Biofabrication Directions in Recapitulating the Immune System-on-a-Chip.

Ever since the implementation of microfluidics in the biomedical field, in vitro models have experienced unprecedented progress that has led to a new generation of highly complex miniaturized cell culture platforms, known as Organs-on-a-Chip (OoC). These devices aim to emulate biologically relevant environments, encompassing perfusion and other mechanical and/or biochemical stimuli, to recapitulate key physiological events. While OoCs excel in simulating diverse organ functions, the integration of the immune organs and immune cells, though recent and challenging, is pivotal for a more comprehensive representation of human physiology. This comprehensive review covers the state of the art in the intricate landscape of immune OoC models, shedding light on the pivotal role of biofabrication technologies in bridging the gap between conceptual design and physiological relevance. The multifaceted aspects of immune cell behavior, crosstalk, and immune responses that are aimed to be replicated within microfluidic environments, emphasizing the need for precise biomimicry are explored. Furthermore, the latest breakthroughs and challenges of biofabrication technologies in immune OoC platforms are described, guiding researchers toward a deeper understanding of immune physiology and the development of more accurate and human predictive models for a.o., immune-related disorders, immune development, immune programming, and immune regulation.

Biomimetic models of the glomerulus.

The use of biomimetic models of the glomerulus has the potential to improve our understanding of the pathogenesis of kidney diseases and to enable progress in therapeutics. Current in vitro models comprise organ-on-a-chip, scaffold-based and organoid approaches. Glomerulus-on-a-chip designs mimic components of glomerular microfluidic flow but lack the inherent complexity of the glomerular filtration barrier. Scaffold-based 3D culture systems and organoids provide greater microenvironmental complexity but do not replicate fluid flows and dynamic responses to fluidic stimuli. As the available models do not accurately model the structure or filtration function of the glomerulus, their applications are limited. An optimal approach to glomerular modelling is yet to be developed, but the field will probably benefit from advances in biofabrication techniques. In particular, 3D bioprinting technologies could enable the fabrication of constructs that recapitulate the complex structure of the glomerulus and the glomerular filtration barrier. The next generation of in vitro glomerular models must be suitable for high(er)-content or/and high(er)-throughput screening to enable continuous and systematic monitoring. Moreover, coupling of glomerular or kidney models with those of other organs is a promising approach to enable modelling of partial or full-body responses to drugs and prediction of therapeutic outcomes.