Abstract: PO0513
Demonstrating Preclinical Proof of Concept of an Implantable Bioartificial Kidney (iBAK)
Session Information
- Bioengineering: Organoids and Organs-on-a-Chip
November 04, 2021 | Location: On-Demand, Virtual Only
Abstract Time: 10:00 AM - 12:00 PM
Category: Bioengineering
- 300 Bioengineering
Authors
- Chen, Caressa, University of California San Francisco, San Francisco, California, United States
- Santandreu, Ana, University of California San Francisco, San Francisco, California, United States
- Blaha, Charles, University of California San Francisco, San Francisco, California, United States
- Wright, Nathan, University of California San Francisco, San Francisco, California, United States
- Moyer, Jarrett, University of California San Francisco, San Francisco, California, United States
- Kim, Eun jung, University of California San Francisco, San Francisco, California, United States
- Baltazar, Francisco Javier, University of California San Francisco, San Francisco, California, United States
- Chui, Benjamin W., University of California San Francisco, San Francisco, California, United States
- Haniff, Tariq M., University of California San Francisco, San Francisco, California, United States
- Brakeman, Paul R., University of California San Francisco, San Francisco, California, United States
- Vartanian, Shant M., University of California San Francisco, San Francisco, California, United States
- Humes, H. David, University of Michigan Michigan Medicine, Ann Arbor, Michigan, United States
- Fissell, William Henry, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Roy, Shuvo, University of California San Francisco, San Francisco, California, United States
Group or Team Name
- The Kidney Project
Background
An implantable bioartificial kidney (iBAK) would provide continuous and convenient treatment while overcoming the challenges of dialysis and renal transplant. We previously demonstrated small-scale operational versions of an immunoprotective renal tubule cell-containing bioreactor and a pumpless hemofilter utilizing biomimetic silicon nanopore membranes (SNM). Here we report the successful integration of bioreactor and hemofilter components into an iBAK prototype that demonstrated operational feasibility in swine.
Methods
Designs of the bioreactor and hemofilter were optimized using computational fluid dynamics. Porcine renal (LL-CPK1) cells were cultured on collagen-coated Transwell® (Corning) membranes and inserted into the bioreactor. A hemofilter containing SNM with ~10 nm-wide pores was connected to the bioreactor in series through the hemofilter blood outlet and bioreactor blood inlet. The iBAK was implanted into the retroperitoneum of a healthy Yucatan mini-pig, with anastomoses from the hemofilter blood inlet and bioreactor blood outlet to the iliac artery and vein, respectively, and the bioreactor ultrafiltrate outlet connected to the bladder. The pig did not receive systemic anticoagulation or immunosuppression. After 3 days, patency was assessed via angiogram and the device was explanted for further analysis. Cell viability was assessed using a LIVE/DEAD™ Cell Viability Assay (Invitrogen).
Results
The iBAK was successfully assembled and implanted with no procedural complications. Post-operatively the pig did not demonstrate signs of seroma/hematoma, thromboembolism, infection, or other adverse reactions. 3 days after implant, the device was patent. Ultrafiltrate was noted at both implant and explant, with a flow rate of 0.28 uL/min measured at explant. Cells demonstrated ~80% viability, relative to in vitro controls. No gross thrombi or protein films were observed on the SNM.
Conclusion
We successfully integrated hemofilter and bioreactor components to create a small-scale iBAK. The hemofilter generated ultrafiltrate from blood while the bioreactor sustained renal cells and delivered ultrafiltrate (“urine”) to the bladder. This feasibility study will guide future development of a clinical-scale iBAK.
Funding
- Other NIH Support