Protein-Enabled Size-Selective Defect-Sealing of Atomically Thin 2D Membranes for Dialysis and Nanoscale Separations.

Atomically thin 2D materials present the potential for advancing membrane separations via a combination of high selectivity (from molecular sieving) and high permeance (due to atomic thinness). However, the creation of a high density of precise nanopores (narrow-size-distribution) over large areas in 2D materials remains challenging, and nonselective leakage from nanopore heterogeneity adversely impacts performance. Here, we demonstrate protein-enabled size-selective defect sealing (PDS) for atomically thin graphene membranes over centimeter scale areas by leveraging the size and reactivity of permeating proteins to preferentially seal larger nanopores (≥4 nm) while preserving a significant amount of smaller nanopores (via steric hindrance).

Population Pharmacokinetic Modeling of Cefepime, Meropenem, and Piperacillin-Tazobactam in Patients with Cystic Fibrosis.

Background: Patients with cystic fibrosis (CF) experience recurrent bacterial pulmonary exacerbations. Management of these infections is increasingly challenging due to decreased antimicrobial susceptibility to beta-lactam antibiotics. The pharmacokinetics of these agents are inadequately characterized in patients with CF.

An arteriovenous mock circulatory loop and accompanying bond graph model for in vitro study of peripheral intravascular bioartificial organs.

Background: Silicon nanopore membrane-based implantable bioartificial organs are dependent on arteriovenous implantation of a mechanically robust and biocompatible hemofilter. The hemofilter acts as a low-resistance, high-flow network, with blood flow physiology similar to arteriovenous shunts commonly created for hemodialysis access. A mock circulatory loop (MCL) that mimics shunt physiology is an essential tool for refinement and durability testing of arteriovenous implantable bioartificial organs and silicon blood-interfacing membranes.

Patient Preference Trade-offs for Next-Generation Kidney Replacement Therapies.

Background: Next-generation implantable and wearable KRTs may revolutionize the lives of patients undergoing dialysis by providing more frequent and/or prolonged therapy along with greater mobility compared with in-center hemodialysis. Medical device innovators would benefit from patient input to inform product design and development. Our objective was to determine key risk/benefit considerations for patients with kidney failure and test how these trade-offs could drive patient treatment choices.

Feasibility of an implantable bioreactor for renal cell therapy using silicon nanopore membranes.

The definitive treatment for end-stage renal disease is kidney transplantation, which remains limited by organ availability and post-transplant complications. Alternatively, an implantable bioartificial kidney could address both problems while enhancing the quality and length of patient life. An implantable bioartificial kidney requires a bioreactor containing renal cells to replicate key native cell functions, such as water and solute reabsorption, and metabolic and endocrinologic functions.

Inhibition of Transforming Growth Factor-β Improves Primary Renal Tubule Cell Differentiation in Long-Term Culture.

Patient-oriented applications of cell culture include cell therapy of organ failure like chronic renal failure. Clinical deployment of a cell-based device for artificial renal replacement requires qualitative and quantitative fidelity of a cultured cell to its counterpart. Active specific apicobasal ion transport reabsorbs 90-99% of the filtered load of salt and water in the kidney.

Wearable and implantable artificial kidney devices for end-stage kidney disease treatment: Current status and review.

Background: Chronic kidney disease (CKD) is a major cause of early death worldwide. By 2030, 14.5 million people will have end-stage kidney disease (ESKD, or CKD stage 5), yet only 5.

Functionalizing Polyacrylamide Hydrogels for Renal Cell Culture Under Fluid Shear Stress.

A functional renal tubule bioreactor needs to reproduce the reabsorption and barrier functions of the renal tubule. Our prior work has demonstrated that primary human renal tubule cells respond favorably when cultured on substrates with elasticity similar to healthy tissue and when subjected to fluid shear stress. Polyacrylamide (PA) is widely used in industrial processes such as water purification because it is electrically neutral and chemically inert.

