec 8;21(23):9853-9861. doi: 10.1021/acs.nanolett.1c01920. Epub 2021 Nov 22.

Abstract

Animal testing is often criticized due to ethical issues and complicated translation of the results obtained to the clinical stage of drug development. Existing alternative models for nanopharmaceutical testing still have many limitations and do not significantly decrease the number of animals used. We propose a simple, bioinspired in vitro model for nanopharmaceutical drug testing based on the decellularized spinach leaf's vasculature. This system is similar to human arterioles and capillaries in terms of diameter (300-10 μm) and branching. The model has proven its suitability to access the maneuverability of magnetic nanoparticles, particularly those composed of Fe3O4. Moreover, the thrombosis has been recreated in the model's vasculature. We have tested and compared the effects of both a single-chain urokinase plasminogen activator (scuPA) and a magnetically controlled nanocomposite prepared by heparin-mediated cross-linking of scuPA with Fe3O4 nanoparticles. Compositions were tested both in static and flow conditions.

Keywords: brain vasculature; decellularization; in vitro model; nanomedicine testing; plant scaffold.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomedical Research / methods*
  • Brain / metabolism
  • Humans
  • Nanomedicine*
  • Plant Leaves / metabolism
  • Spinacia oleracea* / metabolism
  • Urokinase-Type Plasminogen Activator / metabolism
  • Urokinase-Type Plasminogen Activator / pharmacology

Substances

  • Urokinase-Type Plasminogen Activator