Thermoforming for Small Feature Replication in Melt Electrowritten Membranes to Model Kidney Proximal Tubule.

A novel approach merging melt electrowriting (MEW) with matched die thermoforming to achieve scaffolds with micron-sized curvatures (200 - 800 µm versus 1000 µm of mandrel printing) for in vitro modeling of the kidney proximal tubule (PT) is proposed. Recent advances in this field emphasize the relevance of accurately replicating the intricate tissue microenvironment, particularly the curvature of the nephrons' tubular segments. While MEW offers promising capabilities for fabricating highly and porous precise 3D structures mimicking the PT, challenges persist in approximating the diameter of tubular scaffolds to match the actual PT.

Blueprints of Architected Materials: A Guide to Metamaterial Design for Tissue Engineering.

Mechanical metamaterials are rationally designed structures engineered to exhibit extraordinary properties, often surpassing those of their constituent materials. The geometry of metamaterials' building blocks, referred to as unit cells, plays an essential role in determining their macroscopic mechanical behavior. Due to their hierarchical design and remarkable properties, metamaterials hold significant potential for tissue engineering; however their implementation in the field remains limited.

Organ-on-a-Chip: ? Fundamentals and Design Aspects.

This review outlines the evolutionary journey from traditional two-dimensional (2D) cell culture to the revolutionary field of organ-on-a-chip technology. Organ-on-a-chip technology integrates microfluidic systems to mimic the complex physiological environments of human organs, surpassing the limitations of conventional 2D cultures. This evolution has opened new possibilities for understanding cell-cell interactions, cellular responses, drug screening, and disease modeling.

Mesenchymal stromal cells secretome restores bioenergetic and redox homeostasis in human proximal tubule cells after ischemic injury.

Background: Ischemia/reperfusion injury is the leading cause of acute kidney injury (AKI). The current standard of care focuses on supporting kidney function, stating the need for more efficient and targeted therapies to enhance repair. Mesenchymal stromal cells (MSCs) and their secretome, either as conditioned medium (CM) or extracellular vesicles (EVs), have emerged as promising options for regenerative therapy; however, their full potential in treating AKI remains unknown.

Animal Models for Studying Protein-Bound Uremic Toxin Removal-A Systematic Review.

Protein-bound uremic toxins (PBUTs) are associated with the progression of chronic kidney disease (CKD) and its associated morbidity and mortality. The conventional dialysis techniques are unable to efficiently remove PBUTs due to their plasma protein binding. Therefore, novel approaches are being developed, but these require validation in animals before clinical trials can begin.

Bioengineered Kidney Tubules Efficiently Clear Uremic Toxins in Experimental Dialysis Conditions.

Patients with end-stage kidney disease (ESKD) suffer from high levels of protein-bound uremic toxins (PBUTs) that contribute to various comorbidities. Conventional dialysis methods are ineffective in removing these PBUTs. A potential solution could be offered by a bioartificial kidney (BAK) composed of porous membranes covered by proximal tubule epithelial cells (PTECs) that actively secrete PBUTs.

Portable, wearable and implantable artificial kidney systems: needs, opportunities and challenges.

Haemodialysis is life sustaining but expensive, provides limited removal of uraemic solutes, is associated with poor patient quality of life and has a large carbon footprint. Innovative dialysis technologies such as portable, wearable and implantable artificial kidney systems are being developed with the aim of addressing these issues and improving patient care. An important challenge for these technologies is the need for continuous regeneration of a small volume of dialysate.

Role of extracellular matrix components and structure in new renal models .

The extracellular matrix (ECM), a complex set of fibrillar proteins and proteoglycans, supports the renal parenchyma and provides biomechanical and biochemical cues critical for spatial-temporal patterning of cell development and acquisition of specialized functions. As models progress towards biomimicry, more attention is paid to reproducing ECM-mediated stimuli. ECM's role in models of renal function and disease used to investigate kidney injury and regeneration is discussed.

Postbiotics and Kidney Disease.

Chronic kidney disease (CKD) is projected to become the fifth global cause of death by 2040 as a result of key shortcomings in the current methods available to diagnose and treat kidney diseases. In this regard, the novel holobiont concept, used to describe an individual host and its microbial community, may pave the way towards a better understanding of kidney disease pathogenesis and progression. Microbiota-modulating or -derived interventions include probiotics, prebiotics, synbiotics and postbiotics.

Donor Heterogeneity in the Human Macrophage Response to a Biomaterial Under Hyperglycemia .

Macrophages have a commanding role in scaffold-driven tissue regeneration. Depending on their polarization state, macrophages mediate the formation and remodeling of new tissue by secreting growth factors and cytokines. Therefore, successful outcomes of material-driven tissue vascular tissue engineering depend largely on the immuno-regenerative potential of the recipient.

Organs-on-chip technology: a tool to tackle genetic kidney diseases.

Chronic kidney disease (CKD) is a major healthcare burden that takes a toll on the quality of life of many patients. Emerging evidence indicates that a substantial proportion of these patients carry a genetic defect that contributes to their disease. Any effort to reduce the percentage of patients with a diagnosis of nephropathy heading towards kidney replacement therapies should therefore be encouraged.

