Development of a physiologically accurate 3D blood-brain barrier hydrogel model

Abstract

The blood-brain barrier (BBB) is a tightly interconnected network of cells that creates a semi-permeable barrier between the central nervous system and the rest of the human body, taking in nutrients and blocking/excreting waste/potentially toxic chemicals from the brain, maintaining the brain's health and stability. When toxins are able to make it past the BBB, the BBB is degraded and can lead to further neurodegenerative disorders such as Alzheimer's and dementia. In order to better understand the structure of the BBB, the causes of its degradation, and potentially curing diseases, drug delivery experiments have been performed on the brain. However, since the drug carriers tested often may be perceived as toxins to the brain due to their large size or composition, researchers have leaned towards making in vitro 3D hydrogel models of the BBB. This project aims at making an in vitro 3D BBB hydrogel model that is physiologically accurate as possible. Components in the biological BBB were researched and these gels containing these polymers were created in order to determine if homogenous gels could be made and if they would support healthy human astrocyte (HAst) growth. Numerous compositions of hyaluronic acid, collagen IV, and a crosslinker were found to both create homogenous gels and support healthy astrocyte growth. Additionally, the processing steps for making these hydrogels was optimized further in order to ensure as much homogeneity as possible in the final gel.