A critical review of current progress in 3D kidney biomanufacturing: advances, challenges, and recommendations

Abstract

The widening gap between organ availability and need is resulting in a worldwide crisis, particularly concerning kidney transplantation. Regenerative medicine options are becoming increasingly advanced and are taking advantage of progress in novel manufacturing techniques, including 3D bioprinting, to deliver potentially viable alternatives. Cell-integrated and wearable artificial kidneys aim to create convenient and efficient systems of filtration and restore elements of immunoregulatory function. Whilst preliminary clinical trials demonstrated promise, manufacturing and trial design issues and identification of suitable and sustainable cell sources have shown that more development is required for market progression. Tissue engineering and advances in biomanufacturing techniques offer potential solutions for organ shortages; however, due to the complex kidney structure, previous attempts have fallen short. With the recent development and progression of 3D bioprinting, cell positioning and resolution of material deposition in organ manufacture have never seen greater control. Cell sources for constructing kidney building blocks and populating both biologic and artificial scaffolds and matrices have been identified, but in vitro culturing and/or differentiation, in addition to maintaining phenotype and viability during and after lengthy and immature manufacturing processes, presents additional problems. For all techniques, significant process barriers, clinical pathway identification for translation of models to humans, scaffold material availability, and long-term biocompatibility need to be addressed prior to clinical realisation.

Probing expert opinions on the future of kidney replacement therapies

“…Wearable peritoneal dialysis that incorporates lower glucose levels, reducing the osmotic stress on the peritoneum 24 Biohybrid implantable kidney 1 -Implanted artificial kidney Combining artificial filters and living cells currently in preclinical testing 23 2 -Xenotransplanted or Chimeric kidneys Transplantation of kidney living cells or tissue from one species to another or tissue deriving from donor and recipient 26 3 -3D/4D bioprinting Utilization of 3D/4D printing-like techniques to combine cells, growth factors, and biomaterials to fabricate whole kidney or parts of it 27 4 -Bioartificial renal epithelial cell system (BRECS) implantable kidney (37.74%), followed by portable/wearable devices (33.36%). Enhanced dialysis and regenerated kidney were the approaches chosen by, respectively, 14.86% and 14.04% of the respondents.…”

3D Bioprinting-Based Vascularized Tissue Models Mimicking Tissue-Specific Architecture and Pathophysiology for in vitro Studies

“…Nephrons, the functional units of the kidney, consist of Bowman's capsule glomerulus, and tubules, such as the proximal and distal convoluted tubules and loop of Henle. Nephrons closely interact with blood vessels, such as the renal artery and vein (Wragg et al, 2019;Gupta et al, 2020). Given that kidney models are typically based on fluidic systems, several techniques are employed to manufacture 3D in vitro kidney models, including soft lithography, molding, and hollow fibers (Wilmer et al, 2016;Wragg et al, 2019;Zanetti, 2019;Singh et al, 2020).…”

“…Nephrons closely interact with blood vessels, such as the renal artery and vein (Wragg et al, 2019;Gupta et al, 2020). Given that kidney models are typically based on fluidic systems, several techniques are employed to manufacture 3D in vitro kidney models, including soft lithography, molding, and hollow fibers (Wilmer et al, 2016;Wragg et al, 2019;Zanetti, 2019;Singh et al, 2020). Although these models exhibited microfluidic conditions, they cannot fully mimic the complex tubule structure that may affect renal tubule cell performance in vitro (Wilmer et al, 2016;Wragg et al, 2019;Singh et al, 2020).…”

“…Given that kidney models are typically based on fluidic systems, several techniques are employed to manufacture 3D in vitro kidney models, including soft lithography, molding, and hollow fibers (Wilmer et al, 2016;Wragg et al, 2019;Zanetti, 2019;Singh et al, 2020). Although these models exhibited microfluidic conditions, they cannot fully mimic the complex tubule structure that may affect renal tubule cell performance in vitro (Wilmer et al, 2016;Wragg et al, 2019;Singh et al, 2020). 3D bioprinting research has largely focused on the fabrication of perfusable systems with convoluted structures to recapitulate the architecture and functions of native proximal tubules (Homan et al, 2016;Lin et al, 2019;Singh et al, 2020).…”

Current Advances in 3D Tissue and Organ Reconstruction

“…In the kidney, a variety of successful strategies were developed [ 197 ]. However, the current techniques still show important limitations that impede the obtainment of a complete and functional whole-organ.…”