Kidney Week

Abstract: SA-PO557

Surgical Refinement of Silicon Nanopore Membrane Devices for Implantable Kidney Replacement Therapy: 7-Year Experience across 90 Prototypes

Session Information

• Bioengineering
  October 26, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Bioengineering

• 400 Bioengineering

Authors

• Moyer, Jarrett, University of California San Francisco, San Francisco, California, United States

Jarrett Moyer, MD

• Blaha, Charles, University of California San Francisco, San Francisco, California, United States

Charles Blaha

• Wilson, Mark W., University of California San Francisco, San Francisco, California, United States

Mark W. Wilson, MD

• Vartanian, Shant M., University of California San Francisco, San Francisco, California, United States

Shant M. Vartanian, MD

• Frassetto, Lynda, University of California San Francisco, San Francisco, California, United States

Lynda Frassetto, MD, FASN

• Fissell, William Henry, Vanderbilt University Medical Center, Nashville, Tennessee, United States

William Henry Fissell, MD

• Roy, Shuvo, University of California San Francisco, San Francisco, California, United States

Shuvo Roy, PhD

Background

Silicon nanopore membranes (SNM) are highly permeable and selective filters providing a pathway to next-generation implantable renal replacement therapies (RRT). SNM enable needle-free hemodialyzers, low-resistance hemofilters, and immuno-protective renal tubular cell bioreactors. Implantation of these first-of-their-kind prototypes requires strategies to overcome the recipient anatomy, immune response, and blood-materials interactions. Here we describe iterative refinement of surgical technique over seven years and 90 implants of SNM RRT prototypes.

Methods

Surgical refinement was iterative with experimental results from of each of the 90 implants informing subsequent ones. Initial prototypes housed 2 cm² of SNM surface area, progressing to 832 cm² over the seven-year period. Implants occurred in the dorsolateral neck or retroperitoneum of swine with vascular anastomoses to the cervical or iliac vessels, respectively. The retroperitoneum accommodated devices with more SNM area (mean 204 cm² compared to 20 cm² in the neck). Prototypes were implanted for 3-32 days with subjects receiving anti-platelet agents. Patency was assessed using angiography and direct visualization upon retrieval.

Results

Patency across all prototypes was 67% (60/90) for up to 32 days. An advanced hemofilter housing 166 cm² of SNM surface area exhibited 100% patency (n=9). Of 30 thrombosed prototypes, 17 were due to mechanical obstruction from graft kinks. The largest SNM RRT prototypes were more likely to kink (5 of 8, compared to 10 kinks in 82 small-scale prototypes, p=0.005). Following observation of kinks in 75% of initial implants, a series of protective silicone graft sleeves was applied leading to a reduction to 16% kink rate (p=0.020).

Conclusion

Iterative adaptation of surgical approach and SNM RRT prototypes across 90 implants achieved patency for up to 32 days, while enabling a 416-fold increase in blood-contacting silicon surface with no systemic anticoagulation. Mechanical obstruction to blood flow proved to be the most common cause of device failure and was more likely to occur in the largest prototype. Protection of the vascular graft interface with a silicone sleeve reduced the rate of graft kinks.

Funding

• NIDDK Support