# Human in vitro models of neurovasculature and the application to pre-clinical intracerebral haemorrhage research

## TL;DR

This review highlights the need for human-based lab models to study brain hemorrhage and evaluates current 2D and 3D models for their usefulness in understanding and treating the condition.

## Contribution

The paper provides a comprehensive evaluation and recommendations for adapting 3D microphysiological models for intracerebral haemorrhage research.

## Key findings

- Fully human in vitro models are urgently needed for accurate intracerebral haemorrhage research.
- 3D models like cerebral organoids and perfusion-based systems offer promising alternatives to animal models.
- Each model has distinct advantages and limitations for studying ICH pathophysiology and recovery mechanisms.

## Abstract

Haemorrhagic stroke continues to be a leading cause of death and disability globally, with limited treatment options. Pre-clinical models must adapt to offer translationally relevant and physiologically accurate alternatives to animals. The development of complex co-culture blood-brain barrier models and the incorporation of hydrogels and biomaterials has resulted in microphysiological 3D platforms. Amongst such 3D platforms, cerebral organoids have transformed the field of neuroscience. Additionally, emerging techniques for vascularisation and perfusion now provide, for the first time, an entirely human-based model of the cerebrovasculature. In this review, we explore the relevance of various in vitro platforms - such as transwells, hydrogels and other biomaterials, microfluidics, spheroids, organoids, and perfusion-based systems - for pre-clinical research into haemorrhagic stroke. We discuss the advantages and limitations of each model, with a particular focus on the aspects of disease pathophysiology that hold promise for clinical translation. With some adaptation, intracerebral haemorrhage research can benefit from these models for elucidating pathology and recovery mechanisms that can be exploited therapeutically.

Created in BioRender. Lomora, M. (2025) https://BioRender.com/v8poxfs.Image 1

Created in BioRender. Lomora, M. (2025) https://BioRender.com/v8poxfs.

•This review underlines the urgency for a fully human in vitro model of intracerebral haemorrhage (ICH) pathology.•An in-depth insight into the advantages and limitations of 2D and 3D in vitro model systems for ICH disease modelling.•Recommendations for the adaptation of microphysiological 3D brain models for comprehensive ICH modelling.

This review underlines the urgency for a fully human in vitro model of intracerebral haemorrhage (ICH) pathology.

An in-depth insight into the advantages and limitations of 2D and 3D in vitro model systems for ICH disease modelling.

Recommendations for the adaptation of microphysiological 3D brain models for comprehensive ICH modelling.