Utility of ventral mesencephalic tissue explants for assessment of neurotrophin-functionalised biomaterial hydrogels in the context of Parkinson's disease therapeutics

Background: Biomaterial-based therapies offer significant potential in regenerative approaches for Parkinson’s disease (PD). For preliminary ex vivo assessment of the efficacy/safety of such approaches, the use of explanted tissue containing the dopaminergic pathways affected by PD provides significant advantages over the use of cell culture models.

Aim: Thus, the aim of this study was to assess the utility of ventral mesencephalic tissue explants for assessment of the efficacy and safety of GDNF or GDF-5 functionalised collagen hydrogels ex vivo.

Methods: For this study, 30 embryonic day 14 rat embryos were dissected to obtain the mesencephalic-diencephalic tube which was maintained in tissue culture using the air media interface method². Explants were then exposed to 5 µg/µl GDF-5 or GDNF either as a bolus or encapsulated in a collagen hydrogel for various time-points, after which they were fixed for histological analyses. Free floating tyrosine hydroxylase immunohistochemistry was completed to identify survival and development of dopaminergic neurons.

Results: Exposure to the collagen hydrogels did not have any detrimental effects on the explanted tissue viability ex vivo. Moreover, when the hydrogels were functionalised with GDNF or GDF-5, this improved dopaminergic axonal outgrowth from the cells.

Conclusions: This experiment successfully demonstrates the utility of ventral mesencephalic tissue explants for assessment of the efficacy/safety neurotrophin-functionalised collagen hydrogels. This approach offers advantages over cellular models for the preliminary assessment of biomaterial-based regenerative therapies for PD.