Organ-on-Chip Platform with Transient Membrane for Vascularisation of Brain Organoids

Abstract

Organ-on-Chip (OoC) is a technology that aims to increase the efficiency of drug development processes and organ models by engineering well-defined cell culture environments. Physiological relevant mechanical, chemical, or electrical cues provide in vivo-like microenvironments for realistic cell maturation. Biodegradable technologies have gained attention for the development of novel OoCs by integrating transient features to the culture platforms imitating the ever-changing environment inside the human body. Current efforts to replicate durable brain tissue models from organoids are limited by the lack of sufficient vascularisation introducing cell necrosis inside the 3D cell culture.
This report presents the design and fabrication of a 3D-printed OoC-platform that combines two independent cell protocols for a Vessel-on-Chip and a cortical brain organoid. The microfluidic chip is embedded with a biodegradable membrane, that separates the two cell cultures for a strictly defined time period. The membrane, composed of bayberry wax, lanolin, and carbonyl iron particles, enables the controlled opening via alternating magnetic field exposure. The thermal behaviour of the membrane is analysed with DSC and the magnetic particles with a SQUID magnetometer. Inductive heating experiments determine the optimal composite composition and exposure profile to facilitate membrane opening and subsequent communication between neural and vascular cells. The integrated membrane proved to be successful during the injection and evacuation phase. This positive result paves the way for co-culturing two inherently different cell protocols on a single chip. This master project lays the foundation for collaborative efforts towards vascularised brain organoids-on-chip and showcases the potential of additive manufacturing and biodegradable materials in OoC technology.