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Abstract: PO0498

Biomimetic Thin Film Scaffolds Support Renal Cell-Based Filtration and Reabsorption

Session Information

Category: Bioengineering

  • 300 Bioengineering

Authors

  • Gallegos, Thomas F., IVIVA Medical, Woburn, Massachusetts, United States
  • Klassen, Charles, IVIVA Medical, Woburn, Massachusetts, United States

Group or Team Name

  • IVIVA Medical
Background

End stage renal disease affects millions of patients worldwide. Allotransplantation is the only curative treatment, yet it is only accessible to a fraction of patients. Hemodialysis does not adequately replace lost renal function. Engineered kidney replacing devices could be an alternative, however, excepting native extracellular matrix, no biologic scaffolding system to support cell-based filtration and absorption has yet been developed.

Methods

Biomimetic thin film scaffolds were fabricated by 3D printing, embedding, and leaching opposing networks of sacrificial material across 5µm thick microporous biologic membranes. The separate channel systems were co-seeded with primary glomerular microvascular endothelial cells and immortalized podocytes (glomerular grafts, N=3), or human umbilical vein endothelial cells and immortalized proximal tubule epithelial cells (tubular grafts, N=4) to recapitulate glomerular and proximal tubule anatomy and physiology.

Results

Scaffolds supported cell engraftment, polarization, and barrier formation in vascular and epithelial channels, and enabled filtration and reabsorption. Acellular scaffold vascular perfusion at 30mmHg resulted in a flow rate of 5.82mL/min/cm 2 (N=9), producing filtrate at 8.01µl/min/cm 2 of membrane. Confluent glomerular grafts produced filtrate at a rate of 3.76µL/min/cm 2 (48h, N=3). At 1 week, mature tubular grafts retained 96.8% of Inulin-FITC in the tubular epithelium (N=3). At maturity, glucose was transported into the vascular channel at a 24 hour rate of 0.11mg/mL/cm 2 (N=4).

Conclusion

Biomimetic thin film scaffolds support formation of perfusable 3D tissues and higher level renal cell based functions such as filtration and reabsorption in vitro. At scale, cellular constructs could enable fabrication of a fully biologic implantable renal replacement device.

Funding

  • Other U.S. Government Support