Construction and Evaluation of a Bio-Engineered Pump to Enable Subpulmonary Support of the Fontan Circulation: A Proof-of-Concept Study

Abstract

Create a bio-engineered pump (BEP) intended for subpulmonary Fontan circulation support consisting of a biological blood reservoir flanked by valves that can be externally compressed and produce a 2-6 mmHg pressure gradient across the device without flow obstruction. Decellularlized urinary bladder matrix (UBM), previously shown to be a suitable substrate for endothelial cells, underwent a lamination process to created bilayer UBM sheets which were then used to create biological reservoirs. Reservoir testing included compliance and pressure evaluation. BEPs were constructed by securing the biological reservoir between inlet (Vi) and outlet (Vo) valves and compressed with a polyurethane balloon (A). The BEP function was evaluated in a simple flow loop representative of a modified subpulmonary Fontan circulation with representative vena cava (IVC) and pulmonary artery (PA) with a baseline "filling pressure" of 6 mmHg at a flow rate of 4.0 liters per minute (LPM). BEPs were successfully constructed (B). The devices demonstrated high compliance with small pressure increases at low volumes (4.25 mmHg/mL) and were able to withstand internal pressure increases >70 mmHg. Placement of a non-active BEP into the flow loop caused a flow rate change from ∼4.0 LPM to ∼3.9 LPM with < 1 mmHg pressure change between the IVC and PA (C). A BEP with biological reservoir fill volume of 92 mL operating at 60 cycles per minute produced pulsatile downstream flows at an average of 4.0 LPM and generated a pressure gradient across the device maintaining upstream pressure of 6 mmHg and producing downstream pressure of 13 mmHg (D). Urinary bladder matrix can be formed into a biological reservoir and used to construct a bio-engineered pump. In a simple flow loop representative of a subpulmonary Fontan circulation, the BEP can produce pulsatile downstream flow and create a favorable pressure gradient across the device while maintaining a low upstream pressure.