In this new era of technological advancement, three-dimensional (3D) printing has emerged in medicine, promising to revolutionize surgical practices. Three-dimensional printing could be defined as “translating” a digital image into a 3D solid object by printing consecutive thin layers of materials. The fusion of tissue engineering and 3D printing has given rise to bioprinting. This technique employs biocompatible printers and "bio-ink" to create intricate tissue structures, while the complete fabrication of functional organs remains a research objective. 3D bioprinting has already shown promising results, especially in the field of microfluidic devices with the development of tissues demonstrating proximal tubules, glomerulus, and tubuloinerstitium functions. Such models could be applied in renal disease modeling and during drug development for nephrotoxicity investigation.
First Author | Cell Lines-Subjects | Printer Type/Bioink | Printing Strategy | Aim | Results | |
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1. | Homan KA. [17] | PTEC | AGB 10000, (©Aerotech Inc., Pittsburgh, PA, USA)/gelatin-fibrin hydrogel, fugitive ink, silicone elastomer | Scaffold based | Develop 3D convoluted renal proximal tubules within microfluidic chips | The microfluidic-based model showed high cell viability, gene expression pattern close to primary renal PTEC, and superior functional albumin uptake compared with 2D controls |
2. | Lin NYC. [18] | PTEC, vascular endothelial cells | 3D-Bioplotter (©EnvisionTEC)/gelatin-fibrin-based ECM, fugitive ink | Scaffold based | Vascularized proximal tubules (microfluidic platform) demonstrating reabsorption of solutes (tubular-vascular exchange) | The model demonstrated active albumin and glucose reabsorption. |
3. | King MS [19] | HUVEC, adult, renal, fibroblast, and renal PTEC | NovoGen Bioprinter Instrument (©Organovo Inc., San Diego, CA, USA)/NovoGel Bio-Ink | Scaffold based | Develop a renal proximal tubule model in vitro supported by renal fibroblast and endothelial cells. | The model demonstrated functions of the native proximal tubule, drug-induced nephrotoxicity, and renal fibrosis. |
4. | Ali M. [20] | Porcine kidneys/human primary kidney cells | ITOP system/KdECMMA-based | Scaffold based | Investigate the role of KdECMMA-based bio-ink in supporting 3D bioprinted renal constructs from human primary kidney cells | The constructs demonstrated high cell viability, and significantly higher sodium reabsorption and hydrolase activity compared to the control group. |
5. | Addario G. [21] | pmTEC, HUVEC fibroblasts | Microfluidic bioprinter (©RX1 Aspect Biosystems, Canada)/alginate, gelatin, pectin | Scaffold based | Development of a microfluidic-based tubulointerstitium model for in-vitro studies | The authors achieved to develop multiple models of different cell-line/bio-ink formulations comparing the cell viability and metabolic activity of the various constructs |
6. | Lawlor KT. [22] | hPSCs | NovoGen MMX extrusion-based 3D cellular bioprinter (©Organovo Inc., San Diego, CA, USA)/Cellular Bio-Ink. | Scaffold free | Develop renal organoids of highly reproducible cell number and viability by extrusion-based 3D cellular bioprinting. | Achieved the formation of renal organoids demonstrating a high resemblance to nephron histology, high reproducibility/cell viability, and drug-induced nephrotoxicity |
7. | Jo H. [23] | Autologous omentum tissue/UUO Rats | Dr. INVIVO (©ROKIT Healthcare, Inc., Seoul, Korea)/fibrinogen, thrombin | Scaffold free | Transplantation of an autologous omentum patch in the renal subcapsular space for immune regulation and tissue regeneration | Reduced tubular injury and downregulation of fibrosis-inducing mechanisms were observed in the omentum patch group. |
8. | Singh NK. [24] | Porcine kidneys, hBMMSC, renal PTEC, and HUVEC, UUO mice | In-house developed 3D cell-printing system/decellularized ECMs, alginate, pluronic | Scaffold based | Develop a 3D microfluidic vascularized renal tubular tissue-on-a-chip. Transplant grafts in UUO mice | Perfusable tubular constructs were developed with the ability to switch between monolayer and bilayer. Markers of tissue maturation were observed regarding renal tubular tissue and vascular tissue. UUO |
ESKD approaches pandemic proportions, which will deteriorate the disequilibrium between available grafts and the demand for transplantable organs. The application of regenerative medicine and bioengineering, including 3D bioprinting, could lead to a new era in renal transplantation. 3D bioprinting has already shown promising results, especially in the field of microfluidic devices with the development of tissues demonstrating proximal tubules, glomerulus, and tubuloinerstitium functions. Such models could be applied in renal disease modeling and during drug development for nephrotoxicity investigation. Finally, focusing on transplantation, studies employing 3D bioprintable tissues for the management of ESKD have demonstrated promising results in animal models restoring part of the renal function.
Alternative promising approaches for the management of ESKD are the use of wearable and implantable artificial kidney devices and xenotransplantation. Wearable hemodialysis devices have achieved proof-of-concept in human clinical trials, while implantable hemodialysis devices have not yet reached human trials. Wearable hemodialysis devices aim to provide continuous renal replacement therapy, achieving higher solute clearance than standard hemodialysis. While wearable and implantable artificial kidney devices demonstrate promising results and, in terms of scalability, could be the most practical approach for ESKD management, they still face several challenges, including the engineering challenge of miniaturizing the devices, optimizing sorbent materials, patient suitability and accessibility, preventive anticoagulation for long-term patency, microbiological contamination, and long-term effectiveness.
Renal xenotransplantation of genetically engineered pigs for human xenotransplantation has, on the other hand, already reached pre-clinical phases and is closer to addressing the graft shortage compared to 3D bioprinting, where the research is still at a founding stage. Specifically, in a recent study, Porrett et al. performed bilateral native nephrectomies in a human brain-dead decedent and then transplanted two bioengineered renal grafts. Notably, the decedent remained hemodynamically stable through reperfusion; no hyperacute rejection or porcine virus transmission was observed, while the kidneys retained viability until termination 74 hours later. In a different study by Montgomery et al., genetically engineered pig kidneys were transplanted into two brain-deaded human recipients, demonstrating urine and creatinine output following reperfusion without signs of hyperacute rejection. Nevertheless, many challenges are still associated with renal xenotransplantation, including long-term viability and functionality, immunological barriers, the risk of zoonotic diseases, ethical and moral concerns, public acceptance, cost, and accessibility.
This entry is adapted from the peer-reviewed paper 10.3390/jcm12206520