# The Future for End-Stage Kidney Disease Treatment: Implantable Bioartificial Kidney Challenge
## 1 Introduction
### Current Extracorporeal Purification between Limitations and New Perspectives
The new synthetic dialysis membranes are composed of hydrophobic polymers blended with Polyvinylpyrrolidone (PVP) or other additives to improve biocompatibility, although the long-term use and sterilization process can elute them, reducing compatibility [28; 29]. To resolve this problem, polyvinylidene fluoride membranes are coated with polyvinyl alcohol and chitosan. This improves biocompatibility [30] and can determine white cells, complement activation, and filter clotting. The issue of filter clotting can be reduced by using membranes with grafted argatroban onto the surface of polysulfone membrane [31], achieving a good anti-thrombogenic effect. Despiteall these implementations, the potential miniaturization of this new type of membrane is limited [32] due to permeability limitations caused by fiber geometry and hydraulic resistance, which requires bulky devices. Another membrane limitation is its relatively broad pore size distribution that limits filtration selectivity, which is now overcome by silicon-based nanoporous membranes (SNMs) presenting uniform nanopores with a deviation between pore sizes of less than 1% [32; 33; 34]. In order to enhance permeability due to their low porosity, these SNMs have been fabricated with arrays of nanoslits (10 nm wide and 4.5 um long) [34], presenting uniform nanopores suitable for hemodialysis and hemofiltration. Their limitation in clinical use concerns the poor silicon hemocompatibility, which requires a hydrophilic coating with polyethylene glycol (PEG) to prevent activation of macrophages, innate immunity dysregulation, and inflammation. This technological solution is not definitive [34], as in an implantable artificial kidney, the PEG can quickly degrade, so much longer-lasting alternatives are needed. The combination of a hemocompatibility inner porous layer based on polyethersulfone/polyvinylpyrrolidone (PES/PVP) and an outer layer of activated carbon dispersed within a matrix of PES/PVP in contact with the dialysate can determine low cell adhesion with improved hemocompatibility, associated with enhanced toxin removal by diffusion/convection and inner membrane layer adsorption by activated carbon particles, which leads to a high toxin concentration gradient across the membrane, thus stimulating the further dissociation of protein-bound toxins from plasmatic proteins. This process can enable the application of lower amounts of dialysate than conventional hemodialysis membranes. Additionally, this membrane structure can protect the patient from bacterial pyrogen contamination from the dialysate [35]. It seems that the development of such membranes introduces important advantages for implantable systems, where a low quantity of dialysate is required for prolonged application. The permanence of such implanted devices for a prolonged period could result in the deterioration of dialysate characteristics, including bacterial contamination, and any form of patient protection could be helpful. To mimic the glomerular filtration, the characteristics of current membranes had to be implemented in the WAK, and the system supplied with a closed-loop dialysate regeneration system. Otherwise, to mimic the tubular reabsorption of water, ions, glucose, and amino acids from the filtrate, it is necessary to imply a specific technology based on ion exchange resin combination, ion exchange membranes, and an externally applied voltage to achieve selective ion reabsorption.