Developing an in vitro model of haematoma for study of intracerebral haemorrhage

Abstract

Intracerebral haemorrhage (ICH) is a devastating neurovascular attack with limited treatment options. Alternative, pre-clinical modelling approaches are required to identify and trial therapeutic drug compounds. In this study we have used alginate hydrogels to model blood insult in vitro. Human whole blood was mixed with alginate and encapsulated into hydrogel beads. Beads were then incorporated in a second layer of alginate containing hyaluronic acid/chitosan nanoparticles to mimic the mechanical properties of brain tissue and create a model haematoma. Beads and model haematomas were characterised to profile size, volume, mechanical properties, release capacity and storage stability over time. Beads and model haematomas stimulate a pro-inflammatory phenotype in human monocytic and macrophage-like cells, however have no pathogenic effect on brain endothelial and neuronal cell survival or function. In conclusion, we have developed an effective strategy to model ICH in vitro, to investigate the human immune response to blood insult.