Supermeres are functional extracellular nanoparticles replete with disease biomarkers and therapeutic targets.

Extracellular vesicles and exomere nanoparticles are under intense investigation as sources of clinically relevant cargo. Here we report the discovery of a distinct extracellular nanoparticle, termed supermere. Supermeres are morphologically distinct from exomeres and display a markedly greater uptake in vivo compared with small extracellular vesicles and exomeres.

Superporous agarose scaffolds for encapsulation of adult human islets and human stem-cell-derived β cells for intravascular bioartificial pancreas applications.

Type 1 diabetic patients with severe hypoglycemia unawareness have benefitted from cellular therapies, such as pancreas or islet transplantation; however, donor shortage and the need for immunosuppression limits widespread clinical application. We previously developed an intravascular bioartificial pancreas (iBAP) using silicon nanopore membranes (SNM) for immunoprotection. To ensure ample nutrient delivery, the iBAP will need a cell scaffold with high hydraulic permeability to provide mechanical support and maintain islet viability and function.

Metformin and Inhibition of Transforming Growth Factor-Beta Stimulate Transport in Primary Renal Tubule Cells.

Patient-oriented applications of cell culture include cell therapy of organ failure like chronic renal failure. Clinical deployment of a cell-based device for artificial renal replacement requires qualitative and quantitative fidelity of a cultured cell to its counterpart. Active specific apicobasal ion transport reabsorbs 90-99% of the filtered load of salt and water in the kidney.

Reconsidering Garth Robinson: fluid flow and the glomerular filtration barrier.

Purpose Of Review: The goal of this review is to present recent models of the filtration barrier that may suggest mechanism-based treatments for proteinuric renal disease. The vast majority of renal failure occurs in diseases of glomerular proteinuria. The physiology of the filtration barrier remains incompletely understood, preventing invention of mechanism-based therapies.

Genome Engineering Renal Epithelial Cells for Enhanced Volume Transport Function.

Introduction: Bioengineering an implantable artificial kidney (IAK) will require renal epithelial cells capable of reabsorption of salt and water. We used genome engineering to modify cells for improved Na/H exchange and HO reabsorption. The non-viral transposon system enables genome engineering cells to stably overexpress one or more transgenes simultaneously.

Ambulatory Hemodialysis-Technology Landscape and Potential for Patient-Centered Treatment.

CKD is a worldwide health problem and the number of patients requiring kidney replacement therapy is rising. In the United States, most patients with ESKD rely on in-center hemodialysis, which is burdensome and does not provide the same long-term benefits as kidney transplantation. Intensive hemodialysis treatments have demonstrated improved clinical outcomes, but its wider adoption is limited by equipment complexity and patient apprehension.

Application of physiological shear stress to renal tubular epithelial cells.

Renal tubular epithelial cells are consistently exposed to flow of glomerular filtrate that creates fluid shear stress at the apical cell surface. This biophysical stimulus regulates several critical renal epithelial cell functions, including transport, protein uptake, and barrier function. Defining the in vivo mechanical conditions in the kidney tubule is important for accurately recapitulating these conditions in vitro.

Reassessment of Exosome Composition.

The heterogeneity of small extracellular vesicles and presence of non-vesicular extracellular matter have led to debate about contents and functional properties of exosomes. Here, we employ high-resolution density gradient fractionation and direct immunoaffinity capture to precisely characterize the RNA, DNA, and protein constituents of exosomes and other non-vesicle material. Extracellular RNA, RNA-binding proteins, and other cellular proteins are differentially expressed in exosomes and non-vesicle compartments.

Substrate Elasticity Governs Differentiation of Renal Tubule Cells in Prolonged Culture.

Successful clinical tissue engineering requires functional fidelity of the cultured cell to its counterpart, but this has been elusive in renal tissue engineering. Typically, renal proximal tubule cells in culture have a flattened morphology and do not express key transporters essential to their function. In this article, we show for the first time that substrate mechanical properties dictate differentiation of cultured renal proximal tubule cells.