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. Here, the authors review current approaches to replication of the glomerulus in vitro with a focus on organ-on-a-chip, scaffolding and organoid technologies. They also discuss future directions of research, including the use of newer 3D biofabrication technologies. Key points The prevalence of kidney failure is increasing worldwide, and glomerulopathy is often a causal or contributing factor. The available in vitro models of the glomerulus are suboptimal, which limits their use for interrogation of pathological mechanisms and testing of drugs. The complexity of the renal corpuscle results in a fragile balance of constituents that can be easily disturbed in pathological situations, leading to irreparable damage. Initiatives for improving current in vitro biomimetic models of the glomerulus focus on replication of the 3D microenvironment using on-a-chip technology, scaffolds and organoids containing glomerular tissue. The suitability of emerging biofabrication techniques, such as 3D bioprinting, for glomerular modelling is yet to be fully assessed. Larger-scale