Biomaterial based strategies to reconstruct the nigrostriatal pathway in organotypic slice co-cultures

Buket Ucar, Janko Kajtez, Bettina M. Foidl, Dimitri Eigel, Carsten Werner, Katherine R. Long, Jenny Emnéus, Joëlle Bizeau, Mihai Lomora, Abhay Pandit, Ben Newland, Christian Humpel*

*Corresponding author for this work

Research output: Contribution to journalJournal article

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Abstract

Protection or repair of the nigrostriatal pathway represents a principal disease-modifying therapeutic strategy for Parkinson's disease (PD). Glial cell line-derived neurotrophic factor (GDNF) holds great therapeutic potential for PD, but its efficacious delivery remains difficult. The aim of this study was to evaluate the potential of different biomaterials (hydrogels, microspheres, cryogels and microcontact printed surfaces) for reconstructing the nigrostriatal pathway in organotypic co-culture of ventral mesencephalon and dorsal striatum. The biomaterials (either alone or loaded with GDNF) were locally applied onto the brain co-slices and fiber growth between the co-slices was evaluated after three weeks in culture based on staining for tyrosine hydroxylase (TH). Collagen hydrogels loaded with GDNF slightly promoted the TH+ nerve fiber growth towards the dorsal striatum, while GDNF loaded microspheres embedded within the hydrogels did not provide an improvement. Cryogels alone or loaded with GDNF also enhanced TH+ fiber growth. Lines of GDNF immobilized onto the membrane inserts via microcontact printing also significantly improved TH+ fiber growth. In conclusion, this study shows that various biomaterials and tissue engineering techniques can be employed to regenerate the nigrostriatal pathway in organotypic brain slices. This comparison of techniques highlights the relative merits of different technologies that researchers can use/develop for neuronal regeneration strategies.
Original languageEnglish
JournalActa Biomaterialia
Volume121
Pages (from-to)250-262
Number of pages13
ISSN1742-7061
DOIs
Publication statusPublished - 2021

Keywords

  • Nigrostriatal pathway regeneration
  • Hydrogel
  • Cryogel
  • Microcontact printing
  • Organotypic brain slices
  • GDNF

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