Pluronic F127 as Transient Barrier for Vascularized Cortical Organoids on-a-Chip

Abstract

Organ-on-a-chip (OoC) technology has revolutionized the biomedical research field by offering dynamic platforms which accurately mimic physiological environments of human tissue. This technology has become a promising option to study human biology in vitro, including disease modeling, drug screening and personalized medicine. Organoids, 3D cell cultures derived from human stem cells, represent a promising tool to investigate 3D tissue growth in vitro. However, integration of vasculature in these organoids remains a significant challenge. Establishment of vasculature is essential to enable significant organoid growth, allowing nutrient and oxygen supply and waste removal.

This report aims to develop a Pluronic F127 based hydrogel as a transient barrier in an OoC-platform that combines cell cultures of Vasculature-on-a-Chip and cortical brain organoids. This transient barrier separates the two cell cultures until sufficient maturation of the cortical organoid. Due to thermoreversible gelation, the Pluronic F127 hydrogel barrier can be removed from the barrier channel by a decrease in temperature. Pluronic F127 and di-acrylated Pluronic F127 hydrogels were synthesizes and characterized using rheometry, differential scanning calorimetry and degradation testing to determine the optimal Pluronic F127 hydrogel. Simultaneously, optimization of the OoC-platform was done by fabrication of the platform using Polydimethylsiloxane (PDMS).

It was shown that the OoC platform for Vascularized Organoids-on-a-Chip could effectively by fabricated using PDMS molding. This was achieved through both PDMS-PDMS and PDMS-glass bonding. Pluronic F127 hydrogels were shown to be a viable option to function as a transient barrier for Vascularized Organoids-on-a-Chip. Pluronic F127 hydrogels effectively blocked fluid flow through the barrier channel for seven days. To increase this time, di-acrylated Pluronic F127 was synthesizes. A degree of acrylation of 57% was achieved. This was shown to be insufficient to significantly increase the longevity of Pluronic F127 hydrogels.

Further research needs to be done to find the optimal synthesis and photo-polymerization conditions of di-acrylated Pluronic F127 hydrogels. Ideally, di-acrylated Pluronic F127 hydrogels exhibit a low degradation rate while maintaining the thermoreversible properties of Pluronic F127 hydrogels.