Bioprinting of 3D Convoluted Renal Proximal Tubules on Perfusable Chips

Abstract

Three-dimensional models of kidney tissue that recapitulate human responses are needed for drug screening, disease modeling, and, ultimately, kidney organ engineering. Here, we report a bioprinting method for creating 3D human renal proximal tubules in vitro that are fully embedded within an extracellular matrix and housed in perfusable tissue chips, allowing them to be maintained for greater than two months. Their convoluted tubular architecture is circumscribed by proximal tubule epithelial cells and actively perfused through the open lumen. These engineered 3D proximal tubules on chip exhibit significantly enhanced epithelial morphology and functional properties relative to the same cells grown on 2D controls with or without perfusion. Upon introducing the nephrotoxin, Cyclosporine A, the epithelial barrier is disrupted in a dose-dependent manner. Our bioprinting method provides a new route for programmably fabricating advanced human kidney tissue models on demand.

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“…Analysis showed that this 3D kidney model exhibits cyclosporine toxicity and albumin uptake as they would in the human body ( Figure 6) [61]. This 3D model represents an improvement over 2D organ-on-chip models and a large step closer to developing a fully-functional kidney [61]. What once seemed like science fiction is now getting closer and closer to reality.…”

“…It was mentioned earlier how scientists plan to do this using fugitive inks [60]. A model for the kidney's proximal tubules has now been created using these techniques [61]. Researchers at Harvard's Wyss Institute.…”

“…Researchers at Harvard's Wyss Institute. 3D-printed a section of kidney microtubule as a 3D "organ-on-chip" model by using pluronic set in a gelatin/fibrinogen matrix and then later replacing the pluronic fugitive ink with kidney microtubule cells ( Figure 5) [61]. Analysis showed that this 3D kidney model exhibits cyclosporine toxicity and albumin uptake as they would in the human body ( Figure 6) [61].…”

“…3D-printed a section of kidney microtubule as a 3D "organ-on-chip" model by using pluronic set in a gelatin/fibrinogen matrix and then later replacing the pluronic fugitive ink with kidney microtubule cells ( Figure 5) [61]. Analysis showed that this 3D kidney model exhibits cyclosporine toxicity and albumin uptake as they would in the human body ( Figure 6) [61]. This 3D model represents an improvement over 2D organ-on-chip models and a large step closer to developing a fully-functional kidney [61].…”

Current progresses of 3D bioprinting based tissue engineering

“…Xiaofeng Cui [27] and colleagues had applied a different strategy by using a natural osteochodral plug (extracted from bovine femoral condyles) as scaffold instead of synthesized polymers, then printed human chondrocytes mixed with modified PEG (polyethylene glycol dimethacrylate) onto the plug using thermal inkjet printer ( Figure 2C), and were able to generate integrated and stabilized new cartilage tissue after 6 weeks of culture. In another trial, Chang H. Lee and colleagues replaced the sheep native meniscus with a PCL-printed scaffold carrying connective tissue growth factor (CTGF) and transforming Smooth muscle cell [40] Epithelial cell [24] growth factor-β3 (TGF-β). These factors stimulated endogenous cells to reconstruct ECM (collagen) and enabled sheep to resume walking capacity about 12 weeks after surgery [14].…”