The kidneys are vital organs performing several essential functions. Their primary function is the filtration of blood and the removal of metabolic waste products as well as fluid homeostasis. Renal filtration is the main pathway for drug removal, highlighting the importance of this organ to the growing field of nanomedicine. The kidneys (i) have a key role in the transport and clearance of nanoparticles (NPs), (ii) are exposed to potential NPs’ toxicity, and (iii) are the targets of diseases that nanomedicine can study, detect, and treat. In this review, we aim to summarize the latest research on kidney-nanoparticle interaction. We first give a brief overview of the kidney’s anatomy and renal filtration, describe how nanoparticle characteristics influence their renal clearance, and the approaches taken to image and treat the kidney, including drug delivery and tissue engineering. Finally, we discuss the future and some of the challenges faced by nanomedicine.

In recent years, tissue engineering has achieved significant advancements towards the repair of damaged tissues. Until this day, the vascularization of engineered tissues remains a challenge to the development of large-scale artificial tissue. Recent breakthroughs in biomaterials and three-dimensional (3D) printing have made it possible to manipulate two or more biomaterials with complementary mechanical and/or biological properties to create hybrid scaffolds that imitate natural tissues. Hydrogels have become essential biomaterials due to their tissue-like physical properties and their ability to include living cells and/or biological molecules. Furthermore, 3D printing, such as dispensing-based bioprinting, has progressed to the point where it can now be utilized to construct hybrid scaffolds with intricate structures. Current bioprinting approaches are still challenged by the need for the necessary biomimetic nano-resolution in combination with bioactive spatiotemporal signals. Moreover, the intricacies of multi-material bioprinting and hydrogel synthesis also pose a challenge to the construction of hybrid scaffolds. This manuscript presents a brief review of scaffold bioprinting to create vascularized tissues, covering the key features of vascular systems, scaffold-based bioprinting methods, and the materials and cell sources used. We will also present examples and discuss current limitations and potential future directions of the technology.

Tubular structures contribute to essential organ functions. Therefore, controlling tubulogenesis is essential for bottom-up tissue engineering approaches. Tissue engineering strategies to form tubular structures utilize extracellular matrix (ECM) components and micropatterned molds. To improve the tubular formation rate, we studied the substrate stiffness’s influence on the tubulogenesis of murine inner medullary collecting duct (mIMCD) cells. mIMCD cells were seeded in micropatterned molds with different compositions of polydimethylsiloxane (PDMS) (1:5, 1:10, 1:15, 1:20, 1:30) and agarose (1%, 2%, 3% 5%). We established the Young’s modulus of the PDMS and agarose substrates and determined the ideal substrate stiffness for tube formation to be between 277 kPa and 2610 kPa. Within our parameters, optimal tube formation was observed at 439.9 kPa, a value similar to the Young’s Modulus found in the basement membrane of the murine renal tubular compartment. We also found that different substrate concentrations of agarose or PDMS are associated with different expression levels of the apical polarization marker Zonula occludens 1 (ZO-1) in the generated tubular structures. In addition to the substrate stiffness, we observed that the tube formation differed based on the substrate material, with agarose showing a generally greater tube formation rate. While previous research demonstrated that ECM stiffness influences cellular behavior towards tube formation, our results suggest that the stiffness of the substrate influences tubular formation independently of the ECM.

During early developmental stages, embryonic kidneys are not fully vascularized and are potentially exposed to hypoxic conditions, which is known to influence cell proliferation and survival, ureteric bud branching, and vascularization of the developing kidney. To optimize the culture conditions of in vitro cultured kidneys and gain further insight into the effect of hypoxia on kidney development, we exposed mouse embryonic kidneys isolated at E11.5, E12.5, and E13.5 to hypoxic and normal culture conditions and compared ureteric bud branching patterns, the growth of the progenitor subpopulation hoxb7+, and the expression patterns of progenitor and differentiation markers. Branching patterns were quantified using whole organ confocal imaging and gradient-vector-based analysis. In our model, hypoxia causes an earlier expression of UB tip cell markers, and a delay in stalk cell marker gene expression. The metanephric mesenchyme (MM) exhibited a later expression of differentiation marker FGF8, marking a delay in nephron formation. Hypoxia further delayed the expression of stroma cell progenitor markers, a delay in cortical differentiation markers, as well as an earlier expression of medullary and ureteral differentiation markers. We conclude that standard conditions do not apply universally and that tissue engineering strategies need to optimize suitable culture conditions for each application. We also conclude that adapting culture conditions to specific aspects of organ development in tissue engineering can help to improve individual stages of tissue generation.

A major obstacle to the implantation of ex vivo engineered tissues is the incorporation of functional vascular supply to support the growth of the new tissue and to minimize ischemic injury. Existing pre-vascularization systems, such as arterio-venous (AV) loop-based systems, require microsurgery, limiting their use to larger animals. We aimed to develop an implantable device that can be pre-vascularized to enable vascularization of tissues in small rodents and test its application on the vascularization of embryonic kidneys. Implanting the chamber between the abdominal aorta and the inferior vena cava, we detected endothelial cells and vascular networks after 48h of implantation. Loading the chamber with collagen I (C), Matrigel (M), or Matrigel + vascular endothelial growth factor (VEGF) (MV) had a strong influence on vascularization speed: Chambers loaded with C took seven days to vascularize, four days for chambers with M, and 2 days for chambers with MV. Implantation of E12.5 mouse embryonic kidneys into pre-vascularized chambers (C, MV) was followed with significant growth and ureteric branching over 22 days. In contrast, the growth of kidneys in non-pre-vascularized chambers was stunted. We concluded that our pre-vascularized chamber is a valuable tool for vascularizing implanted tissues and tissue-engineered constructs. Further optimization will be necessary to control the directional growth of vascular endothelial cells within the chamber and the vascularization grade.