# The Future for End-Stage Kidney Disease Treatment: Implantable Bioartificial Kidney Challenge
## 2 Future Perspective beyond Current Technical Limitations
Likewise, the lack of feedback for aldosterone could indicate a deficiency in potassium secretion and sodium reabsorption, while the lack of ADH target cells could lead to clinically significant variations in plasma osmolality. All such activities cannot be recreated through bioreactors containing a single cell line, requiring different cell types for these specific functions. Concentrating multiple cell lines in a single bioreactor is currently unthinkable. This is due to the different interactions between blood and ultrafiltrate depending on the specific functions that must be performed. An additional problem comes from the thrombogenicity of the device, which may be overcome by using extremely biocompatible materials to minimize the thrombogenic effect of blood contact. Furthermore, in the quest for miniaturization for implantability, the geometry of the ultrafiltration device must provide an adequate and uniform distribution of the blood flow for an ideal ultrafiltration profile [45]. This configuration allows maximization of the blood flow, obtaining the best ultrafiltration in relation to the utmost miniaturized filtering surface to guarantee its implantability. Wearable ultrafiltration devices (WUF) and WAK have already been tested in humans [46] with encouraging clinical results. However, their technical limitations have discouraged their further development; such barriers concern the vascular access provided by a Central Venous Ccatheter (CVC), the need for systemic anticoagulation, the weight of the device (1.1 Kg), its wearable and non-implantable nature, and the low battery life [47]. All the above restraints may be solved with innovations in the field of artificial kidneys through the utilization of new disciplines such as nanotechnology, materials physics, materials engineering, miniaturization, and microfluidics [48], leading to a new era of dialysis in which the new challenge is the development of the iBAK that could eventually save millions of lives [49]. The technological process of transition from in-center to home hemodialysis requires the miniaturization of devices and the introduction of technological innovations that enable their progressive use toward wearability. Current technology is limited, as hemodialysis therapy removes a limited range of uremic toxin discontinuously and requires large volumes of dialysate, thus limiting the portability and patient quality of life and autonomy. The first issue to be addressed concerns the reduced volume of dialysate needed and its regeneration in wearable and implanted devices. The use of different types of sorbents for this purpose has an impact on the ecological footprint of sorbent production and recycling. The reduced removal of uremic toxins resulting from the reduced volume of dialysate in wearable/implanted devices is compensated for by the use of polymeric or inorganic materials in novel dialysis membranes. Such innovative membranes can improve the removal of a broad range of molecules by filtration and adsorption, thus ensuring high efficiency and low levels of membrane fouling compared with currently available membranes for classical hemodialysis. The function of seemingly simplistic uremic toxin removal has to be coupled with biological functions to replace every function of the kidney, such as the production of erythropoietin and vitamin D. This requires the combination of artificial kidneys with bioreactors able to ensure not only the production of hormones but also the catabolism of drugs and the reabsorption of useful molecules from the ultrafiltrate processed in the system (Figure 1). In this way, the physical diffusive and convective processes can be exploited to the fullest to achieve a purification target that maintains the metabolic balance in the patient without leading to the loss of useful molecules in the purification process.