Sulfonated cryogel scaffolds for focal delivery in ex-vivo brain tissue cultures

Dimitri Eigel, Romy Schuster, Max J. Männel, Julian Thiele, Martyna J. Panasiuk, Laura C. Andreae, Carmine Varricchio, Andrea Brancale, Petra B. Welzel, Wieland B. Huttner, Carsten Werner, Ben Newland*, Katherine R. Long

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

Abstract

The human brain has unique features that are difficult to study in animal models, including the mechanisms underlying neurodevelopmental and psychiatric disorders. Despite recent advances in human primary brain tissue culture systems, the use of these models to elucidate cellular disease mechanisms remains limited. A major reason for this is the lack of tools available to precisely manipulate a specific area of the tissue in a reproducible manner. Here we report an easy-to-use tool for site-specific manipulation of human brain tissue in culture. We show that line-shaped cryogel scaffolds synthesized with precise microscale dimensions allow the targeted delivery of a reagent to a specific region of human brain tissue in culture. 3-sulfopropyl acrylate (SPA) was incorporated into the cryogel network to yield a negative surface charge for the reversible binding of molecular cargo. The fluorescent dyes BODIPY and DiI were used as model cargos to show that placement of dye loaded scaffolds onto brain tissue in culture resulted in controlled delivery without a burst release, and labelling of specific regions without tissue damage. We further show that cryogels can deliver tetrodotoxin to tissue, inhibiting neuronal function in a reversible manner. The robust nature and precise dimensions of the cryogel resulted in a user-friendly and reproducible tool to manipulate primary human tissue cultures. These easy-to-use cryogels offer an innovate approach for more complex manipulations of ex-vivo tissue.

Original languageEnglish
Article number120712
JournalBiomaterials
Volume271
DOIs
Publication statusPublished - Apr 2021

Keywords

  • Biomaterial tool
  • Human brain tissue
  • Local delivery
  • Mouse brain tissue
  • Neuronal function
  • Sulfonated cryogel
  • Tissue culture

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