A robust, accurate, sensitive LC-MS/MS method to measure indoxyl sulfate, validated for plasma and kidney cells.

Proximal tubular damage is an important prognostic determinant in various chronic kidney diseases (CKDs). Currently available diagnostic methods do not allow for early disease detection and are neither efficient. Indoxyl sulfate (IS) is an endogenous metabolite and protein-bound uremic toxin that is eliminated via renal secretion, but accumulates in plasma during tubular dysfunction.

The Influence of OAT1 Density and Functionality on Indoxyl Sulfate Transport in the Human Proximal Tubule: An Integrated Computational and In Vitro Study.

Research has shown that traditional dialysis is an insufficient long-term therapy for patients suffering from end-stage kidney disease due to the high retention of uremic toxins in the blood as a result of the absence of the active transport functionality of the proximal tubule (PT). The PT's function is defined by the epithelial membrane transporters, which have an integral role in toxin clearance. However, the intricate PT transporter-toxin interactions are not fully explored, and it is challenging to decouple their effects in toxin removal in vitro.

Diabetic proximal tubulopathy: Can we mimic the disease for in vitro screening of SGLT inhibitors?

Diabetic kidney disease (DKD) is the foremost cause of renal failure. While the glomeruli are severely affected in the course of the disease, the main determinant for disease progression is the tubulointerstitial compartment. DKD does not develop in the absence of hyperglycemia.

Microphysiological Systems to Recapitulate the Gut-Kidney Axis.

Chronic kidney disease (CKD) typically appears alongside other comorbidities, highlighting an underlying complex pathophysiology that is thought to be vastly modulated by the bidirectional gut-kidney crosstalk. By combining advances in tissue engineering, biofabrication, microfluidics, and biosensors, microphysiological systems (MPSs) have emerged as promising approaches for emulating the in vitro interconnection of multiple organs, while addressing the limitations of animal models. Mimicking the (patho)physiological states of the gut-kidney axis in vitro requires an MPS that can simulate not only this direct bidirectional crosstalk but also the contributions of other physiological participants such as the liver and the immune system.

Synthetic Extracellular Matrices as a Toolbox to Tune Stem Cell Secretome.

The application of stem cell-derived secretome in regenerative therapies offers the key advantage that instead of the stem cells, only their effective paracrine compounds are delivered. Ideally, the secretome can be steered by the culture conditions of the stem cells. So far, most studies use stem cells cultured on stiff plastic substrates, not representative of their native 3D environment.

Drugs Commonly Applied to Kidney Patients May Compromise Renal Tubular Uremic Toxins Excretion.

In chronic kidney disease (CKD), the secretion of uremic toxins is compromised leading to their accumulation in blood, which contributes to uremic complications, in particular cardiovascular disease. Organic anion transporters (OATs) are involved in the tubular secretion of protein-bound uremic toxins (PBUTs). However, OATs also handle a wide range of drugs, including those used for treatment of cardiovascular complications and their interaction with PBUTs is unknown.

Introduction of Specific 3D Micromorphologies in Collagen Scaffolds Using Odd and Even Dicarboxylic Acids.

The construction of scaffolds and subsequent incorporation of cells and biologics have been widely investigated to regenerate damaged tissues. Scaffolds act as a template to guide tissue formation, and their characteristics have a considerable impact on the regenerative process. Whereas many technologies exist to induce specific two-dimensional (2D) morphologies into biomaterials, the introduction of three-dimensional (3D) micromorphologies into individual pore walls of scaffolds produced from biological molecules such as collagen poses a challenge.

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

The kidney is frequently involved in adverse effects caused by exposure to foreign compounds, including drugs. An early prediction of those effects is crucial for allowing novel, safe drugs entering the market. Yet, in current pharmacotherapy, drug-induced nephrotoxicity accounts for up to 25% of the reported serious adverse effects, of which one-third is attributed to antimicrobials use.

Synthetic Extracellular Matrices with Nonlinear Elasticity Regulate Cellular Organization.

One of the promises of synthetic materials in cell culturing is that control over their molecular structures may ultimately be used to control their biological processes. Synthetic polymer hydrogels from polyisocyanides (PIC) are a new class of minimal synthetic biomaterials for three-dimensional cell culturing. The macromolecular lengths and densities of biofunctional groups that decorate the polymer can be readily manipulated while preserving the intrinsic nonlinear mechanics, a feature commonly displayed by fibrous biological networks.

The Impact of γ-Irradiation and EtO Degassing on Tissue Remodeling of Collagen-based Hybrid Tubular Templates.

Clinical implementation of novel products for tissue engineering and regenerative medicine requires a validated sterilization method. In this study, we investigated the effect of γ-irradiation and EtO degassing on material characteristics and the effect on template remodeling of hybrid tubular constructs in a large animal model. Hybrid tubular templates were prepared from type I collagen and Vicryl polymers and sterilized by 25 kGray of γ-irradiation or EtO degassing.

From portable dialysis to a bioengineered kidney.

Introduction: Since the advent of peritoneal dialysis (PD) in the 1970s, the principles of dialysis have changed little. In the coming decades, several major breakthroughs are expected.

Areas Covered: Novel wearable and portable dialysis devices for both hemodialysis (HD) and PD are expected first.