A Role for 3D Printing in Kidney-on-a-Chip Platforms
The advancement of “kidney-on-a-chip” platforms—submillimeter-scale fluidic systems designed to recapitulate renal functions in vitro—directly impacts a wide range of biomedical fields, including drug screening, cell and tissue engineering, toxicity testing, and disease modeling. To fabricate kidney-on-a-chip technologies, researchers have primarily adapted traditional micromachining techniques that are rooted in the integrated circuit industry; hence the term “chip.” A significant challenge, however, is that such methods are inherently monolithic, which limits one’s ability to accurately recreate the geometric and architectural complexity of the kidney in vivo. Better reproduction of the anatomical complexity of the kidney will allow for more instructive modeling of physiological and pathophysiological events. Emerging additive manufacturing or “three-dimensional (3D) printing” techniques could provide a promising alternative to conventional methodologies. In this article, we discuss recent progress in the development of both kidney-on-a-chip platforms and state-of-the-art submillimeter-scale 3D printing methods, with a focus on biophysical and architectural capabilities. Lastly, we examine the potential for 3D printing-based approaches to extend the efficacy of kidney-on-a-chip systems.
Keywords3D Printing Kidney-on-a-chip Organ-on-a-chip Bioartificial kidney Additive manufacturing Microfluidics
Compliance with Ethical Standards
Conflict of Interest
Ryan D. Sochol, Navin R. Gupta, and Joseph V. Bonventre declare that they have no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
- 15.Kuribayashi-Shigetomi K, Onoe H, Takeuchi S. Cell Origami. Self-folding of three-dimensional cell-laden microstructures driven by cell traction force. Plos One. 2012;7(12).Google Scholar
- 45.••Jang KJ, Mehr AP, Hamilton GA, McPartlin LA, Chung S, Suh KY, et al. Human kidney proximal tubule-on-a-chip for drug transport and nephrotoxicity assessment. Integr Biol (Camb). 2013;5(9):1119–29. This study utilizes a multilayer microfluidic system—comprised of two chambers separated by a thin, permeable membrane—to model functions of the proximal tubule for drug toxicity testing.CrossRefGoogle Scholar
- 60.Rose B, Post T. Introduction to renal function. Clinical physiology of acid-base and electrolyte disorders. New York: McGraw-Hill; 2001.Google Scholar
- 62.•Wei Z, Amponsah PK, Al-Shatti M, Nie Z, Bandyopadhyay BC. Engineering of polarized tubular structures in a microfluidic device to study calcium phosphate stone formation. Lab Chip. 2012;12(20):4037–40. This work adapts conventional soft lithography methods (which produce rectangular microfluidic channels) to fabricate cylindrical microfluidic channels for investigating renal functions.CrossRefPubMedPubMedCentralGoogle Scholar
- 63.•Oo ZY, Deng R, Hu M, Ni M, Kandasamy K, bin Ibrahim MS et al. The performance of primary human renal cells in hollow fiber bioreactors for bioartificial kidneys. Biomaterials. 2011;32(34):8806-15. The work presents a hollow, cylindrical fibrin-based permeable membrane for renal applications.Google Scholar
- 69.Hull CW. Apparatus for production of three-dimensional objects by stereolithography. Google Patents; 1986.Google Scholar
- 70.Crump SS. Apparatus and method for creating three-dimensional objects. Google Patents; 1992.Google Scholar
- 71.Yamane M, Kawaguchi T, Kagayama S, Higashiyama S, Suzuki K, Sakai J et al. Apparatus and method for forming three-dimensional article. Google Patents; 1991.Google Scholar
- 72.Almquist TA, Smalley DR. Thermal stereolithography. Google Patents; 1997.Google Scholar
- 85.•Klein F, Richter B, Striebel T, Franz CM, Freymann G, Wegener M, et al. Two-component polymer scaffolds for controlled three-dimensional cell culture. Adv Mater. 2011;23(11):1341–5. This study describes a two-photon DLW approach for constructing 3D cellular scaffolds comprised of distinct materials that either promote or limit cellular attachment at specified locations in 3D space.CrossRefPubMedGoogle Scholar
- 96.••Kolesky DB, Truby RL, Gladman AS, Busbee TA, Homan KA, Lewis JA. 3D bioprinting of vascularized, heterogeneous cell-laden tissue constructs. Adv Mater. 2014;26(19):3124–30. This work combines two distinct extrusion-based 3D bioprinting approaches—sacrifical casting and direct deposition of cell-laden inks—to enable interactions between multiple cell types and microvascular networks.CrossRefPubMedGoogle Scholar