Renal Tubular‐ and Vascular Basement Membranes and their Mimicry in Engineering Vascularized Kidney Tubules

Abstract

The high prevalence of chronic kidney disease leads to an increased need for renal replacement therapies. While there are simply not enough donor organs available for transplantation, there is a need to seek other therapeutic avenues as current dialysis modalities are insufficient. The field of regenerative medicine and whole organ engineering is emerging, and researchers are looking for innovative ways to create (part of) a functional new organ. To biofabricate a kidney or its functional units, it is necessary to understand and learn from physiology to be able to mimic the specific tissue properties. Herein is provided an overview of the knowledge on tubular and vascular basement membranes' biochemical components and biophysical properties, and the major differences between the two basement membranes are highlighted. Furthermore, an overview of current trends in membrane technology for developing renal replacement therapies and to stimulate kidney regeneration is provided.

Fabrication of Kidney Proximal Tubule Grafts Using Biofunctionalized Electrospun Polymer Scaffolds

“…5 ± 7.6 and 23.5 ± 13.6 MPa, respectively (Figure c). Interestingly, the tangent moduli of 12% and 16% PCL scaffolds were comparable to the elasticity of native tubular basement membranes, for which values of 3–10 MPa have been reported . Furthermore, 16% and 20% PCL scaffolds exhibited a strain at break of at least 60%, which is a pivotal property, for example, to withstand fluid pressures and to resist the deformation required during implantation.…”

“…Interestingly, the tangent moduli of 12% and 16% PCL scaffolds were comparable to the elasticity of native tubular basement membranes, for which values of 3–10 MPa have been reported. [ 32 ] Furthermore, 16% and 20% PCL scaffolds exhibited a strain at break of at least 60%, which is a pivotal property, for example, to withstand fluid pressures and to resist the deformation required during implantation. The overall weaker mechanical properties of 12% PCL scaffolds can be explained by the earlier reported presence of beaded fibers ( Figure 2c ).…”

“…Considering their excellent properties for high mechanical stability and diffusibility, electrospun nanofiber tubes would be superior to current hydrogel models for the creation of kidney proximal tubule grafts. Furthermore, biofunctionalized nanofiber meshes could mimic the micro‐architecture of the native extracellular matrix (ECM), since the renal basement membrane mainly consists of cross‐linked collagen IV fibers . By mimicking the macromolecular ECM architecture and composition as well as its stiffness, cell–ECM interactions could promote normal tissue homeostasis .…”

“…Furthermore, biofunctionalized nanofiber meshes could mimic the micro-architecture of the native extracellular matrix (ECM), since the renal basement membrane mainly consists of cross-linked collagen IV fibers. [ 27 ] By mimicking the macromolecular ECM architecture and composition as well as its stiffness, cell–ECM interactions could promote normal tissue homeostasis. [ 28 ] Thus, electrospun nanofiber meshes have the potential to provide additional physicochemical cues for proper graft functionality.…”

Kidney-based in vitro models for drug-induced toxicity testing

“…These features need to be taken into consideration when trying to develop new in vitro models. The complex renal ECM, recently reviewed in (van Genderen et al 2018), is in constant remodeling, especially in the transition of healthy to disease state, such as fibrosis.…”