3D Kidney Models for Fibrosis Research, Drug Discovery, and Regenerative Medicine

Chronic kidney disease (CKD) affects nearly 10% of the global population and remains a leading cause of morbidity and mortality worldwide. Disease progression is characterized by persistent fibrosis and a limited capacity for renal regeneration, yet current animal models and conventional two-dimensional (2D) culture systems inadequately reproduce the complexity of the human kidney microenvironment. This limitation highlights the need for physiologically relevant, scalable human models that can accelerate mechanistic studies, therapeutic discovery, and regenerative medicine strategies.

In this presentation, I will discuss complementary humanized three-dimensional (3D) kidney platforms developed to model CKD pathophysiology and advance translational nephrology. The first platform is a perfusable 3D bioprinted tubulointerstitial fibrosis model composed of primary human renal tubular epithelial cells and fibroblasts embedded within a mechanically tunable decellularized porcine kidney extracellular matrix hydrogel. Upon stimulation with transforming growth factor beta 1 (TGF-β1), the constructs recapitulate key features of renal fibrosis, including matrix stiffening, increased extracellular matrix deposition, and upregulation of fibrosis-associated markers such as FN1, VIM, ACTA2, and multiple collagen isoforms. Importantly, treatment with the antifibrotic agent pirfenidone attenuates fibrotic remodeling and reduces the expression of relevant markers, demonstrating the platform’s potential for therapeutic screening and mechanistic investigation.

The second platform focuses on the generation of scalable and functionally enhanced kidney organoids from human induced pluripotent stem cells (hiPSCs). By integrating an early low-dose dimethyl sulfoxide (DMSO) treatment to improve nephron progenitor specification through enhanced SIX2 expression, together with microfluidic bioprinting of core-shell structures containing metanephric mesenchyme and ureteric bud progenitors, we achieved accelerated organoid maturation. These engineered organoids rapidly formed renal vesicles and exhibited functional responses to nephrotoxic injury within two weeks, providing a robust and reproducible system for kidney development and disease studies. Furthermore, strategies for the vascularization of kidney organoids, one of the major bottlenecks of these kidney rudiments, will be presented.

Together, these bioprinted fibrosis models and bioprinted kidney organoids represent complementary, human-relevant platforms for investigating fibrosis progression, evaluating novel therapeutics, and developing regenerative strategies for CKD. Their scalability and translational relevance position them as promising tools for personalized disease modeling, precision drug discovery, and the future of kidney tissue engineering.

Dr. Carlos Mota is an Assistant Professor in the Department of Complex Tissue Regeneration, MERLN Institute for Technology-inspired Regenerative Medicine, Maastricht University. In 2013, he was a postdoc at the Department of Tissue Regeneration, University of Twente, the Netherlands where he developed, in partnership with Screvo B.V., a multiwell array platform for high content screening, targeting the effect of small molecules and biopharmaceutical in cancer therapeutics in vitro and in vivo.

Dr. Mota received his PhD in Biomaterials from the BIOS research doctorate school in Biomolecular Sciences at the University of Pisa, Italy, in March 2012. His doctoral studies were focused on the development of new approaches for the fabrication of polymeric scaffolds for Tissue Engineering applications. Furthermore, he was a researcher at the department of Neurosciences, University of Pisa, where he developed scaffolds for otology surgery applications.

Dr. Mota research interests are focused on application of bioprinting and additive manufacturing techniques for the development of tissue and organ-like constructs. Examples of the current bioprinting research activities are the development of a kidney bioprinted model (ERC-COG, H2020 BIRDIE, Dutch kidney foundation - innovation project, H2020 SINERGIA - ITN Marie Skłodowska Curie), bioprinted thyroid model (H2020 SCREENED project) and biological joints (H2020 Jointpromise project). Novel additive manufacturing technologies and tissue regeneration therapies for bone are also part of his recent research activities within the H2020 FAST project. Dr. Mota and his team have also been investigating middle ear tissue engineering approaches and more specifically the creation of scaffold for the regeneration of the tympanic membrane within the Euronanomed III 4nanoEARDRM project. Beyond these research projects, Dr. Mota received a prestigious European Research Council Consolidator grant in 2024 to continue his research on advanced kidney in vitro models. 

Dr. Mota was an elected board member of the International Society for Biofabrication until 2022 and is a member of TERMIS, the European Society of Biomaterials, EUROoCS and vice-chair of the kidney working group at hDMT consortium.